Geographical and Temporal Variations in Female Breast Cancer Mortality in the Municipalities of Andalusia (Southern Spain)

PubMed Central

Ocaña-Riola, Ricardo; Montaño-Remacha, Carmen; Mayoral-Cortés, José María

2016-01-01

The last published figures have shown geographical variations in mortality with respect to female breast cancer in European countries. However, national health policies need a dynamic image of the geographical variations within the country. The aim of this paper was to describe the spatial distribution of age-specific mortality rates from female breast cancer in the municipalities of Andalusia (southern Spain) and to analyze its evolution over time from 1981 to 2012. An ecological study was devised. Two spatio-temporal hierarchical Bayesian models were estimated. One of these was used to estimate the age-specific mortality rate for each municipality, together with its time trends, and the other was used to estimate the age-specific rate ratio compared with Spain as a whole. The results showed that 98% of the municipalities exhibited a decreasing or a flat mortality trend for all the age groups. In 2012, the geographical variability of the age-specific mortality rates was small, especially for population groups below 65. In addition, more than 96.6% of the municipalities showed an age-specific mortality rate similar to the corresponding rate for Spain, and there were no identified significant clusters. This information will contribute towards a reflection on the past, present and future of breast cancer outcomes in Andalusia. PMID:27879690

Lung cancer mortality in France. Trend analysis and projection between 1975 and 2012, using a Bayesian age-period-cohort model.

PubMed

Eilstein, Daniel; Uhry, Zoé; Lim, Tek-Ang; Bloch, Juliette

2008-03-01

Lung cancer is currently the most common cancer in the world and as such is an important public health concern. One of the main challenges is to foresee the evolution of trends in lung cancer mortality rates in order to anticipate the future burden of this disease as well as to plan the supply of adequate health care. The aim of this study is to propose a quantification of future lung cancer mortality rates by gender in France until the year 2012. Lung cancer mortality data in France (1978-2002) were extracted from the National Statistics of Death and analyzed by 5-year age-groups and periods, using a Bayesian age-period-cohort model. Between 1978 and 2002, female lung cancer mortality rate rises by 3.3%year(-1). For men, a slow increase is observed until 1988-1992 followed by a declining trend. In 1998-2002, age-standardized mortality rates were, respectively, 45.5 and 7.6 per 100000 for males and for females. By 2008-2012 these figures would reach 40.8 (95% credibility interval (CI): 32.7, 50.0) and 12.1 (CI: 11.7, 12.6) per 100000, respectively, which represents among women a 4.7% annual increase (CI: 4.5, 5.0). Our results highlight the relevance of pursuing public health measures in order to cope more actively with tobacco smoking in the prevention strategy against lung cancer specifically among women.

Spatial gender-age-period-cohort analysis of pancreatic cancer mortality in Spain (1990–2013)

PubMed Central

Etxeberria, Jaione; Goicoa, Tomás; López-Abente, Gonzalo; Riebler, Andrea

2017-01-01

Recently, the interest in studying pancreatic cancer mortality has increased due to its high lethality. In this work a detailed analysis of pancreatic cancer mortality in Spanish provinces was performed using recent data. A set of multivariate spatial gender-age-period-cohort models was considered to look for potential candidates to analyze pancreatic cancer mortality rates. The selected model combines features of APC (age-period-cohort) models with disease mapping approaches. To ensure model identifiability sum-to-zero constraints were applied. A fully Bayesian approach based on integrated nested Laplace approximations (INLA) was considered for model fitting and inference. Sensitivity analyses were also conducted. In general, estimated average rates by age, cohort, and period are higher in males than in females. The higher differences according to age between males and females correspond to the age groups [65, 70), [70, 75), and [75, 80). Regarding the cohort, the greatest difference between men and women is observed for those born between the forties and the sixties. From there on, the younger the birth cohort is, the smaller the difference becomes. Some cohort differences are also identified by regions and age-groups. The spatial pattern indicates a North-South gradient of pancreatic cancer mortality in Spain, the provinces in the North being the ones with the highest effects on mortality during the studied period. Finally, the space-time evolution shows that the space pattern has changed little over time. PMID:28199327

Cancer heterogeneity: converting a limitation into a source of biologic information.

PubMed

Rübben, Albert; Araujo, Arturo

2017-09-08

Analysis of spatial and temporal genetic heterogeneity in human cancers has revealed that somatic cancer evolution in most cancers is not a simple linear process composed of a few sequential steps of mutation acquisitions and clonal expansions. Parallel evolution has been observed in many early human cancers resulting in genetic heterogeneity as well as multilineage progression. Moreover, aneuploidy as well as structural chromosomal aberrations seems to be acquired in a non-linear, punctuated mode where most aberrations occur at early stages of somatic cancer evolution. At later stages, the cancer genomes seem to get stabilized and acquire only few additional rearrangements. While parallel evolution suggests positive selection of driver mutations at early stages of somatic cancer evolution, stabilization of structural aberrations at later stages suggests that negative selection takes effect when cancer cells progressively lose their tolerance towards additional mutation acquisition. Mixing of genetically heterogeneous subclones in cancer samples reduces sensitivity of mutation detection. Moreover, driver mutations present only in a fraction of cancer cells are more likely to be mistaken for passenger mutations. Therefore, genetic heterogeneity may be considered a limitation negatively affecting detection sensitivity of driver mutations. On the other hand, identification of subclones and subclone lineages in human cancers may lead to a more profound understanding of the selective forces which shape somatic cancer evolution in human cancers. Identification of parallel evolution by analyzing spatial heterogeneity may hint to driver mutations which might represent additional therapeutic targets besides driver mutations present in a monoclonal state. Likewise, stabilization of cancer genomes which can be identified by analyzing temporal genetic heterogeneity might hint to genes and pathways which have become essential for survival of cancer cell lineages at later stages of cancer evolution. These genes and pathways might also constitute patient specific therapeutic targets.

The Genomic Evolution of Prostate Cancer

DTIC Science & Technology

2017-06-01

management and grant writing skills. 15. SUBJECT TERMS Cancer genetics , tumor evolution, tumor heterogeneity, prostate cancer, exome sequencing 16...aggressive disease, it is unclear if the genetic alterations more common in late disease are present early on, but at low frequency, or if they only...from localized to metastatic prostate cancer. 2. KEYWORDS: Cancer genetics , tumor evolution, tumor heterogeneity, prostate cancer, exome sequencing

The multiple facets of Peto's paradox: a life-history model for the evolution of cancer suppression

PubMed Central

Brown, Joel S.; Cunningham, Jessica J.; Gatenby, Robert A.

2015-01-01

Large animals should have higher lifetime probabilities of cancer than small animals because each cell division carries an attendant risk of mutating towards a tumour lineage. However, this is not observed—a (Peto's) paradox that suggests large and/or long-lived species have evolved effective cancer suppression mechanisms. Using the Euler–Lotka population model, we demonstrate the evolutionary value of cancer suppression as determined by the ‘cost’ (decreased fecundity) of suppression verses the ‘cost’ of cancer (reduced survivorship). Body size per se will not select for sufficient cancer suppression to explain the paradox. Rather, cancer suppression should be most extreme when the probability of non-cancer death decreases with age (e.g. alligators), maturation is delayed, fecundity rates are low and fecundity increases with age. Thus, the value of cancer suppression is predicted to be lowest in the vole (short lifespan, high fecundity) and highest in the naked mole rat (long lived with late female sexual maturity). The life history of pre-industrial humans likely selected for quite low levels of cancer suppression. In modern humans that live much longer, this level results in unusually high lifetime cancer risks. The model predicts a lifetime risk of 49% compared with the current empirical value of 43%. PMID:26056365

Cancer and intercellular cooperation

PubMed Central

Dieli, Anna Maria

2017-01-01

The major transitions approach in evolutionary biology has shown that the intercellular cooperation that characterizes multicellular organisms would never have emerged without some kind of multilevel selection. Relying on this view, the Evolutionary Somatic view of cancer considers cancer as a breakdown of intercellular cooperation and as a loss of the balance between selection processes that take place at different levels of organization (particularly single cell and individual organism). This seems an elegant unifying framework for healthy organism, carcinogenesis, tumour proliferation, metastasis and other phenomena such as ageing. However, the gene-centric version of Darwinian evolution, which is often adopted in cancer research, runs into empirical problems: proto-tumoural and tumoural features in precancerous cells that would undergo ‘natural selection’ have proved hard to demonstrate; cells are radically context-dependent, and some stages of cancer are poorly related to genetic change. Recent perspectives propose that breakdown of intercellular cooperation could depend on ‘fields’ and other higher-level phenomena, and could be even mutations independent. Indeed, the field would be the context, allowing (or preventing) genetic mutations to undergo an intra-organism process analogous to natural selection. The complexities surrounding somatic evolution call for integration between multiple incomplete frameworks for interpreting intercellular cooperation and its pathologies. PMID:29134064

Predictive genomics: a cancer hallmark network framework for predicting tumor clinical phenotypes using genome sequencing data.

PubMed

Wang, Edwin; Zaman, Naif; Mcgee, Shauna; Milanese, Jean-Sébastien; Masoudi-Nejad, Ali; O'Connor-McCourt, Maureen

2015-02-01

Tumor genome sequencing leads to documenting thousands of DNA mutations and other genomic alterations. At present, these data cannot be analyzed adequately to aid in the understanding of tumorigenesis and its evolution. Moreover, we have little insight into how to use these data to predict clinical phenotypes and tumor progression to better design patient treatment. To meet these challenges, we discuss a cancer hallmark network framework for modeling genome sequencing data to predict cancer clonal evolution and associated clinical phenotypes. The framework includes: (1) cancer hallmarks that can be represented by a few molecular/signaling networks. 'Network operational signatures' which represent gene regulatory logics/strengths enable to quantify state transitions and measures of hallmark traits. Thus, sets of genomic alterations which are associated with network operational signatures could be linked to the state/measure of hallmark traits. The network operational signature transforms genotypic data (i.e., genomic alterations) to regulatory phenotypic profiles (i.e., regulatory logics/strengths), to cellular phenotypic profiles (i.e., hallmark traits) which lead to clinical phenotypic profiles (i.e., a collection of hallmark traits). Furthermore, the framework considers regulatory logics of the hallmark networks under tumor evolutionary dynamics and therefore also includes: (2) a self-promoting positive feedback loop that is dominated by a genomic instability network and a cell survival/proliferation network is the main driver of tumor clonal evolution. Surrounding tumor stroma and its host immune systems shape the evolutionary paths; (3) cell motility initiating metastasis is a byproduct of the above self-promoting loop activity during tumorigenesis; (4) an emerging hallmark network which triggers genome duplication dominates a feed-forward loop which in turn could act as a rate-limiting step for tumor formation; (5) mutations and other genomic alterations have specific patterns and tissue-specificity, which are driven by aging and other cancer-inducing agents. This framework represents the logics of complex cancer biology as a myriad of phenotypic complexities governed by a limited set of underlying organizing principles. It therefore adds to our understanding of tumor evolution and tumorigenesis, and moreover, potential usefulness of predicting tumors' evolutionary paths and clinical phenotypes. Strategies of using this framework in conjunction with genome sequencing data in an attempt to predict personalized drug targets, drug resistance, and metastasis for cancer patients, as well as cancer risks for healthy individuals are discussed. Accurate prediction of cancer clonal evolution and clinical phenotypes will have substantial impact on timely diagnosis, personalized treatment and personalized prevention of cancer. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

Measuring cancer evolution from the genome.

PubMed

Graham, Trevor A; Sottoriva, Andrea

2017-01-01

The temporal dynamics of cancer evolution remain elusive, because it is impractical to longitudinally observe cancers unperturbed by treatment. Consequently, our knowledge of how cancers grow largely derives from inferences made from a single point in time - the endpoint in the cancer's evolution, when it is removed from the body and studied in the laboratory. Fortuitously however, the cancer genome, by virtue of ongoing mutations that uniquely mark clonal lineages within the tumour, provides a rich, yet surreptitious, record of cancer development. In this review, we describe how a cancer's genome can be analysed to reveal the temporal history of mutation and selection, and discuss why both selective and neutral evolution feature prominently in carcinogenesis. We argue that selection in cancer can only be properly studied once we have some understanding of what the absence of selection looks like. We review the data describing punctuated evolution in cancer, and reason that punctuated phenotype evolution is consistent with both gradual and punctuated genome evolution. We conclude that, to map and predict evolutionary trajectories during carcinogenesis, it is critical to better understand the relationship between genotype change and phenotype change. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Temporal trends and regional variations in gastrointestinal cancer mortality in Peru, 2005-2014.

PubMed

Hernández-Vásquez, Akram; Bendezú-Quispe, Guido; Azañedo, Diego; Huarez, Bertha; Rodríguez-Lema, Belén

2016-01-01

To estimate and analyze the evolution of mortality rates of gastrointestinal (GI) cancer in Peru and its regions between 2005-2014. We performed a nationwide secondary analysis of Peru's Health Ministry registry of deaths during the period 2005-2014, with a focus on regional differences. Deaths registered with codes C15 to C25 (malignant neoplasms of digestive organs) from the ICD-10 were included. Calculation of age-standarized mortality rates and years of life lost (YLL) due to GI cancer per 100,000 habitants were also performed. Data of 67,527 deaths from GI cancers was analyzed, 35,055 (51.91%) were women. In 2005, the number of GI cancer deaths was 6,484, for 2014, 7,532 cases were recorded. The GI cancer age-standarized mortality rates at the country level showed a decrease of 12.70% between 2005-2014. Stomach cancer presented the highest age-standarized mortality rate despite showing a downward trend in the last years, equal for gallbladder, liver and biliary tract, and esophagus cancer. Colorectal, small intestine and anus cancer show a progressive increase. In 2014, Callao (48.8), Huancavelica (48.5), La Libertad (39.6), Lambayeque (40.5) and Huanuco (38.9) had the highest rates. The three types of GI cancers with the highest rates of YLL in 2014 were stomach cancer (118.51), followed by liver and biliary tract cancer (58.68) and colorectal (44.86). GI cancer mortality in Peru is high and a priority issue in regions like Huancavelica, Huanuco, Callao, La Libertad and Lambayeque. Stomach cancer remains the most frequent GI cancer, but with a downward trend in the study period.

[Head and neck cancer patients included at home enteral nutrition by tube].

PubMed

Cots Seignot, I; Cárdenas Lagranja, G; Puiggròs Llop, C; Chicharro Serrano, L; Pérez-Portabella Maristany, C; Planas Vilà, M

2009-01-01

To know characteristics and the patients' evolution with head and neck cancer who received radiotherapy treatment and they were included at a home enteral nutrition (HEN) by feeding tube programme. To analyse the weight evolution according to the start of HEN before or after radiotherapy. Observational study of tube feeding patients with head and neck cancer who were included in HEN programme in our hospital for two years. Variables analysed: gender, age, Body Mass Index (BMI), Karnofsky Index (KI), reason for nutritional support, type of feeding tube, formula used and prescribed caloric contribution, necessity to change access device and HEN days. 62 patients were studied (77.4% men; 22.6% women). Age 64 +/- 10.1 years (rang: 39-90). The dysphagia was the main cause to begin enteral nutrition by feeding tube in these patients. Naso-gastric tube was prevalence (67.7%). The most used formula was polymeric hypercaloric diet with a mean of caloric contribution of 1,629 +/- 267.09 kcal/day. Overall, there was a weight loss in all patients during the study period time. However, patients who began the HEN by feeding tube before the radiotherapy treatment, the BMI did not decrease. All patients who began feeding tube before oncological treatment didn't lose weight for the period of study.

Disparities in the Clinical Evolution of Anal Neoplasia in an HIV-Infected Cohort.

PubMed

Cachay, Edward R; Agmas, Wollelaw; Christopher Mathews, Wm

2018-02-01

A recent meta-analysis suggested that anal intraepithelial neoplasia and invasive anal cancer are more prevalent among black men having sex with men (MSM). We conducted a retrospective cohort of HIV-infected adult patients under care between 2001 and 2012. Disparities in clinical evolution of anal intraepithelial neoplasia to high-grade squamous intraepithelial lesion (HSIL) and invasive anal cancer were evaluated in a three-state Markov model adjusted for cytology misclassification. We studied sociodemographic covariate effects for each state transition using multivariable models controlling for antiretroviral therapy and infrared coagulation treatment of HSIL. Among 2804 patients with a median age of 40 years, 78% were MSM and 38% non-white. There were no disparities in HSIL prevalence (14%) by age, sex, race, or risk group. After 4.0 years of follow-up, 23 patients developed invasive anal cancer. Females and black patients had lower transition rates from 40 had lower rates of both

A Gene Gravity Model for the Evolution of Cancer Genomes: A Study of 3,000 Cancer Genomes across 9 Cancer Types.

PubMed

Cheng, Feixiong; Liu, Chuang; Lin, Chen-Ching; Zhao, Junfei; Jia, Peilin; Li, Wen-Hsiung; Zhao, Zhongming

2015-09-01

Cancer development and progression result from somatic evolution by an accumulation of genomic alterations. The effects of those alterations on the fitness of somatic cells lead to evolutionary adaptations such as increased cell proliferation, angiogenesis, and altered anticancer drug responses. However, there are few general mathematical models to quantitatively examine how perturbations of a single gene shape subsequent evolution of the cancer genome. In this study, we proposed the gene gravity model to study the evolution of cancer genomes by incorporating the genome-wide transcription and somatic mutation profiles of ~3,000 tumors across 9 cancer types from The Cancer Genome Atlas into a broad gene network. We found that somatic mutations of a cancer driver gene may drive cancer genome evolution by inducing mutations in other genes. This functional consequence is often generated by the combined effect of genetic and epigenetic (e.g., chromatin regulation) alterations. By quantifying cancer genome evolution using the gene gravity model, we identified six putative cancer genes (AHNAK, COL11A1, DDX3X, FAT4, STAG2, and SYNE1). The tumor genomes harboring the nonsynonymous somatic mutations in these genes had a higher mutation density at the genome level compared to the wild-type groups. Furthermore, we provided statistical evidence that hypermutation of cancer driver genes on inactive X chromosomes is a general feature in female cancer genomes. In summary, this study sheds light on the functional consequences and evolutionary characteristics of somatic mutations during tumorigenesis by propelling adaptive cancer genome evolution, which would provide new perspectives for cancer research and therapeutics.

A Gene Gravity Model for the Evolution of Cancer Genomes: A Study of 3,000 Cancer Genomes across 9 Cancer Types

PubMed Central

Lin, Chen-Ching; Zhao, Junfei; Jia, Peilin; Li, Wen-Hsiung; Zhao, Zhongming

2015-01-01

Cancer development and progression result from somatic evolution by an accumulation of genomic alterations. The effects of those alterations on the fitness of somatic cells lead to evolutionary adaptations such as increased cell proliferation, angiogenesis, and altered anticancer drug responses. However, there are few general mathematical models to quantitatively examine how perturbations of a single gene shape subsequent evolution of the cancer genome. In this study, we proposed the gene gravity model to study the evolution of cancer genomes by incorporating the genome-wide transcription and somatic mutation profiles of ~3,000 tumors across 9 cancer types from The Cancer Genome Atlas into a broad gene network. We found that somatic mutations of a cancer driver gene may drive cancer genome evolution by inducing mutations in other genes. This functional consequence is often generated by the combined effect of genetic and epigenetic (e.g., chromatin regulation) alterations. By quantifying cancer genome evolution using the gene gravity model, we identified six putative cancer genes (AHNAK, COL11A1, DDX3X, FAT4, STAG2, and SYNE1). The tumor genomes harboring the nonsynonymous somatic mutations in these genes had a higher mutation density at the genome level compared to the wild-type groups. Furthermore, we provided statistical evidence that hypermutation of cancer driver genes on inactive X chromosomes is a general feature in female cancer genomes. In summary, this study sheds light on the functional consequences and evolutionary characteristics of somatic mutations during tumorigenesis by propelling adaptive cancer genome evolution, which would provide new perspectives for cancer research and therapeutics. PMID:26352260

Dissecting cancer evolution at the macro-heterogeneity and micro-heterogeneity scale.

PubMed

Barber, Louise J; Davies, Matthew N; Gerlinger, Marco

2015-02-01

Intratumour heterogeneity complicates biomarker discovery and treatment personalization, and pervasive cancer evolution is a key mechanism leading to therapy failure and patient death. Thus, understanding subclonal heterogeneity architectures and cancer evolution processes is critical for the development of effective therapeutic approaches which can control or thwart cancer evolutionary plasticity. Current insights into heterogeneity are mainly limited to the macroheterogeneity level, established by cancer subclones that have undergone significant clonal expansion. Novel single cell sequencing and blood-based subclonal tracking technologies are enabling detailed insights into microheterogeneity and the dynamics of clonal evolution. We assess how this starts to delineate the rules governing cancer evolution and novel angles for more effective therapeutic intervention. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Nasopharyngeal carcinoma incidence in North Tunisia: negative trends in adults but not adolescents, 1994-2006.

PubMed

Wided, Ben Ayoub Hizem; Hamouda, Boussen; Hamadi, Hsairi; Mansour, Ben Abdallah

2015-01-01

Nasopharyngeal carcinoma (NPC) is the second most common neoplasm of head and neck in Tunisia. The distribution is bimodal with a first period occurrence between 15 and 20 years old and a second peak at around 50 years of age. Undifferentiated carcinoma of nasopharynx type III (UCNT) is the predominant histological type (93.4%). Data of cancer registry of North Tunisia confirmed that it is an intermediate risk area for NPC with overall ASRs of 3.6 and 1.6/100,000 respectively in males and females. This study aimed to present the evolution of incidence rate of nasopharyngeal carcinoma over a period of 12 years (1994-2006). Data of cancer registry of North Tunisia (NTCR), covering half of the Tunisian population, were used to determine evolution of NPC incidence, calculated by 5 year periods. The estimated annual percentage change (EAPC) was used as an estimate of the trend. To best summarize the behavior or the data trend across years, we used a join-point regression program. Between 1994 and 2006, we observed negative annual average change of standardized incidence in men and women (-3.3% and -2.7%) also for the standardized incidences which showed a rather important decline (26.4% in males and 22.3% in females). The truncated age standardized incidence rate of NPC in adults aged of 30 years old and more (N=1209) decreased by -0.4% per year from 1994 to 2006 over time in north Tunisia dropping from 6.09 to 4.14 person-years. However, the rate was relatively stable during this period among youths aged 0-29 years (N=233) in both sexes. NPC demonstrated a favorable evolution from 1994-2006 probably due to a improvement in socioeconomic conditions.

The multiple facets of Peto's paradox: a life-history model for the evolution of cancer suppression.

PubMed

Brown, Joel S; Cunningham, Jessica J; Gatenby, Robert A

2015-07-19

Large animals should have higher lifetime probabilities of cancer than small animals because each cell division carries an attendant risk of mutating towards a tumour lineage. However, this is not observed--a (Peto's) paradox that suggests large and/or long-lived species have evolved effective cancer suppression mechanisms. Using the Euler-Lotka population model, we demonstrate the evolutionary value of cancer suppression as determined by the 'cost' (decreased fecundity) of suppression verses the 'cost' of cancer (reduced survivorship). Body size per se will not select for sufficient cancer suppression to explain the paradox. Rather, cancer suppression should be most extreme when the probability of non-cancer death decreases with age (e.g. alligators), maturation is delayed, fecundity rates are low and fecundity increases with age. Thus, the value of cancer suppression is predicted to be lowest in the vole (short lifespan, high fecundity) and highest in the naked mole rat (long lived with late female sexual maturity). The life history of pre-industrial humans likely selected for quite low levels of cancer suppression. In modern humans that live much longer, this level results in unusually high lifetime cancer risks. The model predicts a lifetime risk of 49% compared with the current empirical value of 43%. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

A systems approach defining constraints of the genome architecture on lineage selection and evolvability during somatic cancer evolution

PubMed Central

Rübben, Albert; Nordhoff, Ole

2013-01-01

Summary Most clinically distinguishable malignant tumors are characterized by specific mutations, specific patterns of chromosomal rearrangements and a predominant mechanism of genetic instability but it remains unsolved whether modifications of cancer genomes can be explained solely by mutations and selection through the cancer microenvironment. It has been suggested that internal dynamics of genomic modifications as opposed to the external evolutionary forces have a significant and complex impact on Darwinian species evolution. A similar situation can be expected for somatic cancer evolution as molecular key mechanisms encountered in species evolution also constitute prevalent mutation mechanisms in human cancers. This assumption is developed into a systems approach of carcinogenesis which focuses on possible inner constraints of the genome architecture on lineage selection during somatic cancer evolution. The proposed systems approach can be considered an analogy to the concept of evolvability in species evolution. The principal hypothesis is that permissive or restrictive effects of the genome architecture on lineage selection during somatic cancer evolution exist and have a measurable impact. The systems approach postulates three classes of lineage selection effects of the genome architecture on somatic cancer evolution: i) effects mediated by changes of fitness of cells of cancer lineage, ii) effects mediated by changes of mutation probabilities and iii) effects mediated by changes of gene designation and physical and functional genome redundancy. Physical genome redundancy is the copy number of identical genetic sequences. Functional genome redundancy of a gene or a regulatory element is defined as the number of different genetic elements, regardless of copy number, coding for the same specific biological function within a cancer cell. Complex interactions of the genome architecture on lineage selection may be expected when modifications of the genome architecture have multiple and possibly opposed effects which manifest themselves at disparate times and progression stages. Dissection of putative mechanisms mediating constraints exerted by the genome architecture on somatic cancer evolution may provide an algorithm for understanding and predicting as well as modifying somatic cancer evolution in individual patients. PMID:23336076

The turn of the gradient? Educational differences in breast cancer mortality in 18 European populations during the 2000s.

PubMed

Gadeyne, S; Menvielle, G; Kulhanova, I; Bopp, M; Deboosere, P; Eikemo, T A; Hoffmann, R; Kovács, K; Leinsalu, M; Martikainen, P; Regidor, E; Rychtarikova, J; Spadea, T; Strand, B H; Trewin, C; Wojtyniak, B; Mackenbach, J P

2017-07-01

This study aims to investigate the association between educational level and breast cancer mortality in Europe in the 2000s. Unlike most other causes of death, breast cancer mortality tends to be positively related to education, with higher educated women showing higher mortality rates. Research has however shown that the association is changing from being positive over non-existent to negative in some countries. To investigate these patterns, data from national mortality registers and censuses were collected and harmonized for 18 European populations. The study population included all women aged 30-74. Age-standardized mortality rates, mortality rate ratios, and slope and relative indexes of inequality were computed by education. The population was stratified according to age (women aged 30-49 and women aged 50-74). The relation between educational level and breast cancer mortality was predominantly negative in women aged 30-49, mortality rates being lower among highly educated women and higher among low educated women, although few outcomes were statistically significant. Among women aged 50-74, the association was mostly positive and statistically significant in some populations. A comparison with earlier research in the 1990s revealed a changing pattern of breast cancer mortality. Positive educational differences that used to be significant in the 1990s were no longer significant in the 2000s, indicating that inequalities have decreased or disappeared. This evolution is in line with the "fundamental causes" theory which stipulates that whenever medical insights and treatment become available to combat a disease, a negative association with socio-economic position will arise, independently of the underlying risk factors. © 2017 UICC.

The importance of histopathological and clinical variables in predicting the evolution of colon cancer.

PubMed

Diculescu, Mircea; Iacob, Răzvan; Iacob, Speranţa; Croitoru, Adina; Becheanu, Gabriel; Popeneciu, Valentin

2002-09-01

It has been a consensus that prognostic factors should always be taken into account before planning treatment in colorectal cancer. A 5 year prospective study was conducted, in order to assess the importance of several histopathological and clinical prognostic variables in the prediction of evolution in colon cancer. Some of the factors included in the analysis are still subject to dispute by different authors. 46 of 53 screened patients qualified to enter the study and underwent a potentially curative resection of the tumor, followed, when necessary, by adjuvant chemotherapy. Univariate and multivariate analyses were carried out in order to identify independent prognostic indicators. The endpoint of the study was considered the recurrence of the tumor or the detection of metastases. 65.2% of the patients had a good evolution during the follow up period. Multivariate survival analysis performed by Cox proportional hazard model identified 3 independent prognostic factors: Dukes stage (p = 0.00002), the grade of differentiation (p = 0.0009) and the weight loss index, representing the weight loss of the patient divided by the number of months when it was actually lost (p = 0.02). Age under 40 years, sex, microscopic aspect of the tumor, tumor location, anemia degree were not identified by our analysis as having prognostic importance. Histopathological factors continue to be the most valuable source of information regarding the possible evolution of patients with colorectal cancer. Individual clinical symptoms or biological parameters such as erytrocyte sedimentation rate or hemoglobin level are of little or no prognostic value. More research is required relating to the impact of a performance status index (which could include also weight loss index) as another reliable prognostic variable.

Hypermutable DNA chronicles the evolution of human colon cancer

PubMed Central

Naxerova, Kamila; Brachtel, Elena; Salk, Jesse J.; Seese, Aaron M.; Power, Karen; Abbasi, Bardia; Snuderl, Matija; Chiang, Sarah; Kasif, Simon; Jain, Rakesh K.

2014-01-01

Intratumor genetic heterogeneity reflects the evolutionary history of a cancer and is thought to influence treatment outcomes. Here we report that a simple PCR-based assay interrogating somatic variation in hypermutable polyguanine (poly-G) repeats can provide a rapid and reliable assessment of mitotic history and clonal architecture in human cancer. We use poly-G repeat genotyping to study the evolution of colon carcinoma. In a cohort of 22 patients, we detect poly-G variants in 91% of tumors. Patient age is positively correlated with somatic mutation frequency, suggesting that some poly-G variants accumulate before the onset of carcinogenesis during normal division in colonic stem cells. Poorly differentiated tumors have fewer mutations than well-differentiated tumors, possibly indicating a shorter mitotic history of the founder cell in these cancers. We generate poly-G mutation profiles of spatially separated samples from primary carcinomas and matched metastases to build well-supported phylogenetic trees that illuminate individual patients’ path of metastatic progression. Our results show varying degrees of intratumor heterogeneity among patients. Finally, we show that poly-G mutations can be found in other cancers than colon carcinoma. Our approach can generate reliable maps of intratumor heterogeneity in large numbers of patients with minimal time and cost expenditure. PMID:24753616

Cancer in light of experimental evolution.

PubMed

Sprouffske, Kathleen; Merlo, Lauren M F; Gerrish, Philip J; Maley, Carlo C; Sniegowski, Paul D

2012-09-11

Cancer initiation, progression, and the emergence of therapeutic resistance are evolutionary phenomena of clonal somatic cell populations. Studies in microbial experimental evolution and the theoretical work inspired by such studies are yielding deep insights into the evolutionary dynamics of clonal populations, yet there has been little explicit consideration of the relevance of this rapidly growing field to cancer biology. Here, we examine how the understanding of mutation, selection, and spatial structure in clonal populations that is emerging from experimental evolution may be applicable to cancer. Along the way, we discuss some significant ways in which cancer differs from the model systems used in experimental evolution. Despite these differences, we argue that enhanced prediction and control of cancer may be possible using ideas developed in the context of experimental evolution, and we point out some prospects for future research at the interface between these traditionally separate areas. Copyright © 2012 Elsevier Ltd. All rights reserved.

Cancer in Light of Experimental Evolution

PubMed Central

Sprouffske, Kathleen; Merlo, Lauren M.F.; Gerrish, Philip J.; Maley, Carlo C.; Sniegowski, Paul D.

2012-01-01

Cancer initiation, progression, and the emergence of therapeutic resistance are evolutionary phenomena of clonal somatic cell populations. Studies in microbial experimental evolution and the theoretical work inspired by such studies are yielding deep insights into the evolutionary dynamics of clonal populations, yet there has been little explicit consideration of the relevance of this rapidly growing field to cancer biology. Here, we examine how the understanding of mutation, selection, and spatial structure in clonal populations that is emerging from experimental evolution may be applicable to cancer. Along the way, we discuss some significant ways in which cancer differs from the model systems used in experimental evolution. Despite these differences, we argue that enhanced prediction and control of cancer may be possible using ideas developed in the context of experimental evolution, and we point out some prospects for future research at the interface between these traditionally separate areas. PMID:22975007

Evolution of cervical cancer screening and prevention in United States and Canada: Implications for public health practitioners and clinicians☆,☆☆

PubMed Central

Saraiya, M.; Steben, M.; Watson, M.; Markowitz, L.

2015-01-01

Objective Declines in cervical cancer incidence and mortality in Canada and in the United States have been widely attributed to the introduction of the Papanicolaou (Pap) test. This article reviews changes in screening and introduction of HPV vaccination. Method Sentinel events in cervical cancer screening and primary prevention through HPV vaccination in the US and Canada are described. Results Despite commonalities, cervical cancer screening and prevention differ between the two countries. Canada has a combination of opportunistic and organized programs at the provincial and territorial level, while the US has opportunistic screening and vaccination systems. In the US, the HPV test along with the Pap test (co-testing) is part of national recommendations for routine cervical cancer screening for women age 30 and older. Co-testing is not being considered anywhere in Canada, but primary HPV testing is currently recommended (but not implemented) in one province in Canada. Conclusion Many prevention strategies are available for cervical cancer. Continued public health efforts should focus on increasing vaccine coverage in the target age groups and cervical cancer screening for women at appropriate intervals. Ongoing evaluation will be needed to ensure appropriate use of health resources, as vaccinated women become eligible for screening. PMID:23402963

The Ecology and Evolution of Cancer: The Ultra-Microevolutionary Process.

PubMed

Wu, Chung-I; Wang, Hurng-Yi; Ling, Shaoping; Lu, Xuemei

2016-11-23

Although tumorigenesis has been accepted as an evolutionary process ( 20 , 102 ), many forces may operate differently in cancers than in organisms, as they evolve at vastly different time scales. Among such forces, natural selection, here defined as differential cellular proliferation among distinct somatic cell genotypes, is particularly interesting because its action might be thwarted in multicellular organisms ( 20 , 29 ). In this review, selection is analyzed in two stages of cancer evolution: Stage I is the evolution between tumors and normal tissues, and Stage II is the evolution within tumors. The Cancer Genome Atlas (TCGA) data show a low degree of convergent evolution in Stage I, where genetic changes are not extensively shared among cases. An equally important, albeit much less highlighted, discovery using TCGA data is that there is almost no net selection in cancer evolution. Both positive and negative selection are evident but they neatly cancel each other out, rendering total selection ineffective in the absence of recombination. The efficacy of selection is even lower in Stage II, where neutral (non-Darwinian) evolution is increasingly supported by high-density sampling studies ( 81 , 123 ). Because natural selection is not a strong deterministic force, cancers usually evolve divergently even in similar tissue environments.

Analyzing the evolution of young people's brain cancer mortality in Spanish provinces.

PubMed

Ugarte, M D; Adin, A; Goicoa, T; López-Abente, G

2015-06-01

To analyze the spatio-temporal evolution of brain cancer relative mortality risks in young population (under 20 years of age) in Spanish provinces during the period 1986-2010. A new and flexible conditional autoregressive spatio-temporal model with two levels of spatial aggregation was used. Brain cancer relative mortality risks in young population in Spanish provinces decreased during the last years, although a clear increase was observed during the 1990s. The global geographical pattern emphasized a high relative mortality risk in Navarre and a low relative mortality risk in Madrid. Although there is a specific Autonomous Region-time interaction effect on the relative mortality risks this effect is weak in the final estimates when compared to the global spatial and temporal effects. Differences in mortality between regions and over time may be caused by the increase in survival rates, the differences in treatment or the availability of diagnostic tools. The increase in relative risks observed in the 1990s was probably due to improved diagnostics with computerized axial tomography and magnetic resonance imaging techniques. Copyright © 2015 Elsevier Ltd. All rights reserved.

Advances for studying clonal evolution in cancer.

PubMed

Ding, Li; Raphael, Benjamin J; Chen, Feng; Wendl, Michael C

2013-11-01

The "clonal evolution" model of cancer emerged and "evolved" amid ongoing advances in technology, especially in recent years during which next generation sequencing instruments have provided ever higher resolution pictures of the genetic changes in cancer cells and heterogeneity in tumors. It has become increasingly clear that clonal evolution is not a single sequential process, but instead frequently involves simultaneous evolution of multiple subclones that co-exist because they are of similar fitness or are spatially separated. Co-evolution of subclones also occurs when they complement each other's survival advantages. Recent studies have also shown that clonal evolution is highly heterogeneous: different individual tumors of the same type may undergo very different paths of clonal evolution. New methodological advancements, including deep digital sequencing of a mixed tumor population, single cell sequencing, and the development of more sophisticated computational tools, will continue to shape and reshape the models of clonal evolution. In turn, these will provide both an improved framework for the understanding of cancer progression and a guide for treatment strategies aimed at the elimination of all, rather than just some, of the cancer cells within a patient. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Stress-Induced Mutagenesis: Implications in Cancer and Drug Resistance.

PubMed

Fitzgerald, Devon M; Hastings, P J; Rosenberg, Susan M

2017-03-01

Genomic instability underlies many cancers and generates genetic variation that drives cancer initiation, progression, and therapy resistance. In contrast with classical assumptions that mutations occur purely stochastically at constant, gradual rates, microbes, plants, flies, and human cancer cells possess mechanisms of mutagenesis that are upregulated by stress responses. These generate transient, genetic-diversity bursts that can propel evolution, specifically when cells are poorly adapted to their environments-that is, when stressed. We review molecular mechanisms of stress-response-dependent (stress-induced) mutagenesis that occur from bacteria to cancer, and are activated by starvation, drugs, hypoxia, and other stressors. We discuss mutagenic DNA break repair in Escherichia coli as a model for mechanisms in cancers. The temporal regulation of mutagenesis by stress responses and spatial restriction in genomes are common themes across the tree of life. Both can accelerate evolution, including the evolution of cancers. We discuss possible anti-evolvability drugs, aimed at targeting mutagenesis and other variation generators, that could be used to delay the evolution of cancer progression and therapy resistance.

Stress-Induced Mutagenesis: Implications in Cancer and Drug Resistance

PubMed Central

Fitzgerald, Devon M.; Hastings, P.J.; Rosenberg, Susan M.

2017-01-01

Genomic instability underlies many cancers and generates genetic variation that drives cancer initiation, progression, and therapy resistance. In contrast with classical assumptions that mutations occur purely stochastically at constant, gradual rates, microbes, plants, flies, and human cancer cells possess mechanisms of mutagenesis that are upregulated by stress responses. These generate transient, genetic-diversity bursts that can propel evolution, specifically when cells are poorly adapted to their environments—that is, when stressed. We review molecular mechanisms of stress-response-dependent (stress-induced) mutagenesis that occur from bacteria to cancer, and are activated by starvation, drugs, hypoxia, and other stressors. We discuss mutagenic DNA break repair in Escherichia coli as a model for mechanisms in cancers. The temporal regulation of mutagenesis by stress responses and spatial restriction in genomes are common themes across the tree of life. Both can accelerate evolution, including the evolution of cancers. We discuss possible anti-evolvability drugs, aimed at targeting mutagenesis and other variation generators, that could be used to delay the evolution of cancer progression and therapy resistance. PMID:29399660

Apoptosis: its origin, history, maintenance and the medical implications for cancer and aging

NASA Astrophysics Data System (ADS)

Kaczanowski, Szymon

2016-06-01

Programmed cell death is a basic cellular mechanism. Apoptotic-like programmed cell death (called apoptosis in animals) occurs in both unicellular and multicellular eukaryotes, and some apoptotic mechanisms are observed in bacteria. Endosymbiosis between mitochondria and eukaryotic cells took place early in the eukaryotic evolution, and some of the apoptotic-like mechanisms of mitochondria that were retained after this event now serve as parts of the eukaryotic apoptotic machinery. Apoptotic mechanisms have several functions in unicellular organisms: they include kin-selected altruistic suicide that controls population size, sharing common goods, and responding to viral infection. Apoptotic factors also have non-apoptotic functions. Apoptosis is involved in the cellular aging of eukaryotes, including humans. In addition, apoptosis is a key part of the innate tumor-suppression mechanism. Several anticancer drugs induce apoptosis, because apoptotic mechanisms are inactivated during oncogenesis. Because of the ancient history of apoptosis, I hypothesize that there is a deep relationship between mitochondrial metabolism, its role in aerobic versus anaerobic respiration, and the connection between apoptosis and cancer. Whereas normal cells rely primarily on oxidative mitochondrial respiration, most cancer cells use anaerobic metabolism. According to the Warburg hypothesis, the remodeling of the metabolism is one of the processes that leads to cancer. Recent studies indicate that anaerobic, non-mitochondrial respiration is particularly active in embryonic cells, stem cells, and aggressive stem-like cancer cells. Mitochondrial respiration is particularly active during the pathological aging of human cells in neurodegenerative diseases. According to the reversed Warburg hypothesis formulated by Demetrius, pathological aging is induced by mitochondrial respiration. Here, I advance the hypothesis that the stimulation of mitochondrial metabolism leads to pathological aging.

Was skin cancer a selective force for black pigmentation in early hominin evolution?

PubMed Central

Greaves, Mel

2014-01-01

Melanin provides a crucial filter for solar UV radiation and its genetically determined variation influences both skin pigmentation and risk of cancer. Genetic evidence suggests that the acquisition of a highly stable melanocortin 1 receptor allele promoting black pigmentation arose around the time of savannah colonization by hominins at some 1–2 Ma. The adaptive significance of dark skin is generally believed to be protection from UV damage but the pathologies that might have had a deleterious impact on survival and/or reproductive fitness, though much debated, are uncertain. Here, I suggest that data on age-associated cancer incidence and lethality in albinos living at low latitudes in both Africa and Central America support the contention that skin cancer could have provided a potent selective force for the emergence of black skin in early hominins. PMID:24573849

Advances for Studying Clonal Evolution in Cancer

PubMed Central

Raphael, Benjamin J.; Chen, Feng; Wendl, Michael C.

2013-01-01

The “clonal evolution” model of cancer emerged and “evolved” amid ongoing advances in technology, especially in recent years during which next generation sequencing instruments have provided ever higher resolution pictures of the genetic changes in cancer cells and heterogeneity in tumors. It has become increasingly clear that clonal evolution is not a single sequential process, but instead frequently involves simultaneous evolution of multiple subclones that co-exist because they are of similar fitness or are spatially separated. Co-evolution of subclones also occurs when they complement each other’s survival advantages. Recent studies have also shown that clonal evolution is highly heterogeneous: different individual tumors of the same type may undergo very different paths of clonal evolution. New methodological advancements, including deep digital sequencing of a mixed tumor population, single cell sequencing, and the development of more sophisticated computational tools, will continue to shape and reshape the models of clonal evolution. In turn, these will provide both an improved framework for the understanding of cancer progression and a guide for treatment strategies aimed at the elimination of all, rather than just some, of the cancer cells within a patient. PMID:23353056

Cancer is an adaptation that selects in animals against energy dissipation.

PubMed

Muller, Anthonie W J

2017-07-01

As cancer usually follows reproduction, it is generally assumed that cancer does not select. Graham has however argued that juvenile cancer, which precedes reproduction, could during evolution have implemented a "cancer selection" that resulted in novel traits that suppress this juvenile cancer; an example is protection against UV sunlight-induced cancer, required for the emergence of terrestrial animals from the sea. We modify the cancer selection mechanism to the posited "cancer adaptation" mechanism, in which juvenile mortality is enhanced through the diminished care received by juveniles from their (grand) parents when these suffer from cancer in old age. Moreover, it is posited that the cancer adaptation selects against germline "dissipative genes", genes that result in enhanced free energy dissipation. Cancer's progression is interpreted as a cascade at increasing scale of repeated amplification of energy dissipation, a cascade involving heat shock, the Warburg effect, the cytokine IL-6, tumours, and hypermetabolism. Disturbance of any physiological process must enhance energy dissipation if the animal remains functioning normally, what explains multicausality, why "everything gives you cancer". The hypothesis thus comprises two newly invoked partial processes-diminished (grand) parental care and dissipation amplification-and results in a "selection against enhanced energy dissipation" which gives during evolution the benefit of energy conservation. Due to this benefit, cancer would essentially be an adaptation, and not a genetic disease, as assumed in the "somatic mutation theory". Cancer by somatic mutations is only a side process. The cancer adaptation hypothesis is substantiated by (1) cancer's extancy, (2) the failure of the somatic mutation theory, (3) cancer's initiation by a high temperature, (4) the interpretation of cancer's progression as a thermal process, and (5) the interpretation of tumours as organs that implement thermogenesis. The hypothesis could in principle be verified by monitoring in a population over several generations (1) the presence of dissipative genes, (2) the incidence of cancer, and (3) the beneficial effect of dissipative gene removal by cancer on starvation/famine survival. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Application of biomarkers in cancer risk management: evaluation from stochastic clonal evolutionary and dynamic system optimization points of view.

PubMed

Li, Xiaohong; Blount, Patricia L; Vaughan, Thomas L; Reid, Brian J

2011-02-01

Aside from primary prevention, early detection remains the most effective way to decrease mortality associated with the majority of solid cancers. Previous cancer screening models are largely based on classification of at-risk populations into three conceptually defined groups (normal, cancer without symptoms, and cancer with symptoms). Unfortunately, this approach has achieved limited successes in reducing cancer mortality. With advances in molecular biology and genomic technologies, many candidate somatic genetic and epigenetic "biomarkers" have been identified as potential predictors of cancer risk. However, none have yet been validated as robust predictors of progression to cancer or shown to reduce cancer mortality. In this Perspective, we first define the necessary and sufficient conditions for precise prediction of future cancer development and early cancer detection within a simple physical model framework. We then evaluate cancer risk prediction and early detection from a dynamic clonal evolution point of view, examining the implications of dynamic clonal evolution of biomarkers and the application of clonal evolution for cancer risk management in clinical practice. Finally, we propose a framework to guide future collaborative research between mathematical modelers and biomarker researchers to design studies to investigate and model dynamic clonal evolution. This approach will allow optimization of available resources for cancer control and intervention timing based on molecular biomarkers in predicting cancer among various risk subsets that dynamically evolve over time.

Adapting clinical paradigms to the challenges of cancer clonal evolution.

PubMed

Murugaesu, Nirupa; Chew, Su Kit; Swanton, Charles

2013-06-01

Emerging evidence suggests that cancer branched evolution may affect biomarker validation, clinical outcome, and emergence of drug resistance. The changing spatial and temporal nature of cancer subclonal architecture during the disease course suggests the need for longitudinal prospective studies of cancer evolution and robust and clinically implementable pathologic definitions of intratumor heterogeneity, genetic diversity, and chromosomal instability. Furthermore, subclonal heterogeneous events in tumors may evade detection through conventional biomarker strategies and influence clinical outcome. Minimally invasive methods for the study of cancer evolution and new approaches to clinical study design, incorporating understanding of the dynamics of tumor clonal architectures through treatment and during acquisition of drug resistance, have been suggested as important areas for development. Coordinated efforts will be required by the scientific and clinical trial communities to adapt to the challenges of detecting infrequently occurring somatic events that may influence clinical outcome and to understand the dynamics of cancer evolution and the waxing and waning of tumor subclones over time in advanced metastatic epithelial malignancies. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Chemotherapy in Old Women with Breast Cancer: Is Age Still a Predictor for Under Treatment?

PubMed

Meresse, Mégane; Bouhnik, Anne-Déborah; Bendiane, Marc-Karim; Retornaz, Frédérique; Rousseau, Frédérique; Rey, Dominique; Giorgi, Roch

2017-05-01

Breast cancer affects mostly older women but there are no guidelines especially devoted to adjuvant chemotherapy for this population. In this context, this study was carried out in a population-based cohort of French elderly women with breast cancer, to check adherence to the existing national guidelines according to the women's age, taking into account the evolution of the situation over time for women requiring chemotherapy. Between October 2006 and December 2008, all consecutive women included in the French Health registry for a biopsy-proven primary nonmetastatic breast cancer, aged 65-80 years at diagnosis, and living in South Eastern France, were asked to participate in a cohort study. Medical information was collected from physicians. The study population was restricted to the 223 women who were recommended adjuvant chemotherapy according to national guidelines. Those who received chemotherapy were compared to those who did not receive this treatment. Among these 223 women 55% had received chemotherapy. Only three women refused the treatment. Less than 8% have had a geriatric assessment before treatment decision and only two were proposed to participate in a clinical trial. After adjustment for comorbidity score, tumor characteristics, socio-demographic characteristics, and year of diagnosis, increasing patient age was independently associated with decreased guideline concordance for adjuvant chemotherapy. Women aged 75-80 years received chemotherapy more than four times less often than women aged 65-74 years. However, the percentage of women who received chemotherapy increased from 33% to 58% between 2006 and 2008, in parallel with the setting up of Onco-Geriatric Coordination Units in the area. In France, chronological age remains a barrier to receive chemotherapy for older breast cancer women but the establishment of a formal collaboration between oncologists and geriatricians seems to be an effective way to improve care delivery in this population. © 2016 Wiley Periodicals, Inc.

Sexual and reproductive health and HIV services: integrating HIV/AIDS and cervical cancer prevention and control.

PubMed

Belhadj, Hedia; Rasanathan, Jennifer J K; Denny, Lynette; Broutet, Nathalie

2013-05-01

People living with HIV are at an increased risk of acquiring HPV and of developing evolutive cervical cancers (women) and penile and anal cancers (men). Low-cost screening-visual inspection with acetic acid, HPV DNA diagnostics and primary care level treatment, cryotherapy for cervical intraepithelial neoplasia (CIN 2), and primary prevention through HPV vaccination of girls aged 9-13 years-makes the goal of eliminating cervical cancer possible in the long term. Integration of cervical cancer screening and treatment into a sexual and reproductive health service package raises programmatic questions and calls for a continuum of care. The latter is only possible when adequate cytopathology skills and treatment for advanced cancer conditions are available. The present paper highlights the role of member societies of the International Federation of Gynecology and Obstetrics (FIGO) in developing the base for an integrated package that responds to women's sexual and reproductive health needs. Copyright © 2013 International Federation of Gynecology and Obstetrics. All rights reserved.

Visualizing Clonal Evolution in Cancer.

PubMed

Krzywinski, Martin

2016-06-02

Rapid and inexpensive single-cell sequencing is driving new visualizations of cancer instability and evolution. Krzywinski discusses how to present clone evolution plots in order to visualize temporal, phylogenetic, and spatial aspects of a tumor in a single static image. Copyright © 2016 Elsevier Inc. All rights reserved.

Re-Evaluating Clonal Dominance in Cancer Evolution.

PubMed

Burrell, Rebecca A; Swanton, Charles

2016-05-01

Tumours are composed of genetically heterogeneous subclones which may diverge early during tumour growth. However, our strategies for treating and assessing outcome for patients are overwhelmingly based upon the classical linear paradigm for cancer evolution. Increasing numbers of studies are finding that minor subclones can determine clinical disease course, and that temporal and spatial heterogeneity needs to be considered in disease management. In this article we review evidence for cancer clonal heterogeneity, evaluating the importance of tumour subclones and their growth through both Darwinian and neutral evolution. Major shifts in current clinical practice and trial designs, aimed at understanding cancer evolution on a patient-by-patient basis, may be necessary to achieve more successful treatment of heterogeneous metastatic disease. Copyright © 2016 Elsevier Inc. All rights reserved.

Natural Selection in Cancer Biology: From Molecular Snowflakes to Trait Hallmarks.

PubMed

Fortunato, Angelo; Boddy, Amy; Mallo, Diego; Aktipis, Athena; Maley, Carlo C; Pepper, John W

2017-02-01

Evolution by natural selection is the conceptual foundation for nearly every branch of biology and increasingly also for biomedicine and medical research. In cancer biology, evolution explains how populations of cells in tumors change over time. It is a fundamental question whether this evolutionary process is driven primarily by natural selection and adaptation or by other evolutionary processes such as founder effects and drift. In cancer biology, as in organismal evolutionary biology, there is controversy about this question and also about the use of adaptation through natural selection as a guiding framework for research. In this review, we discuss the differences and similarities between evolution among somatic cells versus evolution among organisms. We review what is known about the parameters and rate of evolution in neoplasms, as well as evidence for adaptation. We conclude that adaptation is a useful framework that accurately explains the defining characteristics of cancer. Further, convergent evolution through natural selection provides the only satisfying explanation both for how a group of diverse pathologies have enough in common to usefully share the descriptive label of "cancer" and for why this convergent condition becomes life-threatening. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

Catalog of genetic progression of human cancers: breast cancer.

PubMed

Desmedt, Christine; Yates, Lucy; Kulka, Janina

2016-03-01

With the rapid development of next-generation sequencing, deeper insights are being gained into the molecular evolution that underlies the development and clinical progression of breast cancer. It is apparent that during evolution, breast cancers acquire thousands of mutations including single base pair substitutions, insertions, deletions, copy number aberrations, and structural rearrangements. As a consequence, at the whole genome level, no two cancers are identical and few cancers even share the same complement of "driver" mutations. Indeed, two samples from the same cancer may also exhibit extensive differences due to constant remodeling of the genome over time. In this review, we summarize recent studies that extend our understanding of the genomic basis of cancer progression. Key biological insights include the following: subclonal diversification begins early in cancer evolution, being detectable even in in situ lesions; geographical stratification of subclonal structure is frequent in primary tumors and can include therapeutically targetable alterations; multiple distant metastases typically arise from a common metastatic ancestor following a "metastatic cascade" model; systemic therapy can unmask preexisting resistant subclones or influence further treatment sensitivity and disease progression. We conclude the review by describing novel approaches such as the analysis of circulating DNA and patient-derived xenografts that promise to further our understanding of the genomic changes occurring during cancer evolution and guide treatment decision making.

On-chip dynamic stress control for cancer cell evolution study

NASA Astrophysics Data System (ADS)

Liu, Liyu; Austin, Robert

2010-03-01

The growth and spreading of cancer in host organisms is an evolutionary process. Cells accumulate mutations that help them adapt to changing environments and to obtain survival fitness. However, all cancer--promoting mutations do not occur at once. Cancer cells face selective environmental pressures that drive their evolution in stages. In traditional cancer studies, environmental stress is usually homogenous in space and difficult to change in time. Here, we propose a microfluidic chip employing embedded dynamic traps to generate dynamic heterogeneous microenvironments for cancer cells in evolution studies. Based on polydimethylsiloxane (PDMS) flexible diaphragms, these traps are able to enclose and shield cancer cells or expose them to external environmental stress. Digital controls for each trap determine the nutrition, antibiotics, CO2/O2 conditions, and temperatures to which trapped cells are subjected. Thus, the stress applied to cells can be varied in intensity and duration in each trap independently. The chip can also output cells from specific traps for sequencing and other biological analysis. Hence our design simultaneously monitors and analyzes cell evolution behaviors under dynamic stresses.

Evolution of educational inequalities in site-specific cancer mortality among Belgian men between the 1990s and 2000s using a "fundamental cause" perspective.

PubMed

Vanthomme, Katrien; Vandenheede, Hadewijch; Hagedoorn, Paulien; Gadeyne, Sylvie

2017-07-05

According to the "fundamental cause" theory, emerging knowledge on health-enhancing behaviours and technologies results in health disparities. This study aims to assess (trends in) educational inequalities in site-specific cancer mortality in Belgian men in the 1990s and the 2000s using this framework. Data were derived from record linkage between the Belgian censuses of 1991 and 2001 and register data on mortality. The study population comprised all Belgian men aged 50-79 years during follow-up. Both absolute and relative inequality measures have been calculated. Despite an overall downward trend in cancer mortality, educational differences are observed for the majority of cancer sites in the 2000s. Generally, inequalities are largest for mortality from preventable cancers. Trends over time in inequalities are rather stable compared with the 1990s. Educational differences in site-specific cancer mortality persist in the 2000s in Belgium, mainly for cancers related to behavioural change and medical interventions. Policy efforts focussing on behavioural change and healthcare utilization remain crucial in order to tackle these increasing inequalities.

[Breast cancer in Sub-Saharan African women: review].

PubMed

Ly, Madani; Antoine, Martine; André, Fabrice; Callard, Patrice; Bernaudin, Jean-François; Diallo, Dapa A

2011-07-01

Breast cancer is the second most frequent cancer in Sub-Saharan African women with an incidence of 15-53 per 100,000 women. Using PubMed, we reviewed all the articles published on this topic between 1989 and 2009. Breast cancer is usually diagnosed in women younger than in developed countries (mean age: 42-53 years), with later stages (III or IV, i.e. with axillary nodes and distant metastases). Reported tumors are mostly invasive ductal carcinomas with aggressive characteristics: grade III histoprognosis, absence of hormonal receptors or HER2 expression. According to the new breast cancer classification, nearly half of these tumors should be classified as triple negative. However, studies are rare and require confirmation. In conclusion, data on epidemiology and biology of breast cancer in Sub-Saharan African women are still scarce and need more extensive studies. In these countries, the pattern of breast cancer will likely change in the future, according to the evolution of lifestyle namely urbanisation. There is a great need for commitment of research and clinical resources in Sub-Saharan Africa in order to develop specific strategies.

How the evolution of multicellularity set the stage for cancer

PubMed Central

Trigos, Anna S; Pearson, Richard B; Papenfuss, Anthony T; Goode, David L

2018-01-01

Neoplastic growth and many of the hallmark properties of cancer are driven by the disruption of molecular networks established during the emergence of multicellularity. Regulatory pathways and molecules that evolved to impose regulatory constraints upon networks established in earlier unicellular organisms enabled greater communication and coordination between the diverse cell types required for multicellularity, but also created liabilities in the form of points of vulnerability in the network that when mutated or dysregulated facilitate the development of cancer. These factors are usually overlooked in genomic analyses of cancer, but understanding where vulnerabilities to cancer lie in the networks of multicellular species would provide important new insights into how core molecular processes and gene regulation change during tumourigenesis. We describe how the evolutionary origins of genes influence their roles in cancer, and how connections formed between unicellular and multicellular genes that act as key regulatory hubs for normal tissue homeostasis can also contribute to malignant transformation when disrupted. Tumours in general are characterised by increased dependence on unicellular processes for survival, and major dysregulation of the control structures imposed on these processes during the evolution of multicellularity. Mounting molecular evidence suggests altered interactions at the interface between unicellular and multicellular genes play key roles in the initiation and progression of cancer. Furthermore, unicellular network regions activated in cancer show high degrees of robustness and plasticity, conferring increased adaptability to tumour cells by supporting effective responses to environmental pressures such as drug exposure. Examining how the links between multicellular and unicellular regions get disrupted in tumours has great potential to identify novel drivers of cancer, and to guide improvements to cancer treatment by identifying more effective therapeutic strategies. Recent successes in targeting unicellular processes by novel compounds underscore the logic of such approaches. Further gains could come from identifying genes at the interface between unicellular and multicellular processes and manipulating the communication between network regions of different evolutionary ages. PMID:29337961

The Hallmarks of Aging

PubMed Central

López-Otín, Carlos; Blasco, Maria A.; Partridge, Linda; Serrano, Manuel; Kroemer, Guido

2013-01-01

Aging is characterized by a progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death. This deterioration is the primary risk factor for major human pathologies including cancer, diabetes, cardiovascular disorders, and neurodegenerative diseases. Aging research has experienced an unprecedented advance over recent years, particularly with the discovery that the rate of aging is controlled, at least to some extent, by genetic pathways and biochemical processes conserved in evolution. This review enumerates nine tentative hallmarks that represent common denominators of aging in different organisms, with special emphasis on mammalian aging. These hallmarks are: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient-sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. A major challenge is to dissect the interconnectedness between the candidate hallmarks and their relative contribution to aging, with the final goal of identifying pharmaceutical targets to improve human health during aging with minimal side-effects. PMID:23746838

Identification of neutral tumor evolution across cancer types

PubMed Central

Barnes, Chris P; Graham, Trevor A; Sottoriva, Andrea

2016-01-01

Despite extraordinary efforts to profile cancer genomes, interpreting the vast amount of genomic data in the light of cancer evolution remains challenging. Here we demonstrate that neutral tumor evolution results in a power-law distribution of the mutant allele frequencies reported by next-generation sequencing of tumor bulk samples. We find that the neutral power-law fits with high precision 323 of 904 cancers from 14 types, selected from different cohorts. In malignancies identified as neutral, all clonal selection occurred prior to the onset of cancer growth and not in later-arising subclones, resulting in numerous passenger mutations that are responsible for intra-tumor heterogeneity. Reanalyzing cancer sequencing data within the neutral framework allowed the measurement, in each patient, of both the in vivo mutation rate and the order and timing of mutations. This result provides a new way to interpret existing cancer genomic data and to discriminate between functional and non-functional intra-tumor heterogeneity. PMID:26780609

Genetic Heterogeneity and Clonal Evolution of Tumor Cells and their Impact on Precision Cancer Medicine.

PubMed

Sabaawy, Hatem E

2013-11-18

The efficacy of targeted therapies in leukemias and solid tumors depends upon the accurate detection and sustained targeting of initial and evolving driver mutations and/or aberrations in cancer cells. Tumor clonal evolution of the diverse populations of cancer cells during cancer progression contributes to the longitudinal variations of clonal, morphological, anatomical, and molecular heterogeneity of tumors. Moreover, drug-resistant subclones present at initiation of therapy or emerging as a result of targeted therapies represent major challenges for achieving success of personalized therapies in providing meaningful improvement in cancer survival rates. Here, I briefly portray tumor cell clonal evolution at the cellular and molecular levels, and present the multiple types of genetic heterogeneity in tumors, with a focus on their impact on the implementation of personalized or precision cancer medicine.

Zebrafish as a model to assess cancer heterogeneity, progression and relapse

PubMed Central

Blackburn, Jessica S.; Langenau, David M.

2014-01-01

Clonal evolution is the process by which genetic and epigenetic diversity is created within malignant tumor cells. This process culminates in a heterogeneous tumor, consisting of multiple subpopulations of cancer cells that often do not contain the same underlying mutations. Continuous selective pressure permits outgrowth of clones that harbor lesions that are capable of enhancing disease progression, including those that contribute to therapy resistance, metastasis and relapse. Clonal evolution and the resulting intratumoral heterogeneity pose a substantial challenge to biomarker identification, personalized cancer therapies and the discovery of underlying driver mutations in cancer. The purpose of this Review is to highlight the unique strengths of zebrafish cancer models in assessing the roles that intratumoral heterogeneity and clonal evolution play in cancer, including transgenesis, imaging technologies, high-throughput cell transplantation approaches and in vivo single-cell functional assays. PMID:24973745

Functional versus non-functional intratumor heterogeneity in cancer

PubMed Central

Williams, Marc J.; Werner, Benjamin; Graham, Trevor A.; Sottoriva, Andrea

2016-01-01

ABSTRACT Next-generation sequencing data from human cancers are often difficult to interpret within the context of tumor evolution. We developed a mathematical model describing the accumulation of mutations under neutral evolutionary dynamics and showed that 323/904 cancers (∼30%) from multiple types were consistent with the neutral model of tumor evolution. PMID:27652316

Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triage

PubMed Central

Ames, Bruce N.

2006-01-01

Inadequate dietary intakes of vitamins and minerals are widespread, most likely due to excessive consumption of energy-rich, micronutrient-poor, refined food. Inadequate intakes may result in chronic metabolic disruption, including mitochondrial decay. Deficiencies in many micronutrients cause DNA damage, such as chromosome breaks, in cultured human cells or in vivo. Some of these deficiencies also cause mitochondrial decay with oxidant leakage and cellular aging and are associated with late onset diseases such as cancer. I propose DNA damage and late onset disease are consequences of a triage allocation response to micronutrient scarcity. Episodic shortages of micronutrients were common during evolution. Natural selection favors short-term survival at the expense of long-term health. I hypothesize that short-term survival was achieved by allocating scarce micronutrients by triage, in part through an adjustment of the binding affinity of proteins for required micronutrients. If this hypothesis is correct, micronutrient deficiencies that trigger the triage response would accelerate cancer, aging, and neural decay but would leave critical metabolic functions, such as ATP production, intact. Evidence that micronutrient malnutrition increases late onset diseases, such as cancer, is discussed. A multivitamin-mineral supplement is one low-cost way to ensure intake of the Recommended Dietary Allowance of micronutrients throughout life. PMID:17101959

Concepts in solid tumor evolution.

PubMed

Sidow, Arend; Spies, Noah

2015-04-01

Evolutionary mechanisms in cancer progression give tumors their individuality. Cancer evolution is different from organismal evolution, however, and we discuss where concepts from evolutionary genetics are useful or limited in facilitating an understanding of cancer. Based on these concepts we construct and apply the simplest plausible model of tumor growth and progression. Simulations using this simple model illustrate the importance of stochastic events early in tumorigenesis, highlight the dominance of exponential growth over linear growth and differentiation, and explain the clonal substructure of tumors. Copyright © 2015 Elsevier Ltd. All rights reserved.

Clonal evolution and heterogeneity in metastatic head and neck cancer-An analysis of the Austrian Study Group of Medical Tumour Therapy study group.

PubMed

Melchardt, Thomas; Magnes, Teresa; Hufnagl, Clemens; Thorner, Aaron R; Ducar, Matthew; Neureiter, Daniel; Tränkenschuh, Wolfgang; Klieser, Eckhard; Gaggl, Alexander; Rösch, Sebastian; Rasp, Gerd; Hartmann, Tanja N; Pleyer, Lisa; Rinnerthaler, Gabriel; Weiss, Lukas; Greil, Richard; Egle, Alexander

2018-04-01

Tumour heterogeneity and clonal evolution within a cancer patient are deemed responsible for relapse in malignancies and present challenges to the principles of targeted therapy, for which treatment modality is often decided based on the molecular pathology of the primary tumour. Nevertheless, the clonal architecture in distant relapse of head and neck cancer is fairly unknown. For this project, we analysed a cohort of 386 patients within the Austrian Registry of head and neck cancer. We identified 26 patients with material from the primary tumour, the distant metastasis after curative first-line treatment and a germline sample for analysis of clonal evolution. After pathological analyses, these samples were analysed using a targeted massively parallel sequencing (MPS) panel of 257 genes known to be recurrently mutated in head and neck cancer plus a genome-wide SNP-set. Despite histological diagnosis of distant metastasis, no corresponding mutation in the supposed metastases was found in two of 23 (8.6%) evaluable patients suggesting a primary tumour of the lung instead of a distant metastasis of head and neck cancer. We observed a branched pattern of evolution in 31.6% of the analysed patients. This pattern was associated with a shorter time to distant metastasis, compared with a pattern of punctuated evolution. Structural genomic changes over time were also present in 7 of 12 (60%) evaluable patients with metachronous metastases. Targeted MPS demonstrated substantial heterogeneity at the time of diagnosis and a complex pattern of evolution during disease progression in head and neck cancer. Copy number analyses revealed additional changes that were not detected by mutational analyses. Mutational and structural changes contribute to tumour heterogeneity at diagnosis and progression. Copyright © 2018 Elsevier Ltd. All rights reserved.

Clonal evolution of acute myeloid leukemia highlighted by latest genome sequencing studies.

PubMed

Zhang, Xuehong; Lv, Dekang; Zhang, Yu; Liu, Quentin; Li, Zhiguang

2016-09-06

Decades of years might be required for an initiated cell to become a fully-pledged, metastasized tumor. DNA mutations are accumulated during this process including background mutations that emerge scholastically, as well as driver mutations that selectively occur in a handful of cancer genes and confer the cell a growth advantage over its neighbors. A clone of tumor cells could be superseded by another clone that acquires new mutations and grows more aggressively. Tumor evolutional patterns have been studied for years using conventional approaches that focus on the investigation of a single or a couple of genes. Latest deep sequencing technology enables a global view of tumor evolution by deciphering almost all genome aberrations in a tumor. Tumor clones and the fate of each clone during tumor evolution can be depicted with the help of the concept of variant allele frequency. Here, we summarize the new insights of cancer evolutional progression in acute myeloid leukemia. Cancer evolution is currently thought to start from a clone that has accumulated the requisite somatically-acquired genetic aberrations through a series of increasingly disordered clinical and pathological phases, eventually leading to malignant transformation [1-3]. The observations in invasive colorectal cancer that usually emerges from an antecedent benign adenomatous polyp and in cervical cancer that proceeds through intraepithelial neoplasia support the idea of stepwise or linear cancerous progression [3-5]. Genetically, such progression is achieved by successive waves of clonal expansion during which cells acquire novel genomic alterations including single nucleotide variants (SNVs), small insertions and deletions (indels), and/or copy number variations (CNVs) [6]. The latest improvement in sequencing technology has allowed the deciphering of the whole exome or genome in different types of tumor and normal tissue pairs, providing detailed catalogue about genome aberrations during tumor initiation and progression, which have been reviewed in several papers [7-10]. Here, we focus on demonstrating the cancer clonal evolution pattern revealed by recent deep sequencing studies of samples from acute myeloid leukemia (AML) patients.

Somatic clonal evolution: A selection-centric perspective.

PubMed

Scott, Jacob; Marusyk, Andriy

2017-04-01

It is generally accepted that the initiation and progression of cancers is the result of somatic clonal evolution. Despite many peculiarities, evolution within populations of somatic cells should obey the same Darwinian principles as evolution within natural populations, i.e. variability of heritable phenotypes provides the substrate for context-specific selection forces leading to increased population frequencies of phenotypes, which are better adapted to their environment. Yet, within cancer biology, the more prevalent way to view evolution is as being entirely driven by the accumulation of "driver" mutations. Context-specific selection forces are either ignored, or viewed as constraints from which tumor cells liberate themselves during the course of malignant progression. In this review, we will argue that explicitly focusing on selection forces acting on the populations of neoplastic cells as the driving force of somatic clonal evolution might provide for a more accurate conceptual framework compared to the mutation-centric driver gene paradigm. Whereas little can be done to counteract the "bad luck" of stochastic occurrences of cancer-related mutations, changes in selective pressures and the phenotypic adaptations they induce can, in principle, be exploited to limit the incidence of cancers and to increase the efficiency of existing and future therapies. This article is part of a Special Issue entitled: Evolutionary principles - heterogeneity in cancer?, edited by Dr. Robert A. Gatenby. Copyright © 2017 Elsevier B.V. All rights reserved.

Natural Selection in Cancer Biology: From Molecular Snowflakes to Trait Hallmarks

PubMed Central

Fortunato, Angelo; Boddy, Amy; Mallo, Diego; Aktipis, Athena; Maley, Carlo C.; Pepper, John W.

2017-01-01

Evolution by natural selection is the conceptual foundation for nearly every branch of biology and increasingly also for biomedicine and medical research. In cancer biology, evolution explains how populations of cells in tumors change over time. It is a fundamental question whether this evolutionary process is driven primarily by natural selection and adaptation or by other evolutionary processes such as founder effects and drift. In cancer biology, as in organismal evolutionary biology, there is controversy about this question and also about the use of adaptation through natural selection as a guiding framework for research. In this review, we discuss the differences and similarities between evolution among somatic cells versus evolution among organisms. We review what is known about the parameters and rate of evolution in neoplasms, as well as evidence for adaptation. We conclude that adaptation is a useful framework that accurately explains the defining characteristics of cancer. Further, convergent evolution through natural selection provides the only satisfying explanation both for how a group of diverse pathologies have enough in common to usefully share the descriptive label of “cancer” and for why this convergent condition becomes life-threatening. PMID:28148564

Modeling the evolution space of breakage fusion bridge cycles with a stochastic folding process.

PubMed

Greenman, C D; Cooke, S L; Marshall, J; Stratton, M R; Campbell, P J

2016-01-01

Breakage-fusion-bridge cycles in cancer arise when a broken segment of DNA is duplicated and an end from each copy joined together. This structure then 'unfolds' into a new piece of palindromic DNA. This is one mechanism responsible for the localised amplicons observed in cancer genome data. Here we study the evolution space of breakage-fusion-bridge structures in detail. We firstly consider discrete representations of this space with 2-d trees to demonstrate that there are [Formula: see text] qualitatively distinct evolutions involving [Formula: see text] breakage-fusion-bridge cycles. Secondly we consider the stochastic nature of the process to show these evolutions are not equally likely, and also describe how amplicons become localized. Finally we highlight these methods by inferring the evolution of breakage-fusion-bridge cycles with data from primary tissue cancer samples.

[Clinical, epidemiological and therapeutic features of biliary tract cancers: about 20 cases].

PubMed

Ka, Ibrahima; Faye, Magatte; Diop, Papa Saloum; Faye, Amadou Bocar Niang Aliou Coly; Ndoye, Jean Marc; Fall, Babacar

2018-01-01

Biliary tract cancers mainly occur in two sites: gallbladder cancer which are adenocarcinomas and intra- and extrahepatic cholangiocarcinomas. We conducted a retrospective study of 20 cases with biliary tract cancer in the Department of Surgery at the General Hospital in Grand-Yoff between January 2006 and October 2014. 40% of patients had gallbladder cancer, 60% of patients had common bile duct cancer. Sex ratio was 1. The average age of patients was 58.1 years. The average time to diagnosis was 3.77 months. Symptomatology was dominated by icteric syndrome and right hypochondrium pain. All patients had biological manifestation of cholestatic syndrome. Abdominal ultrasound was performed in 65% of patients, while abdominal CT scan in 85% of cases and MRI in 35% of cases. Advanced cancers were predominant in our case series (n=19). The majority of patients underwent palliative surgery. The most practiced treatment was biliary diversion (50% of patients). There was a predominance of cholangiocarcinomas. The overall operative morbidity rate was 43.75%. The overall mortality rate in our patients with biliary tract cancers of any site was 31.25%. Median survival was 4 months and a half. Biliary tract cancers have multifaceted features and can be differentiated essentially among intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, gallbladder adenocarcinoma whose evolution is globally different but the prognosis is spontaneously poor.

2012 Gordon Research Conference on Mutagenesis - Formal Schedule and Speaker/Poster Program

DOE Office of Scientific and Technical Information (OSTI.GOV)

Demple, Bruce

2012-08-24

The delicate balance among cellular pathways that control mutagenic changes in DNA will be the focus of the 2012 Mutagenesis Gordon Research Conference. Mutagenesis is essential for evolution, while genetic stability maintains cellular functions in all organisms from microbes to metazoans. Different systems handle DNA lesions at various times of the cell cycle and in different places within the nucleus, and inappropriate actions can lead to mutations. While mutation in humans is closely linked to disease, notably cancers, mutational systems can also be beneficial. The conference will highlight topics of beneficial mutagenesis, including full establishment of the immune system, cellmore » survival mechanisms, and evolution and adaptation in microbial systems. Equal prominence will be given to detrimental mutation processes, especially those involved in driving cancer, neurological diseases, premature aging, and other threats to human health. Provisional session titles include Branching Pathways in Mutagenesis; Oxidative Stress and Endogenous DNA Damage; DNA Maintenance Pathways; Recombination, Good and Bad; Problematic DNA Structures; Localized Mutagenesis; Hypermutation in the Microbial World; and Mutation and Disease.« less

Brachytherapy in early prostate cancer--early experience.

PubMed

Jose, B O; Bailen, J L; Albrink, F H; Steinbock, G S; Cornett, M S; Benson, D C; Schmied, W K; Medley, R N; Spanos, W J; Paris, K J; Koerner, P D; Gatenby, R A; Wilson, D L; Meyer, R

1999-01-01

Use of brachytherapy with radioactive seeds in the management of early prostate cancer is commonly used in the United States. The early experience has been reported from the prostate treatment centers in Seattle for the last 10 years. In this manuscript we are reporting our early experience of 150 radioactive seed implantations in early stage prostate cancer using either Iodine 125 or Palladium 103 seeds. The average age of the patient is 66 years and the median Gleason score is 5.4 with a median PSA of 6. A brief description of the evolution of the treatment of prostate cancer as well as the preparation for the seed implantation using the volume study with ultrasound of the prostate, pubic arch study using CT scan of the pelvis and the complete planning using the treatment planning computers are discussed. We also have described the current technique which is used in our experience based on the Seattle guidelines. We plan a follow-up report with the results of the studies with longer follow-up.

Combined CSL and p53 downregulation promotes cancer-associated fibroblast activation

PubMed Central

Procopio, Maria-Giuseppina; Laszlo, Csaba; Labban, Dania Al; Kim, Dong Eun; Bordignon, Pino; Jo, Seunghee; Goruppi, Sandro; Menietti, Elena; Ostano, Paola; Ala, Ugo; Provero, Paolo; Hoetzenecker, Wolfram; Neel, Victor; Kilarski, Witek; Swartz, Melody A.; Brisken, Cathrin; Lefort, Karine; Dotto, G. Paolo

2015-01-01

Stromal fibroblast senescence has been linked to aging-associated cancer risk. However, density and proliferation of cancer-associated fibroblasts (CAF) are frequently increased. Loss or down-modulation of the Notch effector CSL/RBP-Jκ in dermal fibroblasts is sufficient for CAF activation and ensuing keratinocyte-derived tumors. We report that CSL silencing induces senescence of primary fibroblasts from dermis, oral mucosa, breast and lung. CSL functions in these cells as direct repressor of multiple senescence- and CAF-effector genes. It also physically interacts with p53, repressing its activity. CSL is down-modulated in stromal fibroblasts of premalignant skin actinic keratosis lesions and squamous cell carcinomas (SCC), while p53 expression and function is down-modulated only in the latter, with paracrine FGF signaling as likely culprit. Concomitant loss of CSL and p53 overcomes fibroblast senescence, enhances expression of CAF effectors and promotes stromal and cancer cell expansion. The findings support a CAF activation/stromal co-evolution model under convergent CSL/p53 control. PMID:26302407

Current Progresses of Single Cell DNA Sequencing in Breast Cancer Research.

PubMed

Liu, Jianlin; Adhav, Ragini; Xu, Xiaoling

2017-01-01

Breast cancers display striking genetic and phenotypic diversities. To date, several hypotheses are raised to explain and understand the heterogeneity, including theories for cancer stem cell (CSC) and clonal evolution. According to the CSC theory, the most tumorigenic cells, while maintaining themselves through symmetric division, divide asymmetrically to generate non-CSCs with less tumorigenic and metastatic potential, although they can also dedifferentiate back to CSCs. Clonal evolution theory recapitulates that a tumor initially arises from a single cell, which then undergoes clonal expansion to a population of cancer cells. During tumorigenesis and evolution process, cancer cells undergo different degrees of genetic instability and consequently obtain varied genetic aberrations. Yet the heterogeneity in breast cancers is very complex, poorly understood and subjected to further investigation. In recent years, single cell sequencing (SCS) technology developed rapidly, providing a powerful new way to better understand the heterogeneity, which may lay foundations to some new strategies for breast cancer therapies. In this review, we will summarize development of SCS technologies and recent advances of SCS in breast cancer.

Incidence of skin cancers during 5-year follow-up after stopping antioxidant vitamins and mineral supplementation.

PubMed

Ezzedine, Khaled; Latreille, Julie; Kesse-Guyot, Emmanuelle; Galan, Pilar; Hercberg, Serge; Guinot, Christiane; Malvy, Denis

2010-12-01

In the SU.VI.MAX study, antioxidant supplementation for 7.5 years was found to increase skin cancer risk in women but not in men. To investigate the potential residual or delayed effect of antioxidant supplementation on skin cancer incidence after a 5-year post-intervention follow-up. Assessment of skin cancer including melanoma and non-melanoma during the post-intervention follow-up (September 2002-August 2007). The SU.VI.MAX study was a double-blind, placebo-controlled, randomised trial, in which 12,741 French adults (7713 women aged 35-60 years and 5028 men aged 45-60 years) received daily a placebo or a combination of ascorbic acid (120 mg), vitamin E (30 mg), β-carotene (6 mg), selenium (100 μg) and zinc (20mg), from inclusion in 1994 to September 2002. Total skin cancer incidence, including melanoma, squamous cell carcinoma and basal cell carcinoma. During the post-intervention period, 10 melanomas appeared in women and 9 in men (26 and 18, respectively, for the total period of supplementation+post-supplementation). Six squamous cell carcinomas were found in women and 15 in men (10 and 25, respectively, for the total period). Finally, 40 basal cell carcinomas appeared in women and 36 in men (98 and 94, respectively, for the total period). Regarding potential residual or delayed effects of supplementation in women, no increased risk of melanoma was observed during the post-intervention follow-up period. No delayed effects, either on melanoma or non-melanoma skin cancers, were observed for either gender. The risk of skin cancers associated with antioxidant intake declines following interruption of supplementation. This supports a causative role for antioxidants in the evolution of skin cancers. Copyright © 2010 Elsevier Ltd. All rights reserved.

Study on the opinion of university students about the themes of the origin of Universe and evolution of life

NASA Astrophysics Data System (ADS)

de Souza, Rogério F.; de Carvalho, Marcelo; Matsuo, Tiemi; Zaia, Dimas A. M.

2010-04-01

This paper reports the results of a questionnaire administered to university students, about several questions involving the origin of the Universe and life and biological evolution, as well as questions related to more common scientific themes. As few as between 2.4% (philosophy students) and 14% (geography students) did not accept the theory of evolution, because they believed in creation as described in the Bible. However, between 41.5% (philosophy students) and 71.3% (biology students) did not see any conflict between religion and evolution. About 80% of the students believed that the relationship between lung cancer and smoking is well established by science, but this number falls to 65% for biological evolution and 28.9% for the big bang theory. It should be pointed out that for 24.5% and 7.4% of the students the big bang theory and biological evolution, respectively, are poorly established by science. The students who self-reported being Christian but not Roman Catholic are more conservative in the acceptance of biological evolution and the old age of Earth and the Universe than are other groups of students. Other factors, such as family income and the level of education of parents, appear to influence the students' acceptance of themes related to the origin of the Universe and biological evolution.

Order Matters: The Order of Somatic Mutations Influences Cancer Evolution.

PubMed

Kent, David G; Green, Anthony R

2017-04-03

Cancers evolve as a consequence of multiple somatic lesions, with competition between subclones and sequential subclonal evolution. Some driver mutations arise either early or late in the evolution of different individual tumors, suggesting that the final malignant properties of a subclone reflect the sum of mutations acquired rather than the order in which they arose. However, very little is known about the cellular consequences of altering the order in which mutations are acquired. Recent studies of human myeloproliferative neoplasms show that the order in which individual mutations are acquired has a dramatic impact on the cell biological and molecular properties of tumor-initiating cells. Differences in clinical presentation, complications, and response to targeted therapy were all observed and implicate mutation order as an important player in cancer biology. These observations represent the first demonstration that the order of mutation acquisition influences stem and progenitor cell behavior and clonal evolution in any cancer. Thus far, the impact of different mutation orders has only been studied in hematological malignancies, and analogous studies of solid cancers are now required. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

Mitochondrial uncoupling in cancer cells: Liabilities and opportunities.

PubMed

Baffy, Gyorgy

2017-08-01

Acquisition of the endosymbiotic ancestor of mitochondria was a critical event in eukaryote evolution. Mitochondria offered an unparalleled source of metabolic energy through oxidative phosphorylation and allowed the development of multicellular life. However, as molecular oxygen had become the terminal electron acceptor in most eukaryotic cells, the electron transport chain proved to be the largest intracellular source of superoxide, contributing to macromolecular injury, aging, and cancer. Hence, the 'contract of endosymbiosis' represents a compromise between the possibilities and perils of multicellular life. Uncoupling proteins (UCPs), a group of the solute carrier family of transporters, may remove some of the physiologic constraints that link mitochondrial respiration and ATP synthesis by mediating inducible proton leak and limiting oxidative cell injury. This important property makes UCPs an ancient partner in the metabolic adaptation of cancer cells. Efforts are underway to explore the therapeutic opportunities stemming from the intriguing relationship of UCPs and cancer. This article is part of a Special Issue entitled Mitochondria in Cancer, edited by Giuseppe Gasparre, Rodrigue Rossignol and Pierre Sonveaux. Published by Elsevier B.V.

Breast tumor heterogeneity: cancer stem cells or clonal evolution?

PubMed

Campbell, Lauren L; Polyak, Kornelia

2007-10-01

Breast tumors are composed of a variety of cell types with distinct morphologies and behaviors. It is not clear how this tumor heterogeneity comes about. Two popular concepts that attempt to explain this are the cancer stem cell hypothesis and the clonal evolution model. Each of these ideas has been investigated for some time, leading to the accumulation of numerous findings that are used to support one or the other. Although the two views share some similarities, they are fundamentally different notions with very different clinical implications. Analysis of the research backing each concept, along with a review of the results of our recent study investigating putative breast cancer stem cells, suggests how the cancer stem cell hypothesis and the clonal evolution model may be involved in generating breast tumor heterogeneity. An understanding of this process will allow the development of more effective ways to treat and prevent breast cancer.

Mathematical modeling of the malignancy of cancer using graph evolution.

PubMed

Gunduz-Demir, Cigdem

2007-10-01

We report a novel computational method based on graph evolution process to model the malignancy of brain cancer called glioma. In this work, we analyze the phases that a graph passes through during its evolution and demonstrate strong relation between the malignancy of cancer and the phase of its graph. From the photomicrographs of tissues, which are diagnosed as normal, low-grade cancerous and high-grade cancerous, we construct cell-graphs based on the locations of cells; we probabilistically generate an edge between every pair of cells depending on the Euclidean distance between them. For a cell-graph, we extract connectivity information including the properties of its connected components in order to analyze the phase of the cell-graph. Working with brain tissue samples surgically removed from 12 patients, we demonstrate that cell-graphs generated for different tissue types evolve differently and that they exhibit different phase properties, which distinguish a tissue type from another.

[Influence of disease on Matisse and Monet painting].

PubMed

Castillo-Ojugas, Antonio

2003-01-01

Henri Matisse (1869-1954) "Fauvisme", radically changed as for 1941, when he endured a severe surgery due to intestinal cancer. The resulting wound got necrosis, leading to a deficit at his abdominal muscles that impeached him to remain standing and paint. Sitting on his wheelchair, he started to cut out pieces of papers with which we created artistic collages. He died in 1954, aged 84, almost 13 years after his surgery. Claude Monet (1840-1926). After a journey to Venice in 1908, when he was 68 years old, cataracts were detected in Monet's both eyes, leading to the loss of his sight on his left eye and to an abnormal perception of colours on his right one. These alterations can be detected at his pieces of work. The surgery on his right eye en 1923, evoluted to a rare complication, know as "Xantopsia", that is, yellow-coloured sight, which was partially corrected through "Zeiss" linses. He died on lung cancer on 5th December 1926, aged 86.

Tumor evolution: Linear, branching, neutral or punctuated?☆

PubMed Central

Davis, Alexander; Gao, Ruli; Navin, Nicholas

2017-01-01

Intratumor heterogeneity has been widely reported in human cancers, but our knowledge of how this genetic diversity emerges over time remains limited. A central challenge in studying tumor evolution is the difficulty in collecting longitudinal samples from cancer patients. Consequently, most studies have inferred tumor evolution from single time-point samples, providing very indirect information. These data have led to several competing models of tumor evolution: linear, branching, neutral and punctuated. Each model makes different assumptions regarding the timing of mutations and selection of clones, and therefore has different implications for the diagnosis and therapeutic treatment of cancer patients. Furthermore, emerging evidence suggests that models may change during tumor progression or operate concurrently for different classes of mutations. Finally, we discuss data that supports the theory that most human tumors evolve from a single cell in the normal tissue. This article is part of a Special Issue entitled: Evolutionary principles - heterogeneity in cancer?, edited by Dr. Robert A. Gatenby. PMID:28110020

Acute myeloid leukaemia: a paradigm for the clonal evolution of cancer?

PubMed Central

Grove, Carolyn S.; Vassiliou, George S.

2014-01-01

Acute myeloid leukaemia (AML) is an uncontrolled clonal proliferation of abnormal myeloid progenitor cells in the bone marrow and blood. Advances in cancer genomics have revealed the spectrum of somatic mutations that give rise to human AML and drawn our attention to its molecular evolution and clonal architecture. It is now evident that most AML genomes harbour small numbers of mutations, which are acquired in a stepwise manner. This characteristic, combined with our ability to identify mutations in individual leukaemic cells and our detailed understanding of normal human and murine haematopoiesis, makes AML an excellent model for understanding the principles of cancer evolution. Furthermore, a better understanding of how AML evolves can help us devise strategies to improve the therapy and prognosis of AML patients. Here, we draw from recent advances in genomics, clinical studies and experimental models to describe the current knowledge of the clonal evolution of AML and its implications for the biology and treatment of leukaemias and other cancers. PMID:25056697

[Resources of Lycium species and related research progress].

PubMed

Dong, Jing-Zhou; Yang, Jun-Jun; Wang, Ying

2008-09-01

Solanaceae Lycium speices are deciduous shrubs. In ancient Chinese medicine works, Lycium plants are described to work well in nourshing liver and kidney, enhancing eyesight, enriching blood, invigorating sex, reducing rheumatism and so on. More of their functions such as immunity improvement, anti-oxydation, anti-aging, anti-cancer, growth stumulation, hemopoiesis enhancing, incretion regulating, blood sugar reducing, bearing improvement and many other new functions are conformed in modern clinic researches. Lycium is also widely used in brewing, beverage and many other products. The world Lycium-related researches are mostly on Lycium species genesis and evolution, sexual evolution, active ingredient separation and pharmacological effects. The future research direction is indicated in this article, molecular evolution and systematics rather than traditional taxonomy will do better in explanation of present global distribution of Lycium species; comparative genomics research on Lycium will be a whole new way to deep gene resources exploration; relationship of genetic diversity and active ingredient variation on L. barbarum and L. chinense will lay theory basis for new germplasm development, breeding, cultivation and production regionalization.

Cancer as an evolutionary and ecological process.

PubMed

Merlo, Lauren M F; Pepper, John W; Reid, Brian J; Maley, Carlo C

2006-12-01

Neoplasms are microcosms of evolution. Within a neoplasm, a mosaic of mutant cells compete for space and resources, evade predation by the immune system and can even cooperate to disperse and colonize new organs. The evolution of neoplastic cells explains both why we get cancer and why it has been so difficult to cure. The tools of evolutionary biology and ecology are providing new insights into neoplastic progression and the clinical control of cancer.

Cell population heterogeneity and evolution towards drug resistance in cancer: Biological and mathematical assessment, theoretical treatment optimisation.

PubMed

Chisholm, Rebecca H; Lorenzi, Tommaso; Clairambault, Jean

2016-11-01

Drug-induced drug resistance in cancer has been attributed to diverse biological mechanisms at the individual cell or cell population scale, relying on stochastically or epigenetically varying expression of phenotypes at the single cell level, and on the adaptability of tumours at the cell population level. We focus on intra-tumour heterogeneity, namely between-cell variability within cancer cell populations, to account for drug resistance. To shed light on such heterogeneity, we review evolutionary mechanisms that encompass the great evolution that has designed multicellular organisms, as well as smaller windows of evolution on the time scale of human disease. We also present mathematical models used to predict drug resistance in cancer and optimal control methods that can circumvent it in combined therapeutic strategies. Plasticity in cancer cells, i.e., partial reversal to a stem-like status in individual cells and resulting adaptability of cancer cell populations, may be viewed as backward evolution making cancer cell populations resistant to drug insult. This reversible plasticity is captured by mathematical models that incorporate between-cell heterogeneity through continuous phenotypic variables. Such models have the benefit of being compatible with optimal control methods for the design of optimised therapeutic protocols involving combinations of cytotoxic and cytostatic treatments with epigenetic drugs and immunotherapies. Gathering knowledge from cancer and evolutionary biology with physiologically based mathematical models of cell population dynamics should provide oncologists with a rationale to design optimised therapeutic strategies to circumvent drug resistance, that still remains a major pitfall of cancer therapeutics. This article is part of a Special Issue entitled "System Genetics" Guest Editor: Dr. Yudong Cai and Dr. Tao Huang. Copyright © 2016 Elsevier B.V. All rights reserved.

Modeling lung cancer evolution and preclinical response by orthotopic mouse allografts.

PubMed

Ambrogio, Chiara; Carmona, Francisco J; Vidal, August; Falcone, Mattia; Nieto, Patricia; Romero, Octavio A; Puertas, Sara; Vizoso, Miguel; Nadal, Ernest; Poggio, Teresa; Sánchez-Céspedes, Montserrat; Esteller, Manel; Mulero, Francisca; Voena, Claudia; Chiarle, Roberto; Barbacid, Mariano; Santamaría, David; Villanueva, Alberto

2014-11-01

Cancer evolution is a process that is still poorly understood because of the lack of versatile in vivo longitudinal studies. By generating murine non-small cell lung cancer (NSCLC) orthoallobanks and paired primary cell lines, we provide a detailed description of an in vivo, time-dependent cancer malignization process. We identify the acquisition of metastatic dissemination potential, the selection of co-driver mutations, and the appearance of naturally occurring intratumor heterogeneity, thus recapitulating the stochastic nature of human cancer development. This approach combines the robustness of genetically engineered cancer models with the flexibility of allograft methodology. We have applied this tool for the preclinical evaluation of therapeutic approaches. This system can be implemented to improve the design of future treatments for patients with NSCLC. ©2014 American Association for Cancer Research.

Molecular evolution of colorectal cancer: from multistep carcinogenesis to the big bang.

PubMed

Amaro, Adriana; Chiara, Silvana; Pfeffer, Ulrich

2016-03-01

Colorectal cancer is characterized by exquisite genomic instability either in the form of microsatellite instability or chromosomal instability. Microsatellite instability is the result of mutation of mismatch repair genes or their silencing through promoter methylation as a consequence of the CpG island methylator phenotype. The molecular causes of chromosomal instability are less well characterized. Genomic instability and field cancerization lead to a high degree of intratumoral heterogeneity and determine the formation of cancer stem cells and epithelial-mesenchymal transition mediated by the TGF-β and APC pathways. Recent analyses using integrated genomics reveal different phases of colorectal cancer evolution. An initial phase of genomic instability that yields many clones with different mutations (big bang) is followed by an important, previously not detected phase of cancer evolution that consists in the stabilization of several clones and a relatively flat outgrowth. The big bang model can best explain the coexistence of several stable clones and is compatible with the fact that the analysis of the bulk of the primary tumor yields prognostic information.

The reverse evolution from multicellularity to unicellularity during carcinogenesis.

PubMed

Chen, Han; Lin, Fangqin; Xing, Ke; He, Xionglei

2015-03-09

Theoretical reasoning suggests that cancer may result from a knockdown of the genetic constraints that evolved for the maintenance of metazoan multicellularity. By characterizing the whole-life history of a xenograft tumour, here we show that metastasis is driven by positive selection for general loss-of-function mutations on multicellularity-related genes. Expression analyses reveal mainly downregulation of multicellularity-related genes and an evolving expression profile towards that of embryonic stem cells, the cell type resembling unicellular life in its capacity of unlimited clonal proliferation. Also, the emergence of metazoan multicellularity ~600 Myr ago is accompanied by an elevated birth rate of cancer genes, and there are more loss-of-function tumour suppressors than activated oncogenes in a typical tumour. These data collectively suggest that cancer represents a loss-of-function-driven reverse evolution back to the unicellular 'ground state'. This cancer evolution model may account for inter-/intratumoural genetic heterogeneity, could explain distant-organ metastases and hold implications for cancer therapy.

From cancer genomes to cancer models: bridging the gaps

PubMed Central

Baudot, Anaïs; Real, Francisco X.; Izarzugaza, José M. G.; Valencia, Alfonso

2009-01-01

Cancer genome projects are now being expanded in an attempt to provide complete landscapes of the mutations that exist in tumours. Although the importance of cataloguing genome variations is well recognized, there are obvious difficulties in bridging the gaps between high-throughput resequencing information and the molecular mechanisms of cancer evolution. Here, we describe the current status of the high-throughput genomic technologies, and the current limitations of the associated computational analysis and experimental validation of cancer genetic variants. We emphasize how the current cancer-evolution models will be influenced by the high-throughput approaches, in particular through efforts devoted to monitoring tumour progression, and how, in turn, the integration of data and models will be translated into mechanistic knowledge and clinical applications. PMID:19305388

Lung cancer diagnosis and staging in the minimally invasive age with increasing demands for tissue analysis

PubMed Central

Costa, Daniel B.; Wright, Jeffrey; VanderLaan, Paul A.

2015-01-01

The diagnosis and staging of patients with lung cancer in recent decades has increasingly relied on minimally invasive tissue sampling techniques, such as endobronchial ultrasound (EBUS) or endoscopic ultrasound (EUS) needle aspiration, transbronchial biopsy, and transthoracic image guided core needle biopsy. These modalities have been shown to have low complication rates, and provide adequate cellular material for pathologic diagnosis and necessary ancillary molecular testing. As an important component to a multidisciplinary team approach in the care of patients with lung cancer, these minimally invasive modalities have proven invaluable for the rapid and safe acquisition of tissue used for the diagnosis, staging, and molecular testing of tumors to identify the best evidence-based treatment plan. The continuous evolution of the field of lung cancer staging and treatment has translated into improvements in survival and quality of life for patients. Although differences in clinical practice between academic and community hospital settings still exist, improvements in physician education and training as well as adoption of technological advancements should help narrow this gap going forward. PMID:26380180

Blood-Based Analyses of Cancer: Circulating Tumor Cells and Circulating Tumor DNA

PubMed Central

Haber, Daniel A.; Velculescu, Victor E.

2015-01-01

The ability to study nonhematologic cancers through noninvasive sampling of blood is one of the most exciting and rapidly advancing fields in cancer diagnostics. This has been driven both by major technologic advances, including the isolation of intact cancer cells and the analysis of cancer cell–derived DNA from blood samples, and by the increasing application of molecularly driven therapeutics, which rely on such accurate and timely measurements of critical biomarkers. Moreover, the dramatic efficacy of these potent cancer therapies drives the selection for additional genetic changes as tumors acquire drug resistance, necessitating repeated sampling of cancer cells to adjust therapy in response to tumor evolution. Together, these advanced noninvasive diagnostic capabilities and their applications in guiding precision cancer therapies are poised to change the ways in which we select and monitor cancer treatments. Significance Recent advances in technologies to analyze circulating tumor cells and circulating tumor DNA are setting the stage for real-time, noninvasive monitoring of cancer and providing novel insights into cancer evolution, invasion, and metastasis. PMID:24801577

Viral Evolution Core | FNLCR Staging

Cancer.gov

Brandon F. Keele, Ph.D. PI/Senior Principal Investigator, Retroviral Evolution Section Head, Viral Evolution Core Leidos Biomedical Research, Inc. Frederick National Laboratory for Cancer Research Frederick, MD 21702-1201 Tel: 301-846-173

Multifocal clonal evolution characterized using circulating tumour DNA in a case of metastatic breast cancer

PubMed Central

Murtaza, Muhammed; Dawson, Sarah-Jane; Pogrebniak, Katherine; Rueda, Oscar M.; Provenzano, Elena; Grant, John; Chin, Suet-Feung; Tsui, Dana W. Y.; Marass, Francesco; Gale, Davina; Ali, H. Raza; Shah, Pankti; Contente-Cuomo, Tania; Farahani, Hossein; Shumansky, Karey; Kingsbury, Zoya; Humphray, Sean; Bentley, David; Shah, Sohrab P.; Wallis, Matthew; Rosenfeld, Nitzan; Caldas, Carlos

2015-01-01

Circulating tumour DNA analysis can be used to track tumour burden and analyse cancer genomes non-invasively but the extent to which it represents metastatic heterogeneity is unknown. Here we follow a patient with metastatic ER-positive and HER2-positive breast cancer receiving two lines of targeted therapy over 3 years. We characterize genomic architecture and infer clonal evolution in eight tumour biopsies and nine plasma samples collected over 1,193 days of clinical follow-up using exome and targeted amplicon sequencing. Mutation levels in the plasma samples reflect the clonal hierarchy inferred from sequencing of tumour biopsies. Serial changes in circulating levels of sub-clonal private mutations correlate with different treatment responses between metastatic sites. This comparison of biopsy and plasma samples in a single patient with metastatic breast cancer shows that circulating tumour DNA can allow real-time sampling of multifocal clonal evolution. PMID:26530965

Multifocal clonal evolution characterized using circulating tumour DNA in a case of metastatic breast cancer.

PubMed

Murtaza, Muhammed; Dawson, Sarah-Jane; Pogrebniak, Katherine; Rueda, Oscar M; Provenzano, Elena; Grant, John; Chin, Suet-Feung; Tsui, Dana W Y; Marass, Francesco; Gale, Davina; Ali, H Raza; Shah, Pankti; Contente-Cuomo, Tania; Farahani, Hossein; Shumansky, Karey; Kingsbury, Zoya; Humphray, Sean; Bentley, David; Shah, Sohrab P; Wallis, Matthew; Rosenfeld, Nitzan; Caldas, Carlos

2015-11-04

Circulating tumour DNA analysis can be used to track tumour burden and analyse cancer genomes non-invasively but the extent to which it represents metastatic heterogeneity is unknown. Here we follow a patient with metastatic ER-positive and HER2-positive breast cancer receiving two lines of targeted therapy over 3 years. We characterize genomic architecture and infer clonal evolution in eight tumour biopsies and nine plasma samples collected over 1,193 days of clinical follow-up using exome and targeted amplicon sequencing. Mutation levels in the plasma samples reflect the clonal hierarchy inferred from sequencing of tumour biopsies. Serial changes in circulating levels of sub-clonal private mutations correlate with different treatment responses between metastatic sites. This comparison of biopsy and plasma samples in a single patient with metastatic breast cancer shows that circulating tumour DNA can allow real-time sampling of multifocal clonal evolution.

Tracking Genomic Cancer Evolution for Precision Medicine: The Lung TRACERx Study

PubMed Central

Jamal-Hanjani, Mariam; Hackshaw, Alan; Ngai, Yenting; Shaw, Jacqueline; Dive, Caroline; Quezada, Sergio; Middleton, Gary; de Bruin, Elza; Le Quesne, John; Shafi, Seema; Falzon, Mary; Horswell, Stuart; Blackhall, Fiona; Khan, Iftekhar; Janes, Sam; Nicolson, Marianne; Lawrence, David; Forster, Martin; Fennell, Dean; Lee, Siow-Ming; Lester, Jason; Kerr, Keith; Muller, Salli; Iles, Natasha; Smith, Sean; Murugaesu, Nirupa; Mitter, Richard; Salm, Max; Stuart, Aengus; Matthews, Nik; Adams, Haydn; Ahmad, Tanya; Attanoos, Richard; Bennett, Jonathan; Birkbak, Nicolai Juul; Booton, Richard; Brady, Ged; Buchan, Keith; Capitano, Arrigo; Chetty, Mahendran; Cobbold, Mark; Crosbie, Philip; Davies, Helen; Denison, Alan; Djearman, Madhav; Goldman, Jacki; Haswell, Tom; Joseph, Leena; Kornaszewska, Malgorzata; Krebs, Matthew; Langman, Gerald; MacKenzie, Mairead; Millar, Joy; Morgan, Bruno; Naidu, Babu; Nonaka, Daisuke; Peggs, Karl; Pritchard, Catrin; Remmen, Hardy; Rowan, Andrew; Shah, Rajesh; Smith, Elaine; Summers, Yvonne; Taylor, Magali; Veeriah, Selvaraju; Waller, David; Wilcox, Ben; Wilcox, Maggie; Woolhouse, Ian; McGranahan, Nicholas; Swanton, Charles

2014-01-01

The importance of intratumour genetic and functional heterogeneity is increasingly recognised as a driver of cancer progression and survival outcome. Understanding how tumour clonal heterogeneity impacts upon therapeutic outcome, however, is still an area of unmet clinical and scientific need. TRACERx (TRAcking non-small cell lung Cancer Evolution through therapy [Rx]), a prospective study of patients with primary non-small cell lung cancer (NSCLC), aims to define the evolutionary trajectories of lung cancer in both space and time through multiregion and longitudinal tumour sampling and genetic analysis. By following cancers from diagnosis to relapse, tracking the evolutionary trajectories of tumours in relation to therapeutic interventions, and determining the impact of clonal heterogeneity on clinical outcomes, TRACERx may help to identify novel therapeutic targets for NSCLC and may also serve as a model applicable to other cancer types. PMID:25003521

Links between DNA Replication, Stem Cells and Cancer

PubMed Central

Vassilev, Alex; DePamphilis, Melvin L.

2017-01-01

Cancers can be categorized into two groups: those whose frequency increases with age, and those resulting from errors during mammalian development. The first group is linked to DNA replication through the accumulation of genetic mutations that occur during proliferation of developmentally acquired stem cells that give rise to and maintain tissues and organs. These mutations, which result from DNA replication errors as well as environmental insults, fall into two categories; cancer driver mutations that initiate carcinogenesis and genome destabilizing mutations that promote aneuploidy through excess genome duplication and chromatid missegregation. Increased genome instability results in accelerated clonal evolution leading to the appearance of more aggressive clones with increased drug resistance. The second group of cancers, termed germ cell neoplasia, results from the mislocation of pluripotent stem cells during early development. During normal development, pluripotent stem cells that originate in early embryos give rise to all of the cell lineages in the embryo and adult, but when they mislocate to ectopic sites, they produce tumors. Remarkably, pluripotent stem cells, like many cancer cells, depend on the Geminin protein to prevent excess DNA replication from triggering DNA damage-dependent apoptosis. This link between the control of DNA replication during early development and germ cell neoplasia reveals Geminin as a potential chemotherapeutic target in the eradication of cancer progenitor cells. PMID:28125050

Chapter 27 -- Breast Cancer Genomics, Section VI, Pathology and Biological Markers of Invasive Breast Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Spellman, Paul T.; Heiser, Laura; Gray, Joe W.

2009-06-18

Breast cancer is predominantly a disease of the genome with cancers arising and progressing through accumulation of aberrations that alter the genome - by changing DNA sequence, copy number, and structure in ways that that contribute to diverse aspects of cancer pathophysiology. Classic examples of genomic events that contribute to breast cancer pathophysiology include inherited mutations in BRCA1, BRCA2, TP53, and CHK2 that contribute to the initiation of breast cancer, amplification of ERBB2 (formerly HER2) and mutations of elements of the PI3-kinase pathway that activate aspects of epidermal growth factor receptor (EGFR) signaling and deletion of CDKN2A/B that contributes tomore » cell cycle deregulation and genome instability. It is now apparent that accumulation of these aberrations is a time-dependent process that accelerates with age. Although American women living to an age of 85 have a 1 in 8 chance of developing breast cancer, the incidence of cancer in women younger than 30 years is uncommon. This is consistent with a multistep cancer progression model whereby mutation and selection drive the tumor's development, analogous to traditional Darwinian evolution. In the case of cancer, the driving events are changes in sequence, copy number, and structure of DNA and alterations in chromatin structure or other epigenetic marks. Our understanding of the genetic, genomic, and epigenomic events that influence the development and progression of breast cancer is increasing at a remarkable rate through application of powerful analysis tools that enable genome-wide analysis of DNA sequence and structure, copy number, allelic loss, and epigenomic modification. Application of these techniques to elucidation of the nature and timing of these events is enriching our understanding of mechanisms that increase breast cancer susceptibility, enable tumor initiation and progression to metastatic disease, and determine therapeutic response or resistance. These studies also reveal the molecular differences between cancer and normal that may be exploited to therapeutic benefit or that provide targets for molecular assays that may enable early cancer detection, and predict individual disease progression or response to treatment. This chapter reviews current and future directions in genome analysis and summarizes studies that provide insights into breast cancer pathophysiology or that suggest strategies to improve breast cancer management.« less

Milk—A Nutrient System of Mammalian Evolution Promoting mTORC1-Dependent Translation

PubMed Central

Melnik, Bodo C.

2015-01-01

Based on own translational research of the biochemical and hormonal effects of cow’s milk consumption in humans, this review presents milk as a signaling system of mammalian evolution that activates the nutrient-sensitive kinase mechanistic target of rapamycin complex 1 (mTORC1), the pivotal regulator of translation. Milk, a mammary gland-derived secretory product, is required for species-specific gene-nutrient interactions that promote appropriate growth and development of the newborn mammal. This signaling system is highly conserved and tightly controlled by the lactation genome. Milk is sufficient to activate mTORC1, the crucial regulator of protein, lipid, and nucleotide synthesis orchestrating anabolism, cell growth and proliferation. To fulfill its mTORC1-activating function, milk delivers four key metabolic messengers: (1) essential branched-chain amino acids (BCAAs); (2) glutamine; (3) palmitic acid; and (4) bioactive exosomal microRNAs, which in a synergistical fashion promote mTORC1-dependent translation. In all mammals except Neolithic humans, postnatal activation of mTORC1 by milk intake is restricted to the postnatal lactation period. It is of critical concern that persistent hyperactivation of mTORC1 is associated with aging and the development of age-related disorders such as obesity, type 2 diabetes mellitus, cancer, and neurodegenerative diseases. Persistent mTORC1 activation promotes endoplasmic reticulum (ER) stress and drives an aimless quasi-program, which promotes aging and age-related diseases. PMID:26225961

Clonal evolution models of tumor heterogeneity.

PubMed

Shlush, Liran I; Hershkovitz, Dov

2015-01-01

Somatic/clonal evolution is the process of sequential acquisition of vertically transmittable genetic/epigenetic elements in multicellular organisms. Cancer is the result of somatic evolution. Understanding the processes that shape the evolution of individual tumors might help us to treat cancer more efficiently. The initiating genetic/epigenetic events occur in functional cells and provide the cell of origin a selective advantage under a changing environment. The initiating genetic events tend to be enriched in specific tissues (and are sometimes specific for those tissues), as different tissues undergo different changes in the environment that will activate selective forces on different cells of origin. For the initial clonal expansion to occur premalignant clones need to have a relative fitness advantage over their competitors. It is estimated that the premalignant phase can take several years. Once the premalignant clonal expansion is established, the premalignant cells will contribute to the changing environment and will start competing among themselves. In late stages of cancer evolution the environmental changes might be similar across different tissues, including a lack of physical space, a shortage of energy, and activation of the immune system, and more and more of the hallmarks of cancer will evolve. In this review we will explore the possible clinical relevance of the heterogeneity that evolves during this long somatic evolution. Above all, it should be stressed that the earlier the clonal expansion is recognized, the less diverse and less fit for survival the cells in the population are.

Preventing Overdiagnosis and Overtreatment: Just the Next Step in the Evolution of Breast Cancer Care.

PubMed

Mukhtar, Rita A; Wong, Jasmine M; Esserman, Laura J

2015-06-01

The problem of overdiagnosis and overtreatment has been highlighted in breast cancer and many other cancer types, most notably prostate cancer. Addressing this problem presents an opportunity to continue the evolution of breast cancer care. Advances in technology, such as molecular subtyping, have increased the understanding of breast cancer biology and the range of associated behavior, and have provided tools that allow greater personalization of treatment. This article identifies 3 areas of breast cancer care where opportunity currently exists to refine management strategies and help decrease overtreatment and overdiagnosis: the use of adjuvant-external beam radiation in invasive breast cancer, the application of aggressive treatment for all ductal carcinoma in situ, and the authors' approach to breast cancer screening. Personalizing treatment based on patient and tumor characteristics holds promise for minimizing harms and maximizing benefits. This approach will allow continual improvement and ultimately result in providing the right treatment for each patient. Copyright © 2015 by the National Comprehensive Cancer Network.

Clonal status of actionable driver events and the timing of mutational processes in cancer evolution

PubMed Central

McGranahan, Nicholas; Favero, Francesco; de Bruin, Elza C.; Birkbak, Nicolai Juul; Szallasi, Zoltan; Swanton, Charles

2015-01-01

Deciphering whether actionable driver mutations are found in all or a subset of tumor cells will likely be required to improve drug development and precision medicine strategies. We analyzed nine cancer types to determine the subclonal frequencies of driver events, to time mutational processes during cancer evolution, and to identify drivers of subclonal expansions. Although mutations in known driver genes typically occurred early in cancer evolution, we also identified later subclonal “actionable” mutations, including BRAF(V600E), IDH1(R132H), PIK3CA(E545K), EGFR(L858R), and KRAS(G12D), which may compromise the efficacy of targeted therapy approaches. More than 20% of IDH1 mutations in glioblastomas, and 15% of mutations in genes in the PI3K(phosphatidylinositol 3-kinase)–AKT–mTOR (mammalian target of rapamycin) signaling axis across all tumor types were subclonal. Mutations in the RAS–MEK (mitogen-activated protein kinase kinase) signaling axis were less likely to be subclonal than mutations in genes associated with PI3K-AKT-mTORsignaling. Analysis of late mutations revealed a link between APOBEC-mediated mutagenesis and the acquisition of subclonal driver mutations and uncovered putative cancer genes involved in subclonal expansions, including CTNNA2 and ATXN1. Our results provide a pan-cancer census of driver events within the context of intratumor heterogeneity and reveal patterns of tumor evolution across cancers. The frequent presence of subclonal driver mutations suggests the need to stratify targeted therapy response according to the proportion of tumor cells in which the driver is identified. PMID:25877892

The importance of early detection of lip cancer risk groups

NASA Astrophysics Data System (ADS)

Fratila, M.; Rosu, S.

2014-03-01

Oral maxillo-facial region cancer carries major importance in the tumour pathology of the organism being characterized by a high frequency as well as by the variety of the clinical anatomical and topographic forms through which it is presented. Over 60% of labial carcinoma begins as an asymptomatic ulceration, therefore patients do not pay due attention, considering it a "rebellious thrush" and they make a specialized medical appointment in an advanced stage of the tumor. In this study we pursued the frequency of the lip cancer pathology compared to the total CMF; the distribution the lip cancer by sex and age in patients who submitted to the specialized service; the originating environment of the patient with lip cancer; the anatomical location of the lip cancer; the frequency of relapses after treatment; the presence of adenopathy in the first consultation. The study was performed at the Clinic of Cranio-Maxillofacial Surgery, University of Medicine and Pharmacy "Victor Babes" Timişoara and pursued statistical aspects of the lip cancer incidence over a period of five years (2007-2012). Pre- and postoperative patients were monitored constantly, registering in individual sheets the evolution of the disease, monitoring the relapses after treatment and the presence of adenopathy in the first consultation. As shown in the statistics made in the last five years (2007-2012), from a total of 8135 cases with CMF pathology hospitalized in the Timisoara surgery clinic, 163 cases, or 2%, were cancer of the lip. Analyzing the gender distribution shows that males represent 81% of cases while the remaining 19% were found in women. From the study of age distribution, we found that the number of cases increases with age: 153 cases over 60 years old and 58 cases between 20 - 60 years. Personal statistics from the 212 cases of cancer of the lip reveal that 143 (67%) patients were from the rural areas and 69 (33%) from urban areas. Neoplastic pathology is constantly increasing both in frequency as well as in the therapeutic problems raised. In the face and oral cavity cancer catagory, lip represents 2% of all cases and 19-25% of the total facial cancer area. Lip cancer is one of the localizations that, when detected early, can benefit from an effective therapy with high chances of healing. In order to achieve a complex treatment, interdisciplinary collaboration is required, only thus being able to determine both the therapeutic methods as well as their association.

Percutaneous Image-Guided Screw Fixation of Bone Lesions in Cancer Patients: Double-Centre Analysis of Outcomes including Local Evolution of the Treated Focus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cazzato, Roberto Luigi, E-mail: gigicazzato@hotmail.it; Koch, Guillaume, E-mail: guillaume.koch@chru-strasbourg.fr; Buy, Xavier, E-mail: x.buy@bordeaux.unicancer.fr

AimTo review outcomes and local evolution of treated lesions following percutaneous image-guided screw fixation (PIGSF) of pathological/insufficiency fractures (PF/InF) and impeding fractures (ImF) in cancer patients at two tertiary centres.Materials and methodsThirty-two consecutive patients (mean age 67.5 years; range 33–86 years) with a range of tumours and prognoses underwent PIGSF for non/minimally displaced PF/InF and ImF. Screws were placed under CT/fluoroscopy or cone-beam CT guidance, with or without cementoplasty. Clinical outcomes were assessed using a simple 4-point scale (1 = worse; 2 = stable; 3 = improved; 4 = significantly improved). Local evolution was reviewed on most recent follow-up imaging. Technical success, complications, and overall survival were evaluated.ResultsThirty-six lesions weremore » treated with 74 screws mainly in the pelvis and femoral neck (58.2 %); including 47.2 % PF, 13.9 % InF, and 38.9 % ImF. Cementoplasty was performed in 63.9 % of the cases. Technical success was 91.6 %. Hospital stay was ≤3 days; 87.1 % of lesions were improved at 1-month follow-up; three major complications (early screw-impingement radiculopathy; accelerated coxarthrosis; late coxofemoral septic arthritis) and one minor complication were observed. Unfavourable local evolution at imaging occurred in 3/24 lesions (12.5 %) at mean 8.7-month follow-up, including poor consolidation (one case) and screw loosening (two cases, at least 1 symptomatic). There were no cases of secondary fractures.ConclusionsPIGSF is feasible for a wide range of oncologic patients, offering good short-term efficacy, acceptable complication rates, and rapid recovery. Unfavourable local evolution at imaging may be relatively frequent, and requires close clinico-radiological surveillance.« less

Cancer classification in the genomic era: five contemporary problems.

PubMed

Song, Qingxuan; Merajver, Sofia D; Li, Jun Z

2015-10-19

Classification is an everyday instinct as well as a full-fledged scientific discipline. Throughout the history of medicine, disease classification is central to how we develop knowledge, make diagnosis, and assign treatment. Here, we discuss the classification of cancer and the process of categorizing cancer subtypes based on their observed clinical and biological features. Traditionally, cancer nomenclature is primarily based on organ location, e.g., "lung cancer" designates a tumor originating in lung structures. Within each organ-specific major type, finer subgroups can be defined based on patient age, cell type, histological grades, and sometimes molecular markers, e.g., hormonal receptor status in breast cancer or microsatellite instability in colorectal cancer. In the past 15+ years, high-throughput technologies have generated rich new data regarding somatic variations in DNA, RNA, protein, or epigenomic features for many cancers. These data, collected for increasingly large tumor cohorts, have provided not only new insights into the biological diversity of human cancers but also exciting opportunities to discover previously unrecognized cancer subtypes. Meanwhile, the unprecedented volume and complexity of these data pose significant challenges for biostatisticians, cancer biologists, and clinicians alike. Here, we review five related issues that represent contemporary problems in cancer taxonomy and interpretation. (1) How many cancer subtypes are there? (2) How can we evaluate the robustness of a new classification system? (3) How are classification systems affected by intratumor heterogeneity and tumor evolution? (4) How should we interpret cancer subtypes? (5) Can multiple classification systems co-exist? While related issues have existed for a long time, we will focus on those aspects that have been magnified by the recent influx of complex multi-omics data. Exploration of these problems is essential for data-driven refinement of cancer classification and the successful application of these concepts in precision medicine.

Head and Neck Cancer: An Evolving Treatment Paradigm

PubMed Central

Cognetti, David M.; Weber, Randal S.; Lai, Stephen Y.

2009-01-01

Since the inception of this journal in 1948, the understanding of etiologic factors that contribute to and the treatment of head and neck cancer has evolved dramatically. Advances in surgery, radiation therapy, and chemotherapy have improved locoregional control, survival, and quality of life. The outcomes of these treatment modalities have shifted the focus of curative efforts from radical ablation to preservation and restoration of function. This evolution has been documented in the pages of Cancer for the past 6 decades. This review focuses on the evolution of treatment approaches for head and neck cancer and future directions while recognizing the historic contributions recorded within this journal. PMID:18798532

Evaluating Cancer of the Central Nervous System Through Next-Generation Sequencing of Cerebrospinal Fluid

PubMed Central

Pentsova, Elena I.; Shah, Ronak H.; Tang, Jiabin; Boire, Adrienne; You, Daoqi; Briggs, Samuel; Omuro, Antonio; Lin, Xuling; Fleisher, Martin; Grommes, Christian; Panageas, Katherine S.; Meng, Fanli; Selcuklu, S. Duygu; Ogilvie, Shahiba; Distefano, Natalie; Shagabayeva, Larisa; Rosenblum, Marc; DeAngelis, Lisa M.; Viale, Agnes; Berger, Michael F.

2016-01-01

Purpose Cancer spread to the central nervous system (CNS) often is diagnosed late and is unresponsive to therapy. Mechanisms of tumor dissemination and evolution within the CNS are largely unknown because of limited access to tumor tissue. Materials and Methods We sequenced 341 cancer-associated genes in cell-free DNA from cerebrospinal fluid (CSF) obtained through routine lumbar puncture in 53 patients with suspected or known CNS involvement by cancer. Results We detected high-confidence somatic alterations in 63% (20 of 32) of patients with CNS metastases of solid tumors, 50% (six of 12) of patients with primary brain tumors, and 0% (zero of nine) of patients without CNS involvement by cancer. Several patients with tumor progression in the CNS during therapy with inhibitors of oncogenic kinases harbored mutations in the kinase target or kinase bypass pathways. In patients with glioma, the most common malignant primary brain tumor in adults, examination of cell-free DNA uncovered patterns of tumor evolution, including temozolomide-associated mutations. Conclusion The study shows that CSF harbors clinically relevant genomic alterations in patients with CNS cancers and should be considered for liquid biopsies to monitor tumor evolution in the CNS. PMID:27161972

The evolution of tumor metastases during clonal expansion.

PubMed

Haeno, Hiroshi; Michor, Franziska

2010-03-07

Cancer is a leading cause of morbidity and mortality in many countries. Solid tumors generally initiate at one particular site called the primary tumor, but eventually disseminate and form new colonies in other organs. The development of such metastases greatly diminishes the potential for a cure of patients and is thought to represent the final stage of the multi-stage progression of human cancer. The concept of early metastatic dissemination, however, postulates that cancer cell spread might arise early during the development of a tumor. It is important to know whether metastases are present at diagnosis since this determines treatment strategies and outcome. In this paper, we design a stochastic mathematical model of the evolution of tumor metastases in an expanding cancer cell population. We calculate the probability of metastasis at a given time during tumor evolution, the expected number of metastatic sites, and the total number of cancer cells as well as metastasized cells. Furthermore, we investigate the effect of drug administration and tumor resection on these quantities and predict the survival time of cancer patients. The model presented in this paper allows us to determine the probability and number of metastases at diagnosis and to identify the optimum treatment strategy to maximally prolong survival of cancer patients. 2009 Elsevier Ltd. All rights reserved.

Understanding cellular architecture in cancer cells

NASA Astrophysics Data System (ADS)

Bianco, Simone; Tang, Chao

2011-03-01

Understanding the development of cancer is an important goal for today's science. The morphology of cellular organelles, such as the nucleus, the nucleoli and the mitochondria, which is referred to as cellular architecture or cytoarchitecture, is an important indicator of the state of the cell. In particular, there are striking difference between the cellular architecture of a healthy cell versus a cancer cell. In this work we present a dynamical model for the evolution of organelles morphology in cancer cells. Using a dynamical systems approach, we describe the evolution of a cell on its way to cancer as a trajectory in a multidimensional morphology state. The results provided by this work may increase our insight on the mechanism of tumorigenesis and help build new therapeutic strategies.

The Evolution and Expression Pattern of Human Overlapping lncRNA and Protein-coding Gene Pairs.

PubMed

Ning, Qianqian; Li, Yixue; Wang, Zhen; Zhou, Songwen; Sun, Hong; Yu, Guangjun

2017-03-27

Long non-coding RNA overlapping with protein-coding gene (lncRNA-coding pair) is a special type of overlapping genes. Protein-coding overlapping genes have been well studied and increasing attention has been paid to lncRNAs. By studying lncRNA-coding pairs in human genome, we showed that lncRNA-coding pairs were more likely to be generated by overprinting and retaining genes in lncRNA-coding pairs were given higher priority than non-overlapping genes. Besides, the preference of overlapping configurations preserved during evolution was based on the origin of lncRNA-coding pairs. Further investigations showed that lncRNAs promoting the splicing of their embedded protein-coding partners was a unilateral interaction, but the existence of overlapping partners improving the gene expression was bidirectional and the effect was decreased with the increased evolutionary age of genes. Additionally, the expression of lncRNA-coding pairs showed an overall positive correlation and the expression correlation was associated with their overlapping configurations, local genomic environment and evolutionary age of genes. Comparison of the expression correlation of lncRNA-coding pairs between normal and cancer samples found that the lineage-specific pairs including old protein-coding genes may play an important role in tumorigenesis. This work presents a systematically comprehensive understanding of the evolution and the expression pattern of human lncRNA-coding pairs.

Going up or coming down? The changing phases of the lung cancer epidemic from 1967 to 1999 in the 15 European Union countries.

PubMed

Bray, F; Tyczynski, J E; Parkin, D M

2004-01-01

Lung cancer, the most common cause of cancer death in the European Union (EU), continues to have an enormous impact on the health experience of the men and women living in the constituent countries. Information on the course of the lung cancer epidemic is essential in order to formulate an effective cancer control policy. This paper examines recent trends in lung cancer mortality rates in men and women in each of the 15 countries, comparing cross-sectional rates of death in younger (aged 30-64 years) and older populations (aged 65 years or over), and the age, period of death, and birth cohort influences in the younger age group. The latter analysis establishes the importance of year of birth, related to modifications in the tobacco habit among recently born generations. The stage of evolution of the lung cancer epidemic varies markedly by sex and country in terms of the direction, magnitude, and phase of development of national trends. In males, there is some consistency in the direction of the trends between EU countries, declines are apparent in most countries, at least in younger men, with rates in older men either reaching a plateau, or also falling. In younger persons, a decreasing risk of lung cancer death reflects changes in successive birth cohorts, due to modifications in the smoking habit from generation to generation, although these developments are in very different phases across countries. Portugal is the exception to the male trends; there are increases in mortality in both age groups, with little sign of a slowing down by birth cohort. In women, there are unambiguous upsurges in rates seen in younger and older women in almost all EU countries in recent decades, and little sign that the epidemic has or will soon reach a peak. The exceptions are the United Kingdom (UK) and Ireland, where lung cancer death rates are now declining in younger women and stabilising in older women, reflecting a declining risk in women born since about 1950. It is too early to say whether the observed plateau or decline in rates in women born very recently in several countries is real or random. To ascertain whether recent trends in lung cancer mortality will continue, trends in cigarette consumption should also be evaluated. Where data are available by country, the proportion of adult male smokers has, by and large, fallen steadily in the last five decades. In women, recent smoking trends are downwards in Belgium, Denmark, Sweden and the Netherlands, although in Austria and Spain, large increases in smoking prevalence amongst adults are emerging. Unambiguous public health messages must be effectively conveyed to the inhabitants of the EU if the lung cancer epidemic is to be controlled. It is imperative that anti-tobacco strategies urgently target women living in the EU, in order to halt their rapidly increasing risk of lung cancer, and prevent unnecessary, premature deaths among future generations of women.

Clonal Heterogeneity and Tumor Evolution: Past, Present, and the Future.

PubMed

McGranahan, Nicholas; Swanton, Charles

2017-02-09

Intratumor heterogeneity, which fosters tumor evolution, is a key challenge in cancer medicine. Here, we review data and technologies that have revealed intra-tumor heterogeneity across cancer types and the dynamics, constraints, and contingencies inherent to tumor evolution. We emphasize the importance of macro-evolutionary leaps, often involving large-scale chromosomal alterations, in driving tumor evolution and metastasis and consider the role of the tumor microenvironment in engendering heterogeneity and drug resistance. We suggest that bold approaches to drug development, harnessing the adaptive properties of the immune-microenvironment while limiting those of the tumor, combined with advances in clinical trial-design, will improve patient outcome. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

Clinicopathological study of breast diseases presenting to the surgical oncology unit of Donka University Hospital in Conakry, Guinea.

PubMed

Traoré, B; Keita, M; Diane, S; Dankoro, A; Kabba, I S; Keita, N

2012-01-01

The aim of this study was to describe the characteristics and trends in the number of patients presenting with breast diseases (BD), their evolution in time, and the referral route. We reviewed all patients with breast disease who consulted at the Unit of Surgical Oncology of Donka from May 2007 to December 2009, examining the distribution of breast diseases. The numbers of women diagnosed with breast cancers was analysed with respect to time and referral source. There was a progressive increase in the number of patients presenting with breast diseases from year to year: 66 cases in 2007, 134 in 2008 and 227 in 2009. Of 423 patients with breast disease, 184 (43.5%) were diagnosed with breast cancer: 178 women and 6 men. Moreover, the percentage with breast cancer varied significantly according to referral route (p<10-3); 56.0% among patients referred by health professionals and 22.3% in women who self-referred. Mean age at diagnosis of breast cancer was 48 years (n=178), 52.2% were post-menopausal. Women with breast cancer had on average 4.7 full term pregnancies. The tumor was considered aggressive in 62.9% of women because of the rapidity of its evolution. Early stage at diagnosis was made only for 4.3% of the cases. The hormone receptor were positive in 4 of 13 cases (30.7%), and the Cerb2 oncogene was over expressed in 8 of 11 cases (72.7%). A better organisation of the consultation services in a unit of oncology in a developing country can allow a better sorting and a good orientation of the patients and thus allow the early detection of the breast cancer. This requires adequate awareness of the population, a better involvement and adequate training of the health professionals dedicated to the tasks. The study of the Cerb2's expression and the hormone receptor are to be considered for better understanding the aggressiveness of the breast cancer found in our practice.

Biological and Clinical Implications of Clonal Heterogeneity and Clonal Evolution in Multiple Myeloma.

PubMed

Bianchi, Giada; Ghobrial, Irene M

Clonal heterogeneity and clonal evolution have emerged as critical concepts in the field of oncology over the past four decades, largely thanks to the implementation of novel technologies such as comparative genomic hybridization, whole genome/exome sequencing and epigenetic analysis. Along with the identification of cancer stem cells in the majority of neoplasia, the recognition of intertumor and intratumor variability has provided a novel perspective to understand the mechanisms behind tumor evolution and its implication in terms of treatment failure and cancer relapse or recurrence. First hypothesized over two decades ago, clonal heterogeneity and clonal evolution have been confirmed in multiple myeloma (MM), an incurable cancer of plasma cells, almost universally preceded by a pre-malignant conditioned named monoclonal gammopathy of undetermined significance (MGUS). The genetic events and molecular mechanisms underlying such evolution have been difficult to dissect. Moreover, while a role for the bone marrow microenvironment in supporting MM cell survival, proliferation and drug-resistance has been well established, whether it is directly involved in driving evolution from MGUS to MM is at present unclear. We present in this review a historical excursus on the concepts of clonal heterogeneity and clonal evolution in MM with a special emphasis on their role in the progression from MGUS to MM; the contribution of the microenvironment; and the clinical implications in terms of resistance to treatment and disease relapse/recurrence.

Biological and Clinical Implications of Clonal Heterogeneity and Clonal Evolution in Multiple Myeloma

PubMed Central

Bianchi, Giada; Ghobrial, Irene M.

2015-01-01

Clonal heterogeneity and clonal evolution have emerged as critical concepts in the field of oncology over the past four decades, largely thanks to the implementation of novel technologies such as comparative genomic hybridization, whole genome/exome sequencing and epigenetic analysis. Along with the identification of cancer stem cells in the majority of neoplasia, the recognition of intertumor and intratumor variability has provided a novel perspective to understand the mechanisms behind tumor evolution and its implication in terms of treatment failure and cancer relapse or recurrence. First hypothesized over two decades ago, clonal heterogeneity and clonal evolution have been confirmed in multiple myeloma (MM), an incurable cancer of plasma cells, almost universally preceded by a pre-malignant conditioned named monoclonal gammopathy of undetermined significance (MGUS). The genetic events and molecular mechanisms underlying such evolution have been difficult to dissect. Moreover, while a role for the bone marrow microenvironment in supporting MM cell survival, proliferation and drug-resistance has been well established, whether it is directly involved in driving evolution from MGUS to MM is at present unclear. We present in this review a historical excursus on the concepts of clonal heterogeneity and clonal evolution in MM with a special emphasis on their role in the progression from MGUS to MM; the contribution of the microenvironment; and the clinical implications in terms of resistance to treatment and disease relapse/recurrence. PMID:25705146

Punctuated Copy Number Evolution and Clonal Stasis in Triple-Negative Breast Cancer

PubMed Central

Gao, Ruli; Davis, Alexander; McDonald, Thomas O.; Sei, Emi; Shi, Xiuqing; Wang, Yong; Tsai, Pei-Ching; Casasent, Anna; Waters, Jill; Zhang, Hong; Meric-Bernstam, Funda; Michor, Franziska; Navin, Nicholas E.

2016-01-01

Aneuploidy is a hallmark of breast cancer; however, our knowledge of how these complex genomic rearrangements evolve during tumorigenesis is limited. In this study we developed a highly multiplexed single-nucleus-sequencing method to investigate copy number evolution in triple-negative breast cancer patients. We sequenced 1000 single cells from 12 patients and identified 1–3 major clonal subpopulations in each tumor that shared a common evolutionary lineage. We also identified a minor subpopulation of non-clonal cells that were classified as: 1) metastable, 2) pseudo-diploid, or 3) chromazemic. Phylogenetic analysis and mathematical modeling suggest that these data are unlikely to be explained by the gradual accumulation of copy number events over time. In contrast, our data challenge the paradigm of gradual evolution, showing that the majority of copy number aberrations are acquired at the earliest stages of tumor evolution, in short punctuated bursts, followed by stable clonal expansions that form the tumor mass. PMID:27526321

Transmissible cancers in an evolutionary context.

PubMed

Ujvari, Beata; Papenfuss, Anthony T; Belov, Katherine

2016-07-01

Cancer is an evolutionary and ecological process in which complex interactions between tumour cells and their environment share many similarities with organismal evolution. Tumour cells with highest adaptive potential have a selective advantage over less fit cells. Naturally occurring transmissible cancers provide an ideal model system for investigating the evolutionary arms race between cancer cells and their surrounding micro-environment and macro-environment. However, the evolutionary landscapes in which contagious cancers reside have not been subjected to comprehensive investigation. Here, we provide a multifocal analysis of transmissible tumour progression and discuss the selection forces that shape it. We demonstrate that transmissible cancers adapt to both their micro-environment and macro-environment, and evolutionary theories applied to organisms are also relevant to these unique diseases. The three naturally occurring transmissible cancers, canine transmissible venereal tumour (CTVT) and Tasmanian devil facial tumour disease (DFTD) and the recently discovered clam leukaemia, exhibit different evolutionary phases: (i) CTVT, the oldest naturally occurring cell line is remarkably stable; (ii) DFTD exhibits the signs of stepwise cancer evolution; and (iii) clam leukaemia shows genetic instability. While all three contagious cancers carry the signature of ongoing and fairly recent adaptations to selective forces, CTVT appears to have reached an evolutionary stalemate with its host, while DFTD and the clam leukaemia appear to be still at a more dynamic phase of their evolution. Parallel investigation of contagious cancer genomes and transcriptomes and of their micro-environment and macro-environment could shed light on the selective forces shaping tumour development at different time points: during the progressive phase and at the endpoint. A greater understanding of transmissible cancers from an evolutionary ecology perspective will provide novel avenues for the prevention and treatment of both contagious and non-communicable cancers. © 2016 The Authors. BioEssays published by WILEY Periodicals, Inc.

Using Nonlinear Stochastic Evolutionary Game Strategy to Model an Evolutionary Biological Network of Organ Carcinogenesis Under a Natural Selection Scheme

PubMed Central

Chen, Bor-Sen; Tsai, Kun-Wei; Li, Cheng-Wei

2015-01-01

Molecular biologists have long recognized carcinogenesis as an evolutionary process that involves natural selection. Cancer is driven by the somatic evolution of cell lineages. In this study, the evolution of somatic cancer cell lineages during carcinogenesis was modeled as an equilibrium point (ie, phenotype of attractor) shifting, the process of a nonlinear stochastic evolutionary biological network. This process is subject to intrinsic random fluctuations because of somatic genetic and epigenetic variations, as well as extrinsic disturbances because of carcinogens and stressors. In order to maintain the normal function (ie, phenotype) of an evolutionary biological network subjected to random intrinsic fluctuations and extrinsic disturbances, a network robustness scheme that incorporates natural selection needs to be developed. This can be accomplished by selecting certain genetic and epigenetic variations to modify the network structure to attenuate intrinsic fluctuations efficiently and to resist extrinsic disturbances in order to maintain the phenotype of the evolutionary biological network at an equilibrium point (attractor). However, during carcinogenesis, the remaining (or neutral) genetic and epigenetic variations accumulate, and the extrinsic disturbances become too large to maintain the normal phenotype at the desired equilibrium point for the nonlinear evolutionary biological network. Thus, the network is shifted to a cancer phenotype at a new equilibrium point that begins a new evolutionary process. In this study, the natural selection scheme of an evolutionary biological network of carcinogenesis was derived from a robust negative feedback scheme based on the nonlinear stochastic Nash game strategy. The evolvability and phenotypic robustness criteria of the evolutionary cancer network were also estimated by solving a Hamilton–Jacobi inequality – constrained optimization problem. The simulation revealed that the phenotypic shift of the lung cancer-associated cell network takes 54.5 years from a normal state to stage I cancer, 1.5 years from stage I to stage II cancer, and 2.5 years from stage II to stage III cancer, with a reasonable match for the statistical result of the average age of lung cancer. These results suggest that a robust negative feedback scheme, based on a stochastic evolutionary game strategy, plays a critical role in an evolutionary biological network of carcinogenesis under a natural selection scheme. PMID:26244004

Clonal status of actionable driver events and the timing of mutational processes in cancer evolution.

PubMed

McGranahan, Nicholas; Favero, Francesco; de Bruin, Elza C; Birkbak, Nicolai Juul; Szallasi, Zoltan; Swanton, Charles

2015-04-15

Deciphering whether actionable driver mutations are found in all or a subset of tumor cells will likely be required to improve drug development and precision medicine strategies. We analyzed nine cancer types to determine the subclonal frequencies of driver events, to time mutational processes during cancer evolution, and to identify drivers of subclonal expansions. Although mutations in known driver genes typically occurred early in cancer evolution, we also identified later subclonal "actionable" mutations, including BRAF (V600E), IDH1 (R132H), PIK3CA (E545K), EGFR (L858R), and KRAS (G12D), which may compromise the efficacy of targeted therapy approaches. More than 20% of IDH1 mutations in glioblastomas, and 15% of mutations in genes in the PI3K (phosphatidylinositol 3-kinase)-AKT-mTOR (mammalian target of rapamycin) signaling axis across all tumor types were subclonal. Mutations in the RAS-MEK (mitogen-activated protein kinase kinase) signaling axis were less likely to be subclonal than mutations in genes associated with PI3K-AKT-mTOR signaling. Analysis of late mutations revealed a link between APOBEC-mediated mutagenesis and the acquisition of subclonal driver mutations and uncovered putative cancer genes involved in subclonal expansions, including CTNNA2 and ATXN1. Our results provide a pan-cancer census of driver events within the context of intratumor heterogeneity and reveal patterns of tumor evolution across cancers. The frequent presence of subclonal driver mutations suggests the need to stratify targeted therapy response according to the proportion of tumor cells in which the driver is identified. Copyright © 2015, American Association for the Advancement of Science.

Health-related quality of life is a prognostic factor for survival in older patients after colorectal cancer diagnosis: A population-based study.

PubMed

Fournier, Evelyne; Jooste, Valérie; Woronoff, Anne-Sophie; Quipourt, Valérie; Bouvier, Anne-Marie; Mercier, Mariette

2016-01-01

Studies carried out in the context of clinical trials have shown a relationship between survival and health-related quality of life in colorectal cancer patients. We assessed the prognostic value of health-related quality of life at diagnosis and of its longitudinal evolution on survival in older colorectal cancer patients. All patients aged ≥65 years, diagnosed with new colorectal cancer between 2003 and 2005 and registered in the Digestive Cancer Registry of Burgundy were eligible. Patients were asked to complete the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 at inclusion, three, six and twelve months after. Multivariate regression models were used to evaluate the prognostic value of health-related quality of life scores at diagnosis and their deterioration on relative survival. In multivariate analysis, a role functioning dimension lower than median was predictive of lower survival (hazard ratio=3.1, p=0.015). After three and six months of follow-up, patients with greater appetite loss were more likely to die, with hazard ratios of 4.7 (p=0.013) and 3.7 (p=0.002), respectively. Health-related quality of life assessments at diagnosis are independently associated with older colorectal cancer patients' survival. Its preservation should be a major management goal for older cancer patients. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Conditional Selection of Genomic Alterations Dictates Cancer Evolution and Oncogenic Dependencies.

PubMed

Mina, Marco; Raynaud, Franck; Tavernari, Daniele; Battistello, Elena; Sungalee, Stephanie; Saghafinia, Sadegh; Laessle, Titouan; Sanchez-Vega, Francisco; Schultz, Nikolaus; Oricchio, Elisa; Ciriello, Giovanni

2017-08-14

Cancer evolves through the emergence and selection of molecular alterations. Cancer genome profiling has revealed that specific events are more or less likely to be co-selected, suggesting that the selection of one event depends on the others. However, the nature of these evolutionary dependencies and their impact remain unclear. Here, we designed SELECT, an algorithmic approach to systematically identify evolutionary dependencies from alteration patterns. By analyzing 6,456 genomes from multiple tumor types, we constructed a map of oncogenic dependencies associated with cellular pathways, transcriptional readouts, and therapeutic response. Finally, modeling of cancer evolution shows that alteration dependencies emerge only under conditional selection. These results provide a framework for the design of strategies to predict cancer progression and therapeutic response. Copyright © 2017 Elsevier Inc. All rights reserved.

Extrachromosomal oncogene amplification drives tumor evolution and genetic heterogeneity

PubMed Central

Turner, Kristen M.; Deshpande, Viraj; Beyter, Doruk; Koga, Tomoyuki; Rusert, Jessica; Lee, Catherine; Li, Bin; Arden, Karen; Ren, Bing; Nathanson, David A.; Kornblum, Harley I.; Taylor, Michael D.; Kaushal, Sharmeela; Cavenee, Webster K.; Wechsler-Reya, Robert; Furnari, Frank B.; Vandenberg, Scott R.; Rao, P. Nagesh; Wahl, Geoffrey M.; Bafna, Vineet; Mischel, Paul S.

2017-01-01

Human cells have twenty-three pairs of chromosomes but in cancer, genes can be amplified in chromosomes or in circular extrachromosomal DNA (ECDNA), whose frequency and functional significance are not understood1–4. We performed whole genome sequencing, structural modeling and cytogenetic analyses of 17 different cancer types, including 2572 metaphases, and developed ECdetect to conduct unbiased integrated ECDNA detection and analysis. ECDNA was found in nearly half of human cancers varying by tumor type, but almost never in normal cells. Driver oncogenes were amplified most commonly on ECDNA, elevating transcript level. Mathematical modeling predicted that ECDNA amplification elevates oncogene copy number and increases intratumoral heterogeneity more effectively than chromosomal amplification, which we validated by quantitative analyses of cancer samples. These results suggest that ECDNA contributes to accelerated evolution in cancer. PMID:28178237

Analysis of incidence, mortality and survival for pancreatic and biliary tract cancers across Europe, with assessment of influence of revised European age standardisation on estimates.

PubMed

Minicozzi, Pamela; Cassetti, Tiziana; Vener, Claudia; Sant, Milena

2018-05-16

Pancreatic (PC) and biliary tract (BTC) cancers have higher incidence and mortality in Europe than elsewhere. We analysed time-trends in PC/BTC incidence, mortality, and survival across Europe. Since the European standard population (ESP) was recently revised to better represent European age structure, we also assessed the effect of adopting the revised ESP to age-standardise incidence and mortality data. We analysed PCs/BTCs (≥15 years) diagnosed in 2000-2007 and followed-up to end of 2008, in 29 European countries across five regions: UK/Ireland, and northern, central, southern, and eastern Europe. Incidence, mortality, and 5-year relative survival were compared between regions, by age, sex, and period of diagnosis. Variation in age-standardised incidence (PC 12-15/100,000; BTC 2-6) and mortality (PC 10-14; BTC 1-5) was modest. Eastern Europe had highest incidence and mortality, and lowest survival; northern and southern Europe had highest age-specific incidence (most age groups) for PC and BTC, respectively. Incidence and survival increased slightly from 2000 to 2007, particularly in elderly patients and women, but survival remained poor (≤8% for PC; 13-18% for BTC). Use of the revised ESP for age-standardisation did not impact European regional incidence and mortality rankings. Poor survival for PC and BTC, together with increasing incidence, indicate that action is required. Countries with higher incidence had higher risk factor frequency, suggesting that prevention initiatives targeting risk factors should be promoted. Improvements in diagnosis and treatment are also required. Our results provide a baseline from which to monitor evolution of the PC/BTC burden in Europe. Copyright © 2018 Elsevier Ltd. All rights reserved.

Incidence trends for potentially human papillomavirus-related and -unrelated head and neck cancers in France using population-based cancer registries data: 1980-2012.

PubMed

Jéhannin-Ligier, Karine; Belot, Aurélien; Guizard, Anne-Valérie; Bossard, Nadine; Launoy, Guy; Uhry, Zoé

2017-05-01

Human papillomavirus (HPV) has been recently recognised as a carcinogenic factor for a subset of head and neck cancers (HNC). In Europe, France has one of the highest incidence rates of HNC. The aim of this study is to explore changes in HNC incidence in France, potentially in relation with infection by HPV. HNC were classified into two anatomical groups: potentially HPV-related and HPV-unrelated. Trends over the period 1980-2012 were analysed by an age-period-cohort model based on data from eleven French cancer registries. Among men, the age-standardised incidence rate (ASR) of HNC decreased in both groups, but less so for HPV-related sites as compared to unrelated sites, especially in recent years (annual percentage change [APC] over the period 2005-2012: -3.5% vs. -5.4%). Among women, the ASR increased in both groups, but more rapidly for HPV-related as compared to unrelated sites (APC over the period 2005-2012: +1.9% vs. -0.4%). This preferential growth of HPV-related versus unrelated HNC was observed in the cohorts born from 1930 to 1935. The differences in trends between possible HPV-related and HPV-unrelated sites suggest an increasing incidence of HNC due to HPV infection. The difference was less marked in men as compared to women, most likely because of a higher contamination in the HPV-related group by cancers due to tobacco or alcohol consumption. The pattern observed is consistent with observations made in other countries, with studies of HPV prevalence in HNC and the evolution of sexual behaviour in France. © 2017 UICC.

Transmissible cancer in Tasmanian devils: localized lineage replacement and host population response

PubMed Central

Hamede, Rodrigo K.; Pearse, Anne-Maree; Swift, Kate; Barmuta, Leon A.; Murchison, Elizabeth P.; Jones, Menna E.

2015-01-01

Tasmanian devil facial tumour disease (DFTD) is a clonally transmissible cancer threatening the Tasmanian devil (Sarcophilus harrisii) with extinction. Live cancer cells are the infectious agent, transmitted to new hosts when individuals bite each other. Over the 18 years since DFTD was first observed, distinct genetic and karyotypic sublineages have evolved. In this longitudinal study, we investigate the associations between tumour karyotype, epidemic patterns and host demographic response to the disease. Reduced host population effects and low DFTD infection rates were associated with high prevalence of tetraploid tumours. Subsequent replacement by a diploid variant of DFTD coincided with a rapid increase in disease prevalence, population decline and reduced mean age of the population. Our results suggest a role for tumour genetics in DFTD transmission dynamics and epidemic outcome. Future research, for this and other highly pathogenic emerging infectious diseases, should focus on understanding the evolution of host and pathogen genotypes, their effects on susceptibility and tolerance to infection, and their implications for designing novel genetic management strategies. This study provides evidence for a rapid localized lineage replacement occurring within a transmissible cancer epidemic and highlights the possibility that distinct DFTD genetic lineages may harbour traits that influence pathogen fitness. PMID:26336167

Applying Social Network Analysis to Identify the Social Support Needs of Adolescent and Young Adult Cancer Patients and Survivors.

PubMed

Koltai, Kolina; Walsh, Casey; Jones, Barbara; Berkelaar, Brenda L

2018-04-01

This article examines how theoretical and clinical applications of social network analysis (SNA) can inform opportunities for innovation and advancement of social support programming for adolescent and young adult (AYA) cancer patients and survivors. SNA can help address potential barriers and challenges to initiating and sustaining AYA peer support by helping to identify the diverse psychosocial needs among individuals in the AYA age range; find strategic ways to support and connect AYAs at different phases of the cancer trajectory with resources and services; and increase awareness of psychosocial resources and referrals from healthcare providers. Network perspectives on homophily, proximity, and evolution provide a foundational basis to explore the utility of SNA in AYA clinical care and research initiatives. The uniqueness of the AYA oncology community can also provide insight into extending and developing current SNA theories. Using SNA in AYA psychosocial cancer research has the potential to create new ideas and pathways for supporting AYAs across the continuum of care, while also extending theories of SNA. SNA may also prove to be a useful tool for examining social support resources for AYAs with various chronic health conditions and other like groups.

Punctuated Evolution of Prostate Cancer Genomes

PubMed Central

Baca, Sylvan C.; Prandi, Davide; Lawrence, Michael S.; Mosquera, Juan Miguel; Romanel, Alessandro; Drier, Yotam; Park, Kyung; Kitabayashi, Naoki; MacDonald, Theresa Y.; Ghandi, Mahmoud; Van Allen, Eliezer; Kryukov, Gregory V.; Sboner, Andrea; Theurillat, Jean-Philippe; Soong, T. David; Nickerson, Elizabeth; Auclair, Daniel; Tewari, Ashutosh; Beltran, Himisha; Onofrio, Robert C.; Boysen, Gunther; Guiducci, Candace; Barbieri, Christopher E.; Cibulskis, Kristian; Sivachenko, Andrey; Carter, Scott L.; Saksena, Gordon; Voet, Douglas; Ramos, Alex H; Winckler, Wendy; Cipicchio, Michelle; Ardlie, Kristin; Kantoff, Philip W.; Berger, Michael F.; Gabriel, Stacey B.; Golub, Todd R.; Meyerson, Matthew; Lander, Eric S.; Elemento, Olivier; Getz, Gad; Demichelis, Francesca; Rubin, Mark A.; Garraway, Levi A.

2013-01-01

SUMMARY The analysis of exonic DNA from prostate cancers has identified recurrently mutated genes, but the spectrum of genome-wide alterations has not been profiled extensively in this disease. We sequenced the genomes of 57 prostate tumors and matched normal tissues to characterize somatic alterations and to study how they accumulate during oncogenesis and progression. By modeling the genesis of genomic rearrangements, we identified abundant DNA translocations and deletions that arise in a highly interdependent manner. This phenomenon, which we term “chromoplexy”, frequently accounts for the dysregulation of prostate cancer genes and appears to disrupt multiple cancer genes coordinately. Our modeling suggests that chromoplexy may induce considerable genomic derangement over relatively few events in prostate cancer and other neoplasms, supporting a model of punctuated cancer evolution. By characterizing the clonal hierarchy of genomic lesions in prostate tumors, we charted a path of oncogenic events along which chromoplexy may drive prostate carcinogenesis. PMID:23622249

Punctuated evolution of prostate cancer genomes.

PubMed

Baca, Sylvan C; Prandi, Davide; Lawrence, Michael S; Mosquera, Juan Miguel; Romanel, Alessandro; Drier, Yotam; Park, Kyung; Kitabayashi, Naoki; MacDonald, Theresa Y; Ghandi, Mahmoud; Van Allen, Eliezer; Kryukov, Gregory V; Sboner, Andrea; Theurillat, Jean-Philippe; Soong, T David; Nickerson, Elizabeth; Auclair, Daniel; Tewari, Ashutosh; Beltran, Himisha; Onofrio, Robert C; Boysen, Gunther; Guiducci, Candace; Barbieri, Christopher E; Cibulskis, Kristian; Sivachenko, Andrey; Carter, Scott L; Saksena, Gordon; Voet, Douglas; Ramos, Alex H; Winckler, Wendy; Cipicchio, Michelle; Ardlie, Kristin; Kantoff, Philip W; Berger, Michael F; Gabriel, Stacey B; Golub, Todd R; Meyerson, Matthew; Lander, Eric S; Elemento, Olivier; Getz, Gad; Demichelis, Francesca; Rubin, Mark A; Garraway, Levi A

2013-04-25

The analysis of exonic DNA from prostate cancers has identified recurrently mutated genes, but the spectrum of genome-wide alterations has not been profiled extensively in this disease. We sequenced the genomes of 57 prostate tumors and matched normal tissues to characterize somatic alterations and to study how they accumulate during oncogenesis and progression. By modeling the genesis of genomic rearrangements, we identified abundant DNA translocations and deletions that arise in a highly interdependent manner. This phenomenon, which we term "chromoplexy," frequently accounts for the dysregulation of prostate cancer genes and appears to disrupt multiple cancer genes coordinately. Our modeling suggests that chromoplexy may induce considerable genomic derangement over relatively few events in prostate cancer and other neoplasms, supporting a model of punctuated cancer evolution. By characterizing the clonal hierarchy of genomic lesions in prostate tumors, we charted a path of oncogenic events along which chromoplexy may drive prostate carcinogenesis. Copyright © 2013 Elsevier Inc. All rights reserved.

Solutions to Peto's paradox revealed by mathematical modelling and cross-species cancer gene analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Caulin, Aleah F.; Graham, Trevor A.; Wang, Li-San

Whales have 1000-fold more cells than humans and mice have 1000-fold fewer; however, cancer risk across species does not increase with the number of somatic cells and the lifespan of the organism. This observation is known as Peto's paradox. How much would evolution have to change the parameters of somatic evolution in order to equalize the cancer risk between species that differ by orders of magnitude in size? Analysis of previously published models of colorectal cancer suggests that a two- to three-fold decrease in the mutation rate or stem cell division rate is enough to reduce a whale's cancer riskmore » to that of a human. Similarly, the addition of one to two required tumour-suppressor gene mutations would also be sufficient. Also, we surveyed mammalian genomes and did not find a positive correlation of tumour-suppressor genes with increasing body mass and longevity. However, we found evidence of the amplification of TP53 in elephants, MAL in horses and FBXO31 in microbats, which might explain Peto's paradox in those species. Lastly, exploring parameters that evolution may have fine-tuned in large, long-lived organisms will help guide future experiments to reveal the underlying biology responsible for Peto's paradox and guide cancer prevention in humans.« less

Solutions to Peto's paradox revealed by mathematical modelling and cross-species cancer gene analysis

DOE PAGES

Caulin, Aleah F.; Graham, Trevor A.; Wang, Li-San; ...

2015-06-08

Whales have 1000-fold more cells than humans and mice have 1000-fold fewer; however, cancer risk across species does not increase with the number of somatic cells and the lifespan of the organism. This observation is known as Peto's paradox. How much would evolution have to change the parameters of somatic evolution in order to equalize the cancer risk between species that differ by orders of magnitude in size? Analysis of previously published models of colorectal cancer suggests that a two- to three-fold decrease in the mutation rate or stem cell division rate is enough to reduce a whale's cancer riskmore » to that of a human. Similarly, the addition of one to two required tumour-suppressor gene mutations would also be sufficient. Also, we surveyed mammalian genomes and did not find a positive correlation of tumour-suppressor genes with increasing body mass and longevity. However, we found evidence of the amplification of TP53 in elephants, MAL in horses and FBXO31 in microbats, which might explain Peto's paradox in those species. Lastly, exploring parameters that evolution may have fine-tuned in large, long-lived organisms will help guide future experiments to reveal the underlying biology responsible for Peto's paradox and guide cancer prevention in humans.« less

Clonal evolution and tumor-initiating cells: New dimensions in cancer patient treatment.

PubMed

Apostoli, Anthony J; Ailles, Laurie

2016-01-01

Human cancer is not a uniform disease but a plethora of disparate tumor types and subtypes. The differences that exist between individual tumors (intertumoral heterogeneity) present a significant roadblock to the eradication of cancer. It has also become increasingly clear that variations across individual tumors (intratumoral heterogeneity) have important implications to cancer progression and treatment efficacy. Therefore, in order to improve patient care and develop novel chemotherapeutics, the evolving tumor landscape needs to be further explored. Next-generation sequencing (NGS) technologies are revolutionizing the cancer research arena by providing state-of-the-art, high-speed methods of genome sequencing at single-nucleotide resolution, thus enabling an unprecedented detection of tumor-specific genetic abnormalities. These anomalies can be quantified to reveal specific frequencies of DNA alterations that correspond to distinct clonal populations within a given tumor. As such, NGS approaches have also been utilized to explore the heterogeneous landscape of patient tumors as well as to match metastatic and/or recurrent growths and patient-derived engrafts. By sequencing in this manner--through time so to speak--cancer researchers can track shifting clonal populations, make important inferences about tumor evolution and potentially identify tumor subclones that could be viably targeted. This exciting new territory has important implications for the competing clonal evolution and cancer stem cell models of tumor heterogeneity, and also offers a new dimension for cancer treatment and profound hope for patients in the coming years.

[Five-year survival analysis in patients with penile cancer].

PubMed

Montiel-Jarquín, Álvaro José; Contreras-Díaz, Antonio Jesús; Vázquez-Cruz, Eduardo; Chopin-Gazga, Marco Antonio; Romero-Figueroa, María Socorro; Etchegaray-Morales, Ivet; Alvarado-Ortega, Ivan

2017-01-01

Short-term survival of penile cancer is poor. The objective was to describe the 5-years penile cancer survival. Retrospective cohort study. We included patients with penile cancer managed surgically from 2010 to 2014. Descriptive statistics were used for socio-demographic variables and the Kaplan-Meier estimator for survival function. We studied 22 patients with a mean age of 64.95 years and a time of evolution of 25 months after the diagnosis. 68.2% of patients smoked or had human papillomavirus (HPV); they all presented phimosis; 72.7% had pain in the penis and the groin area; 81.8% had palpable lymph nodes and 45.5% lesions ≥ 3 cm; 86.3% were diagnosed in clinical stage IIIa. 59.1% underwent partial penectomy and 86.4% had squamous cell variety. 40.9% of patients died six months after the surgery. 66% of the smokers presented metastasis; all of the patients that smoked and had HPV infection had neurovascular invasion and died; 83.3% of the patients (n = 6) who underwent partial penectomy and positive lymph node dissection due to metastases died. The 5-years mortality of patients with penile cancer was 40.9%. Tobacco use and HPV increase morbidity and mortality in patients with penile cancer; lesions greater than 5 cm are more common in smokers. The size of the lesion increases with the delay in treatment.

Life history tradeoffs in cancer evolution

PubMed Central

Boddy, Amy M.; Gatenby, Robert A.; Brown, Joel S.; Maley, Carlo C.

2014-01-01

Somatic evolution during cancer progression and therapy results in tumor cells that exhibit a wide range of phenotypes including rapid proliferation and quiescence. Evolutionary life history theory may help us understand the diversity of these phenotypes. Fast life history organisms reproduce rapidly while those with slow life histories show less fecundity and invest more resources in survival. Life history theory also provides an evolutionary framework for phenotypic plasticity with potential implications for understanding ‘cancer stem cells’. Life history theory suggests that different therapy dosing schedules could select for fast or slow life history cell phenotypes, with important clinical consequences. PMID:24213474

Phylogenetic ctDNA analysis depicts early stage lung cancer evolution

PubMed Central

Abbosh, Christopher; Birkbak, Nicolai J.; Wilson, Gareth A.; Jamal-Hanjani, Mariam; Constantin, Tudor; Salari, Raheleh; Le Quesne, John; Moore, David A; Veeriah, Selvaraju; Rosenthal, Rachel; Marafioti, Teresa; Kirkizlar, Eser; Watkins, Thomas B K; McGranahan, Nicholas; Ward, Sophia; Martinson, Luke; Riley, Joan; Fraioli, Francesco; Al Bakir, Maise; Grönroos, Eva; Zambrana, Francisco; Endozo, Raymondo; Bi, Wenya Linda; Fennessy, Fiona M.; Sponer, Nicole; Johnson, Diana; Laycock, Joanne; Shafi, Seema; Czyzewska-Khan, Justyna; Rowan, Andrew; Chambers, Tim; Matthews, Nik; Turajlic, Samra; Hiley, Crispin; Lee, Siow Ming; Forster, Martin D.; Ahmad, Tanya; Falzon, Mary; Borg, Elaine; Lawrence, David; Hayward, Martin; Kolvekar, Shyam; Panagiotopoulos, Nikolaos; Janes, Sam M; Thakrar, Ricky; Ahmed, Asia; Blackhall, Fiona; Summers, Yvonne; Hafez, Dina; Naik, Ashwini; Ganguly, Apratim; Kareht, Stephanie; Shah, Rajesh; Joseph, Leena; Quinn, Anne Marie; Crosbie, Phil; Naidu, Babu; Middleton, Gary; Langman, Gerald; Trotter, Simon; Nicolson, Marianne; Remmen, Hardy; Kerr, Keith; Chetty, Mahendran; Gomersall, Lesley; Fennell, Dean; Nakas, Apostolos; Rathinam, Sridhar; Anand, Girija; Khan, Sajid; Russell, Peter; Ezhil, Veni; Ismail, Babikir; Irvin-sellers, Melanie; Prakash, Vineet; Lester, Jason; Kornaszewska, Malgorzata; Attanoos, Richard; Adams, Haydn; Davies, Helen; Oukrif, Dahmane; Akarca, Ayse U; Hartley, John A; Lowe, Helen L; Lock, Sara; Iles, Natasha; Bell, Harriet; Ngai, Yenting; Elgar, Greg; Szallasi, Zoltan; Schwarz, Roland F; Herrero, Javier; Stewart, Aengus; Quezada, Sergio A; Peggs, Karl S.; Van Loo, Peter; Dive, Caroline; Lin, Jimmy; Rabinowitz, Matthew; Aerts, Hugo JWL; Hackshaw, Allan; Shaw, Jacqui A; Zimmermann, Bernhard G.; Swanton, Charles

2017-01-01

Summary The early detection of relapse following primary surgery for non-small cell lung cancer and the characterization of emerging subclones seeding metastatic sites might offer new therapeutic approaches to limit tumor recurrence. The potential to non-invasively track tumor evolutionary dynamics in ctDNA of early-stage lung cancer is not established. Here we conduct a tumour-specific phylogenetic approach to ctDNA profiling in the first 100 TRACERx (TRAcking non-small cell lung Cancer Evolution through therapy (Rx)) study participants, including one patient co-recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and perform tumor volume limit of detection analyses. Through blinded profiling of post-operative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients destined to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastases, providing a new approach for ctDNA driven therapeutic studies PMID:28445469

Similarities in the Age-Specific Incidence of Colon and Testicular Cancers.

PubMed

Soto-Ortiz, Luis; Brody, James P

2013-01-01

Colon cancers are thought to be an inevitable result of aging, while testicular cancers are thought to develop in only a small fraction of men, beginning in utero. These models of carcinogenesis are, in part, based upon age-specific incidence data. The specific incidence for colon cancer appears to monotonically increase with age, while that of testicular cancer increases to a maximum value at about 35 years of age, then declines to nearly zero by the age of 80. We hypothesized that the age-specific incidence for these two cancers is similar; the apparent difference is caused by a longer development time for colon cancer and the lack of age-specific incidence data for people over 84 years of age. Here we show that a single distribution can describe the age-specific incidence of both colon carcinoma and testicular cancer. Furthermore, this distribution predicts that the specific incidence of colon cancer should reach a maximum at about age 90 and then decrease. Data on the incidence of colon carcinoma for women aged 85-99, acquired from SEER and the US Census, is consistent with this prediction. We conclude that the age specific data for testicular cancers and colon cancers is similar, suggesting that the underlying process leading to the development of these two forms of cancer may be similar.

Understanding the "lethal" drivers of tumor-stroma co-evolution: emerging role(s) for hypoxia, oxidative stress and autophagy/mitophagy in the tumor micro-environment.

PubMed

Lisanti, Michael P; Martinez-Outschoorn, Ubaldo E; Chiavarina, Barbara; Pavlides, Stephanos; Whitaker-Menezes, Diana; Tsirigos, Aristotelis; Witkiewicz, Agnieszka; Lin, Zhao; Balliet, Renee; Howell, Anthony; Sotgia, Federica

2010-09-15

We have recently proposed a new model for understanding how tumors evolve. To achieve successful "Tumor-Stroma Co-Evolution", cancer cells induce oxidative stress in adjacent fibroblasts and possibly other stromal cells. Oxidative stress in the tumor stroma mimics the effects of hypoxia, under aerobic conditions, resulting in an excess production of reactive oxygen species (ROS). Excess stromal production of ROS drives the onset of an anti-oxidant defense in adjacent cancer cells, protecting them from apoptosis. Moreover, excess stromal ROS production has a "Bystander-Effect", leading to DNA damage and aneuploidy in adjacent cancer cells, both hallmarks of genomic instability. Finally, ROS-driven oxidative stress induces autophagy and mitophagy in the tumor micro-environment, leading to the stromal over-production of recycled nutrients (including energy-rich metabolites, such as ketones and L-lactate). These recycled nutrients or chemical building blocks then help drive mitochondrial biogenesis in cancer cells, thereby promoting the anabolic growth of cancer cells (via an energy imbalance). We also show that ketones and lactate help "fuel" tumor growth and cancer cell metastasis and can act as chemo-attractants for cancer cells. We have termed this new paradigm for accelerating tumor-stroma co-evolution, "The Autophagic Tumor Stroma Model of Cancer Cell Metabolism". Heterotypic signaling in cancer-associated fibroblasts activates the transcription factors HIF1alpha and NFκB, potentiating the onset of hypoxic and inflammatory response(s), which further upregulates the autophagic program in the stromal compartment. Via stromal autophagy, this hypoxic/inflammatory response may provide a new escape mechanism for cancer cells during anti-angiogenic therapy, further exacerbating tumor recurrence and metastasis.

Understanding intratumor heterogeneity by combining genome analysis and mathematical modeling.

PubMed

Niida, Atsushi; Nagayama, Satoshi; Miyano, Satoru; Mimori, Koshi

2018-04-01

Cancer is composed of multiple cell populations with different genomes. This phenomenon called intratumor heterogeneity (ITH) is supposed to be a fundamental cause of therapeutic failure. Therefore, its principle-level understanding is a clinically important issue. To achieve this goal, an interdisciplinary approach combining genome analysis and mathematical modeling is essential. For example, we have recently performed multiregion sequencing to unveil extensive ITH in colorectal cancer. Moreover, by employing mathematical modeling of cancer evolution, we demonstrated that it is possible that this ITH is generated by neutral evolution. In this review, we introduce recent advances in a research field related to ITH and also discuss strategies for exploiting novel findings on ITH in a clinical setting. © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Highlights in the evolution of diagnosis and treatment of laryngeal cancer.

PubMed

Assimakopoulos, Dimitrios; Patrikakos, George; Lascaratos, John

2003-03-01

To present selected highlights from the evolution of diagnosis of laryngeal disease and treatment of laryngeal cancer from ancient Greece until the 20th century. Historical study of diagnosis of laryngeal disease and treatment of laryngeal cancer from the ancient Greek medical scriptures until the most recent evolutional steps in the 20th century. Original Greek-language texts of ancient and Byzantine medical writers were studied and literature on history of medicine was investigated to reveal early knowledge of diagnostic and therapeutic techniques for laryngeal disease and cancer of the larynx. Diseases of the upper aerodigestive tract were known and treated by ancient Greek physicians, and, later, Byzantine doctors, apart from preserving ancient medical concepts, contributed their own ideas, mainly about surgery and postoperative care. The initial therapeutic approach for the disorders caused by laryngeal tumors was either tracheotomy or endotracheal intubation in an attempt to prevent suffocation. In more recent times, construction of the laryngoscope and other modern examination instruments, as well as the final acceptance of histological diagnosis based on tissue biopsy, has allowed for accurate diagnosis and successful treatment of laryngeal lesions. Preoperational biopsy, application of pharyngoesophageal speech and advanced vocal devices for the laryngectomees, and invention of antibiotic and anesthetic agents had led, by the middle of the 20th century, to the establishment of extended and radical surgical techniques as optional treatment for laryngeal cancer. In addition, the discovery of x-rays and radium introduced radiotherapy as an alternative in the treatment procedure for cancer of the larynx. Progress in the evolution of laryngological diagnosis and practice demanded efforts by many daring and courageous investigators and surgeons, contributing new ideas and techniques in the development of modern laryngology.

Effect of age at diagnosis of breast cancer on the patterns and risk of mortality from all causes: a population-based study in Australia.

PubMed

Beadle, Geoffrey Francis; McCarthy, Nicole Jean; Baade, Peter David

2013-06-01

This retrospective, population-based study investigated the patterns and risks of mortality from breast cancer, other cancers and non-cancer causes according to the age at diagnosis of breast cancer. Mortality was assessed in all Australian women (n = 179,653) aged 30-79 years who were diagnosed with breast cancer between 1982 and 2004 and who survived a minimum of 1 year. The mean follow up was 6.3 years (range 0-23 years). Before December 2005, 52,934 women had died (34,459 of breast cancer, 5019 of other cancers and 13,456 of non-cancer causes). There was an inverse age-related relative risk of mortality (calculated as the standardized mortality ratio [SMR]) from breast cancer (linear trend across age P < 0.01). For breast cancer survivors the age-adjusted SMR was 0.99 for other cancers and 0.81(P < 0.01) for non-cancer causes in comparison with the general population. The SMR for other cancers and non-cancer causes was highest in the 30-39-year-old age group (2.13, P < 0.01 and 2.15, P < 0.01, respectively), and progressively decreased with increasing age, with the 70-79-year-old age group having significantly reduced SMR (0.95, P < 0.05, and 0.78, P < 0.01, respectively, compared with the age-matched general population). There was an inverse age-related relative risk of death from breast cancer, other cancers and non-cancer causes. These findings suggest that younger Australian women require long-term health surveillance and that older women with limited comorbidities require optimal treatment of their breast cancer. © 2012 Wiley Publishing Asia Pty Ltd.

New paradigms in clonal evolution: punctuated equilibrium in cancer.

PubMed

Cross, William Ch; Graham, Trevor A; Wright, Nicholas A

2016-10-01

Evolutionary theories are themselves subject to evolution. Clonal evolution - the model that describes the initiation and progression of cancer - is entering a period of profound change, brought about largely by technological developments in genome analysis. A flurry of recent publications, using modern mathematical and bioinformatics techniques, have revealed both punctuated and neutral evolution phenomena that are poorly explained by the conventional graduated perspectives. In this review, we propose that a hybrid model, inspired by the evolutionary model of punctuated equilibrium, could better explain these recent observations. We also discuss the conceptual changes and clinical implications of variable evolutionary tempos. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

OncoNEM: inferring tumor evolution from single-cell sequencing data.

PubMed

Ross, Edith M; Markowetz, Florian

2016-04-15

Single-cell sequencing promises a high-resolution view of genetic heterogeneity and clonal evolution in cancer. However, methods to infer tumor evolution from single-cell sequencing data lag behind methods developed for bulk-sequencing data. Here, we present OncoNEM, a probabilistic method for inferring intra-tumor evolutionary lineage trees from somatic single nucleotide variants of single cells. OncoNEM identifies homogeneous cellular subpopulations and infers their genotypes as well as a tree describing their evolutionary relationships. In simulation studies, we assess OncoNEM's robustness and benchmark its performance against competing methods. Finally, we show its applicability in case studies of muscle-invasive bladder cancer and essential thrombocythemia.

Rise and fall of subclones from diagnosis to relapse in pediatric B-acute lymphoblastic leukaemia | Office of Cancer Genomics

Cancer.gov

There is incomplete understanding of genetic heterogeneity and clonal evolution during cancer progression. Here we use deep whole-exome sequencing to describe the clonal architecture and evolution of 20 pediatric B-acute lymphoblastic leukaemias from diagnosis to relapse. We show that clonal diversity is comparable at diagnosis and relapse and clonal survival from diagnosis to relapse is not associated with mutation burden.

The age of the Galactic disk - Inflow, chemical evolution, astration, and radioactivity

NASA Technical Reports Server (NTRS)

Clayton, Donald D.

1989-01-01

Theoretical models of Galactic evolution and observational data on the age of the Galaxy are compared, with a focus on recent results. Topics addressed include the infall of material and its effects on the age-metallicity relation, the distribution of metallicity, the present gas fraction and metallicity, and the age spectrum of interstellar nuclei; the chemical evolution of the solar neighborhood; the key results of nuclear cosmochronology; and astration effects on Galactic age. It is found that both nuclear cosmochronology and detailed stellar and Galactic evolution models tend to support an age of 12-16 Gyr.

Similarities in the Age-Specific Incidence of Colon and Testicular Cancers

PubMed Central

Soto-Ortiz, Luis; Brody, James P.

2013-01-01

Colon cancers are thought to be an inevitable result of aging, while testicular cancers are thought to develop in only a small fraction of men, beginning in utero. These models of carcinogenesis are, in part, based upon age-specific incidence data. The specific incidence for colon cancer appears to monotonically increase with age, while that of testicular cancer increases to a maximum value at about 35 years of age, then declines to nearly zero by the age of 80. We hypothesized that the age-specific incidence for these two cancers is similar; the apparent difference is caused by a longer development time for colon cancer and the lack of age-specific incidence data for people over 84 years of age. Here we show that a single distribution can describe the age-specific incidence of both colon carcinoma and testicular cancer. Furthermore, this distribution predicts that the specific incidence of colon cancer should reach a maximum at about age 90 and then decrease. Data on the incidence of colon carcinoma for women aged 85–99, acquired from SEER and the US Census, is consistent with this prediction. We conclude that the age specific data for testicular cancers and colon cancers is similar, suggesting that the underlying process leading to the development of these two forms of cancer may be similar. PMID:23840520

Cancer stem cells: A product of clonal evolution?

PubMed

van Niekerk, Gustav; Davids, Lester M; Hattingh, Suzèl M; Engelbrecht, Anna-Mart

2017-03-01

The cancer stem cell (CSC) model has emerged as a prominent paradigm for explaining tumour heterogeneity. CSCs in tumour recurrence and drug resistance have also been implicated in a number of studies. In fact, CSCs are often identified by their expression of drug-efflux proteins which are also highly expressed in normal stem cells. Similarly, pro-survival or proliferation signalling often exhibited by stem cells is regularly reported as being upregulated by CSC. Here we review evidence suggesting that many aspects of CSCs are more readily described by clonal evolution. As an example, cancer cells often exhibit copy number gains of genes involved in drug-efflux proteins and pro-survival signalling. Consequently, clonal selection for stem cell traits may result in cancer cells developing "stemness" traits which impart a fitness advantage, without strictly following a CSC model. Finally, since symmetric cell division would give rise to more cells than asymmetric division, it is expected that more advanced tumours would depart from a CSC. Collectively, these observations suggest clonal evolution may explain many aspects of the CSC. © 2016 UICC.

Testicular Cancer Survivorship: Research Strategies and Recommendations

PubMed Central

Beard, Clair; Allan, James M.; Dahl, Alv A.; Feldman, Darren R.; Oldenburg, Jan; Daugaard, Gedske; Kelly, Jennifer L.; Dolan, M. Eileen; Hannigan, Robyn; Constine, Louis S.; Oeffinger, Kevin C.; Okunieff, Paul; Armstrong, Greg; Wiljer, David; Miller, Robert C.; Gietema, Jourik A.; van Leeuwen, Flora E.; Williams, Jacqueline P.; Nichols, Craig R.; Einhorn, Lawrence H.; Fossa, Sophie D.

2010-01-01

Testicular cancer represents the most curable solid tumor, with a 10-year survival rate of more than 95%. Given the young average age at diagnosis, it is estimated that effective treatment approaches, in particular, platinum-based chemotherapy, have resulted in an average gain of several decades of life. This success, however, is offset by the emergence of considerable long-term morbidity, including second malignant neoplasms, cardiovascular disease, neurotoxicity, nephrotoxicity, pulmonary toxicity, hypogonadism, decreased fertility, and psychosocial problems. Data on underlying genetic or molecular factors that might identify those patients at highest risk for late sequelae are sparse. Genome-wide association studies and other translational molecular approaches now provide opportunities to identify testicular cancer survivors at greatest risk for therapy-related complications to develop evidence-based long-term follow-up guidelines and interventional strategies. We review research priorities identified during an international workshop devoted to testicular cancer survivors. Recommendations include 1) institution of lifelong follow-up of testicular cancer survivors within a large cohort setting to ascertain risks of emerging toxicities and the evolution of known late sequelae, 2) development of comprehensive risk prediction models that include treatment factors and genetic modifiers of late sequelae, 3) elucidation of the effect(s) of decades-long exposure to low serum levels of platinum, 4) assessment of the overall burden of medical and psychosocial morbidity, and 5) the eventual formulation of evidence-based long-term follow-up guidelines and interventions. Just as testicular cancer once served as the paradigm of a curable malignancy, comprehensive follow-up studies of testicular cancer survivors can pioneer new methodologies in survivorship research for all adult-onset cancer. PMID:20585105

Evolution of a contagious cancer: epigenetic variation in Devil Facial Tumour Disease

PubMed Central

Ujvari, Beata; Pearse, Anne-Maree; Peck, Sarah; Harmsen, Collette; Taylor, Robyn; Pyecroft, Stephen; Madsen, Thomas; Papenfuss, Anthony T.; Belov, Katherine

2013-01-01

The emergence of Devil Facial Tumour Disease (DFTD), a highly contagious cancer, is driving Tasmanian devils (Sarcophilus harrisii) to extinction. The cancer is a genetically and chromosomally stable clonal cell line which is transmitted by biting during social interactions. In the present study, we explore the Devil Facial Tumour (DFT) epigenome and the genes involved in DNA methylation homeostasis. We show that tumour cells have similar levels of methylation to peripheral nerves, the tissue from which DFTD originated. We did not observe any strain or region-specific epimutations. However, we revealed a significant increase in hypomethylation in DFT samples over time (p < 0.0001). We propose that loss of methylation is not because of a maintenance deficiency, as an upregulation of DNA methyltransferase 1 gene was observed in tumours compared with nerves (p < 0.005). Instead, we believe that loss of methylation is owing to active demethylation, supported by the temporal increase in MBD2 and MBD4 (p < 0.001). The implications of these changes on disease phenotypes need to be explored. Our work shows that DFTD should not be treated as a static entity, but rather as an evolving parasite with epigenetic plasticity. Understanding the role of epimutations in the evolution of this parasitic cancer will provide unique insights into the role of epigenetic plasticity in cancer evolution and progression in traditional cancers that arise and die with their hosts. PMID:23135679

20-Years of Population-Based Cancer Registration in Hepatitis B and Liver Cancer Prevention in The Gambia, West Africa

PubMed Central

Bah, Ebrima; Carrieri, Maria Patrizia; Hainaut, Pierre; Bah, Yusupha; Nyan, Ousman; Taal, Makie

2013-01-01

Background The Gambia Hepatitis Intervention Study (GHIS) was designed as a randomised control trial of infant hepatitis B vaccination applied to public health policy, with the main goal of preventing primary liver cancer later in adult life in The Gambia. To that effect, the National Cancer Registry of The Gambia (NCR), a population-based cancer registry (PBCR), was established in 1986 to actively collect data on all cancer diagnosis nation-wide. We extracted 20-years (1990-2009) of data to assess for the first time, the evolution of the most common cancers, also describe and demonstrate the role of the PBCR in a hepatitis B and liver cancer prevention programme in this population. Methods and Findings We estimated Age-Standardised Incidence Rates (ASR (W)) of the most common cancers registered during the period by gender. The registration period was divided into four 5-year intervals and incidence rates were estimated for each interval. The most common cancers in males were liver, prostate, lung plus bronchus, non-Hodgkin lymphoma (NHL) and stomach, accounting for 60%, 5%, 4%, 5% and 3%, respectively. Similarly, cancers of the cervix uteri, liver, breast and NHL, were the most common in females, accounting for 33%, 24%, 11% and 4% of the female cancers, respectively. Conclusions Cancer incidence has remained relatively stable over time, but as shown elsewhere in sub-Saharan Africa the disease is a threat in The Gambia. The infection related cancers which are mostly preventable (HBV in men and HPV/HIV in women) were the most common. At the moment the data is not enough to detect an effect of hepatitis B vaccination on liver cancer incidence in The Gambia. However, we observed that monitoring case occurrence through PBCR is a key public health pre-requisite for rational planning and implementation of targeted interventions for improving the health of the population. PMID:24098724

Applying ecological and evolutionary theory to cancer: a long and winding road.

PubMed

Thomas, Frédéric; Fisher, Daniel; Fort, Philippe; Marie, Jean-Pierre; Daoust, Simon; Roche, Benjamin; Grunau, Christoph; Cosseau, Céline; Mitta, Guillaume; Baghdiguian, Stephen; Rousset, François; Lassus, Patrice; Assenat, Eric; Grégoire, Damien; Missé, Dorothée; Lorz, Alexander; Billy, Frédérique; Vainchenker, William; Delhommeau, François; Koscielny, Serge; Itzykson, Raphael; Tang, Ruoping; Fava, Fanny; Ballesta, Annabelle; Lepoutre, Thomas; Krasinska, Liliana; Dulic, Vjekoslav; Raynaud, Peggy; Blache, Philippe; Quittau-Prevostel, Corinne; Vignal, Emmanuel; Trauchessec, Hélène; Perthame, Benoit; Clairambault, Jean; Volpert, Vitali; Solary, Eric; Hibner, Urszula; Hochberg, Michael E

2013-01-01

Since the mid 1970s, cancer has been described as a process of Darwinian evolution, with somatic cellular selection and evolution being the fundamental processes leading to malignancy and its many manifestations (neoangiogenesis, evasion of the immune system, metastasis, and resistance to therapies). Historically, little attention has been placed on applications of evolutionary biology to understanding and controlling neoplastic progression and to prevent therapeutic failures. This is now beginning to change, and there is a growing international interest in the interface between cancer and evolutionary biology. The objective of this introduction is first to describe the basic ideas and concepts linking evolutionary biology to cancer. We then present four major fronts where the evolutionary perspective is most developed, namely laboratory and clinical models, mathematical models, databases, and techniques and assays. Finally, we discuss several of the most promising challenges and future prospects in this interdisciplinary research direction in the war against cancer.

Lay Awareness of the Relationship between Age and Cancer Risk.

PubMed

Taber, Jennifer M; Klein, William M P; Suls, Jerry M; Ferrer, Rebecca A

2017-04-01

Cross-sectional studies suggest many people are unaware that cancer risk increases with age, but this misbelief has rarely been studied prospectively, nor are its moderators known. To assess whether people recognize that cancer risk increases with age and whether beliefs differ according to gender, education, smoking status, and family history of cancer. First, items from the cross-sectional Health Information National Trends Survey (n = 2069) were analyzed to examine the association of age and perceived cancer risk. Second, the prospective National Survey of Midlife Development in the United States (n = 3896) was used to assess whether perceived cancer risk changes over a decade. Third, beliefs about the age at which cancer occurs were analyzed using the US Awareness and Beliefs about Cancer survey (n = 1080). As a comparator, perceived risk of heart disease was also examined. Cross-sectionally, older age was associated with lower perceived cancer risk but higher perceived heart disease risk. Prospectively, perceived cancer risk remained stable, whereas perceived heart attack risk increased. Seventy percent of participants reported a belief that cancer is equally likely to affect people of any age. Across three surveys, women and former smokers/smokers who recently quit tended to misunderstand the relationship between age and cancer risk and also expressed relatively higher perceived cancer risk overall. Data from three national surveys indicated that people are unaware that age is a risk factor for cancer. Moreover, those who were least aware perceived the highest risk of cancer regardless of age.

Genomic Evolution of Breast Cancer Metastasis and Relapse

DOE PAGES

Yates, Lucy R.; Knappskog, Stian; Wedge, David; ...

2017-08-14

Patterns of genomic evolution between primary and metastatic breast cancer have not been studied in large numbers, despite patients with metastatic breast cancer having dismal survival. We sequenced whole genomes or a panel of 365 genes on 299 samples from 170 patients with locally relapsed or metastatic breast cancer. Several lines of analysis indicate that clones seeding metastasis or relapse disseminate late from primary tumors, but continue to acquire mutations, mostly accessing the same mutational processes active in the primary tumor. Most distant metastases acquired driver mutations not seen in the primary tumor, drawing from a wider repertoire of cancermore » genes than early drivers. Lastly, these include a number of clinically actionable alterations and mutations inactivating SWI-SNF and JAK2-STAT3 pathways.« less

Genetic evolution of pancreatic cancer: lessons learnt from the pancreatic cancer genome sequencing project

PubMed Central

Iacobuzio-Donahue, Christine A

2012-01-01

Pancreatic cancer is a disease caused by the accumulation of genetic alterations in specific genes. Elucidation of the human genome sequence, in conjunction with technical advances in the ability to perform whole exome sequencing, have provided new insight into the mutational spectra characteristic of this lethal tumour type. Most recently, exomic sequencing has been used to clarify the clonal evolution of pancreatic cancer as well as provide time estimates of pancreatic carcinogenesis, indicating that a long window of opportunity may exist for early detection of this disease while in the curative stage. Moving forward, these mutational analyses indicate potential targets for personalised diagnostic and therapeutic intervention as well as the optimal timing for intervention based on the natural history of pancreatic carcinogenesis and progression. PMID:21749982

Genomic Evolution of Breast Cancer Metastasis and Relapse

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yates, Lucy R.; Knappskog, Stian; Wedge, David

Patterns of genomic evolution between primary and metastatic breast cancer have not been studied in large numbers, despite patients with metastatic breast cancer having dismal survival. We sequenced whole genomes or a panel of 365 genes on 299 samples from 170 patients with locally relapsed or metastatic breast cancer. Several lines of analysis indicate that clones seeding metastasis or relapse disseminate late from primary tumors, but continue to acquire mutations, mostly accessing the same mutational processes active in the primary tumor. Most distant metastases acquired driver mutations not seen in the primary tumor, drawing from a wider repertoire of cancermore » genes than early drivers. Lastly, these include a number of clinically actionable alterations and mutations inactivating SWI-SNF and JAK2-STAT3 pathways.« less

Evolution of metastasis revealed by mutational landscapes of chemically induced skin cancers | Office of Cancer Genomics

Cancer.gov

Human tumors show a high level of genetic heterogeneity, but the processes that influence the timing and route of metastatic dissemination of the subclones are unknown. Here we have used whole-exome sequencing of 103 matched benign, malignant and metastatic skin tumors from genetically heterogeneous mice to demonstrate that most metastases disseminate synchronously from the primary tumor, supporting parallel rather than linear evolution as the predominant model of metastasis.

Evolution of radiation resistance in a complex microenvironment

NASA Astrophysics Data System (ADS)

Kim, So Hyun; Austin, Robert; Mehta, Monal; Kahn, Atif

2013-03-01

Radiation treatment responses in brain cancers are typically associated with short progression-free intervals in highly lethal malignancies such as glioblastomas. Even as patients routinely progress through second and third line salvage therapies, which are usually empirically selected, surprisingly little information exists on how cancer cells evolve resistance. We will present experimental results showing how in the presence of complex radiation gradients evolution of resistance to radiation occurs. Sponsored by the NCI/NIH Physical Sciences Oncology Centers

Cancer-Incidence, prevalence and mortality in the oldest-old. A comprehensive review.

PubMed

Nolen, Shantell C; Evans, Marcella A; Fischer, Avital; Corrada, Maria M; Kawas, Claudia H; Bota, Daniela A

2017-06-01

Chronic health conditions are commonplace in older populations. The process of aging impacts many of the world's top health concerns. With the average life expectancy continuing to climb, understanding patterns of morbidity in aging populations has become progressively more important. Cancer is an age-related disease, whose risk has been proven to increase with age. Limited information is published about the epidemiology of cancer and the cancer contribution to mortality in the 85+ age group, often referred to as the oldest-old. In this review, we perform a comprehensive assessment of the most recent (2011-2016) literature on cancer prevalence, incidence and mortality in the oldest-old. The data shows cancer prevalence and cancer incidence increases until ages 85-89, after which the rates decrease into 100+ ages. However the number of overall cases has steadily increased over time due to the rise in population. Cancer mortality continues to increase after age 85+. This review presents an overview of plausible associations between comorbidity, genetics and age-related physiological effects in relation to cancer risk and protection. Many of these age-related processes contribute to the lowered risk of cancer in the oldest-old, likewise other certain health conditions may "protect" from cancer in this age group. Copyright © 2017 Elsevier B.V. All rights reserved.

[Long-term evolution of a patient diagnosed of small lung cancer with extension to the central nervous system].

PubMed

Barrado Los Arcos, M; Rico Osés, M; Errasti Viader, M; Campo Vargas, M; Zelaya Huerta, M V; Martínez López, E

2016-01-01

Cell lung cancer is the principal cause of cancer death in men and women. We report the case of a man diagnosed with small cell lung cancer, metastatic from the outset. The disease is stable at present, forty-seven months from dia-gnosis, after receiving different treatment modalities.

Just like the rest of evolution in Mother Nature, the evolution of cancers may be driven by natural selection, and not by haphazard mutations

PubMed Central

Zhang, Ju; Lou, Xiaomin; Zellmer, Lucas; Liu, Siqi; Xu, Ningzhi; Liao, D. Joshua

2014-01-01

Sporadic carcinogenesis starts from immortalization of a differentiated somatic cell or an organ-specific stem cell. The immortalized cell incepts a new or quasinew organism that lives like a parasite in the patient and usually proceeds to progressive simplification, constantly engendering intermediate organisms that are simpler than normal cells. Like organismal evolution in Mother Nature, this cellular simplification is a process of Darwinian selection of those mutations with growth- or survival-advantages, from numerous ones that occur randomly and stochastically. Therefore, functional gain of growth- or survival-sustaining oncogenes and functional loss of differentiation-sustaining tumor suppressor genes, which are hallmarks of cancer cells and contribute to phenotypes of greater malignancy, are not drivers of carcinogenesis but are results from natural selection of advantageous mutations. Besides this mutation-load dependent survival mechanism that is evolutionarily low and of an asexual nature, cancer cells may also use cell fusion for survival, which is an evolutionarily-higher mechanism and is of a sexual nature. Assigning oncogenes or tumor suppressor genes or their mutants as drivers to induce cancer in animals may somewhat coerce them to create man-made oncogenic pathways that may not really be a course of sporadic cancer formations in the human. PMID:25594068

Aging and inflammation: etiological culprits of cancer.

PubMed

Ahmad, Aamir; Banerjee, Sanjeev; Wang, Zhiwei; Kong, Dejuan; Majumdar, Adhip P N; Sarkar, Fazlul H

2009-12-01

The biochemical phenomenon of aging, as universal as it is, still remains poorly understood. A number of diseases are associated with aging either as a cause or consequence of the aging process. The incidence of human cancers increases exponentially with age and therefore cancer stands out as a disease that is intricately connected to the process of aging. Emerging evidence clearly suggests that there is a symbiotic relationship between aging, inflammation and chronic diseases such as cancer; however, it is not clear whether aging leads to the induction of inflammatory processes thereby resulting in the development and maintenance of chronic diseases or whether inflammation is the causative factor for inducing both aging and chronic diseases such as cancer. Moreover, the development of chronic diseases especially cancer could also lead to the induction of inflammatory processes and may cause premature aging, suggesting that longitudinal research strategies must be employed for dissecting the interrelationships between aging, inflammation and cancer. Here, we have described our current understanding on the importance of inflammation, activation of NF-kappaB and various cytokines and chemokines in the processes of aging and in the development of chronic diseases especially cancer. We have also reviewed the prevailing theories of aging and provided succinct evidence in support of novel theories such as those involving cancer stem cells, the molecular understanding of which would likely hold a great promise towards unraveling the complex relationships between aging, inflammation and cancer.

Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution.

PubMed

Abbosh, Christopher; Birkbak, Nicolai J; Wilson, Gareth A; Jamal-Hanjani, Mariam; Constantin, Tudor; Salari, Raheleh; Le Quesne, John; Moore, David A; Veeriah, Selvaraju; Rosenthal, Rachel; Marafioti, Teresa; Kirkizlar, Eser; Watkins, Thomas B K; McGranahan, Nicholas; Ward, Sophia; Martinson, Luke; Riley, Joan; Fraioli, Francesco; Al Bakir, Maise; Grönroos, Eva; Zambrana, Francisco; Endozo, Raymondo; Bi, Wenya Linda; Fennessy, Fiona M; Sponer, Nicole; Johnson, Diana; Laycock, Joanne; Shafi, Seema; Czyzewska-Khan, Justyna; Rowan, Andrew; Chambers, Tim; Matthews, Nik; Turajlic, Samra; Hiley, Crispin; Lee, Siow Ming; Forster, Martin D; Ahmad, Tanya; Falzon, Mary; Borg, Elaine; Lawrence, David; Hayward, Martin; Kolvekar, Shyam; Panagiotopoulos, Nikolaos; Janes, Sam M; Thakrar, Ricky; Ahmed, Asia; Blackhall, Fiona; Summers, Yvonne; Hafez, Dina; Naik, Ashwini; Ganguly, Apratim; Kareht, Stephanie; Shah, Rajesh; Joseph, Leena; Marie Quinn, Anne; Crosbie, Phil A; Naidu, Babu; Middleton, Gary; Langman, Gerald; Trotter, Simon; Nicolson, Marianne; Remmen, Hardy; Kerr, Keith; Chetty, Mahendran; Gomersall, Lesley; Fennell, Dean A; Nakas, Apostolos; Rathinam, Sridhar; Anand, Girija; Khan, Sajid; Russell, Peter; Ezhil, Veni; Ismail, Babikir; Irvin-Sellers, Melanie; Prakash, Vineet; Lester, Jason F; Kornaszewska, Malgorzata; Attanoos, Richard; Adams, Haydn; Davies, Helen; Oukrif, Dahmane; Akarca, Ayse U; Hartley, John A; Lowe, Helen L; Lock, Sara; Iles, Natasha; Bell, Harriet; Ngai, Yenting; Elgar, Greg; Szallasi, Zoltan; Schwarz, Roland F; Herrero, Javier; Stewart, Aengus; Quezada, Sergio A; Peggs, Karl S; Van Loo, Peter; Dive, Caroline; Lin, C Jimmy; Rabinowitz, Matthew; Aerts, Hugo J W L; Hackshaw, Allan; Shaw, Jacqui A; Zimmermann, Bernhard G; Swanton, Charles

2017-04-26

The early detection of relapse following primary surgery for non-small-cell lung cancer and the characterization of emerging subclones, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and analyse the tumour-volume detection limit. Through blinded profiling of postoperative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients who are very likely to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastasis, providing a new approach for ctDNA-driven therapeutic studies.

Evolution of oral cancer treatment in an andalusian population sample: Rehabilitation with prosthetic obturation and removable partial prosthesis

PubMed Central

Flores-Ruiz, Rafael; Castellanos-Cosano, Lizette; Serrera-Figallo, María-Angeles; Gutiérrez-Corrales, Aida; Gonzalez-Martin, Maribel; Gutiérrez-Pérez, Jose-Luis

2017-01-01

Background Radical surgical resection as a treatment modality for oral cancer often leads to an extensive deficit in both the maxillary and mandibular levels, where the use of a palatal obturator prosthesis (POP) or removable partial denture (RPP). The aim of this study was to evaluate the treatment with POP and RPP in patients treated for oral cancer in the Unit of Prosthetic Rehabilitation of the University Hospital Virgen del Rocío in a period of 20 years. Material and Methods Retrospective descriptive study during the years 1991 and 2011 analyzing oral cancer type, characteristics, treatment and follow-up. The sample consisted of patients whose tumor had previously been removed and who had been referred to the Oncological Rehabilitation Unit of the Oral and Maxillofacial Surgery Unit of the “Virgen del Rocío” University Hospital for rehabilitation. The inclusion criteria were patients whose underlying pathology was any type of neoplasia, which after its treatment had been referred to the aforementioned Oncological Prosthetic Rehabilitation unit. Results Of the 45 patients included in our study, 15 patients were rehabilitated with palatal obturator (33.3%) and 5 patients with removable partial denture (11.1%). The mean age of the sample of patients with POP was 57.3 ± 9.23, while the mean age of the sample of patients with RPP was 58 ± 13.5. The most common underlying pathology in patients with POP was squamous cell carcinoma (60%), whereas in patients with RPP it was 100%. The most frequent location found among POP patients was the upper jaw, while in the PRP patients there was no predominant location. The univariate and multivariate logistic regressions did not show any statistically significant association between the independent variables age, sex, smoking habit and alcoholic habit with the dependent variable type of rehabilitating prosthesis. Conclusions Based on our data, we can conclude that RPP is used in few cases of oncological rehabilitation. The POP has a greater use, as long as the defect in the bones of the facial middle third is limited. Key words:Head and neck cancer, reconstructive surgery, Palatal obturators, removable partial dentures. PMID:28936292

Evolution of oral cancer treatment in an andalusian population sample: Rehabilitation with prosthetic obturation and removable partial prosthesis.

PubMed

Flores-Ruiz, Rafael; Castellanos-Cosano, Lizette; Serrera-Figallo, María-Angeles; Gutiérrez-Corrales, Aida; Gonzalez-Martin, Maribel; Gutiérrez-Pérez, Jose-Luis; Torres-Lagares, Daniel

2017-08-01

Radical surgical resection as a treatment modality for oral cancer often leads to an extensive deficit in both the maxillary and mandibular levels, where the use of a palatal obturator prosthesis (POP) or removable partial denture (RPP). The aim of this study was to evaluate the treatment with POP and RPP in patients treated for oral cancer in the Unit of Prosthetic Rehabilitation of the University Hospital Virgen del Rocío in a period of 20 years. Retrospective descriptive study during the years 1991 and 2011 analyzing oral cancer type, characteristics, treatment and follow-up. The sample consisted of patients whose tumor had previously been removed and who had been referred to the Oncological Rehabilitation Unit of the Oral and Maxillofacial Surgery Unit of the "Virgen del Rocío" University Hospital for rehabilitation. The inclusion criteria were patients whose underlying pathology was any type of neoplasia, which after its treatment had been referred to the aforementioned Oncological Prosthetic Rehabilitation unit. Of the 45 patients included in our study, 15 patients were rehabilitated with palatal obturator (33.3%) and 5 patients with removable partial denture (11.1%). The mean age of the sample of patients with POP was 57.3 ± 9.23, while the mean age of the sample of patients with RPP was 58 ± 13.5. The most common underlying pathology in patients with POP was squamous cell carcinoma (60%), whereas in patients with RPP it was 100%. The most frequent location found among POP patients was the upper jaw, while in the PRP patients there was no predominant location. The univariate and multivariate logistic regressions did not show any statistically significant association between the independent variables age, sex, smoking habit and alcoholic habit with the dependent variable type of rehabilitating prosthesis. Based on our data, we can conclude that RPP is used in few cases of oncological rehabilitation. The POP has a greater use, as long as the defect in the bones of the facial middle third is limited. Key words: Head and neck cancer, reconstructive surgery, Palatal obturators, removable partial dentures.

Evolution of Emotional Symptoms Over Time Among Daughters of Patients With Breast Cancer.

PubMed

Wellisch, David K; Ormseth, Sarah R; Aréchiga, Adam E

2015-01-01

This study longitudinally profiled anxiety and depressive symptoms of daughters of patients with breast cancer and examined the mother׳s survival status, the daughter׳s age at the time of mother׳s diagnosis, and the style of family communication about breast cancer as moderators of change in symptomatology across participants׳ first 3 appointments at the University of California, Los Angeles Revlon Breast Center High Risk Clinic. We evaluated the effects of hypothesized predictors on change in anxiety and depressive symptoms, 3 (symptomatology at first, second, and third clinic visits) × 2 (mother survived or died) × 2 (<20 or ≥20y old at diagnosis) × 2 (open or closed family communication) repeated-measures analyses of variance were employed. There was a main effect for time of diagnosis on state anxiety, demonstrating a significant reduction in anxiety across clinic visits overall (p < 0.001). There were also significant 3-way interactions. For state anxiety, mother׳s survival status moderated the time of diagnosis × age at diagnosis and time of diagnosis × family communication interaction effects. For daughters whose mothers died, decreased anxiety was observed in those who were younger at the time of diagnosis (p = 0.001). For daughters whose mothers survived, anxiety was decreased for those with closed family communication styles (p = 0.001). The time of diagnosis × mother׳s survival × age at diagnosis interaction was also significant for depressive symptoms (p = 0.001). Among daughters whose mothers died, those who were younger showed decreases in symptoms (p = 0.004). These daughters appeared to benefit from the high-risk program as demonstrated by decreased symptomatology, particularly daughters whose mothers died who were younger at the time of diagnosis. Copyright © 2015 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.

Sexual selection affects the evolution of lifespan and ageing in the decorated cricket Gryllodes sigillatus.

PubMed

Archer, C R; Zajitschek, F; Sakaluk, S K; Royle, N J; Hunt, J

2012-10-01

Recent work suggests that sexual selection can influence the evolution of ageing and lifespan by shaping the optimal timing and relative costliness of reproductive effort in the sexes. We used inbred lines of the decorated cricket, Gryllodes sigillatus, to estimate the genetic (co)variance between age-dependent reproductive effort, lifespan, and ageing within and between the sexes. Sexual selection theory predicts that males should die sooner and age more rapidly than females. However, a reversal of this pattern may be favored if reproductive effort increases with age in males but not in females. We found that male calling effort increased with age, whereas female fecundity decreased, and that males lived longer and aged more slowly than females. These divergent life-history strategies were underpinned by a positive genetic correlation between early-life reproductive effort and ageing rate in both sexes, although this relationship was stronger in females. Despite these sex differences in life-history schedules, age-dependent reproductive effort, lifespan, and ageing exhibited strong positive intersexual genetic correlations. This should, in theory, constrain the independent evolution of these traits in the sexes and may promote intralocus sexual conflict. Our study highlights the importance of sexual selection to the evolution of sex differences in ageing and lifespan in G. sigillatus. © 2012 The Author(s). Evolution© 2012 The Society for the Study of Evolution.

Single Cell Oncogenesis

NASA Astrophysics Data System (ADS)

Lu, Xin

It is believed that cancer originates from a single cell that has gone through generations of evolution of genetic and epigenetic changes that associate with the hallmarks of cancer. In some cancers such as various types of leukemia, cancer is clonal. Yet in other cancers like glioblastoma (GBM), there is tremendous tumor heterogeneity that is likely to be caused by simultaneous evolution of multiple subclones within the same tissue. It is obvious that understanding how a single cell develops into a clonal tumor upon genetic alterations, at molecular and cellular levels, holds the key to the real appreciation of tumor etiology and ultimate solution for therapeutics. Surprisingly very little is known about the process of spontaneous tumorigenesis from single cells in human or vertebrate animal models. The main reason is the lack of technology to track the natural process of single cell changes from a homeostatic state to a progressively cancerous state. Recently, we developed a patented compound, photoactivatable (''caged'') tamoxifen analogue 4-OHC and associated technique called optochemogenetic switch (OCG switch), which we believe opens the opportunity to address this urgent biological as well as clinical question about cancer. We propose to combine OCG switch with genetically engineered mouse models of head and neck squamous cell carcinoma and high grade astrocytoma (including GBM) to study how single cells, when transformed through acute loss of tumor suppressor genes PTEN and TP53 and gain of oncogenic KRAS, can develop into tumor colonies with cellular and molecular heterogeneity in these tissues. The abstract is for my invited talk in session ``Beyond Darwin: Evolution in Single Cells'' 3/18/2016 11:15 AM.

Translational Implications of Tumor Heterogeneity

PubMed Central

Jamal-Hanjani, Mariam; Quezada, Sergio A.; Larkin, James; Swanton, Charles

2015-01-01

Advances in next-generation sequencing and bioinformatics have led to an unprecedented view of the cancer genome and its evolution. Genomic studies have demonstrated the complex and heterogeneous clonal landscape of tumors of different origins, and the potential impact of intratumor heterogeneity on treatment response and resistance, cancer progression and the risk of disease relapse. However, the significance of subclonal mutations, in particular mutations in driver genes, and their evolution through time and their dynamics in response to cancer therapies, is yet to be determined. The necessary tools are now available to prospectively determine whether clonal heterogeneity can be used as a biomarker of clinical outcome, and to what extent subclonal somatic alterations might influence clinical outcome. Studies that employ longitudinal tissue sampling, integrating both genomic and clinical data, have the potential to reveal the subclonal composition and track the evolution of tumors in order to address these questions, and to begin to define the breadth of genetic diversity in different tumor types, and its relevance to patient outcome. Such studies may provide further evidence for novel drug resistance mechanisms informing novel combinatorial, adaptive and tumour immune-therapies placed within the context of tumor evolution. PMID:25770293

Evolution of Breast Cancer Screening in the Medicare Population: Clinical and Economic Implications

PubMed Central

Killelea, Brigid K.; Long, Jessica B.; Chagpar, Anees B.; Ma, Xiaomei; Wang, Rong; Ross, Joseph S.

2014-01-01

Background Newer approaches to mammography, including digital image acquisition and computer-aided detection (CAD), and adjunct imaging (e.g., magnetic resonance imaging [MRI]) have diffused into clinical practice. The impact of these technologies on screening-related cost and outcomes remains undefined, particularly among older women. Methods Using the Surveillance, Epidemiology, and End Results–Medicare linked database, we constructed two cohorts of women without a history of breast cancer and followed each cohort for 2 years. We compared the use and cost of screening mammography including digital mammography and CAD, adjunct procedures including breast ultrasound, MRI, and biopsy between the period of 2001 and 2002 and the period of 2008 and 2009 using χ2 and t test. We also assessed the change in breast cancer stage and incidence rates using χ2 and Poisson regression. All statistical tests were two-sided. Results There were 137150 women (mean age = 76.0 years) in the early cohort (2001–2002) and 133097 women (mean age = 77.3 years) in the later cohort (2008–2009). The use of digital image acquisition for screening mammography increased from 2.0% in 2001 and 2002 to 29.8% in 2008 and 2009 (P < .001). CAD use increased from 3.2% to 33.1% (P < .001). Average screening-related cost per capita increased from $76 to $112 (P < .001), with annual national fee-for-service Medicare spending increasing from $666 million to $962 million. There was no statistically significant change in detection rates of early-stage tumors (2.45 vs 2.57 per 1000 person-years; P = .41). Conclusions Although breast cancer screening–related costs increased substantially from 2001 through 2009 among Medicare beneficiaries, a clinically significant change in stage at diagnosis was not observed. PMID:25031307

[Assessment of the acceptance of set meals served at the "Sant Joan de Reus" University Hospital].

PubMed

Guillén, N; Torrentó, M; Alvadalejo, R; Salas-Salvadó, J

2004-01-01

Despite the fact that, in most of the series published, cancer is the most frequent base pathology for the indication of home parenteral nutrition (HPN), the use of this technique in terminally-ill patients is still a controversial issue. Our goal has been to review the evolution of cancer patients with HPN treatment from "La Paz" Hospital with a view to studying the indication, evolution and complications. We review a total of 9 terminal oncological patients who had been treated with HPN between January 2000 and December 2002, with a mean age of 60.4 (44-81) years, the most common base cancer was gastric adenocarcinoma (44%). Intestinal obstruction in the context of peritoneal carcinomatosis was the reason for indicating HPN in 89% of cases and the median survival time was 71 (23-131) days. Catheter infection was the most frequent complication with 1.4 episodes/patient. The existence of a Home Support Team meant follow-up of patients was easier, with HPN being estimated as the treatment provided in 67% of cases. 56% of the patients were not sufficiently informed as to their underlying illness. Although HPN is one more therapeutic resource, which may or may not be used in some terminal oncological patients, we must refine the indication as much as possible to take into account a series of "systematic guarantees" including fulfilment of pertinent clinical criteria, informed consent and the adoption of a collective decision with the involvement of all the professionals monitoring the patient. We propose an action algorithm to help in improving the decision-taking process in these patients.

Cancer risks after radiation exposure in middle age.

PubMed

Shuryak, Igor; Sachs, Rainer K; Brenner, David J

2010-11-03

Epidemiological data show that radiation exposure during childhood is associated with larger cancer risks compared with exposure at older ages. For exposures in adulthood, however, the relative risks of radiation-induced cancer in Japanese atomic bomb survivors generally do not decrease monotonically with increasing age of adult exposure. These observations are inconsistent with most standard models of radiation-induced cancer, which predict that relative risks decrease monotonically with increasing age at exposure, at all ages. We analyzed observed cancer risk patterns as a function of age at exposure in Japanese atomic bomb survivors by using a biologically based quantitative model of radiation carcinogenesis that incorporates both radiation induction of premalignant cells (initiation) and radiation-induced promotion of premalignant damage. This approach emphasizes the kinetics of radiation-induced initiation and promotion, and tracks the yields of premalignant cells before, during, shortly after, and long after radiation exposure. Radiation risks after exposure in younger individuals are dominated by initiation processes, whereas radiation risks after exposure at later ages are more influenced by promotion of preexisting premalignant cells. Thus, the cancer site-dependent balance between initiation and promotion determines the dependence of cancer risk on age at radiation exposure. For example, in terms of radiation induction of premalignant cells, a quantitative measure of the relative contribution of initiation vs promotion is 10-fold larger for breast cancer than for lung cancer. Reflecting this difference, radiation-induced breast cancer risks decrease with age at exposure at all ages, whereas radiation-induced lung cancer risks do not. For radiation exposure in middle age, most radiation-induced cancer risks do not, as often assumed, decrease with increasing age at exposure. This observation suggests that promotional processes in radiation carcinogenesis become increasingly important as the age at exposure increases. Radiation-induced cancer risks after exposure in middle age may be up to twice as high as previously estimated, which could have implications for occupational exposure and radiological imaging.

Oral cancer statistics in India on the basis of first report of 29 population-based cancer registries

PubMed Central

Sharma, Swati; Satyanarayana, L; Asthana, Smitha; Shivalingesh, KK; Goutham, Bala Subramanya; Ramachandra, Sujatha

2018-01-01

Objectives: To summarize and provide an overview of age-specific oral cancer incidence reported in 29 population-based cancer registry in India. Materials and Methods: Secondary data on age-adjusted rates (AARs) of incidence of oral cancer and other associated sites for all ages (0–75 years) were collected from the report of the National Cancer Registry Programme 2012–2014 in 29 population-based control registries. Results: Among both males and females, mouth cancer had maximum Age adjusted incidence rates (64.8) in the central zone, while oropharynx cancer had minimum AAR (0) in all regions. Conclusion: Oral cancer incidence increases with age with typical pattern of cancer of associated sites of oral cavity seen in the northeast region. PMID:29731552

Cancer burden with ageing population in urban regions in China: projection on cancer registry data from World Health Organization.

PubMed

Tsoi, Kelvin K F; Hirai, Hoyee W; Chan, Felix C H; Griffiths, Sian; Sung, Joseph J Y

2017-01-01

China is facing the challenges of an expanding ageing population and the impact of rapid urbanization, cancer rates are subsequently increasing. This study focuses on the changes of the ageing population and projects the incidence of common ageing-related cancers in the urban regions in China up to 2030. Cancer incidence data and population statistics in China were extracted from the International Agency for Research on Cancer. Due to improving longevity in China, continuous and remarkable increasing trends for the lung, colorectal and prostate cancers are expected. The rate of expanding ageing population was taken into account when predicting the trend of cancer incidence; the estimations of ageing-related cancers were more factual and significant than using the conventional approach of age standardization. The incidence rates of lung, colorectal and prostate cancers will continue to rise in the future decades due to the rise of ageing population. Lifestyle modification such as cutting tobacco smoking rates and promoting healthier diets as well as cancer screening programs should be a health system priority in order to decrease the growing burden of cancer-related mortality and morbidity. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Dynamics of Tumor Heterogeneity Derived from Clonal Karyotypic Evolution.

PubMed

Laughney, Ashley M; Elizalde, Sergi; Genovese, Giulio; Bakhoum, Samuel F

2015-08-04

Numerical chromosomal instability is a ubiquitous feature of human neoplasms. Due to experimental limitations, fundamental characteristics of karyotypic changes in cancer are poorly understood. Using an experimentally inspired stochastic model, based on the potency and chromosomal distribution of oncogenes and tumor suppressor genes, we show that cancer cells have evolved to exist within a narrow range of chromosome missegregation rates that optimizes phenotypic heterogeneity and clonal survival. Departure from this range reduces clonal fitness and limits subclonal diversity. Mapping of the aneuploid fitness landscape reveals a highly favorable, commonly observed, near-triploid state onto which evolving diploid- and tetraploid-derived populations spontaneously converge, albeit at a much lower fitness cost for the latter. Finally, by analyzing 1,368 chromosomal translocation events in five human cancers, we find that karyotypic evolution also shapes chromosomal translocation patterns by selecting for more oncogenic derivative chromosomes. Thus, chromosomal instability can generate the heterogeneity required for Darwinian tumor evolution. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

A stochastic model for tumor geometry evolution during radiation therapy in cervical cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Yifang; Lee, Chi-Guhn; Chan, Timothy C. Y., E-mail: tcychan@mie.utoronto.ca

2014-02-15

Purpose: To develop mathematical models to predict the evolution of tumor geometry in cervical cancer undergoing radiation therapy. Methods: The authors develop two mathematical models to estimate tumor geometry change: a Markov model and an isomorphic shrinkage model. The Markov model describes tumor evolution by investigating the change in state (either tumor or nontumor) of voxels on the tumor surface. It assumes that the evolution follows a Markov process. Transition probabilities are obtained using maximum likelihood estimation and depend on the states of neighboring voxels. The isomorphic shrinkage model describes tumor shrinkage or growth in terms of layers of voxelsmore » on the tumor surface, instead of modeling individual voxels. The two proposed models were applied to data from 29 cervical cancer patients treated at Princess Margaret Cancer Centre and then compared to a constant volume approach. Model performance was measured using sensitivity and specificity. Results: The Markov model outperformed both the isomorphic shrinkage and constant volume models in terms of the trade-off between sensitivity (target coverage) and specificity (normal tissue sparing). Generally, the Markov model achieved a few percentage points in improvement in either sensitivity or specificity compared to the other models. The isomorphic shrinkage model was comparable to the Markov approach under certain parameter settings. Convex tumor shapes were easier to predict. Conclusions: By modeling tumor geometry change at the voxel level using a probabilistic model, improvements in target coverage and normal tissue sparing are possible. Our Markov model is flexible and has tunable parameters to adjust model performance to meet a range of criteria. Such a model may support the development of an adaptive paradigm for radiation therapy of cervical cancer.« less

Sorting cancer karyotypes using double-cut-and-joins, duplications and deletions.

PubMed

Zeira, Ron; Shamir, Ron

2018-05-03

Problems of genome rearrangement are central in both evolution and cancer research. Most genome rearrangement models assume that the genome contains a single copy of each gene and the only changes in the genome are structural, i.e., reordering of segments. In contrast, tumor genomes also undergo numerical changes such as deletions and duplications, and thus the number of copies of genes varies. Dealing with unequal gene content is a very challenging task, addressed by few algorithms to date. More realistic models are needed to help trace genome evolution during tumorigenesis. Here we present a model for the evolution of genomes with multiple gene copies using the operation types double-cut-and-joins, duplications and deletions. The events supported by the model are reversals, translocations, tandem duplications, segmental deletions, and chromosomal amplifications and deletions, covering most types of structural and numerical changes observed in tumor samples. Our goal is to find a series of operations of minimum length that transform one karyotype into the other. We show that the problem is NP-hard and give an integer linear programming formulation that solves the problem exactly under some mild assumptions. We test our method on simulated genomes and on ovarian cancer genomes. Our study advances the state of the art in two ways: It allows a broader set of operations than extant models, thus being more realistic, and it is the first study attempting to reconstruct the full sequence of structural and numerical events during cancer evolution. Code and data are available in https://github.com/Shamir-Lab/Sorting-Cancer-Karyotypes. ronzeira@post.tau.ac.il, rshamir@tau.ac.il. Supplementary data are available at Bioinformatics online.

An Evolution-Guided Analysis Reveals a Multi-Signaling Regulation of Fas by Tyrosine Phosphorylation and its Implication in Human Cancers

PubMed Central

Chakrabandhu, Krittalak; Huault, Sébastien; Durivault, Jérôme; Lang, Kévin; Ta Ngoc, Ly; Bole, Angelique; Doma, Eszter; Dérijard, Benoit; Gérard, Jean-Pierre; Pierres, Michel; Hueber, Anne-Odile

2016-01-01

Demonstrations of both pro-apoptotic and pro-survival abilities of Fas (TNFRSF6/CD95/APO-1) have led to a shift from the exclusive “Fas apoptosis” to “Fas multisignals” paradigm and the acceptance that Fas-related therapies face a major challenge, as it remains unclear what determines the mode of Fas signaling. Through protein evolution analysis, which reveals unconventional substitutions of Fas tyrosine during divergent evolution, evolution-guided tyrosine-phosphorylated Fas proxy, and site-specific phosphorylation detection, we show that the Fas signaling outcome is determined by the tyrosine phosphorylation status of its death domain. The phosphorylation dominantly turns off the Fas-mediated apoptotic signal, while turning on the pro-survival signal. We show that while phosphorylations at Y232 and Y291 share some common functions, their contributions to Fas signaling differ at several levels. The findings that Fas tyrosine phosphorylation is regulated by Src family kinases (SFKs) and the phosphatase SHP-1 and that Y291 phosphorylation primes clathrin-dependent Fas endocytosis, which contributes to Fas pro-survival signaling, reveals for the first time the mechanistic link between SFK/SHP-1-dependent Fas tyrosine phosphorylation, internalization route, and signaling choice. We also demonstrate that levels of phosphorylated Y232 and Y291 differ among human cancer types and differentially respond to anticancer therapy, suggesting context-dependent involvement of Fas phosphorylation in cancer. This report provides a new insight into the control of TNF receptor multisignaling by receptor phosphorylation and its implication in cancer biology, which brings us a step closer to overcoming the challenge in handling Fas signaling in treatments of cancer as well as other pathologies such as autoimmune and degenerative diseases. PMID:26942442

Cancer Specific Mortality in Men Diagnosed with Prostate Cancer before Age 50 Years: A Nationwide Population Based Study.

PubMed

Thorstenson, Andreas; Garmo, Hans; Adolfsson, Jan; Bratt, Ola

2017-01-01

We compared clinical characteristics and cancer specific mortality in men diagnosed with prostate cancer before vs after age 50 years. A total of 919 men 35 to 49 years old and 45,098 men 50 to 66 years old who were diagnosed with prostate cancer between 1998 and 2012 were identified in PCBaSe (Prostate Cancer data Base Sweden). Cancer specific mortality was compared among age groups (35 to 49, 50 to 59, 60 to 63 and 64 to 66 years) with and without adjusting for cancer characteristics, comorbidity and education in a multivariable Cox proportional hazards model. Clinical cancer characteristics indicated that most nonmetastatic cancer in men younger than 50 years was detected after prostate specific antigen testing. The proportion of nonmetastatic vs metastatic disease at diagnosis was similar in all age groups. A strong association between younger age and poor prognosis was apparent in men in whom metastatic disease was diagnosed before age 50 to 55 years. The crude and adjusted HRs of cancer specific mortality were 1.41 (95% CI 1.12-1.79) and 1.28 (95% CI 1.01-1.62) in men diagnosed before age 50 and at age 50 to 59 years, respectively. In men with nonmetastatic disease crude cancer specific mortality increased with older age but adjusted cancer specific mortality was similar in all age groups. Our findings suggest that an aggressive form of metastatic prostate cancer is particularly common in men younger than 50 to 55 years. Genetic studies and trials of intensified systemic treatment are warranted in this patient group. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Advanced glycation end products increase carbohydrate responsive element binding protein expression and promote cancer cell proliferation.

PubMed

Chen, Hanbei; Wu, Lifang; Li, Yakui; Meng, Jian; Lin, Ning; Yang, Dianqiang; Zhu, Yemin; Li, Xiaoyong; Li, Minle; Xu, Ye; Wu, Yuchen; Tong, Xuemei; Su, Qing

2014-09-01

Diabetic patients have increased levels of advanced glycation end products (AGEs) and the role of AGEs in regulating cancer cell proliferation is unclear. Here, we found that treating colorectal and liver cancer cells with AGEs promoted cell proliferation. AGEs stimulated both the expression and activation of a key transcription factor called carbohydrate responsive element binding protein (ChREBP) which had been shown to promote glycolytic and anabolic activity as well as proliferation of colorectal and liver cancer cells. Using siRNAs or the antagonistic antibody for the receptor for advanced glycation end-products (RAGE) blocked AGEs-induced ChREBP expression or cell proliferation in cancer cells. Suppressing ChREBP expression severely impaired AGEs-induced cancer cell proliferation. Taken together, these results demonstrate that AGEs-RAGE signaling enhances cancer cell proliferation in which AGEs-mediated ChREBP induction plays an important role. These findings may provide new explanation for increased cancer progression in diabetic patients. Copyright © 2014. Published by Elsevier Ireland Ltd.

Influence of Social Determinants, Lifestyle, Emotional Well-Being and the Use of Unconventional Therapies in Breast Cancer Progression in a Cohort of Women in Barcelona: Protocol for the DAMA Cohort

PubMed Central

Continente, Xavier; Serral, Gemma; Bargalló, Xavi; Doménech, Montserrat; Espinosa-Bravo, Martín; Grau, Jaume; Macià, Francesc; Manzanera, Rafael; Pla, Margarida; Quintana, M Jesus; Sala, Maria; Vidal, Eulalia

2017-01-01

Background Breast cancer continues to be the most commonly diagnosed cancer in women. Breast cancer survivors face numerous problems, especially after completing the first year of intense treatment. We present the protocol for an ongoing study to analyze the impact of a series of factors on breast cancer survival related to lifestyle, emotional well-being, and use of complementary and alternative medicine (CAM). Objective We aim to analyze the influence of social determinants, lifestyle changes, emotional well-being, and use of CAM in the progression of breast cancer in women diagnosed with breast cancer between 2003 and 2013 in Barcelona, Spain. Methods We will perform a mixed cohort study (prospective and retrospective) of women diagnosed with breast cancer, created using a convenience sample in which we study the evolution of the disease (relapse, death, or remaining disease-free). Once identified, we sent the women information about the study and an informed consent form that they are required to sign in order to participate; a total of 2235 women were recruited. We obtained the following information from all participants: sociodemographic profile via a phone interview, and a self-administered survey of information about the study’s objectives (lifestyles, emotional well-being, health care services, and the use of CAM). Lastly, we examined clinical records to obtain data on the tumor at the time of diagnosis, the treatment received, the occurrence of relapses (if any), and the tumor typology. We present data on the women’s social profile based on descriptive data obtained from the telephone interview (welcome survey). Results Based on the welcome survey, which was completed by 2712 women, 14.42% (391/2712) of respondents were <50 years of age, 45.50% (1234/2712) were between 50 and 65 years of age, and 40.08% (1087/2712) were >65 years of age. A total of 43.69% (1185/2712) belonged to the highest social classes (I and II), 31.27% (848/2712) to the middle class (III), and 23.49% (637/2712) to the working classes (IV and V). Approximately 22.71% (616/2712) lived alone, 38.31% (1039/2712) lived with one person, and 38.97% (1057/2712) lived with two or more people. Conclusions We obtained information from a large cohort of women, but this study has limitations related to the convenience sampling strategy, one of which is reduced representativeness. Conversely, being a self-administered survey, the study introduces biases, especially from respondents that answered on paper. However, the information that the study provides will serve as the basis for designing future interventions aimed at improving the knowledge gaps indicated for women with breast cancer. PMID:29254913

Stress-triggered atavistic reprogramming (STAR) addiction: driving force behind head and neck cancer?

PubMed Central

Masuda, Muneyuki; Wakasaki, Takahiro; Toh, Satoshi

2016-01-01

Recent results of the Cancer Genome Atlas on head and neck squamous cell carcinoma (HNSCC) revealed that HNSCC lacked predominant gain-of-function mutations in oncogenes, whereas an essential role for epigenetics in oncogenesis has become apparent. In parallel, it has gained general acceptance that cancer is considered as complex adaptive system, which evolves responding environmental selective pressures. This somatic evolution appears to proceed concurrently with the acquisition of an atavistic pluripotent state (i.e., “stemness”), which is inducible by intrinsic epigenetic reprogramming program as demonstrated by induced pluripotent stem (iPS) cells. This Nobel prize-winning discovery has markedly accelerated and expanded cancer stem cell research from the point of epigenetic reprogramming. Taken together, we hypothesize that stress-triggered atavistic reprogramming (STAR) may be the major driving force of HNSCC evolution. In this perspective, we discuss the possible mechanisms of STAR in HNSCC, focusing on recent topics of epigenetic reprogramming in developmental and cancer cell biology. PMID:27429838

Family History of Breast Cancer, Breast Density, and Breast Cancer Risk in a U.S. Breast Cancer Screening Population.

PubMed

Ahern, Thomas P; Sprague, Brian L; Bissell, Michael C S; Miglioretti, Diana L; Buist, Diana S M; Braithwaite, Dejana; Kerlikowske, Karla

2017-06-01

Background: The utility of incorporating detailed family history into breast cancer risk prediction hinges on its independent contribution to breast cancer risk. We evaluated associations between detailed family history and breast cancer risk while accounting for breast density. Methods: We followed 222,019 participants ages 35 to 74 in the Breast Cancer Surveillance Consortium, of whom 2,456 developed invasive breast cancer. We calculated standardized breast cancer risks within joint strata of breast density and simple (1 st -degree female relative) or detailed (first-degree, second-degree, or first- and second-degree female relative) breast cancer family history. We fit log-binomial models to estimate age-specific breast cancer associations for simple and detailed family history, accounting for breast density. Results: Simple first-degree family history was associated with increased breast cancer risk compared with no first-degree history [Risk ratio (RR), 1.5; 95% confidence interval (CI), 1.0-2.1 at age 40; RR, 1.5; 95% CI, 1.3-1.7 at age 50; RR, 1.4; 95% CI, 1.2-1.6 at age 60; RR, 1.3; 95% CI, 1.1-1.5 at age 70). Breast cancer associations with detailed family history were strongest for women with first- and second-degree family history compared with no history (RR, 1.9; 95% CI, 1.1-3.2 at age 40); this association weakened in higher age groups (RR, 1.2; 95% CI, 0.88-1.5 at age 70). Associations did not change substantially when adjusted for breast density. Conclusions: Even with adjustment for breast density, a history of breast cancer in both first- and second-degree relatives is more strongly associated with breast cancer than simple first-degree family history. Impact: Future efforts to improve breast cancer risk prediction models should evaluate detailed family history as a risk factor. Cancer Epidemiol Biomarkers Prev; 26(6); 938-44. ©2017 AACR . ©2017 American Association for Cancer Research.

MicroRNA-Based Linkage between Aging and Cancer: from Epigenetics View Point.

PubMed

Saeidimehr, Saeid; Ebrahimi, Ammar; Saki, Najmaldin; Goodarzi, Parisa; Rahim, Fakher

2016-01-01

Ageing is a complex process and a broad spectrum of physical, psychological, and social changes over time. Accompanying diseases and disabilities, which can interfere with cancer treatment and recovery, occur in old ages. MicroRNAs (miRNAs) are a set of small non-coding RNAs, which have considerable roles in post-transcriptional regulation at gene expression level. In this review, we attempted to summarize the current knowledge of miRNAs functions in ageing, with mainly focuses on malignancies and all underlying genetic, molecular and epigenetics mechanisms. The evidences indicated the complex and dynamic nature of miRNA-based linkage of ageing and cancer at genomics and epigenomics levels which might be generally crucial for understanding the mechanisms of age-related cancer and ageing. Recently in the field of cancer and ageing, scientists claimed that uric acid can be used to regulate reactive oxygen species (ROS), leading to cancer and ageing prevention; these findings highlight the role of miRNA-based inhibition of the SLC2A9 antioxidant pathway in cancer, as a novel way to kill malignant cells, while a patient is fighting with cancer.

Age-dependent associations between androgenetic alopecia and prostate cancer risk.

PubMed

Muller, David C; Giles, Graham G; Sinclair, Rod; Hopper, John L; English, Dallas R; Severi, Gianluca

2013-02-01

Both prostate cancer and androgenetic alopecia are strongly age-related conditions that are considered to be androgen dependent, but studies of the relationship between them have yielded inconsistent results. We aimed to assess whether androgenetic alopecia at ages 20 and 40 years are associated with risk of prostate cancer. At a follow-up of the Melbourne Collaborative Cohort Study, men were asked to assess their hair pattern at ages 20 and 40 years relative to eight categories in showcards. Cases were men notified to the Victorian Cancer Registry with prostate cancer diagnosed between cohort enrollment (1990-1994) and follow-up attendance (2003-2009). Flexible parametric survival models were used to estimate age-varying HRs and predicted cumulative probabilities of prostate cancer by androgenetic alopecia categories. Of 9,448 men that attended follow-up and provided data on androgenetic alopecia, we identified 476 prostate cancer cases during a median follow-up of 11 years four months. Cumulative probability of prostate cancer was greater at all ages up to 76 years, for men with vertex versus no androgenetic alopecia at age of 40 years. At age of 76 years, the estimated probabilities converged to 0.15. Vertex androgenetic alopecia at 40 years was also associated with younger age of diagnosis for prostate cancer cases. Vertex androgenetic alopecia at age of 40 years might be a marker of increased risk of early-onset prostate cancer. If confirmed, these results suggest that the apparently conflicting findings of previous studies might be explained by failure to adequately model the age-varying nature of the association between androgenetic alopecia and prostate cancer.

Epigenetics: origins and implications for cancer epidemiology.

PubMed

Nise, Melissa S; Falaturi, Puran; Erren, Thomas C

2010-02-01

This paper provides information on the evolution of the 'epigenetics' concept since Aristotle and draws attention to the importance of epigenetic implications for cancer epidemiology in the years to come. Clearly, to understand origins of the concept of epigenetics, it is worthwhile to consider historical arguments associated with evolution. Equally clearly, in the last half of the 20th century, great advances in the understanding of epigenetics and, more specifically, great advances in the understanding of epigenetics in cancer have been made. However, reaping the full benefits of epigenetics lies beyond the predominant experimental studies of today. In general, epigenetics opens many doors in the field of cancer, but it also adds another level of complex, inter-related, and multi-dimensional information to research, and to its interpretation. Overall, future cancer studies should consider, or at least be sensitive to, epigenetic effects and mechanisms. Moving the focus beyond 'pristine' inheritance via DNA alone, cancer epidemiology investigating epigenetic exposures such as environmental factors (exposure to heavy metals, air pollution, arsenic and other toxins), dietary patterns (starvation, famine, contamination), and lifestyle habits (smoking, level of physical activity, and BMI) in populations has the prospect to significantly benefit future cancer prevention and treatment schemes.

History, evolution, and current status of radiologic imaging tests for colorectal cancer screening.

PubMed

Levine, Marc S; Yee, Judy

2014-11-01

Colorectal cancer screening is thought to be an effective tool with which to reduce the mortality from colorectal cancer through early detection and removal of colonic adenomas and early colon cancers. In this article, we review the history, evolution, and current status of imaging tests of the colon-including single-contrast barium enema, double-contrast barium enema, computed tomographic (CT) colonography, and magnetic resonance (MR) colonography-for colorectal cancer screening. Despite its documented value in the detection of colonic polyps, the double-contrast barium enema has largely disappeared as a screening test because it is widely perceived as a labor-intensive, time-consuming, and technically demanding procedure. In the past decade, the barium enema has been supplanted by CT colonography as the major imaging test in colorectal cancer screening in the United States, with MR colonography emerging as another viable option in Europe. Although MR colonography does not require ionizing radiation, the radiation dose for CT colonography has decreased substantially, and regular screening with this technique has a high benefit-to-risk ratio. In recent years, CT colonography has been validated as an effective tool for use in colorectal cancer screening that is increasingly being disseminated.

Aging Impacts Transcriptome but not Genome of Hormone-dependentBreast Cancers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yau, Christina; Fedele, Vita; Roydasgupta, Ritu

Age is one of the most important risk factors for human malignancies, including breast cancer; in addition, age-at-diagnosis has been shown to be an independent indicator of breast cancer prognosis. However, except for inherited forms of breast cancer, there is little genetic or epigenetic understanding of the biological basis linking aging with sporadic breast cancer incidence and its clinical behavior.

Online CME Series Can Nutrition Simultaneously Affect Cancer and Aging? | Division of Cancer Prevention

Cancer.gov

Aging is considered by some scientists to be a normal physiological process, while others believe it is a disease. Increased cancer risk in the elderly raises the question regarding the common pathways for cancer and aging. Undeniably, nutrition plays an important role in both cases and this webinar will explore whether nutrition can simultaneously affect cancer and aging. |

The changing age distribution of prostate cancer in Canada.

PubMed

Neutel, C Ineke; Gao, Ru-Nie; Blood, Paul A; Gaudette, Leslie A

2007-01-01

Prostate cancer incidence rates are still increasing steadily; mortality rates are levelling, possibly decreasing; and hospitalization rates for many diagnoses are decreasing. Our objective is to examine changes in age distributions of prostate cancer during these times of change. Prostate cancer cases were derived from the Canadian Cancer Registry, prostate cancer deaths from Vital Statistics, hospitalizations from the Hospital Morbidity File. Age-standardized rates were calculated based on the 1991 Canadian population. A prevalence correction for incidence rates was calculated. Age-specific incidence rates increased until 1995 for all ages, but a superimposed peak (1991-94) was greatest between ages 60-79. After 1995, increases in incidence continued for the under-70 age groups. Prevalence correction indicated the greatest underestimation of incidence rates for the oldest ages, but was less in Canada than in the United States. Mortality rates increased until 1994, then levelled and slowly decreased; age-specific mortality rates showed the greatest increase for the oldest ages but the earliest downturn for younger age groups. While hospitalizations dropped drastically after 1991, this drop was confined to elderly men (70+). Dramatic changes in age distributions of prostate cancer incidence, mortality and hospitalizations altered age profiles of men with prostate cancer. This illustrated the changing nature of prostate cancer as a public health issue and has important implications for health care provision, e.g., the increased numbers of younger new patients have different needs from the increasing numbers of elderly long-term patients who now spend less time in hospital.

The evolution of lung cancer screening.

PubMed

Wilkinson, Neal W; Loewen, Gregory M; Klippenstein, Donald L; Litwin, Alan M; Anderson, Timothy M

2003-12-01

In the 1970s, four trials failed to demonstrate any mortality reduction using a combination of chest X-ray (CXR) and/or sputum cytology. The recent early lung cancer action project (ELCAP) demonstrated that modern screening is capable of detecting Stage I lung cancers. Bronchial epithelial changes leading up to cancers are now being understood to include histologic changes and genetic alterations. Emerging molecular markers detected in sputum and serum show promise in the future of lung cancer screening.

Pipeline for large-scale microdroplet bisulfite PCR-based sequencing allows the tracking of hepitype evolution in tumors.

PubMed

Herrmann, Alexander; Haake, Andrea; Ammerpohl, Ole; Martin-Guerrero, Idoia; Szafranski, Karol; Stemshorn, Kathryn; Nothnagel, Michael; Kotsopoulos, Steve K; Richter, Julia; Warner, Jason; Olson, Jeff; Link, Darren R; Schreiber, Stefan; Krawczak, Michael; Platzer, Matthias; Nürnberg, Peter; Siebert, Reiner; Hampe, Jochen

2011-01-01

Cytosine methylation provides an epigenetic level of cellular plasticity that is important for development, differentiation and cancerogenesis. We adopted microdroplet PCR to bisulfite treated target DNA in combination with second generation sequencing to simultaneously assess DNA sequence and methylation. We show measurement of methylation status in a wide range of target sequences (total 34 kb) with an average coverage of 95% (median 100%) and good correlation to the opposite strand (rho = 0.96) and to pyrosequencing (rho = 0.87). Data from lymphoma and colorectal cancer samples for SNRPN (imprinted gene), FGF6 (demethylated in the cancer samples) and HS3ST2 (methylated in the cancer samples) serve as a proof of principle showing the integration of SNP data and phased DNA-methylation information into "hepitypes" and thus the analysis of DNA methylation phylogeny in the somatic evolution of cancer.

Is the secret for a successful aging to keep track of cancer pathways?

PubMed

Tramontano, Donatella; De Amicis, Francesca

2018-06-15

A successful aging could be gained by life satisfaction, social functioning, or psychological resources and, definitely, by increasing resistance to diverse age-related pathologies. Nowadays, cancer can be considered an age-related disease since the incidence of most cancers increases with age, rising more rapidly beginning in midlife. Although adults with extended longevity are less likely to develop cancer, it is now emerging that aging and cancer share common molecular links, and thus targeting these mechanisms may be suitable to treat multiple disorders, for the prolonging of healthy aging. At present, one of the cornerstones of antiaging is hormone-replacement therapy to treat diseases associated with a state of age-related sex-hormone deficiency in women and men; however, many studies question the relationship of hormone replacement to cancer recurrence. Here, we discuss signaling and metabolic molecular crossroad linking aging and cancer. This is useful to argue about the current knowledge of prolongevity and druggable targets and to motivate specific intervention strategies that could modify practices of the aging population, activating multiple longevity pathways but keeping track of cancer pathways, thereby potentially preserving health status. © 2018 Wiley Periodicals, Inc.

Sociological Transition and Breast Cancer in the Arab World: the Experience of Lebanon

PubMed

A Lakkis, Najla; Adib, Salim M; Hamadeh, Ghassan; El Jarrah, Rana; H Osman, Mona

2017-05-01

Background: Breast cancer is the leading cause of cancer death among females in Lebanon. This study aimed at analyzing its epidemiology in the country over time. Methods: Data were extracted from the Lebanese National Cancer Registry (NCR) for the years 2004 through 2010. Age-standardized and age-specific incidence rates for cancers per 100,000 population were calculated. Results: Breast cancer ranked first, accounting for an average of 37.6% of all new female cancer cases in Lebanon during the period of 2004-2010. Breast cancer was found to have been increasing faster than other hormone-related women’s cancers (i.e. of the ovaries and corpus uteri). The breast cancer age-standardized incidence rates (world population) (ASRw) increased steadily from 2004 (71.0) to 2010 (105.9), making the burden comparable to that in developed countries, reflecting the influence of sociological and reproductive patterns transitioning from regional norms to global trends. The age-specific incidence rates for breast cancer rose steeply from around age 35-39 years, to reach a first peak in the age group 45-49 years, and then dropped slightly between 50 and 64 years to rise again thereafter and reach a second peak in the 75+ age group. Five-year age-specific rates among Lebanese women between 35 and 49 years were among the highest observed worldwide in 2008. Conclusion: Breast cancer is continuously on the rise in Lebanon. The findings of this study support the national screening recommendation of starting breast cancer screening at the age of 40 years. It is mandatory to conduct an in-depth analysis of contributing factors and develop consequently a comprehensive National Breast Cancer Control strategy. Creative Commons Attribution License

Sociological Transition and Breast Cancer in the Arab World: the Experience of Lebanon

PubMed Central

Lakkis, Najla A; Adib, Salim M; Hamadeh, Ghassan; Jarrah, Rana El; Osman, Mona H

2017-01-01

Background: Breast cancer is the leading cause of cancer death among females in Lebanon. This study aimed at analyzing its epidemiology in the country over time. Methods: Data were extracted from the Lebanese National Cancer Registry (NCR) for the years 2004 through 2010. Age-standardized and age-specific incidence rates for cancers per 100,000 population were calculated. Results: Breast cancer ranked first, accounting for an average of 37.6% of all new female cancer cases in Lebanon during the period of 2004-2010. Breast cancer was found to have been increasing faster than other hormone-related women’s cancers (i.e. of the ovaries and corpus uteri). The breast cancer age-standardized incidence rates (world population) (ASRw) increased steadily from 2004 (71.0) to 2010 (105.9), making the burden comparable to that in developed countries, reflecting the influence of sociological and reproductive patterns transitioning from regional norms to global trends. The age-specific incidence rates for breast cancer rose steeply from around age 35-39 years, to reach a first peak in the age group 45-49 years, and then dropped slightly between 50 and 64 years to rise again thereafter and reach a second peak in the 75+ age group. Five-year age-specific rates among Lebanese women between 35 and 49 years were among the highest observed worldwide in 2008. Conclusion: Breast cancer is continuously on the rise in Lebanon. The findings of this study support the national screening recommendation of starting breast cancer screening at the age of 40 years. It is mandatory to conduct an in-depth analysis of contributing factors and develop consequently a comprehensive National Breast Cancer Control strategy. PMID:28612586

Cancer Evolution: Mathematical Models and Computational Inference

PubMed Central

Beerenwinkel, Niko; Schwarz, Roland F.; Gerstung, Moritz; Markowetz, Florian

2015-01-01

Cancer is a somatic evolutionary process characterized by the accumulation of mutations, which contribute to tumor growth, clinical progression, immune escape, and drug resistance development. Evolutionary theory can be used to analyze the dynamics of tumor cell populations and to make inference about the evolutionary history of a tumor from molecular data. We review recent approaches to modeling the evolution of cancer, including population dynamics models of tumor initiation and progression, phylogenetic methods to model the evolutionary relationship between tumor subclones, and probabilistic graphical models to describe dependencies among mutations. Evolutionary modeling helps to understand how tumors arise and will also play an increasingly important prognostic role in predicting disease progression and the outcome of medical interventions, such as targeted therapy. PMID:25293804

Cancer-Related Distress in Young Adults Compared to Middle-Aged and Senior Adults.

PubMed

Burgoyne, Mary Jo; Bingen, Kristin; Leuck, Julianne; Dasgupta, Mahua; Ryan, Polly; Hoffmann, Raymond G

2015-06-01

Little is known about cancer-related distress during young adulthood. Results from the few studies that have directly assessed this age group have indicated that young adults (YAs) may be at greater risk of developing psychosocial difficulties due to their unique challenges of coping with cancer. This study's objective was to investigate cancer-related distress in YAs compared to older adults. This retrospective cross-sectional study compared the distress level of YAs (18-39 years old) with that of middle-aged (40-64 years old) and senior adults (65-90 years old) using the Distress Thermometer (DT) and associated Problem List (PL). Factors that may be associated with distress by age group were examined, including demographics, cancer type, and PL items endorsed. YAs had higher cancer-related distress than senior adults but similar distress levels to middle-aged adults. Findings from distress comparisons across demographics, cancer types, and PL items endorsed suggest that YAs and middle-aged adults had similar distress patterns when compared to senior adults, who had the lowest DT scores. Multivariable analyses indicated age-related risk factors for high distress, including gynecologic cancers for YAs; divorced, single, or unemployed statuses for middle-aged adults; and being of Hispanic ethnicity for senior adults. Female gender and practical, emotional, and physical problems were associated with distress for all age groups. There is a differential impact of cancer by age. It is important to screen for cancer-related distress, paying attention to risk factors by age to determine age-appropriate supportive care needs.

A holistic approach to study the effects of natural antioxidants on inflammation and liver cancer.

PubMed

Costantini, Susan; Colonna, Giovanni; Castello, Giuseppe

2014-01-01

The limited effectiveness of chemotherapy and the high recurrence rate of cancers highlight the urgent need to identify new molecular targets and to develop new treatments. Numerous epidemiological studies have recently highlighted the existence of an inverse association between fruit and vegetable consumption, natural antioxidants, and cancer risk; in fact, antioxidant intake through diet or supplements of plant origin is strongly recommended for cancer prevention and cure. In general, antioxidants are substances of vegetable, mineral, or animal origin that neutralize free radicals and protect the body from their negative actions on the plasma membrane, proteins, and DNA. Hence, cancer can be prevented by the stimulation of the immune system to destroy cancer cells or to block their proliferation. Since living organisms may be studied as a whole complex system by the "omics sciences" which tend toward understanding and describing the global information of genes, mRNA, proteins, and metabolites, our aim is to use bioinformatics and systems biology to study cytokinome, which plays an important role in the evolution of inflammatory processes and is also a key component in the evolution of cancer, a disease recognized as depending on chronic inflammation and also with the concomitant presence of type 2 diabetes and obesity. On the whole, we define cytokinome as the totality of these proteins and their interactions in and around biological cells. Understanding the complex interaction network of cytokines in patients affected by cancers should be very useful both to follow the evolution of cancer from its early stages and to define innovative therapeutic strategies by using systems biology approaches. In this paper, we review some results of our group in the light of the "omics" logic, and in particular (1) the need for a global approach to study complex systems such as multifactorial cancer and, in particular, hepatocellular carcinoma, (2) the correlation between natural antioxidants, inflammation, and liver cancer, (3) the challenge and significance of the cytokinome profile, (4) the evaluation of the cytokinome profile of patients with type 2 diabetes and/or chronic hepatitis C infection, and (5) adipokine interactome.

Demographic history, selection and functional diversity of the canine genome.

PubMed

Ostrander, Elaine A; Wayne, Robert K; Freedman, Adam H; Davis, Brian W

2017-12-01

The domestic dog represents one of the most dramatic long-term evolutionary experiments undertaken by humans. From a large wolf-like progenitor, unparalleled diversity in phenotype and behaviour has developed in dogs, providing a model for understanding the developmental and genomic mechanisms of diversification. We discuss pattern and process in domestication, beginning with general findings about early domestication and problems in documenting selection at the genomic level. Furthermore, we summarize genotype-phenotype studies based first on single nucleotide polymorphism (SNP) genotyping and then with whole-genome data and show how an understanding of evolution informs topics as different as human history, adaptive and deleterious variation, morphological development, ageing, cancer and behaviour.

[Is physical activity an elixir?].

PubMed

Lacza, Gyöngyvér; Radák, Zsolt

2013-05-19

Physical exercise has systemic effects, and it can regulate all the organs. The relative maximal aerobic oxygen uptake (VO2max) could have been important in the evolution of humans, since higher VO2max meant better hunting abilities for the Stone Age man. However, it appears that high level of VO2max is also important today, in the 21st century to prevent cardiovascular diseases, cancer and neurodegenerative diseases. High level of VO2max is not just preventive against a wide spectrum of diseases, but it associated with better function of many organs. Relevant data suggest that high level of VO2max is a key factor in prevention of diseases and survival even at the modern civilized world.

The MiAge Calculator: a DNA methylation-based mitotic age calculator of human tissue types.

PubMed

Youn, Ahrim; Wang, Shuang

2018-01-01

Cell division is important in human aging and cancer. The estimation of the number of cell divisions (mitotic age) of a given tissue type in individuals is of great interest as it allows not only the study of biological aging (using a new molecular aging target) but also the stratification of prospective cancer risk. Here, we introduce the MiAge Calculator, a mitotic age calculator based on a novel statistical framework, the MiAge model. MiAge is designed to quantitatively estimate mitotic age (total number of lifetime cell divisions) of a tissue using the stochastic replication errors accumulated in the epigenetic inheritance process during cell divisions. With the MiAge model, the MiAge Calculator was built using the training data of DNA methylation measures of 4,020 tumor and adjacent normal tissue samples from eight TCGA cancer types and was tested using the testing data of DNA methylation measures of 2,221 tumor and adjacent normal tissue samples of five other TCGA cancer types. We showed that within each of the thirteen cancer types studied, the estimated mitotic age is universally accelerated in tumor tissues compared to adjacent normal tissues. Across the thirteen cancer types, we showed that worse cancer survivals are associated with more accelerated mitotic age in tumor tissues. Importantly, we demonstrated the utility of mitotic age by showing that the integration of mitotic age and clinical information leads to improved survival prediction in six out of the thirteen cancer types studied. The MiAge Calculator is available at http://www.columbia.edu/∼sw2206/softwares.htm .

Cumulative incidence of cancer after solid organ transplantation.

PubMed

Hall, Erin C; Pfeiffer, Ruth M; Segev, Dorry L; Engels, Eric A

2013-06-15

Solid organ transplantation recipients have elevated cancer incidence. Estimates of absolute cancer risk after transplantation can inform prevention and screening. The Transplant Cancer Match Study links the US transplantation registry with 14 state/regional cancer registries. The authors used nonparametric competing risk methods to estimate the cumulative incidence of cancer after transplantation for 2 periods (1987-1999 and 2000-2008). For recipients from 2000 to 2008, the 5-year cumulative incidence, stratified by organ, sex, and age at transplantation, was estimated for 6 preventable or screen-detectable cancers. For comparison, the 5-year cumulative incidence was calculated for the same cancers in the general population at representative ages using Surveillance, Epidemiology, and End Results data. Among 164,156 recipients, 8520 incident cancers were identified. The absolute cancer risk was slightly higher for recipients during the period from 2000 to 2008 than during the period from 1987 to 1999 (5-year cumulative incidence: 4.4% vs. 4.2%; P = .006); this difference arose from the decreasing risk of competing events (5-year cumulative incidence of death, graft failure, or retransplantation: 26.6% vs. 31.9%; P < .001). From 2000 to 2008, the 5-year cumulative incidence of non-Hodgkin lymphoma was highest at extremes of age, especially in thoracic organ recipients (ages 0-34 years: range, 1.74%-3.28%; aged >50 years; range, 0.36%-2.22%). For recipients aged >50 years, the 5-year cumulative incidence was higher for colorectal cancer (range, 0.33%-1.94%) than for the general population at the recommended screening age (aged 50 years: range, 0.25%-0.33%). For recipients aged >50 years, the 5-year cumulative incidence was high for lung cancer among thoracic organ recipients (range, 1.16%-3.87%) and for kidney cancer among kidney recipients (range, 0.53%-0.84%). The 5-year cumulative incidence for prostate cancer and breast cancer was similar or lower in transplantation recipients than at the recommended ages of screening in the general population. Subgroups of transplantation recipients have a high absolute risk of some cancers and may benefit from targeted prevention or screening. Copyright © 2013 American Cancer Society.

Disparities of Cancer Incidence in Michigan’s American Indians: Spotlight on Breast Cancer

PubMed Central

Roen, Emily L.; Copeland, Glenn E.; Pinagtore, Noel L.; Meza, Rafael; Soliman, Amr S.

2014-01-01

Introduction In American Indians (AI), cancer is a leading cause of mortality, yet their disease burden is not fully understood due to unaddressed racial misclassification in cancer registries. This study describes cancer trends among AIs in Michigan, focusing on breast cancer, in a linked data set of Indian Health Service (IHS), tribal and state cancer registry data adjusted for misclassification. Methods AI status was based upon reported race and linkage to IHS data and tribal registries. Data with complete linkage on all incident cancer cases in Michigan from 1995-2004 was used to calculate age-standardized incidence estimates for invasive all-site and female breast cancers stratified by racial group. For female breast cancers, stage and age-specific incidence and percent distributions of early versus late-stage cancers and age of diagnosis were calculated. Results Over 50% of all AI cases were identified through IHS and/or tribal linkage. In the linked data, AIs had the lowest rates of all-sites and breast cancer. For breast cancers, AI women had a greater late-stage cancer burden and a younger mean age of diagnosis as compared to whites. Although the age-specific rate for whites was greater than for AI women in nearly all age groups, the difference in hazard ratio increased with increasing age. Conclusions Our state-specific information will help formulate effective, tailored cancer prevention strategies to this population in Michigan. The data linkages used in our study are crucial for generating accurate rates and can be effective in addressing misclassification of the AI population and formulating cancer prevention strategies for AI nationwide. PMID:24676851

Age and Cancer Risk

PubMed Central

White, Mary C.; Holman, Dawn M.; Boehm, Jennifer E.; Peipins, Lucy A.; Grossman, Melissa; Henley, S. Jane

2015-01-01

This article challenges the idea that cancer cannot be prevented among older adults by examining different aspects of the relationship between age and cancer. Although the sequential patterns of aging cannot be changed, several age-related factors that contribute to disease risk can be. For most adults, age is coincidentally associated with preventable chronic conditions, avoidable exposures, and modifiable risk behaviors that are causally associated with cancer. Midlife is a period of life when the prevalence of multiple cancer risk factors is high and incidence rates begin to increase for many types of cancer. However, current evidence suggests that for most adults, cancer does not have to be an inevitable consequence of growing older. Interventions that support healthy environments, help people manage chronic conditions, and promote healthy behaviors may help people make a healthier transition from midlife to older age and reduce the likelihood of developing cancer. Because the number of adults reaching older ages is increasing rapidly, the number of new cancer cases will also increase if current incidence rates remain unchanged. Thus, the need to translate the available research into practice to promote cancer prevention, especially for adults at midlife, has never been greater. PMID:24512933

Risks and probabilities of breast cancer: short-term versus lifetime probabilities.

PubMed Central

Bryant, H E; Brasher, P M

1994-01-01

OBJECTIVE: To calculate age-specific short-term and lifetime probabilities of breast cancer among a cohort of Canadian women. DESIGN: Double decrement life table. SETTING: Alberta. SUBJECTS: Women with first invasive breast cancers registered with the Alberta Cancer Registry between 1985 and 1987. MAIN OUTCOME MEASURES: Lifetime probability of breast cancer from birth and for women at various ages; short-term (up to 10 years) probability of breast cancer for women at various ages. RESULTS: The lifetime probability of breast cancer is 10.17% at birth and peaks at 10.34% at age 25 years, after which it decreases owing to a decline in the number of years over which breast cancer risk will be experienced. However, the probability of manifesting breast cancer in the next year increases steadily from the age of 30 onward, reaching 0.36% at 85 years. The probability of manifesting the disease within the next 10 years peaks at 2.97% at age 70 and decreases thereafter, again owing to declining probabilities of surviving the interval. CONCLUSIONS: Given that the incidence of breast cancer among Albertan women during the study period was similar to the national average, we conclude that currently more than 1 in 10 women in Canada can expect to have breast cancer at some point during their life. However, risk varies considerably over a woman's lifetime, with most risk concentrated after age 49. On the basis of the shorter-term age-specific risks that we present, the clinician can put breast cancer risk into perspective for younger women and heighten awareness among women aged 50 years or more. PMID:8287343

[Karnosfsky index as a mortality predicting factor in patients on home-based enteral nutrition].

PubMed

Puiggròs, C; Lecha, M; Rodríguez, T; Pérez-Portabella, C; Planas, M

2009-01-01

Karnofsky Index (KI) is a widely used functional scale developed for oncology patients. It has proved useful as outcome predictor with cancer and geriatric patients. Theoretically, KI could be used to predict mortality in patients with home enteral nutrition (HEN). To determine baseline KI and its 6-month evolution in HEN patients, and to assess its relation with the mortality rate. Observational and prospective study carried out during 2002 and 2003 with tube feeding neurologic and cancer patients followed during 10 months since their HEN programme inclusion. 201 patients were included, 131 (65.2%) with neurological diseases and 70 (34.8%) with neoplasm. There were not significant differences between groups in age, days with HEN and mortality rate at the end of the study period (35.1% in neurologic patients and 40% in cancer ones). 27.1% of cancer patients had resumed full oral nutrition after ten months from the beginning of the study, whereas only 10.7% of neurologic patients did (p < 0.05). In the three measurement phases (initial, past-3 and past-6 months) KI values were higher for cancer patients than for neurologic ones (p < 0.001). In both groups we didn't found statistically significant differences in KI along the three measurements. A significant relation was observed overall between initial KI values and average survival after 10 months (p < 0.001), and an inverse relation was found between the former and mortality rate (p < 0.001). KI is a useful tool to predict mortality rate in cancer and neurologic patients under HEN.

Sex differences, sexual selection, and ageing: an experimental evolution approach.

PubMed

Maklakov, Alexei A; Bonduriansky, Russell; Brooks, Robert C

2009-10-01

Life-history (LH) theory predicts that selection will optimize the trade-off between reproduction and somatic maintenance. Reproductive ageing and finite life span are direct consequences of such optimization. Sexual selection and conflict profoundly affect the reproductive strategies of the sexes and thus can play an important role in the evolution of life span and ageing. In theory, sexual selection can favor the evolution of either faster or slower ageing, but the evidence is equivocal. We used a novel selection experiment to investigate the potential of sexual selection to influence the adaptive evolution of age-specific LH traits. We selected replicate populations of the seed beetle Callosobruchus maculatus for age at reproduction ("Young" and "Old") either with or without sexual selection. We found that LH selection resulted in the evolution of age-specific reproduction and mortality but these changes were largely unaffected by sexual selection. Sexual selection depressed net reproductive performance and failed to promote adaptation. Nonetheless, the evolution of several traits differed between males and females. These data challenge the importance of current sexual selection in promoting rapid adaptation to environmental change but support the hypothesis that sex differences in LH-a historical signature of sexual selection-are key in shaping trait responses to novel selection.

Impaired immune function in children and adults with Fanconi anemia.

PubMed

Myers, Kasiani C; Sauter, Sharon; Zhang, Xue; Bleesing, Jacob J; Davies, Stella M; Wells, Susanne I; Mehta, Parinda A; Kumar, Ashish; Marmer, Daniel; Marsh, Rebecca; Brown, Darron; Butsch Kovacic, Melinda

2017-11-01

Fanconi anemia (FA) is a rare genetic disorder characterized by genome instability, bone marrow failure, and cancer predisposition. Previously, small studies have reported heterogeneous immune dysfunction in FA. We performed a detailed immunologic assessment in a large FA cohort who have not undergone bone marrow transplantation or developed malignancies. Comprehensive quantitative and functional immunologic assessment of 29 FA individuals was compared to healthy age-matched controls. Compared to non-FA persons of similar ages, FA individuals showed lower absolute total B cells (P < 0.001), lower memory B cells (P < 0.001), and decreased IgM (P < 0.001) but normal IgG. NK cells (P < 0.001) and NK cytotoxicity (P < 0.001) were decreased. CD4 + T cells were decreased (P = 0.022), while CD8 + T cell and absolute T-cell numbers were comparable. Cytotoxic T cells (P < 0.003), and antigen proliferation response to tetanus (P = 0.019) and candida (P = 0.019), were diminished in FA. Phytohemagglutinin responses and plasma cytokines were normal. Within FA subjects, adults and older children (≥10 years) exhibited higher CD8 + T cells than younger children (P = 0.004). Documented atypical infections were infrequent, although oral human papilloma virus (HPV) prevalence was higher (31% positive) in FA. Overall, these results demonstrate a high rate of significant humoral and cellular immune dysfunction. Continued longitudinal study of immune function is critical to understand evolution with age, bone marrow failure, and cancer development. © 2017 Wiley Periodicals, Inc.

The evolution of anti-angiogenic therapy for kidney cancer

PubMed Central

Lee, Chung-Han; Motzer, Robert J.

2017-01-01

Tyrosine kinase inhibitors that target pro-angiogenic pathways improve progression-free and overall survival in patients with metastatic kidney cancer and were thus tested in the adjuvant setting in studies published this past year. 2016 also saw the emergence of new inhibitors of pro-angiogenic pathways that might represent the next step in kidney cancer therapy. PMID:28100904

Death certificate only proportions should be age adjusted in studies comparing cancer survival across populations and over time.

PubMed

Brenner, Hermann; Castro, Felipe A; Eberle, Andrea; Emrich, Katharina; Holleczek, Bernd; Katalinic, Alexander; Jansen, Lina

2016-01-01

The proportion of cases notified by death certificate only (DCO) is a commonly used data quality indicator in studies comparing cancer survival across regions and over time. We aimed to assess dependence of DCO proportions on the age structure of cancer patients. Using data from a national cancer survival study in Germany, we determined age specific and overall (crude) DCO proportions for 24 common forms of cancer. We then derived overall (crude) DCO proportions expected in case of shifts of the age distribution of the cancer populations by 5 and 10 years, respectively, assuming age specific DCO proportions to remain constant. Median DCO proportions across the 24 cancers were 2.4, 3.7, 5.5, 8.5 and 23.9% in age groups 15-44, 45-54, 55-64, 65-74, and 75+, respectively. A decrease of ages by 5 and 10 years resulted in decreases of cancer specific crude DCO proportions ranging from 0.4 to 4.8 and from 0.7 to 8.6 percent units, respectively. Conversely, an increase of ages by 5 and 10 years led to increases of cancer specific crude DCO proportions ranging from 0.8 to 4.8 and from 1.8 to 9.6 percent units, respectively. These changes were of similar magnitude (but in opposite direction) as changes in crude 5-year relative survival resulting from the same shifts in age distribution. The age structure of cancer patient populations has a substantial impact on DCO proportions. DCO proportions should therefore be age adjusted in comparative studies on cancer survival across regions and over time. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Age Specific Incidence Anomaly Suggests that Cancers Originate During Development

NASA Astrophysics Data System (ADS)

Brody, James P.

The accumulation of genetic alterations causes cancers. Since this accumulation takes time, the incidence of most cancers is thought to increase exponentially with age. However, careful measurements of the age-specific incidence show that the specific incidence for many forms of cancer rises with age to a maximum, and then decreases. This decrease in the age-specific incidence with age is an anomaly. Understanding this anomaly should lead to a better understanding of how tumors develop and grow. Here we derive the shape of the age-specific incidence, showing that it should follow the shape of a Weibull distribution. Measurements indicate that the age-specific incidence for colon cancer does indeed follow a Weibull distribution. This analysis leads to the interpretation that for colon cancer two subpopulations exist in the general population: a susceptible population and an immune population. Colon tumors will only occur in the susceptible population. This analysis is consistent with the developmental origins of disease hypothesis and generalizable to many other common forms of cancer.

Diversity of ageing across the tree of life.

PubMed

Jones, Owen R; Scheuerlein, Alexander; Salguero-Gómez, Roberto; Camarda, Carlo Giovanni; Schaible, Ralf; Casper, Brenda B; Dahlgren, Johan P; Ehrlén, Johan; García, María B; Menges, Eric S; Quintana-Ascencio, Pedro F; Caswell, Hal; Baudisch, Annette; Vaupel, James W

2014-01-09

Evolution drives, and is driven by, demography. A genotype moulds its phenotype's age patterns of mortality and fertility in an environment; these two patterns in turn determine the genotype's fitness in that environment. Hence, to understand the evolution of ageing, age patterns of mortality and reproduction need to be compared for species across the tree of life. However, few studies have done so and only for a limited range of taxa. Here we contrast standardized patterns over age for 11 mammals, 12 other vertebrates, 10 invertebrates, 12 vascular plants and a green alga. Although it has been predicted that evolution should inevitably lead to increasing mortality and declining fertility with age after maturity, there is great variation among these species, including increasing, constant, decreasing, humped and bowed trajectories for both long- and short-lived species. This diversity challenges theoreticians to develop broader perspectives on the evolution of ageing and empiricists to study the demography of more species.

The expected benefit of preventive mastectomy on breast cancer incidence and mortality in BRCA mutation carriers, by age at mastectomy.

PubMed

Giannakeas, Vasily; Narod, Steven A

2018-01-01

Preventive breast surgery is offered to unaffected BRCA mutation carriers to prevent breast cancer incidence and mortality. The clinical benefit of preventive mastectomy can be measured in several ways, including extension of life expectancy (mean years of life gained) and by estimating the probability of surviving until age 80. We sought to estimate the expected benefit of a preventive mastectomy at various ages, using these indices of mortality, by simulating hypothetical cohorts of women. The age-specific annual risks of developing breast cancer were used to estimate the actuarial risk of developing breast cancer by age 80 for women with a BRCA1 or BRCA2 mutation. The probability of developing breast cancer before age 80 was then modified to include competing causes of death, including from ovarian cancer. The mortality rate from breast cancer after a diagnosis of breast cancer was set at 2% annually for the first 10 years and then 1% annually for years ten to twenty. The incidence rate and mortality rate from ovarian cancer were based on published literature. We assumed that preventive mastectomy was associated with complete protection against subsequent breast cancer. A series of simulations was conducted to evaluate the reduction in the probability of death (from all causes) until age 80, according to the age at mastectomy. The actuarial risk of developing breast cancer until age 80 was estimated to be 70.8%. The actual risk (incorporating competing risks) was 64.0%. The probability of being alive at age 80 by having a mastectomy at age 25 increased by 8.7% (from 42.7 to 51.3%). The estimated benefit declined with age at mastectomy; for surgery done at age 50 the improvement in survival to age 80 was much more modest (2.8% at age 80, from 42.7 to 45.5%). Among BRCA mutation carriers, the mortality benefit of preventive mastectomy at age 25 is substantial, but the expected benefit declines rapidly with increasing age at surgery.

Prediction of cancer incidence and mortality in Korea, 2014.

PubMed

Jung, Kyu-Won; Won, Young-Joo; Kong, Hyun-Joo; Oh, Chang-Mo; Lee, Duk Hyoung; Lee, Jin Soo

2014-04-01

We studied and reported on cancer incidence and mortality rates as projected for the year 2014 in order to estimate Korea's current cancer burden. Cancer incidence data from 1999 to 2011 were obtained from the Korea National Cancer Incidence Database, and cancer mortality data from 1993 to 2012 were acquired from Statistics Korea. Cancer incidence in 2014 was projected by fitting a linear regression model to observed age-specific cancer incidence rates against observed years, then multiplying the projected age-specific rates by the age-specific population. For cancer mortality, a similar procedure was employed, except that a Joinpoint regression model was used to determine at which year the linear trend changed significantly. A total of 265,813 new cancer cases and 74,981 cancer deaths are expected to occur in Korea in 2014. Further, the crude incidence rate per 100,000 of all sites combined will likely reach 524.7 and the age-standardized incidence rate, 338.5. Meanwhile, the crude mortality rate of all sites combined and age-standardized rate are projected to be 148.0 and 84.6, respectively. Given the rapid rise in prostate cancer cases, it is anticipated to be the fourth most frequently occurring cancer site in men for the first time. Cancer has become the most prominent public health concern in Korea, and as the population ages, the nation's cancer burden will continue to increase.

Trends in gynaecological cancers in the largest obstetrics and gynaecology hospital in China from 2003 to 2013.

PubMed

Li, XueLian; Zheng, SaiHua; Chen, ShangJie; Qin, Feng; Lau, Sandy; Chen, Qi

2015-07-01

The incidence and the trend of gynaecological cancers have been suggested to vary by ethnicity and geographical regions. Whether the incidence and type of gynaecological cancers in China is different have not been fully investigated. In this study, we reported the trend of gynaecological cancers in China. Data on 13,518 women with gynaecological cancers were collected from the largest obstetrics and gynaecology hospital in China from 2003 to 2013. Data included age at diagnosis and the annual number of women with diagnosed endometrial, ovarian, cervical cancer and other gynaecological cancers. The number of women with diagnosed gynaecological cancers increased by almost sixfold in 2013 compared to that in 2003. It was largely due to the increase of women with newly diagnosed cervical cancer. The percentage of women with endometrial and ovarian cancer within total gynaecological cancers was decreased, whilst the percentage of cervical cancer significantly increased between 2003 and 2013. The mean age of women with endometrial or ovarian cancer at diagnosis was 53 or 48 years, respectively, which was no difference over 11 years. However, the mean age of women with cervical cancer at diagnosis was significantly delayed from 42 years in 2003 to 46 years since 2011. This was also confirmed by the age-specific distribution of gynaecological cancers over 11 years. Our study found that the age onset of endometrial and ovarian cancer has not changed over 11 years. But the age onset of cervical cancer is delayed since 2011 in China.

Toward a genetics of cancer resistance

PubMed Central

Klein, George

2009-01-01

Two of three humans never get cancer. Even the majority of heavy smokers remain cancer free. Is this a matter of chance, or are there cancer-resistant genotypes? Based on the evidence discussed, it would appear that evolution has favored a limited number of relatively common resistance genes that may nip incipient cancerous foci in the bud, i.e., to stop them at their inception. It is further suggested that resistance genes may act at the level of tissue organization in a dominant fashion. PMID:19129501

Perceived control and psychological distress in women with breast cancer: a longitudinal study.

PubMed

Bárez, Milagros; Blasco, Tomas; Fernández-Castro, Jordi; Viladrich, Carme

2009-04-01

The relationship between perceived control and psychological distress in cancer patients has been widely studied, but longitudinal designs are scarce. The aim of this study was to examine whether perceived control could predict changes in the evolution of psychological distress in breast cancer patients at stages I or II. One hundred and one women were assessed on five occasions: one week after surgery, and again 1, 3, 6 and 12 months later, using the Mental Adjustment to Cancer (MAC) Scale, a Self-Efficacy Scale, the Personal Competence Scale, the Hospital Anxiety and Depression Scale (HADS), the Profile of Mood Sates (POMS), and the EORTC questionnaire of quality of life. Latent growth curve (LGC) model analysis was used to test the relationship between perceived control and psychological distress in a longitudinal, 1-year study. The results showed that perceived control increases linearly and that distress also decreases linearly. Moreover, the evolution of distress can be predicted from the initial value and the rate of change of perceived control. This close relationship between perceived control and psychological distress was found to be independent of the evolution of the physical state. These findings suggest that perceived control could be used as an early predictor of psychological adjustment to illness.

AN AGE-PERIOD-COHORT ANALYSIS OF CANCER INCIDENCE AMONG THE OLDEST OLD

PubMed Central

Hanson, Heidi A.; Smith, Ken R.; Stroup, Antoinette M.; Harrell, C. Janna

2014-01-01

Separating and understanding the effects of age, period, and cohort on major health conditions in the population over eighty-five, the oldest-old, will lead to better population projections of morbidity and mortality. We used age-period-cohort (APC) analyses to describe the simultaneous effects of age, period and cohort on cancer incidence rates in an attempt to understand the population dynamics underlying their patterns. Data from the Utah Cancer Registry (UCR), the US Census, the National Center for Health Statistics (NCHS) and the National Cancer Institute’s Surveillence Epidemiology and End Results (SEER) program were used to generate age-specific estimates of cancer incidence for ages 65–99 from 1973–2002 for Utah. Our results showed increasing cancer incidence rates up to the 85–89 age group followed by declines for ages 90–99 when not confounded by the distinct influence of period and cohort effects. We found significant period and cohort effects, suggesting the role of environmental mechanisms in cancer incidence trends between the ages of 85 and 100. PMID:25396304

Evolution and clinical impact of co-occurring genetic alterations in advanced-stage EGFR-mutant lung cancers. | Office of Cancer Genomics

Cancer.gov

A widespread approach to modern cancer therapy is to identify a single oncogenic driver gene and target its mutant-protein product (for example, EGFR-inhibitor treatment in EGFR-mutant lung cancers). However, genetically driven resistance to targeted therapy limits patient survival. Through genomic analysis of 1,122 EGFR-mutant lung cancer cell-free DNA samples and whole-exome analysis of seven longitudinally collected tumor samples from a patient with EGFR-mutant lung cancer, we identified critical co-occurring oncogenic events present in most advanced-stage EGFR-mutant lung cancers.

Arresting Evolution.

PubMed

Bull, James J; Barrick, Jeffrey E

2017-12-01

Evolution in the form of selective breeding has long been harnessed as a useful tool by humans. However, rapid evolution can also be a danger to our health and a stumbling block for biotechnology. Unwanted evolution can underlie the emergence of drug and pesticide resistance, cancer, and weeds. It makes live vaccines and engineered cells inherently unreliable and unpredictable, and therefore potentially unsafe. Yet, there are strategies that have been and can possibly be used to stop or slow many types of evolution. We review and classify existing population genetics-inspired methods for arresting evolution. Then, we discuss how genome editing techniques enable a radically new set of approaches to limit evolution. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Gastrointestinal cancer risk in patients with a family history of gastrointestinal cancer.

PubMed

Chung, Joo Won; Park, Jae Jun; Lim, Yun Jeong; Lee, Jun; Kim, Sun Moon; Han, Joung Ho; Jeon, Seong Ran; Lee, Hong Sub; Kim, Yong Sung; Song, Si Young

2018-06-25

This study was performed to evaluate the relationship between family history of gastrointestinal (GI) cancers and incidence of any GI cancer in the Korean population. Between January 2015 and July 2016, 711 GI cancer patients and 849 controls in 16 hospitals in Korea were enrolled. Personal medical histories, life styles, and family history of GI cancers were collected via questionnaire. There was a significant difference in the incidence of family history of GI cancer between GI cancer patients and controls (p=0.002). Patients with family history of GI cancer tended to be diagnosed as GI cancer at younger age than those without family history (p=0.016). The family members of GI cancer patients who were diagnosed before 50 years of age were more frequently diagnosed as GI cancer before the age of 50 years (p=0.017). After adjusting for major confounding factors, age (adjusted odds ratio [AOR] 1.065, 95% confidence interval [CI]; 1.053-1.076), male gender (AOR 2.270, 95% CI; 1.618-3.184), smoking (AOR 1.570, 95% CI; 1.130-2.182), and sibling's history of GI cancer (AOR 1.973, 95% CI; 1.246-3.126) remained independently associated with GI cancers. GI cancer patients tended to have a first relative with a history of concordant GI cancer. Personal factors (old age and male) and lifestyle (smoking) contribute to the development of GI cancer, independently. Individuals with high risk for GI cancers may be advised to undergo screening at an earlier age.

Birth weight, childhood body mass index, and height in relation to mammographic density and breast cancer: a register-based cohort study.

PubMed

Andersen, Zorana J; Baker, Jennifer L; Bihrmann, Kristine; Vejborg, Ilse; Sørensen, Thorkild I A; Lynge, Elsebeth

2014-01-20

High breast density, a strong predictor of breast cancer may be determined early in life. Childhood anthropometric factors have been related to breast cancer and breast density, but rarely simultaneously. We examined whether mammographic density (MD) mediates an association of birth weight, childhood body mass index (BMI), and height with the risk of breast cancer. 13,572 women (50 to 69 years) in the Copenhagen mammography screening program (1991 through 2001) with childhood anthropometric measurements in the Copenhagen School Health Records Register were followed for breast cancer until 2010. With logistic and Cox regression models, we investigated associations among birth weight, height, and BMI at ages 7 to 13 years with MD (mixed/dense or fatty) and breast cancer, respectively. 8,194 (60.4%) women had mixed/dense breasts, and 716 (5.3%) developed breast cancer. Childhood BMI was significantly inversely related to having mixed/dense breasts at all ages, with odds ratios (95% confidence intervals) ranging from 0.69 (0.66 to 0.72) at age 7 to 0.56 (0.53 to 0.58) at age 13, per one-unit increase in z-score. No statistically significant associations were detected between birth weight and MD, height and MD, or birth weight and breast cancer risk. BMI was inversely associated with breast cancer, with hazard ratios of 0.91 (0.83 to 0.99) at age 7 and 0.92 (0.84 to 1.00) at age 13, whereas height was positively associated with breast cancer risk (age 7, 1.06 (0.98 to 1.14) and age 13, 1.08 (1.00 to 1.16)). After additional adjustment for MD, associations of BMI with breast cancer diminished (age 7, 0.97 (0.88 to 1.06) and age 13, 1.01 (0.93 to 1.11)), but remained with height (age 7, 1.06 (0.99 to 1.15) and age 13, 1.09 (1.01 to 1.17)). Among women 50 years and older, childhood body fatness was inversely associated with the breast cancer risk, possibly via a mechanism mediated by MD, at least partially. Childhood tallness was positively associated with breast cancer risk, seemingly via a pathway independent of MD. Birth weight was not associated with MD or breast cancer in this age group.

Age-specific nonpersistence of endocrine therapy in postmenopausal patients diagnosed with hormone receptor-positive breast cancer: a TEAM study analysis.

PubMed

van de Water, Willemien; Bastiaannet, Esther; Hille, Elysée T M; Meershoek-Klein Kranenbarg, Elma M; Putter, Hein; Seynaeve, Caroline M; Paridaens, Robert; de Craen, Anton J M; Westendorp, Rudi G J; Liefers, Gerrit-Jan; van de Velde, Cornelis J H

2012-01-01

Early discontinuation of adjuvant endocrine therapy may affect the outcome of treatment in breast cancer patients. The aim of this study was to assess age-specific persistence and age-specific survival outcome based on persistence status. Patients enrolled in the Tamoxifen Exemestane Adjuvant Multinational trial were included. Nonpersistence was defined as discontinuing the assigned endocrine treatment within 1 year of follow-up because of adverse events, intercurrent illness, patient refusal, or other reasons. Endpoints were the breast cancer-specific and overall survival times. Analyses were stratified by age at diagnosis (<65 years, 65-74 years, ≥75 years). Overall, 3,142 postmenopausal breast cancer patients were included: 1,682 were aged <65 years, 951 were aged 65-74 years, and 509 were aged ≥75 years. Older age was associated with a higher proportion of nonpersistence within 1 year of follow-up. In patients aged <65 years, nonpersistent patients had lower breast cancer-specific and overall survival probabilities. In patients aged 65-74 years and patients aged ≥75 years, the survival times of persistent and nonpersistent patients were similar. Nonpersistence within 1 year of follow-up was associated with lower breast cancer-specific and overall survival probabilities in patients aged <65 years, but it was not associated with survival outcomes in patients aged 65-74 years or in patients aged ≥75 years. These results suggest that extrapolation of outcomes from a young to an elderly breast cancer population may be insufficient and urge age-specific breast cancer studies.

Capturing tumor heterogeneity and clonal evolution in solid cancers using circulating tumor DNA analysis.

PubMed

Perdigones, Nieves; Murtaza, Muhammed

2017-06-01

Circulating tumor DNA analysis has emerged as a potential noninvasive alternative to tissue biopsies for tumor genotyping in patients with metastatic cancer. This is particularly attractive in cases where tissue biopsies are contraindicated or repeat genotyping after progression on treatment is required. However, tissue and plasma analysis results are not always concordant and clinical interpretation of discordant results is not completely understood. Discordant results could arise due to analytical limits of assays used for tumor and plasma DNA analysis or due to low overall contribution of tumor-specific DNA in plasma. Once these factors are ruled out, tissue-plasma concordance and quantitative levels of somatic mutations in plasma can capture tumor heterogeneity. During longitudinal follow-up of patients, this feature can be leveraged to track subclonal evolution and to guide combination or sequential adaptive treatment. Here, we summarize recent results evaluating the opportunities and limitations of circulating tumor DNA analysis in the context of tumor heterogeneity and subclonal evolution in patients with advanced cancers. Copyright © 2017 Elsevier Inc. All rights reserved.

Clonal evolution in breast cancer revealed by single nucleus genome sequencing.

PubMed

Wang, Yong; Waters, Jill; Leung, Marco L; Unruh, Anna; Roh, Whijae; Shi, Xiuqing; Chen, Ken; Scheet, Paul; Vattathil, Selina; Liang, Han; Multani, Asha; Zhang, Hong; Zhao, Rui; Michor, Franziska; Meric-Bernstam, Funda; Navin, Nicholas E

2014-08-14

Sequencing studies of breast tumour cohorts have identified many prevalent mutations, but provide limited insight into the genomic diversity within tumours. Here we developed a whole-genome and exome single cell sequencing approach called nuc-seq that uses G2/M nuclei to achieve 91% mean coverage breadth. We applied this method to sequence single normal and tumour nuclei from an oestrogen-receptor-positive (ER(+)) breast cancer and a triple-negative ductal carcinoma. In parallel, we performed single nuclei copy number profiling. Our data show that aneuploid rearrangements occurred early in tumour evolution and remained highly stable as the tumour masses clonally expanded. In contrast, point mutations evolved gradually, generating extensive clonal diversity. Using targeted single-molecule sequencing, many of the diverse mutations were shown to occur at low frequencies (<10%) in the tumour mass. Using mathematical modelling we found that the triple-negative tumour cells had an increased mutation rate (13.3×), whereas the ER(+) tumour cells did not. These findings have important implications for the diagnosis, therapeutic treatment and evolution of chemoresistance in breast cancer.

Recurrent chromosomal gains and heterogeneous driver mutations characterise papillary renal cancer evolution

PubMed Central

Kovac, Michal; Navas, Carolina; Horswell, Stuart; Salm, Max; Bardella, Chiara; Rowan, Andrew; Stares, Mark; Castro-Giner, Francesc; Fisher, Rosalie; de Bruin, Elza C.; Kovacova, Monika; Gorman, Maggie; Makino, Seiko; Williams, Jennet; Jaeger, Emma; Jones, Angela; Howarth, Kimberley; Larkin, James; Pickering, Lisa; Gore, Martin; Nicol, David L.; Hazell, Steven; Stamp, Gordon; O’Brien, Tim; Challacombe, Ben; Matthews, Nik; Phillimore, Benjamin; Begum, Sharmin; Rabinowitz, Adam; Varela, Ignacio; Chandra, Ashish; Horsfield, Catherine; Polson, Alexander; Tran, Maxine; Bhatt, Rupesh; Terracciano, Luigi; Eppenberger-Castori, Serenella; Protheroe, Andrew; Maher, Eamonn; El Bahrawy, Mona; Fleming, Stewart; Ratcliffe, Peter; Heinimann, Karl; Swanton, Charles; Tomlinson, Ian

2015-01-01

Papillary renal cell carcinoma (pRCC) is an important subtype of kidney cancer with a problematic pathological classification and highly variable clinical behaviour. Here we sequence the genomes or exomes of 31 pRCCs, and in four tumours, multi-region sequencing is undertaken. We identify BAP1, SETD2, ARID2 and Nrf2 pathway genes (KEAP1, NHE2L2 and CUL3) as probable drivers, together with at least eight other possible drivers. However, only ~10% of tumours harbour detectable pathogenic changes in any one driver gene, and where present, the mutations are often predicted to be present within cancer sub-clones. We specifically detect parallel evolution of multiple SETD2 mutations within different sub-regions of the same tumour. By contrast, large copy number gains of chromosomes 7, 12, 16 and 17 are usually early, monoclonal changes in pRCC evolution. The predominance of large copy number variants as the major drivers for pRCC highlights an unusual mode of tumorigenesis that may challenge precision medicine approaches. PMID:25790038

Diastolic Dysfunction Following Anthracycline-Based Chemotherapy in Breast Cancer Patients: Incidence and Predictors

PubMed Central

González, Iria; Del Castillo, Silvia; Muñiz, Javier; Morales, Luis J.; Moreno, Fernando; Jiménez, Rosa; Cristóbal, Carmen; Graupner, Catherine; Talavera, Pedro; Curcio, Alejandro; Martínez, Paula; Guerra, Juan A.; Alonso, Joaquín J.

2015-01-01

Introduction. Cardiotoxicity represents a major limitation for the use of anthracyclines or trastuzumab in breast cancer patients. Data from longitudinal studies of diastolic dysfunction (DD) in this group of patients are scarce. The objective of the present study was to assess the incidence, evolution, and predictors of DD in patients with breast cancer treated with anthracyclines. Methods. This analytical, observational cohort study comprised 100 consecutive patients receiving anthracycline-based chemotherapy (CHT) for breast cancer. All patients underwent clinical evaluation, echocardiogram, and measurement of cardiac biomarkers at baseline, end of anthracycline-based CHT, and at 3 months and 9 months after anthracycline-based CHT was completed. Fifteen patients receiving trastuzumab were followed with two additional visits at 6 and 12 months after the last dose of anthracycline-based CHT. A multivariate analysis was performed to find variables related to the development of DD. Fifteen of the 100 patients had baseline DD and were excluded from this analysis. Results. At the end of follow-up (median: 12 months, interquartile range: 11.1–12.8), 49 patients (57.6%) developed DD. DD was persistent in 36 (73%) but reversible in the remaining 13 patients (27%). Four patients developed cardiotoxicity (three patients had left ventricular systolic dysfunction and one suffered a sudden cardiac death). None of the patients with normal diastolic function developed systolic dysfunction during follow-up. In the logistic regression model, body mass index (BMI) and age were independently related to the development of DD, with the following odds ratio values: BMI: 1.19 (95% confidence interval [CI]: 1.04–1.36), and age: 1.12 (95% CI: 1.03–1.19). Neither cardiac biomarkers nor remaining clinical variables were predictors of DD. Conclusion. Development of diastolic dysfunction after treatment with anthracycline or anthracycline- plus trastuzumab chemotherapy is common. BMI and age were independently associated with DD following anthracycline chemotherapy. Implications for Practice: This study characterizes the incidence of diastolic dysfunction in a cohort of patients undergoing anthracycline treatment. The incidence of diastolic dysfunction during follow-up was 57% and persisted at the last follow-up visit in 73% of patients. Age and body mass index were found to be independent predictors of anthracycline-related diastolic dysfunction. These findings may help identify patients at higher risk for developing a clinically relevant anthracycline cardiotoxicity from those at lower risk and to differentiate monitoring programs for breast cancer patients according to their risk. PMID:26185196

Clinical Features, Non-Infectious Manifestations and Survival Analysis of 161 Children with Primary Immunodeficiency in Mexico: A Single Center Experience Over two Decades.

PubMed

Lugo Reyes, Saul Oswaldo; Ramirez-Vazquez, Guadalupe; Cruz Hernández, Alonso; Medina-Torres, Edgar A; Ramirez-Lopez, Ana Belen; España-Cabrera, Corín; Hernandez-Lopez, Citlali A; Yamazaki-Nakashimada, Marco A; Espinosa-Rosales, Francisco J; Espinosa-Padilla, Sara E; Murata, Chiharu

2016-01-01

The hallmark of Primary immunodeficiencies (PID) is unusual infection, although other immunological non-infectious manifestations such as autoimmunity, allergy and cancer are often present. Most published reports focus on one disease or defect groups, so that a global prevalence of non-infectious manifestations of PID is hard to find. We aimed to describe the clinical features of our pediatric patients with PID, as well as the frequency and evolution of allergy, cancer and autoimmunity. We reviewed all the available charts of patients being followed for PID from 1991 to the spring of 2012 at the National Institute of Pediatrics, Mexico City, to describe their demographic, clinical and laboratory features. Their diagnoses were established by pediatric immunologists in accordance to ESID criteria, including routine immunological workup and specialized diagnostic assays. We divided patients by decade of diagnosis to analyze their survival curves. There were 168 charts available, from which we excluded one duplicate and six equivocal diagnoses. We studied the charts of 161 PID patients (68% male, 86% alive), mostly from the center of the country, with a positive family history in 27% and known consanguinity in 11%. Eighty percent of the patients were diagnosed during the last decade. Current median age was 124 months; median age at onset of infections, 12 months; median age at diagnosis, 52 months; median age at death, 67.5 months. Severe infection and bleeding were the cause of 22 deaths. Eighty-six percent of all patients had at least one infection, while non-infectious manifestations had a global prevalence of 36%, namely: autoimmunity 19%, allergies 17%, and cancer 2.4%. Survival curves were not significantly different when compared by decade of diagnosis. Compared to other registry reports, we found a lower prevalence of antibody defects, and of associated allergy and cancer. We could only locate two isolated IgA deficiencies and four cases of cancer among our PID patients. Although antibody defects are the most prevalent group (30%), the distribution we found is similar to that reported in Iran, Kuwait, Egypt and Taiwan, with a close 27% share for phagocyte defects, and 26% for the formerly called "well-defined" syndromes. Of note, autoimmune and inflammatory complications are high among our patients with chronic granulomatous disease, as has been reported in both the United States and Japan, but not in Europe.

Stage-specific incidence rates and trends of prostate cancer by age, race, and ethnicity, United States, 2004-2014.

PubMed

Li, Jun; Siegel, David A; King, Jessica B

2018-05-01

Current literature shows different findings on the contemporary trends of distant-stage prostate cancer incidence, in part, due to low study population coverage and wide age groupings. This study aimed to examine the stage-specific incidence rates and trends of prostate cancer by age (5-year grouping), race, and ethnicity using nationwide cancer registry data. Data on prostate cancer cases came from the 2004-2014 United States Cancer Statistics data set. We calculated stage-specific incidence and 95% confidence intervals by age (5-year age grouping), race, and ethnicity. To measure the changes in rates over time, we calculated annual percentage change (APC). We identified 2,137,054 incident prostate cancers diagnosed during 2004-2014, with an age-adjusted incidence rate of 453.8 per 100,000. Distant-stage prostate cancer incidence significantly decreased during 2004-2010 (APC = -1.2) and increased during 2010-2014 (APC = 3.3). Significant increases in distant prostate cancer incidence also occurred in men aged older than or equal to 50 years except men aged 65-74 and older than or equal to 85 years, in men with white race (APC = 3.9), and non-Hispanic ethnicity (APC = 3.5). Using data representing over 99% of U.S. population, we found that incidence rates of distant-stage prostate cancer significantly increased during 2010-2014 among men in certain ages, in white, and with non-Hispanic ethnicity. Published by Elsevier Inc.

LONG-TERM MECHANICAL CIRCULATORY SUPPORT (DESTINATION THERAPY): ON TRACK TO COMPETE WITH HEART TRANSPLANTATIO?

PubMed Central

Kirklin, James K.; Naftel, David C.; Pagani, Francis D.; Kormos, Robert L.; Stevenson, Lynne; Miller, Marissa; Young, James B.

2012-01-01

Objective(s) Average two-year survival following cardiac transplantation is approximately 80%. The evolution and subsequent approval of larger pulsatile and, more recently, continuous flow mechanical circulatory support (MCS) technology for destination therapy (DT) offers the potential for triage of some patients awaiting cardiac transplantation to DT. Methods The National Heart, Lung and Blood Institute Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) is a national multi-institutional study of chronic mechanical circulatory support. Between June 2006 and December 2011, 127 pulsatile and 1160 continuous flow pumps (24% of total primary LVADs) carried an initial strategy of DT therapy. Results By multivariable analysis, risk factors (p<0.05) for mortality following DT included older age, larger body mass index, history of cancer, history of cardiac surgery, INTERMACS level I (cardiogenic shock), dialysis, increased BUN, use of a pulsatile flow device and use of a RVAD. Among continuous flow LVAD patients who were not in cardiogenic shock, a particularly favorable survival was associated with no cancer, patients not in cardiogenic shock, and BUN < 50, resulting in one and two year survival of 88 and 80%. Conclusions 1) Evolution from pulsatile to continuous flow technology has dramatically improved one and two year survival; 2) Destination Therapy is not appropriate for patients with rapid hemodynamic deterioration; or severe right ventricular failure 4) Important subsets of continuous flow DT patients now enjoy survival which is competitive with heart transplantation out to about two years. PMID:22795459

Characterizing biased cancer-related cognitive processing: relationships with BRCA1/2 genetic mutation status, personal cancer history, age, and prophylactic surgery.

PubMed

Carpenter, Kristen M; Eisenberg, Stacy; Weltfreid, Sharone; Low, Carissa A; Beran, Tammy; Stanton, Annette L

2014-09-01

This study evaluated associations of cancer-related cognitive processing with BRCA1/2 mutation carrier status, personal cancer history, age, and election of prophylactic surgery in women at high risk for breast cancer. In a 2 (BRCA1/2 mutation carrier status) × 2 (personal cancer history) matched-control design, with age as an additional predictor, participants (N = 115) completed a computerized cancer Stroop task. Dependent variables were response latency to cancer-related stimuli (reaction time [RT]) and cancer-related cognitive interference (cancer RT minus neutral RT). RT and interference were tested as predictors of prophylactic surgery in the subsequent four years. RT for cancer-related words was significantly slower than other word groups, indicating biased processing specific to cancer-related stimuli. Participants with a cancer history evidenced longer RT to cancer-related words than those without a history; moreover, a significant Cancer History × Age interaction indicated that, among participants with a cancer history, the typical advantage associated with younger age on Stroop tasks was absent. BRCA mutation carriers demonstrated more cancer-related cognitive interference than noncarriers. Again, the typical Stroop age advantage was absent among carriers. Exploratory analyses indicated that BRCA+ status and greater cognitive interference predicted greater likelihood of undergoing prophylactic surgery. Post hoc tests suggest that cancer-related distress does not account for these relationships. In the genetic testing context, younger women with a personal cancer history or who are BRCA1/2 mutation carriers might be particularly vulnerable to biases in cancer-related cognitive processing. Biased processing was associated marginally with greater likelihood of prophylactic surgery. (PsycINFO Database Record (c) 2014 APA, all rights reserved).

Oxidative stress in cancer associated fibroblasts drives tumor-stroma co-evolution: A new paradigm for understanding tumor metabolism, the field effect and genomic instability in cancer cells.

PubMed

Martinez-Outschoorn, Ubaldo E; Balliet, Renee M; Rivadeneira, Dayana B; Chiavarina, Barbara; Pavlides, Stephanos; Wang, Chenguang; Whitaker-Menezes, Diana; Daumer, Kristin M; Lin, Zhao; Witkiewicz, Agnieszka K; Flomenberg, Neal; Howell, Anthony; Pestell, Richard G; Knudsen, Erik S; Sotgia, Federica; Lisanti, Michael P

2010-08-15

Loss of stromal fibroblast caveolin-1 (Cav-1) is a powerful single independent predictor of poor prognosis in human breast cancer patients, and is associated with early tumor recurrence, lymph node metastasis and tamoxifen-resistance. We developed a novel co-culture system to understand the mechanism(s) by which a loss of stromal fibroblast Cav-1 induces a "lethal tumor micro-environment." Here, we propose a new paradigm to explain the powerful prognostic value of stromal Cav-1. In this model, cancer cells induce oxidative stress in cancer-associated fibroblasts, which then acts as a "metabolic" and "mutagenic" motor to drive tumor-stroma co-evolution, DNA damage and aneuploidy in cancer cells. More specifically, we show that an acute loss of Cav-1 expression leads to mitochondrial dysfunction, oxidative stress and aerobic glycolysis in cancer associated fibroblasts. Also, we propose that defective mitochondria are removed from cancer-associated fibroblasts by autophagy/mitophagy that is induced by oxidative stress. As a consequence, cancer associated fibroblasts provide nutrients (such as lactate) to stimulate mitochondrial biogenesis and oxidative metabolism in adjacent cancer cells (the "Reverse Warburg Effect"). We provide evidence that oxidative stress in cancer-associated fibroblasts is sufficient to induce genomic instability in adjacent cancer cells, via a bystander effect, potentially increasing their aggressive behavior. Finally, we directly demonstrate that nitric oxide (NO) over-production, secondary to Cav-1 loss, is the root cause for mitochondrial dysfunction in cancer associated fibroblasts. In support of this notion, treatment with anti-oxidants (such as N-acetyl-cysteine, metformin and quercetin) or NO inhibitors (L-NAME) was sufficient to reverse many of the cancer-associated fibroblast phenotypes that we describe. Thus, cancer cells use "oxidative stress" in adjacent fibroblasts (i) as an "engine" to fuel their own survival via the stromal production of nutrients and (ii) to drive their own mutagenic evolution towards a more aggressive phenotype, by promoting genomic instability. We also present evidence that the "field effect" in cancer biology could also be related to the stromal production of ROS and NO species. eNOS-expressing fibroblasts have the ability to downregulate Cav-1 and induce mitochondrial dysfunction in adjacent fibroblasts that do not express eNOS. As such, the effects of stromal oxidative stress can be laterally propagated, amplified and are effectively "contagious"--spread from cell-to-cell like a virus--creating an "oncogenic/mutagenic" field promoting widespread DNA damage.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Junfeng, E-mail: chenjunfeng@fzu.edu.cn; Zou, Linchi, E-mail: zoulinchi1201@163.com; Li, Qiang

The microstructure evolution of the 7050 Al alloy treated by age-forming was studied using a designed device which can simulate the age-forming process. The grain shape, grain boundary misorientation and grain orientation evolution of 7050 Al alloy during age-forming have been quantitatively characterized by electron backscattering diffraction technique. The results show that age-forming produced abundant low-angle boundaries and elongated grains, which attributed to stress induced dislocation movement and grain boundary migration during the age-forming process. On the other side, the stress along rolling direction caused some unstable orientation grains to rotate towards the Brass and S orientations during the age-formingmore » process. Hence, the intensity of the rolling texture orientation in age-formed samples is enhanced. But this effect decays gradually with increasing aging time, since stress decreases and precipitation hardening occurs during the age-forming process. - Highlights: • Quantitative analysis of grain evolution of 7050 Al alloys during age-forming • Stress induces some grain rotation of 7050 Al alloys during age-forming. • Creep leads to elongate grain of 7050 Al alloys during age-forming. • Obtains a trend on texture evolution during age-forming applied stress.« less

Effectiveness of cervical screening after age 60 years according to screening history: Nationwide cohort study in Sweden.

PubMed

Wang, Jiangrong; Andrae, Bengt; Sundström, Karin; Ploner, Alexander; Ström, Peter; Elfström, K Miriam; Dillner, Joakim; Sparén, Pär

2017-10-01

The relatively high incidence of cervical cancer in women at older ages is a continuing concern in countries with long-established cervical screening. Controversy remains on when and how to cease screening. Existing population-based studies on the effectiveness of cervical screening at older ages have not considered women's screening history. We performed a nationwide cohort study to investigate the incidence of cervical cancer after age 60 years and its association with cervical screening at age 61-65, stratified by screening history at age 51-60. Using the Total Population Register, we identified 569,132 women born between 1 January 1919 and 31 December 1945, resident in Sweden since age 51. Women's cytological screening records, cervical cancer occurrence, and FIGO stage (for those diagnosed with cancer) were retrieved from national registers and medical charts. We calculated the cumulative incidence of cervical cancer from age 61 to age 80 using a survival function considering competing risk, and estimated the hazard ratio (HR) of cervical cancer in relation to screening status at age 61-65 from Cox models, adjusted for birth cohort and level of education, conditioning on women's screening history in their 50s. In women unscreened in their 50s, the cumulative incidence up to age 80 was 5.0 per 1,000 women, and screening at age 61-65 was associated with a lower risk for cervical cancer (HR = 0.42, 95% CI 0.24-0.72), corresponding to a decrease of 3.3 cancer cases per 1,000 women. A higher cumulative incidence and similarly statistically significant risk decrease was seen for women with abnormal smears in their 50s. In women adequately or inadequately screened with only normal results between age 51 and age 60, the cumulative incidence of cervical cancer from age 61 to 80 was 1.6 and 2.5 per 1,000 women, respectively, and further screening at age 61-65 was not associated with statistically significant decreases of cervical cancer risk up to age 80, but with fewer cancer cases of advanced stages at age 61-65. Adjustment for potential lifestyle confounders was limited. In this study, cervical screening with cytology at age 61-65 was associated with a statistically significant reduction of subsequent cervical cancer risk for women who were unscreened, or screened with abnormalities, in their 50s. In women screened with normal results in their 50s, the risk for future cancer was not sizeable, and the risk reduction associated with continued screening appeared limited. These findings should inform the current debate regarding age and criteria to discontinue cervical screening.

Age-specific incidence of all neoplasms after colorectal cancer.

PubMed

Levi, Fabio; Randimbison, Lalao; Blanc-Moya, Rafael; La Vecchia, Carlo

2014-10-01

Patients diagnosed with a specific neoplasm tend to have a subsequent excess risk of the same neoplasm. The age incidence of a second neoplasm at the same site is approximately constant with age, and consequently the relative risk is greater at younger age. It is unclear whether such a line of reasoning can be extended from a specific neoplasm to the incidence of all neoplasms in subjects diagnosed with a defined neoplasm. We considered the age-specific incidence of all non-hormone-related epithelial neoplasms after a first primary colorectal cancer (n = 9542) in the Vaud Cancer Registry data set. In subjects with a previous colorectal cancer, the incidence rate of all other epithelial non-hormone-related cancers was stable around 800 per 100,000 between age 30 and 60 years, and rose only about twofold to reach 1685 at age 70 to 79 years and 1826 per 100,000 at age 80 years or older. After excluding synchronous cancers, the rise was only about 1.5-fold, that is, from about 700 to 1000. In the general population, the incidence rate of all epithelial non-hormone-related cancers was 29 per 100,000 at age 30 to 39 years, and rose 30-fold to 883 per 100,000 at age 70 to 79 years. Excluding colorectal cancers, the rise of all non-hormone-related cancers was from 360 per 100,000 at age 40 to 49 years to 940 at age 70 to 79 years after colorectal cancer, and from 90 to 636 per 100,000 in the general population (i.e., 2.6- vs. 7.1-fold). The rise of incidence with age of all epithelial non-hormone-related second cancers after colorectal cancer is much smaller than in the general population. This can possibly be related to the occurrence of a single mutational event in a population of susceptible individuals, although alternative models are plausible within the complexity of the process of carcinogenesis. Copyright © 2014 Elsevier Inc. All rights reserved.

Dietary consumption of advanced glycation end products and pancreatic cancer in the prospective NIH-AARP Diet and Health Study.

PubMed

Jiao, Li; Stolzenberg-Solomon, Rachael; Zimmerman, Thea Palmer; Duan, Zhigang; Chen, Liang; Kahle, Lisa; Risch, Adam; Subar, Amy F; Cross, Amanda J; Hollenbeck, Albert; Vlassara, Helen; Striker, Gary; Sinha, Rashmi

2015-01-01

Advanced glycation end products (AGEs) are a heterogeneous group of compounds present in uncooked foods as well as in foods cooked at high temperatures. AGEs have been associated with insulin resistance, oxidative stress, and chronic inflammation in patients with diabetes. Dietary AGEs are an important contributor to the AGE pool in the body. N(ϵ)-(carboxymethyl)lysine (CML) AGE is one of the major biologically and chemically well-characterized AGE markers. The consumption of red meat, which is CML-AGE rich, has been positively associated with pancreatic cancer in men. With the use of a published food CML-AGE database, we estimated the consumption of CML AGE in the prospective NIH-AARP Diet and Health Study and evaluated the association between CML-AGE consumption and pancreatic cancer and the mediating effect of CML AGE on the association between red meat consumption and pancreatic cancer. Multivariate Cox proportional hazard regression models were used to estimate HRs and 95% CIs for pancreatic cancer. During an average of 10.5 y of follow-up, we identified 2193 pancreatic cancer cases (1407 men and 786 women) from 528,251 subjects. With the comparison of subjects in the fifth and the first quintiles of CML-AGE consumption, we observed increased pancreatic cancer risk in men (HR: 1.43; 95% CI: 1.06, 1.93, P-trend = 0.003) but not women (HR: 1.14; 95% CI: 0.76, 1.72, P-trend = 0.42). Men in the highest quintile of red meat consumption had higher risk of pancreatic cancer (HR: 1.35; 95% CI: 1.07, 1.70), which attenuated after adjustment for CML-AGE consumption (HR: 1.20; 95% CI: 0.95, 1.53). Dietary CML-AGE consumption was associated with modestly increased risk of pancreatic cancer in men and may partially explain the positive association between red meat and pancreatic cancer. © 2015 American Society for Nutrition.

Association of paternal age at birth and the risk of breast cancer in offspring: a case control study

PubMed Central

Choi, Ji-Yeob; Lee, Kyoung-Mu; Park, Sue Kyung; Noh, Dong-Young; Ahn, Sei-Hyun; Yoo, Keun-Young; Kang, Daehee

2005-01-01

Background Older paternal age may increase the germ cell mutation rate in the offspring. Maternal age may also mediate in utero exposure to pregnancy hormones in the offspring. To evaluate the association between paternal and maternal age at birth with the risk of breast cancer in female offspring, a case-control study was conducted in Korea. Methods Histologically confirmed breast cancer cases (n = 1,011) and controls (n = 1,011) with no present or previous history of cancer, matched on year of birth and menopausal status, were selected from several teaching hospitals and community in Seoul during 1995–2003. Information on paternal and maternal ages and other factors was collected by interviewed questionnaire. Odds ratio (OR) and 95% confidence interval (95% CI) were estimated by unconditional logistic regression model adjusting for family history of breast cancer in 1st or 2nd degree relatives, and lifetime estrogen exposure duration. Results The risk of breast cancer significantly increased as the paternal age increased (p for trend = 0.025). The association was stronger after controlling for maternal age; women whose fathers were aged ≥40 years at their birth had 1.6-fold increased risk of breast cancer compared with fathers aged <30 years. This association was profound in breast cancer cases in premenopausal women (OR = 1.9, 95% CI = 1.12–3.26, for paternal aged ≥40 vs. <30) (p for trend = 0.031). Although the risk of breast cancer increased as maternal age increased up to the intermediate, and then reduced; the risks in women whose mother were aged 25–29, 30–34, and ≥35 yrs at birth compared to women whose mothers were aged <25 years, were 1.2, 1.4, and 0.8, respectively, the trend was not significant (p for trend = 0.998). Conclusion These findings suggest that older paternal age increases the risk of breast cancer in their female offspring. PMID:16259637

Association of paternal age at birth and the risk of breast cancer in offspring: a case control study.

PubMed

Choi, Ji-Yeob; Lee, Kyoung-Mu; Park, Sue Kyung; Noh, Dong-Young; Ahn, Sei-Hyun; Yoo, Keun-Young; Kang, Daehee

2005-10-31

Older paternal age may increase the germ cell mutation rate in the offspring. Maternal age may also mediate in utero exposure to pregnancy hormones in the offspring. To evaluate the association between paternal and maternal age at birth with the risk of breast cancer in female offspring, a case-control study was conducted in Korea. Histologically confirmed breast cancer cases (n = 1,011) and controls (n = 1,011) with no present or previous history of cancer, matched on year of birth and menopausal status, were selected from several teaching hospitals and community in Seoul during 1995-2003. Information on paternal and maternal ages and other factors was collected by interviewed questionnaire. Odds ratio (OR) and 95% confidence interval (95% CI) were estimated by unconditional logistic regression model adjusting for family history of breast cancer in 1st or 2nd degree relatives, and lifetime estrogen exposure duration. The risk of breast cancer significantly increased as the paternal age increased (p for trend = 0.025). The association was stronger after controlling for maternal age; women whose fathers were aged >or=40 years at their birth had 1.6-fold increased risk of breast cancer compared with fathers aged <30 years. This association was profound in breast cancer cases in premenopausal women (OR = 1.9, 95% CI = 1.12-3.26, for paternal aged >or=40 vs. <30) (p for trend = 0.031). Although the risk of breast cancer increased as maternal age increased up to the intermediate, and then reduced; the risks in women whose mother were aged 25-29, 30-34, and >or=35 yrs at birth compared to women whose mothers were aged <25 years, were 1.2, 1.4, and 0.8, respectively, the trend was not significant (p for trend = 0.998). These findings suggest that older paternal age increases the risk of breast cancer in their female offspring.

Cancer stem cells: impact, heterogeneity, and uncertainty

PubMed Central

Magee, Jeffrey A.; Piskounova, Elena; Morrison, Sean J.

2015-01-01

The differentiation of tumorigenic cancer stem cells into non-tumorigenic cancer cells confers heterogeneity to some cancers beyond that explained by clonal evolution or environmental differences. In such cancers, functional differences between tumorigenic and non-tumorigenic cells influence response to therapy and prognosis. However, it remains uncertain whether the model applies to many, or few, cancers due to questions about the robustness of cancer stem cell markers and the extent to which existing assays underestimate the frequency of tumorigenic cells. In cancers with rapid genetic change, reversible changes in cell states, or biological variability among patients the stem cell model may not be readily testable. PMID:22439924

Metabolic Syndrome and Breast Cancer Risk.

PubMed

Wani, Burhan; Aziz, Shiekh Aejaz; Ganaie, Mohammad Ashraf; Mir, Mohammad Hussain

2017-01-01

The study was meant to estimate the prevalence of metabolic syndrome in patients with breast cancer and to establish its role as an independent risk factor on occurrence of breast cancer. Fifty women aged between 40 and 80 years with breast cancer and fifty controls of similar age were assessed for metabolic syndrome prevalence and breast cancer risk factors, including age at menarche, reproductive status, live births, breastfeeding, and family history of breast cancer, age at diagnosis of breast cancer, body mass index, and metabolic syndrome parameters. Metabolic syndrome prevalence was found in 40.0% of breast cancer patients, and 18.0% of those in control group ( P = 0.02). An independent and positive association was seen between metabolic syndrome and breast cancer risk (odds ratio = 3.037; 95% confidence interval 1.214-7.597). Metabolic syndrome is more prevalent in breast cancer patients and is an independent risk factor for breast cancer.

Risk factors, lifetime risk, and age at onset of breast cancer.

PubMed

Fraser, G E; Shavlik, D

1997-08-01

We evaluated the relationship between exposure variables and both lifetime risk and mean age at diagnosis of breast cancer in subjects from the Adventist Health Study who developed breast cancer before the age of 91 years. Multiple decrement life-table analysis was used. This study provided data from 20,341 women followed for 6 years. In the total population, 30-year-old women with a parental history of any cancer or a maternal history of breast cancer had, respectively, 72% (P < 0.002) and 98% (P < 0.03) higher lifetime risks of breast cancer. Thirty-year-old women who had their first delivery after age 24 years or body mass indices above the 50th percentile had, respectively, 53% (P < 0.007) or 57% (P = 0.01) greater lifetime risk of breast cancer. Women who exercised infrequently had a 27% higher life-time risk (P = 0.09) and an age at diagnosis of breast cancer 6.6 years younger (P < 0.005) than other women. Standard risk factors account for substantial increases in lifetime risk of breast cancer and may be associated with differences in age at diagnosis.

Increase in incidental detection of thyroid cancer in Osaka, Japan.

PubMed

Toyoda, Yasuhiro; Tabuchi, Takahiro; Nakata, Kayo; Morishima, Toshitaka; Nakayama, Tomio; Miyashiro, Isao; Hojo, Shigeyuki; Yoshioka, Setsuko

2018-05-22

We examined age-specific and age-adjusted incidence rates of thyroid cancer according to the route of thyroid cancer detection from 1992-2012, using Osaka Cancer Registry data. The detection routes were categorized into 'symptomatic' and 'incidental detection'. Age-specific incidence rates of incidentally-detected thyroid cancer consistently increased during the study period, especially after 2001, for all sex and age groups other than childhood. The rate of symptomatic thyroid cancer did not largely differ. Age-adjusted incidence rates of symptomatic thyroid cancer were around 1.5 and 4.5 per 100,000 among men and women, respectively. The rate of incidentally-detected thyroid cancer increased from 0.1 and 0.1 per 100,000 person-years among men and women in 1992-1994 to 2.0 and 4.9, respectively in 2010-2012. Age-adjusted mortality rates among both sexes during study period leveled off. This finding suggests that the thyroid cancer incidence rate in Osaka increased with incidental detection. We need to continue careful monitoring to confirm these findings. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Breast cancer among women over 75 years: an important public health problem?

PubMed

van Schoor, Guido; Otten, Johannes D M; den Heeten, Gerard J; Holland, Roland; Broeders, Mireille J M; Verbeek, André L M

2012-06-01

Women aged >75 years are not invited for mammographic screening; if diagnosed with breast cancer, due to their anticipated short-life expectancy, they are expected to die of other causes. To describe the breast cancer health problem in women aged >75 years, we estimated breast cancer incidence in this age group and the risk of breast cancer death in patients diagnosed after 75 years of age in Nijmegen, the Netherlands. Our findings demonstrate that in this age group, 3.3% of the women will be diagnosed with breast cancer, and that one in three of these incident cases die of this disease. These patients could have benefited from continued screening.

[Cancer incidence in a Cancer Care Unit of the Mexican Social Security Institute (IMSS) in Toluca, Mexico].

PubMed

Gómez-Villanueva, Angel; Chacón Sánchez, Jesús; Santillán Arreygue, Leopoldo; Sánchez González, Yolanda; Romero-Figueroa, María del Socorro

2014-01-01

In 2000, malignant tumors were responsible for 12% of nearly 56 million deaths that occurred in the world from all causes. To determine the incidence of cancer in a Cancer Care Unit of IMSS in Toluca, Mexico. Prospective cross-sectional study; we identified the primary tumor, age, family history of cancer, comorbidities, risk factors, and ECOG in patients with newly diagnosed cancer. We identified 446 cases, 66.1% were women. The age group of age 50 to 59 had the highest number of cases (98). The most common cancers in women are breast, cervical, and ovarian cancer, and in men, testicular, prostate, and colorectal cancer. The most common cancers in both sexes were breast cancer, cervical cancer, colorectal cancer, ovarian cancer, and testicular cancer.

Advanced glycation end products promote ChREBP expression and cell proliferation in liver cancer cells by increasing reactive oxygen species.

PubMed

Chen, Hanbei; Li, Yakui; Zhu, Yemin; Wu, Lifang; Meng, Jian; Lin, Ning; Yang, Dianqiang; Li, Minle; Ding, WenJin; Tong, Xuemei; Su, Qing

2017-08-01

The aim of the study was to elucidate the mechanism by which advanced glycation end products (AGEs) promote cell proliferation in liver cancer cells.We treated liver cancer HepG2 cells with 200 mg/L AGEs or bovine serum albumin (BSA) and assayed for cell viability, cell cycle, and apoptosis. We performed real-time PCR and Western blot analysis for RNA and protein levels of carbohydrate responsive element-binding protein (ChREBP) in AGEs- or BSA-treated HepG2 cells. We analyzed the level of reactive oxygen species (ROS) in HepG2 cells treated with AGEs or BSA.We found that increased S-phase cell percentage and decreased apoptosis contributed to AGEs-induced liver cancer cell proliferation. Real-time PCR and Western blot analysis showed that AGEs stimulated RNA and protein levels of ChREBP, a transcription factor promoting glycolysis and maintaining cell proliferation in liver cancer cells. Intriguingly, the level of ROS was higher in AGEs-treated liver cancer cells. Treating liver cancer cells with antioxidant N-acetyl cystein (NAC) partly blocked AGEs-induced ChREBP expression and cell proliferation.Our results suggest that the AGEs-ROS-ChREBP pathway plays a critical role in promoting ChREBP expression and liver cancer cell proliferation.

Reproductive, lifestyle, and anthropometric risk factors for cancer in elderly women.

PubMed

Poynter, Jenny N; Inoue-Choi, Maki; Ross, Julie A; Jacobs, David R; Robien, Kimberly

2013-04-01

With an increasing elderly population, the United States will experience an increased cancer burden in the coming years. We evaluated associations between anthropometric, lifestyle, and reproductive factors and risk of breast, ovarian, and colorectal cancer in a prospective study of postmenopausal women with a focus on diagnoses occurring among very elderly women (≥75 years). For each cancer type, we estimated associations with relevant exposures in 2 age bands (<75 vs. ≥75 years of age). During 22 years of follow-up, 322 ovarian, 1,311 colon, 315 rectal, and 2,664 breast cancers occurred among 37,459 postmenopausal women (mean age at baseline 62 years, range 55-71 years). For ovarian cancer, we identified few significant associations in either age band. Colon cancer cases had a higher body mass index and were less likely to report estrogen or aspirin use than non-cases, yet these associations were consistent in both age bands. Few risk factors were identified for rectal cancer in women of 75 years of age or more. For breast cancer, notably different patterns were revealed, with alcohol consumption associated with risk in the younger group and previous hysterectomy associated with risk only in the older group. These analyses suggest some important differences in risk factors for cancer depending on the age at diagnosis. This study suggests that etiologic differences may exist in cancers occurring in the very elderly women. The ongoing demographic shift in the United States provides a strong rationale for studies evaluating cancer etiology in the elderly.

Obesity and age at diagnosis of endometrial cancer.

PubMed

Nevadunsky, Nicole S; Van Arsdale, Anne; Strickler, Howard D; Moadel, Alyson; Kaur, Gurpreet; Levitt, Joshua; Girda, Eugenia; Goldfinger, Mendel; Goldberg, Gary L; Einstein, Mark H

2014-08-01

Obesity is an established risk factor for development of endometrial cancer. We hypothesized that obesity might also be associated with an earlier age at endometrial cancer diagnosis, because mechanisms that drive the obesity-endometrial cancer association might also accelerate tumorigenesis. A retrospective chart review was conducted of all cases of endometrial cancer diagnosed from 1999 to 2009 at a large medical center in New York City. The association of body mass index (BMI) with age at endometrial cancer diagnosis, comorbidities, stage, grade, and radiation treatment was examined using analysis of variance and linear regression. Overall survival by BMI category was assessed using Kaplan-Meier method and the log-rank test. A total of 985 cases of endometrial cancer were identified. The mean age at endometrial cancer diagnosis was 67.1 years (±11.9 standard deviation) in women with a normal BMI, whereas it was 56.3 years (±10.3 standard deviation) in women with a BMI greater than 50. Age at diagnosis of endometrioid-type cancer decreased linearly with increasing BMI (y=67.89-1.86x, R=0.049, P<.001). This association persisted after multivariable adjustment (R=0.181, P<.02). A linear association between BMI and age of nonendometrioid cancers was not found (P=.12). There were no differences in overall survival by BMI category. Obesity is associated with earlier age at diagnosis of endometrioid-type endometrial cancers. Similar associations were not, however, observed with nonendometrioid cancers, consistent with different pathways of tumorigenesis. II.

Effect of micro-oxygenation and wood type on the phenolic composition and color of an aged red wine.

PubMed

Sánchez-Iglesias, Montserrat; González-Sanjosé, Ma Luisa; Pérez-Magariño, Silvia; Ortega-Heras, Miriam; González-Huerta, Carlos

2009-12-23

Many studies have recently been published focused on the effects of micro-oxygenation on the quality of wines, its application modes, and doses, etc. However, there are still few scientific papers on how previously micro-oxygenated wines perform during storage or barrel aging. This study focused on the evolution of the phenolic composition, especially of anthocyanins, and color, together with astringency and tannins, during micro-oxygenation before barrel aging. In addition, to evaluate whether wine evolution during aging depends on barrel type, wines were aged in four different oak barrel types. Tempranillo wines, some micro-oxygenated before malolactic fermentation and others not, were aged for 12 months in American, French, Central European, and Spanish oak, following wine evolution during that period. The study was carried out for two consecutive vintages. Results showed that all wines evolved similarly; therefore, the micro-oxygenation treatment neither accelerated nor delayed the typical changes of aging. Slightly different evolutions were detected according to the barrel wood type, whether or not the wine was micro-oxygenated. The varied evolutions must therefore be associated with the differences from each oak type (structure, grain and density, composition, etc.).

Investigating the prostate specific antigen, body mass index and age relationship: is an age-BMI-adjusted PSA model clinically useful?

PubMed

Harrison, Sean; Tilling, Kate; Turner, Emma L; Lane, J Athene; Simpkin, Andrew; Davis, Michael; Donovan, Jenny; Hamdy, Freddie C; Neal, David E; Martin, Richard M

2016-12-01

Previous studies indicate a possible inverse relationship between prostate-specific antigen (PSA) and body mass index (BMI), and a positive relationship between PSA and age. We investigated the associations between age, BMI, PSA, and screen-detected prostate cancer to determine whether an age-BMI-adjusted PSA model would be clinically useful for detecting prostate cancer. Cross-sectional analysis nested within the UK ProtecT trial of treatments for localized cancer. Of 18,238 men aged 50-69 years, 9,457 men without screen-detected prostate cancer (controls) and 1,836 men with prostate cancer (cases) met inclusion criteria: no history of prostate cancer or diabetes; PSA < 10 ng/ml; BMI between 15 and 50 kg/m 2 . Multivariable linear regression models were used to investigate the relationship between log-PSA, age, and BMI in all men, controlling for prostate cancer status. In the 11,293 included men, the median PSA was 1.2 ng/ml (IQR: 0.7-2.6); mean age 61.7 years (SD 4.9); and mean BMI 26.8 kg/m 2 (SD 3.7). There were a 5.1% decrease in PSA per 5 kg/m 2 increase in BMI (95% CI 3.4-6.8) and a 13.6% increase in PSA per 5-year increase in age (95% CI 12.0-15.1). Interaction tests showed no evidence for different associations between age, BMI, and PSA in men above and below 3.0 ng/ml (all p for interaction >0.2). The age-BMI-adjusted PSA model performed as well as an age-adjusted model based on National Institute for Health and Care Excellence (NICE) guidelines at detecting prostate cancer. Age and BMI were associated with small changes in PSA. An age-BMI-adjusted PSA model is no more clinically useful for detecting prostate cancer than current NICE guidelines. Future studies looking at the effect of different variables on PSA, independent of their effect on prostate cancer, may improve the discrimination of PSA for prostate cancer.

Association of Mismatch Repair Mutation With Age at Cancer Onset in Lynch Syndrome: Implications for Stratified Surveillance Strategies.

PubMed

Ryan, Neil A J; Morris, Julie; Green, Kate; Lalloo, Fiona; Woodward, Emma R; Hill, James; Crosbie, Emma J; Evans, D Gareth

2017-12-01

Lynch syndrome is caused by dominantly inherited germline mutations that predispose individuals to colorectal, endometrial, ovarian, and other cancers through inactivation of the cellular mismatch repair system. Lynch syndrome–associated cancers are amenable to surveillance strategies that may improve survival. The age at which surveillance should start is disputed. To determine whether mutated gene and type of mutation influence age at onset of Lynch syndrome–associated cancers. A retrospective cohort study of individuals with Lynch syndrome–associated colorectal, endometrial, and/or ovarian cancers whose medical records were included in the clinical database of a large quaternary referral center for genomic medicine in the Northwest of England. Mutated gene (MLH1, MSH2, MSH6, and/or PMS2) and type of mutation (truncating, splicing, or large rearrangement). Age at cancer diagnosis. A total of 1063 individuals with proven Lynch syndrome were included, 495 male and 568 female (mean age 52 years; age range, 10-93 years [children were included in the database, but no children developed cancer]). There were 546 men and women with colorectal cancer, 162 women with endometrial cancer, and 49 women with ovarian cancer; mean follow-up was 68.2 months. Among MLH1 mutation carriers, mutations in MLH1 were associated with colorectal cancer in 249 (61%) of 409 men and women; endometrial cancer in 53 of 196 (27%) women; and ovarian cancer in 15 (8%) of 196 women. Among MSH2 mutation carriers, mutations in MSH2 (the most prevalent mutations overall) were most commonly associated with female-specific cancers: endometrial cancer in 83 (30%) of 279 women; ovarian cancer in 28 (10%) of 279 women; and colorectal cancer in 239 (50%) 479 men and women. Mutations in MSH6 were less prevalent, and MSH6 mutation carriers presented with colorectal and endometrial cancer at later ages than carriers of mutations in MSH2 or MLH1. When stratified by mutation type, women with truncating MLH1 mutations had later ages of onset of endometrial cancer than those with nontruncating mutations (median difference, 6.6 years; 95% CI, 2.7-10.4; P = .002). Carriers of truncating MLH1 mutations presented with colorectal cancer at later ages than those with other mutations, but the difference was not statistically significant. Individuals with known Lynch syndrome could be risk stratified by mutated gene and mutation type in tailored surveillance programs. Specifically, individuals with MSH6 mutations could be offered cancer surveillance from a later age. Furthermore, those with truncating MLH1 mutations could begin endometrial cancer surveillance later than those with nontruncating mutations.

Temporal evolution of age data under transient pumping conditions

NASA Astrophysics Data System (ADS)

Leray, S.; de Dreuzy, J.-R.; Aquilina, L.; Vergnaud-Ayraud, V.; Labasque, T.; Bour, O.; Le Borgne, T.

2014-04-01

While most age data derived from tracers have been analyzed in steady-state flow conditions, we determine their temporal evolution when starting a pumping. Our study is based on a model made up of a shallowly dipping aquifer overlain by a less permeable aquitard characteristic of the crystalline aquifer of Plœmeur (Brittany, France). Under a pseudo transient flow assumption (instantaneous shift between two steady-state flow fields), we solve the transport equation with a backward particle-tracking method and determine the temporal evolution of the concentrations at the pumping well of CFC-11, CFC-12, CFC-113 and SF6. Apparent ages evolve because of the modifications of the flow pattern and because of the non-linear evolution of the tracer atmospheric concentrations. To identify the respective role of these two causes, we propose two successive analyses. We first convolute residence time distributions initially arising at different times at the same sampling time. We secondly convolute one residence time distribution at various sampling times. We show that flow pattern modifications control the apparent ages evolution in the first pumping year when the residence time distribution is modified from a piston-like distribution to a much broader distribution. In the first pumping year, the apparent age evolution contains transient information that can be used to better constrain hydrogeological systems and slightly compensate for the small number of tracers. Later, the residence time distribution hardly evolves and apparent ages only evolve because of the tracer atmospheric concentrations. In this phase, apparent age time-series do not reflect any evolution in the flow pattern.

Assessing Breast Cancer Risk Estimates Based on the Gail Model and Its Predictors in Qatari Women.

PubMed

Bener, Abdulbari; Çatan, Funda; El Ayoubi, Hanadi R; Acar, Ahmet; Ibrahim, Wanis H

2017-07-01

The Gail model is the most widely used breast cancer risk assessment tool. An accurate assessment of individual's breast cancer risk is very important for prevention of the disease and for the health care providers to make decision on taking chemoprevention for high-risk women in clinical practice in Qatar. To assess the breast cancer risk among Arab women population in Qatar using the Gail model and provide a global comparison of risk assessment. In this cross-sectional study of 1488 women (aged 35 years and older), we used the Gail Risk Assessment Tool to assess the risk of developing breast cancer. Sociodemographic features such as age, lifestyle habits, body mass index, breast-feeding duration, consanguinity among parents, and family history of breast cancer were considered as possible risks. The mean age of the study population was 47.8 ± 10.8 years. Qatari women and Arab women constituted 64.7% and 35.3% of the study population, respectively. The mean 5-year and lifetime breast cancer risks were 1.12 ± 0.52 and 10.57 ± 3.1, respectively. Consanguineous marriage among parents was seen in 30.6% of participants. We found a relationship between the 5-year and lifetime risks of breast cancer and variables such as age, age at menarche, gravidity, parity, body mass index, family history of cancer, menopause age, occupation, and level of education. The linear regression analysis identified the predictors for breast cancer in women such as age, age at menarche, age of first birth, family history and age of menopausal were considered the strong predictors and significant contributing risk factors for breast cancer after adjusting for ethnicity, parity and other variables. The current study is the first to evaluate the performance of the Gail model for Arab women population in the Gulf Cooperation Council. Gail model is an appropriate breast cancer risk assessment tool for female population in Qatar.

Young and worried: Age and fear of recurrence in breast cancer survivors.

PubMed

Lebel, Sophie; Beattie, Sara; Arès, Isabelle; Bielajew, Catherine

2013-06-01

Fear of cancer recurrence (FCR) is a frequently cited and unmet need of cancer survivors. While the relation between age and FCR is well documented, the mechanisms that may explain this phenomenon remain to be investigated. This study examined four possible mechanisms of the relation between age and FCR: motherhood, severity of the cancer (defined as cancer stage and chemotherapy), anxiety, and illness intrusiveness. 3,239 women with breast cancer (mean time since diagnosis: 6.6 years) completed the Concerns About Recurrence Scale (CARS), the State Trait Anxiety Inventory (STAI), and the Illness Intrusiveness Ratings Scale (IIRS) within a larger web-based study. Women were divided into four groups based on their current age: < 34, 35-49, 50-64, and >65. Multivariate analyses were performed with age category and motherhood as the independent variables and the CARS subscales as the dependent variables, controlling for age of children and relevant covariates. Severity of the cancer, anxiety, and illness intrusiveness were simultaneously tested as mediators of the relation between age and FCR. Results indicated that age category was related to FCR, F = 10.37, p < .001. Follow-up tests revealed that women under 34 or 35-49 expressed the highest levels of FCR. Mothers, regardless of their ages or the ages of their children, expressed greater FCR. Illness intrusiveness and to a lesser extent anxiety were mediators of the relation between age and FCR, while severity of the cancer was not. Younger age was associated with more FCR among breast cancer patients, regardless of motherhood status. Our findings suggest new, potentially valuable ways of managing FCR by helping affected people to reduce anxiety and illness intrusiveness. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Increased age and race-specific incidence of cervical cancer after correction for hysterectomy prevalence in the United States from 2000 to 2009.

PubMed

Rositch, Anne F; Nowak, Rebecca G; Gravitt, Patti E

2014-07-01

Invasive cervical cancer is thought to decline in women over 65 years old, the age at which cessation of routine cervical cancer screening is recommended. However, national cervical cancer incidence rates do not account for the high prevalence of hysterectomy in the United States. Using estimates of hysterectomy prevalence from the Behavioral Risk Factor Surveillance System (BRFSS), hysterectomy-corrected age-standardized and age-specific incidence rates of cervical cancer were calculated from the Surveillance, Epidemiology, and End Results (SEER) 18 registry in the United States from 2000 to 2009. Trends in corrected cervical cancer incidence across age were analyzed using Joinpoint regression. Unlike the relative decline in uncorrected rates, corrected rates continue to increase after age 35-39 (APC(CORRECTED) = 10.43) but at a slower rate than in 20-34 years (APC(CORRECTED) = 161.29). The highest corrected incidence was among 65- to 69-year-old women, with a rate of 27.4 cases per 100,000 women as opposed to the highest uncorrected rate of 15.6 cases per 100,000 aged 40 to 44 years. Correction for hysterectomy had the largest impact on older, black women given their high prevalence of hysterectomy. Correction for hysterectomy resulted in higher age-specific cervical cancer incidence rates, a shift in the peak incidence to older women, and an increase in the disparity in cervical cancer incidence between black and white women. Given the high and nondeclining rate of cervical cancer in women over the age of 60 to 65 years, when women are eligible to exit screening, risk and screening guidelines for cervical cancer in older women may need to be reconsidered. © 2014 American Cancer Society.

Molecular epidemiology and phylogenetic analysis of human papillomavirus infection in women with cervical lesions and cancer from the coastal region of Ecuador.

PubMed

Bedoya-Pilozo, Cesar H; Medina Magües, Lex G; Espinosa-García, Maylen; Sánchez, Martha; Parrales Valdiviezo, Johanna V; Molina, Denisse; Ibarra, María A; Quimis-Ponce, María; España, Karool; Párraga Macias, Karla E; Cajas Flores, Nancy V; Orlando, Solon A; Robalino Penaherrera, Jorge A; Chedraui, Peter; Escobar, Saul; Loja Chango, Rita D; Ramirez-Morán, Cecibel; Espinoza-Caicedo, Jasson; Sánchez-Giler, Sunny; Limia, Celia M; Alemán, Yoan; Soto, Yudira; Kouri, Vivian; Culasso, Andrés C A; Badano, Inés

The aim of the present study was to gather information regarding the molecular epidemiology of Human papillomavirus (HPV) and related risk factors in a group of women with low- and high-grade cervical lesions and cancer from the coastal region of Ecuador. In addition, we studied the evolution of HPV variants from the most prevalent types and provided a temporal framework for their emergence, which may help to trace the source of dissemination within the region. We analyzed 166 samples, including 57 CIN1, 95 CIN2/3 and 14 cancer cases. HPV detection and typing was done by PCR-sequencing (MY09/MY11). HPV variants and estimation of the time to most recent common ancestor (tMRCA) was assessed through phylogeny and coalescence analysis. HPV DNA was found in 54.4% of CIN1, 74.7% of CIN2/3 and 78.6% of cancer samples. HPV16 (38.9%) and HPV58 (19.5%) were the most prevalent types. Risk factors for the development of cervical lesions/cancer were the following: three or more pregnancies (OR=4.3), HPV infection (OR=3.7 for high-risk types; OR=3.5 for HPV16), among others. With regard to HPV evolution, HPV16 isolates belonged to lineages A (69%) and D (31%) whereas HPV58 isolates belonged only to lineage A. The period of emergence of HPV16 was in association with human populations (tMRCA=91052 years for HPV16A and 27000 years for HPV16D), whereas HPV58A preceded Homo sapiens evolution (322257 years). This study provides novel data on HPV epidemiology and evolution in Ecuador, which will be fundamental in the vaccine era. Copyright © 2017 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.

CLONAL EVOLUTION IN CANCER

PubMed Central

Greaves, Mel; Maley, Carlo C.

2012-01-01

Cancers evolve by a reiterative process of clonal expansion, genetic diversification and clonal selection within the adaptive landscapes of tissue ecosystems. The dynamics are complex with highly variable patterns of genetic diversity and resultant clonal architecture. Therapeutic intervention may decimate cancer clones, and erode their habitats, but inadvertently provides potent selective pressure for the expansion of resistant variants. The inherently Darwinian character of cancer lies at the heart of therapeutic failure but perhaps also holds the key to more effective control. PMID:22258609

Age at exposure to ionising radiation and cancer mortality among Hanford workers: follow up through 1994

PubMed Central

Wing, S; Richardson, D

2005-01-01

Background: Studies of workers at the plutonium production factory in Hanford, WA have led to conflicting conclusions about the role of age at exposure as a modifier of associations between ionising radiation and cancer. Aims: To evaluate the influence of age at exposure on radiation risk estimates in an updated follow up of Hanford workers. Methods: A cohort of 26 389 workers hired between 1944 and 1978 was followed through 1994 to ascertain vital status and causes of death. External radiation dose estimates were derived from personal dosimeters. Poisson regression was used to estimate associations between mortality and cumulative external radiation dose at all ages, and in specific age ranges. Results: A total of 8153 deaths were identified, 2265 of which included cancer as an underlying or contributory cause. Estimates of the excess relative risk per Sievert (ERR/Sv) for cumulative radiation doses at all ages combined were negative for all cause and leukaemia and positive for all cancer and lung cancer. Cumulative doses accrued at ages below 35, 35–44, and 45–54 showed little association with mortality. For cumulative dose accrued at ages 55 and above (10 year lag), the estimated ERR/Sv for all cancers was 3.24 (90% CI: 0.80 to 6.17), primarily due to an association with lung cancer (ERR/Sv: 9.05, 90% CI: 2.96 to 17.92). Conclusions: Associations between radiation and cancer mortality in this cohort are primarily a function of doses at older ages and deaths from lung cancer. The association of older age radiation exposures and cancer mortality is similar to observations from several other occupational studies. PMID:15961623

Epigenetic susceptibility factors for prostate cancer with aging.

PubMed

Damaschke, N A; Yang, B; Bhusari, S; Svaren, J P; Jarrard, D F

2013-12-01

Increasing age is a significant risk factor for prostate cancer. The prostate is exposed to environmental and endogenous stress that may underlie this remarkable incidence. DNA methylation, genomic imprinting, and histone modifications are examples of epigenetic factors known to undergo change in the aging and cancerous prostate. In this review we examine the data linking epigenetic alterations in the prostate with aging to cancer development. An online search of current and past peer reviewed literature on epigenetic changes with cancer and aging was performed. Relevant articles were analyzed. Epigenetic changes are responsible for modifying expression of oncogenes and tumor suppressors. Several of these changes may represent a field defect that predisposes to cancer development. Focal hypermethylation occurs at CpG islands in the promoters of certain genes including GSTP1, RARβ2, and RASSF1A with both age and cancer, while global hypomethylation is seen in prostate cancer and known to occur in the colon and other organs. A loss of genomic imprinting is responsible for biallelic expression of the well-known Insulin-like Growth Factor 2 (IGF2) gene. Loss of imprinting (LOI) at IGF2 has been documented in cancer and is also known to occur in benign aging prostate tissue marking the presence of cancer. Histone modifications have the ability to dictate chromatin structure and direct gene expression. Epigenetic changes with aging represent molecular mechanisms to explain the increased susceptibly of the prostate to develop cancer in older men. These changes may provide an opportunity for diagnostic and chemopreventive strategies given the epigenome can be modified. © 2013 Wiley Periodicals, Inc.

Vital Signs: Trends in Incidence of Cancers Associated with Overweight and Obesity - United States, 2005-2014.

PubMed

Steele, C Brooke; Thomas, Cheryll C; Henley, S Jane; Massetti, Greta M; Galuska, Deborah A; Agurs-Collins, Tanya; Puckett, Mary; Richardson, Lisa C

2017-10-03

Overweight and obesity are associated with increased risk of at least 13 different types of cancer. Data from the United States Cancer Statistics for 2014 were used to assess incidence rates, and data from 2005 to 2014 were used to assess trends for cancers associated with overweight and obesity (adenocarcinoma of the esophagus; cancers of the breast [in postmenopausal women], colon and rectum, endometrium, gallbladder, gastric cardia, kidney, liver, ovary, pancreas, and thyroid; meningioma; and multiple myeloma) by sex, age, race/ethnicity, state, geographic region, and cancer site. Because screening for colorectal cancer can reduce colorectal cancer incidence through detection of precancerous polyps before they become cancerous, trends with and without colorectal cancer were analyzed. In 2014, approximately 631,000 persons in the United States received a diagnosis of a cancer associated with overweight and obesity, representing 40% of all cancers diagnosed. Overweight- and obesity-related cancer incidence rates were higher among older persons (ages ≥50 years) than younger persons; higher among females than males; and higher among non-Hispanic black and non-Hispanic white adults compared with other groups. Incidence rates for overweight- and obesity-related cancers during 2005-2014 varied by age, cancer site, and state. Excluding colorectal cancer, incidence rates increased significantly among persons aged 20-74 years; decreased among those aged ≥75 years; increased in 32 states; and were stable in 16 states and the District of Columbia. The burden of overweight- and obesity-related cancer is high in the United States. Incidence rates of overweight- and obesity-related cancers except colorectal cancer have increased in some age groups and states. The burden of overweight- and obesity-related cancers might be reduced through efforts to prevent and control overweight and obesity. Comprehensive cancer control strategies, including use of evidence-based interventions to promote healthy weight, could help decrease the incidence of these cancers in the United States.

A flowgraph model for bladder carcinoma

PubMed Central

2014-01-01

Background Superficial bladder cancer has been the subject of numerous studies for many years, but the evolution of the disease still remains not well understood. After the tumor has been surgically removed, it may reappear at a similar level of malignancy or progress to a higher level. The process may be reasonably modeled by means of a Markov process. However, in order to more completely model the evolution of the disease, this approach is insufficient. The semi-Markov framework allows a more realistic approach, but calculations become frequently intractable. In this context, flowgraph models provide an efficient approach to successfully manage the evolution of superficial bladder carcinoma. Our aim is to test this methodology in this particular case. Results We have built a successful model for a simple but representative case. Conclusion The flowgraph approach is suitable for modeling of superficial bladder cancer. PMID:25080066

Association between age factors and strategies for promoting participation in gastric and colorectal cancer screenings.

PubMed

Hamashima, Chisato; Sano, Hiroshi

2018-03-27

Despite the long history of cancer screening in Japan, the participation rates in gastric and colorectal cancer screenings have not increased. Strategies for improving the participation rates have been proposed, but differences in their effects among different age groups remain unclear. The Japanese government conducted a national survey in all municipalities in Japan in 2010 to investigate whether the implementation of promotion strategies increased participation in cancer screening. We investigated the association between age factors and strategies for promoting participation in cancer screening based on this national survey. Multiple regression analysis with generalized linear model was performed using the participation rates in gastric and colorectal cancer screenings as dependent variables, and the following strategies for promoting participation as independent variables: 1) personal invitation letters, 2) household invitation letters, 3) home visits by community nurses, 4) screenings in medical offices, and 5) free cancer screening programs. One thousand six hundred thirty nine municipalities for gastric cancer screening and 1666 municipalities for colorectal cancer screening were selected for the analysis. In gastric and colorectal cancer screenings, the participation rates of individuals aged 60-69 years was higher than those of other age groups. Personal and household invitation letters were effective promotion strategies for all age groups, which encouraged even older people to participate in gastric and colorectal cancer screenings. Screening in medical offices and free screenings were not effective in all age groups. Home visits were effective, but their adoption was limited to small municipalities. To clarify whether promotion strategies can increase the participation rate in cancer screening among different age groups, 5 strategies were assessed on the basis of a national survey. Although personal and household invitation letters were effective strategies for promoting participation in cancer screening for all age groups, these strategies equally encouraged older people to participate in gastric and colorectal cancer screenings. If resource for sending invitation letters are limited, priority should be given to individuals who are in their 50s and 60s for gastric and colorectal cancer screening.

Burden of cancer mortality and differences attributable to demographic aging and risk factors in Argentina, 1986-2011.

PubMed

Pou, Sonia Alejandra; Tumas, Natalia; Coquet, Julia Becaria; Niclis, Camila; Román, María Dolores; Díaz, María Del Pilar

2017-03-09

The world faces an aging population that implies a large number of people affected with chronic diseases. Argentina has reached an advanced stage of demographic transition and presents a comparatively high rate of cancer mortality within Latin America. The objectives of this study were to examine cancer mortality trends in the province of Córdoba, Argentina, between 1986 and 2011, and to analyze the differences attributable to risk variations and demographic changes. Longitudinal series of age-standardized mortality rates for overall, breast and prostate cancers were modeled by Joinpoint regression to estimate the annual percent change. The Bashir & Estève method was used to split crude mortality rate variation into three components: mortality risk, population age structure and population size. A decreasing cancer age-standardized mortality rates trend was observed (1986-2011 annual percent change: -1.4, 95%CI: -1.6, -1.2 in men; -0.8, 95%CI: -1.0, -0.6 in women), with a significant shift in 1996. There were positive crude mortality rate net changes for overall female cancer, breast and prostate cancers, which were primarily attributable to demographic changes. Inversely, overall male cancer crude mortality rate showed a 9.15% decrease, mostly due to mortality risk. Despite favorable age-standardized mortality rates trends, the influence of population aging reinforces the challenge to control cancer in populations with an increasingly aged demographic structure.

Age differences in dual information-processing modes: implications for cancer decision making.

PubMed

Peters, Ellen; Diefenbach, Michael A; Hess, Thomas M; Västfjäll, Daniel

2008-12-15

Age differences in affective/experiential and deliberative processes have important theoretical implications for cancer decision making, as cancer is often a disease of older adulthood. The authors examined evidence for adult age differences in affective and deliberative information processes, reviewed the sparse evidence about age differences in decision making, and introduced how dual process theories and their findings might be applied to cancer decision making. Age-related declines in the efficiency of deliberative processes predict poorer-quality decisions as we age, particularly when decisions are unfamiliar and the information is numeric. However, age-related adaptive processes, including an increased focus on emotional goals and greater experience, can influence decision making and potentially offset age-related declines. A better understanding of the mechanisms that underlie cancer decision processes in our aging population should ultimately allow us to help older adults to better help themselves.

Age Differences in Dual Information-Processing Modes: Implications for Cancer Decision Making

PubMed Central

Peters, Ellen; Diefenbach, Michael A.; Hess, Thomas M.; Västfjäll, Daniel

2008-01-01

Age differences in affective/experiential and deliberative processes have important theoretical implications for cancer decision making as cancer is often a disease of older adulthood. We examine evidence for adult age differences in affective and deliberative information processes, review the sparse evidence about age differences in decision making and introduce how dual process theories and their findings might be applied to cancer decision making. Age-related declines in the efficiency of deliberative processes predict poorer-quality decisions as we age, particularly when decisions are unfamiliar and the information is numeric. However, age-related adaptive processes, including an increased focus on emotional goals and greater experience, can influence decision making and potentially offset age-related declines. A better understanding of the mechanisms that underlie cancer decision processes in our aging population should ultimately allow us to help older adults to better help themselves. PMID:19058148

Predictive Modeling of Polymer Mechanical Behavior Coupled to Chemical Change/ Technique Development for Measuring Polymer Physical Aging.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kropka, Jamie Michael; Stavig, Mark E.; Arechederra, Gabe Kenneth

Develop an understanding of the evolution of glassy polymer mechanical response during aging and the mechanisms associated with that evolution. That understanding will be used to develop constitutive models to assess the impact of stress evolution in encapsulants on NW designs.

Familial clustering in subgroups of gastric cancer stratified by histology, age group and location.

PubMed

Eto, K; Ohyama, S; Yamaguchi, T; Wada, T; Suzuki, Y; Mitsumori, N; Kashiwagi, H; Anazawa, S; Yanaga, K; Urashima, M

2006-09-01

To assess the risk of gastric cancer in a Japanese patient population with the disease by stratification with histology, age, tumour location and the association with family history of gastric or non-gastric tumours. A retrospective analysis of 1400 consecutive patients with gastric cancer and 13,467 age- and gender-matched controls from a pre-recorded database using conditional logistic regression models. Young patients (< or = 43 years of age) with gastric cancer of intestinal type had a strong association with family history of gastric cancer in first degree-relatives (OR=12.5). Moreover, when a history of gastric cancer was observed in both parents, there was an increased risk of gastric cancer intestinal type (OR=7.8), more commonly in the proximal and mid-stomach. In contrast, there was an increased risk of diffuse-type cancer when both parents suffered non-gastric cancers (OR=2.1). These data suggest that the degree of familial clustering differ in gastric cancer subgroups stratified by histology, age, and stomach location in this Japanese population.

Glycative stress from advanced glycation end products (AGEs) and dicarbonyls: An emerging biological factor in cancer onset and progression.

PubMed

Lin, Jer-An; Wu, Chi-Hao; Lu, Chi-Cheng; Hsia, Shih-Min; Yen, Gow-Chin

2016-08-01

In recent years, glycative stress from exogenous or endogenous advanced glycation end products (AGEs) and highly reactive dicarbonyls has gained great attention for its putative effects on cancer development. AGEs are a group of compounds formed from the complex chemical reaction of reducing sugars with compounds containing an amino group. AGEs bind to and activate the receptor for AGEs (RAGE), which is a predominant modulator of inflammation-associated cancer, and AGEs induce reactive oxygen species that are an important regulator of the hallmarks of cancer. Dicarbonyls, which are formed during glycolysis, lipid oxidation, or protein degradation, include glyoxal, methylglyoxal, and 3-deoxyglucosone and are regarded as major precursors of AGEs. These dicarbonyls not only fuel the AGE pool in living organisms but also evoke carbonyl stress, which may contribute to the carbonylative damage of carbohydrates, lipids, proteins, or DNA. Carbonylative damage then leads to many lesions, some of which are implicated in the pathogenesis of cancer. In this review, studies regarding the effects of AGEs and dicarbonyls on cancer onset or progression are systematically discussed, and the utilization of AGE inhibitors and dicarbonyl scavengers in cancer therapy are noted. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Observing Clonal Dynamics across Spatiotemporal Axes: A Prelude to Quantitative Fitness Models for Cancer.

PubMed

McPherson, Andrew W; Chan, Fong Chun; Shah, Sohrab P

2018-02-01

The ability to accurately model evolutionary dynamics in cancer would allow for prediction of progression and response to therapy. As a prelude to quantitative understanding of evolutionary dynamics, researchers must gather observations of in vivo tumor evolution. High-throughput genome sequencing now provides the means to profile the mutational content of evolving tumor clones from patient biopsies. Together with the development of models of tumor evolution, reconstructing evolutionary histories of individual tumors generates hypotheses about the dynamics of evolution that produced the observed clones. In this review, we provide a brief overview of the concepts involved in predicting evolutionary histories, and provide a workflow based on bulk and targeted-genome sequencing. We then describe the application of this workflow to time series data obtained for transformed and progressed follicular lymphomas (FL), and contrast the observed evolutionary dynamics between these two subtypes. We next describe results from a spatial sampling study of high-grade serous (HGS) ovarian cancer, propose mechanisms of disease spread based on the observed clonal mixtures, and provide examples of diversification through subclonal acquisition of driver mutations and convergent evolution. Finally, we state implications of the techniques discussed in this review as a necessary but insufficient step on the path to predictive modelling of disease dynamics. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.

Cytogenetic clonal evolution in myelodysplastic syndromes is associated with inferior prognosis.

PubMed

Neukirchen, Judith; Lauseker, Michael; Hildebrandt, Barbara; Nolting, Ann-Christin; Kaivers, Jennifer; Kobbe, Guido; Gattermann, Norbert; Haas, Rainer; Germing, Ulrich

2017-12-01

The karyotype of bone marrow cells at the time of diagnosis is a strong prognostic parameter for overall survival as well as acute myeloid leukemia (AML) progression in patients with myelodysplastic syndromes (MDS). However, to the authors' knowledge, few data exist regarding the prognostic impact of cytogenetic clonal evolution during the course of MDS. The authors evaluated follow-up karyotype analyses in 549 patients from the Dusseldorf MDS Registry. Clonal evolution was detectable in 24% of the entire cohort and in 18% of 294 patients receiving best supportive care. The authors noted a clear adverse effect of clonal evolution on the risk of leukemic transformation (hazard ratio, 2.233; P = .036) and overall survival (hazard ratio, 3.677; P<.001). The authors also analyzed the prognostic influence of subclones detectable at the time of diagnosis. Again, such a finding was associated with a significantly shorter overall survival and a higher 5-year-probability of acute myeloid leukemia progression (30% vs 22%). The results of the current study support the belief that follow-up karyotype analyses should be performed, especially in patients with lower-risk and intermediate-risk MDS, to identify those patients who are at higher risk of disease progression and therefore might benefit from earlier or more intensive treatment. Cancer 2017;123:4608-4616. © 2017 American Cancer Society. © 2017 American Cancer Society.

Paired Exome Analysis Reveals Clonal Evolution and Potential Therapeutic Targets in Urothelial Carcinoma.

PubMed

Lamy, Philippe; Nordentoft, Iver; Birkenkamp-Demtröder, Karin; Thomsen, Mathilde Borg Houlberg; Villesen, Palle; Vang, Søren; Hedegaard, Jakob; Borre, Michael; Jensen, Jørgen Bjerggaard; Høyer, Søren; Pedersen, Jakob Skou; Ørntoft, Torben F; Dyrskjøt, Lars

2016-10-01

Greater knowledge concerning tumor heterogeneity and clonality is needed to determine the impact of targeted treatment in the setting of bladder cancer. In this study, we performed whole-exome, transcriptome, and deep-focused sequencing of metachronous tumors from 29 patients initially diagnosed with early-stage bladder tumors (14 with nonprogressive disease and 15 with progressive disease). Tumors from patients with progressive disease showed a higher variance of the intrapatient mutational spectrum and a higher frequency of APOBEC-related mutations. Allele-specific expression was also higher in these patients, particularly in tumor suppressor genes. Phylogenetic analysis revealed a common origin of the metachronous tumors, with a higher proportion of clonal mutations in the ancestral branch; however, 19 potential therapeutic targets were identified as both ancestral and tumor-specific alterations. Few subclones were present based on PyClone analysis. Our results illuminate tumor evolution and identify candidate therapeutic targets in bladder cancer. Cancer Res; 76(19); 5894-906. ©2016 AACR. ©2016 American Association for Cancer Research.

Evolution of Resistance to Targeted Anti-Cancer Therapies during Continuous and Pulsed Administration Strategies

PubMed Central

Foo, Jasmine; Michor, Franziska

2009-01-01

The discovery of small molecules targeted to specific oncogenic pathways has revolutionized anti-cancer therapy. However, such therapy often fails due to the evolution of acquired resistance. One long-standing question in clinical cancer research is the identification of optimum therapeutic administration strategies so that the risk of resistance is minimized. In this paper, we investigate optimal drug dosing schedules to prevent, or at least delay, the emergence of resistance. We design and analyze a stochastic mathematical model describing the evolutionary dynamics of a tumor cell population during therapy. We consider drug resistance emerging due to a single (epi)genetic alteration and calculate the probability of resistance arising during specific dosing strategies. We then optimize treatment protocols such that the risk of resistance is minimal while considering drug toxicity and side effects as constraints. Our methodology can be used to identify optimum drug administration schedules to avoid resistance conferred by one (epi)genetic alteration for any cancer and treatment type. PMID:19893626

[Trends and evolutions of French breast cancer research: a bibliometric study].

PubMed

Thonon, Frédérique; Saghatchian, Mahasti; Nerfie, Alexia; Delaloge, Suzette

2015-05-01

This article presents a bibliometric study carried out in order to describe the trends and evolutions of French breast cancer research from 2003 to 2013. The results show an increase in the number of publications, especially international publications coordinated by non-French institutions. The most visible topics, in terms of number of publications by keywords, are related to biology, clinical trials and genetics. Most publications are written by authors affiliated to comprehensive cancer centres, followed by universities, research centres, university hospitals and governmental agencies. The importance of publications by topic varies throughout the years: there has been an increase of the number of publications related to targeted therapies or genomics. The importance of institutions or country affiliation of authors varies with the topics. This study, especially the analysis by keywords, enables the coordinators of research programs to identify the predominant actors and themes. Copyright © 2015 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ames, B.N.; Cathcart, R.; Schwiers, E.

During primate evolution, a major factor in lengthening life-span and decreasing age-specific cancer rates may have been improved protective mechanisms against oxygen radicals. We propose that one of these protective systems is plasma uric acid, the level of which increased markedly during primate evolution as a consequence of a series of mutations. Uric acid is a powerful antioxidant and is a scavenger of singlet oxygen and radicals. We show that, at physiological concentrations, urate reduces the oxo-heme oxidant formed by peroxide reaction with hemoglobin, protects erythrocyte ghosts against lipid peroxidation, and protects erythrocytes from peroxidative damage leading to lysis. Uratemore » is about as effective an antioxidant as ascorbate in these experiments. Urate is much more easily oxidized than deoxynucleosides by singlet oxygen and is destroyed by hydroxyl radicals at a comparable rate. The plasma urate level in humans (about 300 ..mu..M) is considerably higher than the ascorbate level, making it one of the major antioxidants in humans. Previous work on urate reported in the literature supports our experiments and interpretations, although the findings were not discussed in a physiological context.« less

Cancer incidence and mortality in China, 2014

PubMed Central

Chen, Wanqing; Sun, Kexin; Zheng, Rongshou; Zeng, Hongmei; Zhang, Siwei; Xia, Changfa; Yang, Zhixun; Li, He; Zou, Xiaonong; He, Jie

2018-01-01

Background National Central Cancer Registry of China (NCCRC) updated nationwide cancer statistics using population-based cancer registry data in 2014 collected from all available cancer registries. Methods In 2017, 449 cancer registries submitted cancer registry data in 2014, among which 339 registries’ data met the criteria of quality control and were included in analysis. These cancer registries covered 288,243,347 population, accounting for about 21.07% of the national population in 2014. Numbers of nationwide new cancer cases and deaths were estimated using calculated incidence and mortality rates and corresponding national population stratified by area, sex, age group and cancer type. The world Segi’s population was applied for age-standardized rates. Results A total of 3,804,000 new cancer cases were diagnosed, the crude incidence rate was 278.07/100,000 (301.67/100,000 in males, 253.29/100,000 in females) and the age-standardized incidence rate by world standard population (ASIRW) was 186.53/100,000. Calculated age-standardized incidence rate was higher in urban areas than in rural areas (191.6/100,000 vs. 179.2/100,000). South China had the highest cancer incidence rate while Southwest China had the lowest incidence rate. Cancer incidence rate was higher in female for population between 20 to 54 years but was higher in male for population younger than 20 years or over 54 years. A total of 2,296,000 cancer deaths were reported, the crude mortality rate was 167.89/100,000 (207.24/100,000 in males, 126.54/100,000 in females) and the age-standardized mortality rate by world standard population (ASMRW) was 106.09/100,000. Calculated age-standardized mortality rate was higher in rural areas than in urban areas (110.3/100,000 vs. 102.5/100,000). East China had the highest cancer mortality rate while North China had the lowest mortality rate. The mortality rate in male was higher than that in female. Common cancer types and major causes of cancer death differed between age group and sex. Conclusions Heavy cancer burden and its disparities between area, sex and age group pose a major challenge to public health in China. Nationwide cancer registry plays a crucial role in cancer prevention and control. PMID:29545714

The identification of age-associated cancer markers by an integrative analysis of dynamic DNA methylation changes.

PubMed

Wang, Yihan; Zhang, Jingyu; Xiao, Xingjun; Liu, Hongbo; Wang, Fang; Li, Song; Wen, Yanhua; Wei, Yanjun; Su, Jianzhong; Zhang, Yunming; Zhang, Yan

2016-03-07

As one of the most widely studied epigenetic modifications, DNA methylation has an important influence on human traits and cancers. Dynamic variations in DNA methylation have been reported in malignant neoplasm and aging; however, the mechanisms remain poorly understood. By constructing an age-associated and cancer-related weighted network (ACWN) based on the correlation of the methylation level and the protein-protein interaction, we found that DNA methylation changes associated with age were closely related to the occurrence of cancer. Additional analysis of 102 module genes mined from the ACWN revealed discrimination based on two main patterns. One pattern involved methylation levels that increased with aging and were higher in cancer patients compared with normal controls (HH pattern). The other pattern involved methylation levels that decreased with aging and were lower in cancer compared with normal (LL pattern). Upon incorporation with gene expression levels, 25 genes were filtered based on negative regulation by DNA methylation. These genes were regarded as potential cancer risk markers that were influenced by age in the process of carcinogenesis. Our results will facilitate further studies regarding the impact of the epigenetic effects of aging on diseases and will aid in the development of tailored cancer preventive strategies.

The identification of age-associated cancer markers by an integrative analysis of dynamic DNA methylation changes

PubMed Central

Wang, Yihan; Zhang, Jingyu; Xiao, Xingjun; Liu, Hongbo; Wang, Fang; Li, Song; Wen, Yanhua; Wei, Yanjun; Su, Jianzhong; Zhang, Yunming; Zhang, Yan

2016-01-01

As one of the most widely studied epigenetic modifications, DNA methylation has an important influence on human traits and cancers. Dynamic variations in DNA methylation have been reported in malignant neoplasm and aging; however, the mechanisms remain poorly understood. By constructing an age-associated and cancer-related weighted network (ACWN) based on the correlation of the methylation level and the protein-protein interaction, we found that DNA methylation changes associated with age were closely related to the occurrence of cancer. Additional analysis of 102 module genes mined from the ACWN revealed discrimination based on two main patterns. One pattern involved methylation levels that increased with aging and were higher in cancer patients compared with normal controls (HH pattern). The other pattern involved methylation levels that decreased with aging and were lower in cancer compared with normal (LL pattern). Upon incorporation with gene expression levels, 25 genes were filtered based on negative regulation by DNA methylation. These genes were regarded as potential cancer risk markers that were influenced by age in the process of carcinogenesis. Our results will facilitate further studies regarding the impact of the epigenetic effects of aging on diseases and will aid in the development of tailored cancer preventive strategies. PMID:26949191

Patterns of Cancer in Kurdistan - Results of Eight Years Cancer Registration in Sulaymaniyah Province-Kurdistan-Iraq.

PubMed

Khoshnaw, Najmaddin; Mohammed, Hazha A; Abdullah, Dana A

2015-01-01

Cancer has become a major health problem associated with high mortality worldwide, especially in developing countries. The aim of our study was to evaluate the incidence rates of different types of cancer in Sulaymaniyah from January-2006 to January-2014. The data were compared with those reported for other middle east countries. This retrospective study depended on data collected from Hiwa hospital cancer registry unit, death records and histopathology reports in all Sulaymaniyah teaching hospitals, using international classification of diseases. A total of 8,031 cases were registered during the eight year period, the annual incidence rate in all age groups rose from 38 to 61.7 cases/100,000 population/year, with averages over 50 in males and 50.7 in females. The male to female ratio in all age groups were 0.98, while in the pediatric age group it was 1.33. The hematological malignancies in all age groups accounted for 20% but in the pediatric group around half of all cancer cases. Pediatric cancers were occluding 7% of total cancers with rates of 10.3 in boys and 8.7 in girls. The commonest malignancies by primary site were leukemia, lymphoma, brain, kidney and bone. In males in all age groups they were lung, leukaemia, lymphoma, colorectal, prostate, bladder, brain, stomach, carcinoma of unknown primary (CUP) and skin, while in females they were breast, leukaemia, lymphoma, colorectal, ovary, lung, brain, CUP, and stomach. Most cancers were increased with increasing age except breast cancer where decrease was noted in older ages. High mortality rates were found with leukemia, lung, lymphoma, colorectal, breast and stomach cancers. We here found an increase in annual cancer incidence rates across the period of study, because of increase of cancer with age and higher rates of hematological malignancies. Our study is valuable for Kurdistan and Iraq because it provides more accurate data about the exact patterns of cancer and mortality in our region.

[Liquid biopsies, a revolution in oncology?].

PubMed

Jordan, Bertrand

2015-01-01

The detection and analysis of circulating tumour DNA and/or circulating tumour cells in the blood of cancer patients open new possibilities for cancer characterisation and management. The approach has generated much commercial interest, but still requires more proof of clinical utility; it is however likely to play an important role in monitoring the evolution of cancer cells during therapy. © 2015 médecine/sciences – Inserm.

Reduced risk of colorectal cancer among recent generations in New Zealand.

PubMed Central

Cox, B.; Little, J.

1992-01-01

Male and female age standardised mortality and incidence rates of colorectal cancer have increased over the most recent 30 years in New Zealand. Among men and women aged 40 to 74, age standardised mortality and incidence rates increased 18 to 105%. However, age standardised mortality and incidence rates among younger men and women have declined from 14 to 69%. Analysis of trends in age specific mortality and incidence rates indicates that the occurrence of colorectal cancer has been declining equally for men and women in successive cohorts born about 1943 to 1953 in New Zealand. This decline in the frequency of colorectal cancer among recent generations was apparent for both the right and left sides of the colon and the rectum. Age-specific trends in coronary heart disease and breast cancer differed from those apparent for colorectal cancer, suggesting that the factors producing the reduction in colorectal cancer risk may affect these diseases among different age groups or may not be of major aetiological importance in these diseases. These trends provide empirical evidence that the occurrence of colorectal cancer can be reduced by at least 50% with a substantial component of the risk being determined before the age of 30. Further study is needed to establish whether changes in risk factors at older ages contribute to the prevention of the disease. PMID:1503913

Mortality of breast cancer in Taiwan, 1971-2010: temporal changes and an age-period-cohort analysis.

PubMed

Ho, M-L; Hsiao, Y-H; Su, S-Y; Chou, M-C; Liaw, Y-P

2015-01-01

The current paper describes the age, period and cohort effects on breast cancer mortality in Taiwan. Female breast cancer mortality data were collected from the Taiwan death registries for 1971-2010. The annual percentage changes, age- standardised mortality rates (ASMR) and age-period-cohort model were calculated. The mortality rates increased with advancing age groups when fixing the period. The percentage change in the breast cancer mortality rate increased from 54.79% at aged 20-44 years, to 149.78% in those aged 45-64 years (between 1971-75 and 2006-10). The mortality rates in the 45-64 age group increased steadily from 1971 to 1975 and 2006-10. The 1951 birth cohorts (actual birth cohort; 1947-55) showed peak mortalities in both the 50-54 and 45-49 age groups. We found that the 1951 birth cohorts had the greatest mortality risk from breast cancer. This might be attributed to the DDT that was used in large amounts to prevent deaths from malaria in Taiwan. However, future researches require DDT data to evaluate the association between breast cancer and DDT use.

Impact of Age and Comorbidity on Cervical and Breast Cancer Literacy of African Americans, Latina, and Arab Women.

PubMed

Talley, Costellia H; Williams, Karen Patricia

2015-09-01

This study examines the relationship between age, comorbidity, and breast and cervical cancer literacy in a sample of African American, Latina, and Arab women (N = 371) from Detroit, Michigan. The Age-adjusted Charlson Comorbidity Index (ACC) was used characterize the impact of age and comorbidity on breast and cervical cancer literacy. The relationship between ACC and breast and cervical cancer screening, and group differences, were assessed. There was a statistically significant difference between breast cancer literacy scores. ACC had a greater impact on breast cancer literacy for African Americans. Copyright © 2015 Elsevier Inc. All rights reserved.

[Causes of death among prostate cancer patients of different ages].

PubMed

Dariy, E V

2016-02-01

To date, there is no unified approach to evaluating and treating patients with suspected prostate cancer taking into account their age and comorbidities. That was the rationale for conducting this study. To assess the clinical course of prostate cancer in men of all ages with comorbidities. The study included 408 patients aged 50 to 92 years (mean age 74.3 years) with histologically verified prostate cancer. 30 (7.4%) patients had stage T1 disease, 273 (66.9%) - T2, 91 (22.3%) - T3 and 14 (3.4%) - T4. The maximum follow-up was 22 years, the minimum one - 6 months (on average 15.4 years). During the follow-up 159 patients died (39%), 51 of them (32%) of prostate cancer, 108 (68%) - from other diseases. Among the latter the causes of death were cancer (20.4%), cardiovascular and bronchopulmonary diseases (79.6%). Cancer-specific survival rate was 41.4 +/-12,4%, the survival rate for other diseases 23.4 +/-10,6% (p<0.05). We need a differentiated approach to selecting treatment for patients with prostate cancer, especially of old age, including the option for active surveillance of patients with clinically insignificant prostate cancer.

Tracking the Evolution of Non-Small-Cell Lung Cancer.

PubMed

Jamal-Hanjani, Mariam; Wilson, Gareth A; McGranahan, Nicholas; Birkbak, Nicolai J; Watkins, Thomas B K; Veeriah, Selvaraju; Shafi, Seema; Johnson, Diana H; Mitter, Richard; Rosenthal, Rachel; Salm, Max; Horswell, Stuart; Escudero, Mickael; Matthews, Nik; Rowan, Andrew; Chambers, Tim; Moore, David A; Turajlic, Samra; Xu, Hang; Lee, Siow-Ming; Forster, Martin D; Ahmad, Tanya; Hiley, Crispin T; Abbosh, Christopher; Falzon, Mary; Borg, Elaine; Marafioti, Teresa; Lawrence, David; Hayward, Martin; Kolvekar, Shyam; Panagiotopoulos, Nikolaos; Janes, Sam M; Thakrar, Ricky; Ahmed, Asia; Blackhall, Fiona; Summers, Yvonne; Shah, Rajesh; Joseph, Leena; Quinn, Anne M; Crosbie, Phil A; Naidu, Babu; Middleton, Gary; Langman, Gerald; Trotter, Simon; Nicolson, Marianne; Remmen, Hardy; Kerr, Keith; Chetty, Mahendran; Gomersall, Lesley; Fennell, Dean A; Nakas, Apostolos; Rathinam, Sridhar; Anand, Girija; Khan, Sajid; Russell, Peter; Ezhil, Veni; Ismail, Babikir; Irvin-Sellers, Melanie; Prakash, Vineet; Lester, Jason F; Kornaszewska, Malgorzata; Attanoos, Richard; Adams, Haydn; Davies, Helen; Dentro, Stefan; Taniere, Philippe; O'Sullivan, Brendan; Lowe, Helen L; Hartley, John A; Iles, Natasha; Bell, Harriet; Ngai, Yenting; Shaw, Jacqui A; Herrero, Javier; Szallasi, Zoltan; Schwarz, Roland F; Stewart, Aengus; Quezada, Sergio A; Le Quesne, John; Van Loo, Peter; Dive, Caroline; Hackshaw, Allan; Swanton, Charles

2017-06-01

Among patients with non-small-cell lung cancer (NSCLC), data on intratumor heterogeneity and cancer genome evolution have been limited to small retrospective cohorts. We wanted to prospectively investigate intratumor heterogeneity in relation to clinical outcome and to determine the clonal nature of driver events and evolutionary processes in early-stage NSCLC. In this prospective cohort study, we performed multiregion whole-exome sequencing on 100 early-stage NSCLC tumors that had been resected before systemic therapy. We sequenced and analyzed 327 tumor regions to define evolutionary histories, obtain a census of clonal and subclonal events, and assess the relationship between intratumor heterogeneity and recurrence-free survival. We observed widespread intratumor heterogeneity for both somatic copy-number alterations and mutations. Driver mutations in EGFR, MET, BRAF, and TP53 were almost always clonal. However, heterogeneous driver alterations that occurred later in evolution were found in more than 75% of the tumors and were common in PIK3CA and NF1 and in genes that are involved in chromatin modification and DNA damage response and repair. Genome doubling and ongoing dynamic chromosomal instability were associated with intratumor heterogeneity and resulted in parallel evolution of driver somatic copy-number alterations, including amplifications in CDK4, FOXA1, and BCL11A. Elevated copy-number heterogeneity was associated with an increased risk of recurrence or death (hazard ratio, 4.9; P=4.4×10 -4 ), which remained significant in multivariate analysis. Intratumor heterogeneity mediated through chromosome instability was associated with an increased risk of recurrence or death, a finding that supports the potential value of chromosome instability as a prognostic predictor. (Funded by Cancer Research UK and others; TRACERx ClinicalTrials.gov number, NCT01888601 .).

Papillomaviruses: Viral evolution, cancer and evolutionary medicine.

PubMed

Bravo, Ignacio G; Félez-Sánchez, Marta

2015-01-28

Papillomaviruses (PVs) are a numerous family of small dsDNA viruses infecting virtually all mammals. PVs cause infections without triggering a strong immune response, and natural infection provides only limited protection against reinfection. Most PVs are part and parcel of the skin microbiota. In some cases, infections by certain PVs take diverse clinical presentations from highly productive self-limited warts to invasive cancers. We propose PVs as an excellent model system to study the evolutionary interactions between the immune system and pathogens causing chronic infections: genotypically, PVs are very diverse, with hundreds of different genotypes infecting skin and mucosa; phenotypically, they display extremely broad gradients and trade-offs between key phenotypic traits, namely productivity, immunogenicity, prevalence, oncogenicity and clinical presentation. Public health interventions have been launched to decrease the burden of PV-associated cancers, including massive vaccination against the most oncogenic human PVs, as well as systematic screening for PV chronic anogenital infections. Anti-PVs vaccines elicit protection against infection, induce cross-protection against closely related viruses and result in herd immunity. However, our knowledge on the ecological and intrapatient dynamics of PV infections remains fragmentary. We still need to understand how the novel anthropogenic selection pressures posed by vaccination and screening will affect viral circulation and epidemiology. We present here an overview of PV evolution and the connection between PV genotypes and the phenotypic, clinical manifestations of the diseases they cause. This differential link between viral evolution and the gradient cancer-warts-asymptomatic infections makes PVs a privileged playground for evolutionary medicine research. © The Author(s) 2015. Published by Oxford University Press on behalf of the Foundation for Evolution, Medicine, and Public Health.

Mild Lung Restriction in Breast Cancer Patients After Hypofractionated and Conventional Radiation Therapy: A 3-Year Follow-Up

DOE Office of Scientific and Technical Information (OSTI.GOV)

Verbanck, Sylvia, E-mail: sylvia.verbanck@uzbrussel.be; Hanon, Shane; Schuermans, Daniel

Purpose: To assess the effect of radiation therapy on lung function over the course of 3 years. Methods and Materials: Evolution of restrictive and obstructive lung function parameters was investigated in 108 breast cancer participants in a randomized, controlled trial comparing conventional radiation therapy (CR) and hypofractionated tomotherapy (TT) (age at inclusion ranging 32-81 years). Spirometry, plethysmography, and hemoglobin-corrected diffusing capacity were assessed at baseline and after 3 months and 1, 2, and 3 years. Natural aging was accounted for by considering all lung function parameters in terms of percent predicted values using the most recent reference values for women aged up to 80 years. Results:more » In the patients with negligible history of respiratory disease or smoking (n=77), the greatest rate of functional decline was observed during the initial 3 months, this acute decrease being more marked in the CR versus the TT arm. During the remainder of the 3-year follow-up period, values (in terms of percent predicted) were maintained (diffusing capacity) or continued to decline at a slower rate (forced vital capacity). However, the average decline of the restrictive lung function parameters over a 3-year period did not exceed 9% predicted in either the TT or the CR arm. Obstructive lung function parameters remained unaffected throughout. Including also the 31 patients with a history of respiratory disease or more than 10 pack-years showed a very similar restrictive pattern. Conclusions: In women with breast cancer, both conventional radiation therapy and hypofractionated tomotherapy induce small but consistent restrictive lung patterns over the course of a 3-year period, irrespective of baseline respiratory status or smoking history. The fastest rate of lung function decline generally occurred in the first 3 months.« less

QuickStats: Brain Cancer Death Rates Among Children and Teens Aged 1-19 Years,* by Sex† and Age Group - United States, 2013-2015.

PubMed

2017-05-05

The death rate for brain cancer, the most common cancer cause of death for children and teens aged 1-19 years, was 24% higher in males (0.73 per 100,000) than females (0.59) aged 1-19 years during 2013-2015. Death rates were higher for males than females for all age groups, but the difference did not reach statistical significance for the age group 5-9 years. Death rates caused by brain cancer were highest at ages 5-9 years (0.98 for males and 0.85 for females).

Age-Specific Incidence of Breast Cancer Subtypes: Understanding the Black–White Crossover

PubMed Central

2012-01-01

Background Breast cancer incidence is higher among black women than white women before age 40 years, but higher among white women than black women after age 40 years (black–white crossover). We used newly available population-based data to examine whether the age-specific incidences of breast cancer subtypes vary by race and ethnicity. Methods We classified 91908 invasive breast cancers diagnosed in California between January 1, 2006, and December 31, 2009, by subtype based on tumor expression of estrogen receptor (ER) and progesterone receptor (PR)—together referred to as hormone receptor (HR)—and human epidermal growth factor receptor 2 (HER2). Breast cancer subtypes were classified as ER or PR positive and HER2 negative (HR+/HER2−), ER or PR positive and HER2 positive (HR+/HER2+), ER and PR negative and HER2 positive (HR−/HER2+), and ER, PR, and HER2 negative (triple-negative). We calculated and compared age-specific incidence rates, incidence rate ratios, and 95% confidence intervals by subtype and race (black, white, Hispanic, and Asian). All P values are two-sided. Results We did not observe an age-related black–white crossover in incidence for any molecular subtype of breast cancer. Compared with white women, black women had statistically significantly higher rates of triple-negative breast cancer at all ages but statistically significantly lower rates of HR+/HER2− breast cancers after age 35 years (all P < .05). The age-specific incidence of HR+/HER2+ and HR−/HER2+ subtypes did not vary markedly between white and black women. Conclusions The black–white crossover in breast cancer incidence occurs only when all breast cancer subtypes are combined and relates largely to higher rates of triple-negative breast cancers and lower rates of HR+/HER2− breast cancers in black vs white women. PMID:22773826

Cancer evolution: mathematical models and computational inference.

PubMed

Beerenwinkel, Niko; Schwarz, Roland F; Gerstung, Moritz; Markowetz, Florian

2015-01-01

Cancer is a somatic evolutionary process characterized by the accumulation of mutations, which contribute to tumor growth, clinical progression, immune escape, and drug resistance development. Evolutionary theory can be used to analyze the dynamics of tumor cell populations and to make inference about the evolutionary history of a tumor from molecular data. We review recent approaches to modeling the evolution of cancer, including population dynamics models of tumor initiation and progression, phylogenetic methods to model the evolutionary relationship between tumor subclones, and probabilistic graphical models to describe dependencies among mutations. Evolutionary modeling helps to understand how tumors arise and will also play an increasingly important prognostic role in predicting disease progression and the outcome of medical interventions, such as targeted therapy. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society of Systematic Biologists.

[Successful pregnancies after oocyte and embryo vitrification].

PubMed

Salazar, Francisco Hernández; Loza, Erik Omar Okhuysen; Lucas, Maria Teresa Huerta J; Gutiérrez, Gustavo Romero

2008-02-01

Cryopreservation of human oocytes represents a solution for ethic conflict about frozen embryo storage for patients with risk to develop ovarian hyperstimulation syndrome; also is an available technique to preserve fertility in women with cancer under treatment, in poor response patients, in case of premature ovarian failure or aging and for other medical or social conditions that require to delay pregnancies, as well as to make easier oocyte donation programs. This paper reports two cases of successful pregnancies after embryo and oocyte vitrification, as well as their results. The technique of vitrification with the cryotop method is an excellent alternative, efficient, fast and cheap for oocyte and embryo cryopreservation with high ranges of fertilization, cleavage and pregnancies with a normal evolution.

High incidence of thyroid cancer among patients with acromegaly.

PubMed

Kaldrymidis, Dimitrios; Papadakis, Georgios; Tsakonas, Georgios; Kaldrymidis, Philippos; Flaskas, Theofanis; Seretis, Andreas; Pantazi, Eleni; Kostoglou-Athanassiou, Ifigenia; Peppa, Melpomeni; Roussou, Paraskevi; Diamanti-Kandarakis, Evanthia

2016-01-01

Several studies have suggested that patients with acromegaly have an increased risk of thyroid, colorectal, breast and prostate cancers. In this study we determined the prevalence of malignant neoplasms in patients with acromegaly. Cancer risk was evaluated in a cohort of 110 patients (M/F 48/62, age 58.63±13.8 years, range 30-86) with acromegaly. Mean age at diagnosis of acromegaly was 46.37±13.11 years. Mean period of time since diagnosis of acromegaly was 12.26+9.6 years. From 110 patients, cancer was diagnosed in 26 (23.6%) patients. Thyroid cancer was the most common cancer and was diagnosed in 13 patients (11.8%); other cancers encountered were gastric cancer (N=2), endometrial cancer (N-2), and breast cancer, colon cancer, prostate cancer (N-2), myelodysplastic syndrome, renal cell carcinoma, lung cancer and pancreatic carcinoma, one case each. Age, gender, age at the time of diagnosis of acromegaly, tumor size of pituitary adenoma and duration of disease were not associated with cancer development. This study suggests that patients with acromegaly have an increased risk of thyroid cancer and therefore they should undergo regular screening with hormonal and ultrasound evaluation of the thyroid and FNAB when required.

Thyroid disorders and breast cancer risk in Asian population: a nationwide population-based case-control study in Taiwan.

PubMed

Weng, Chien-Hsiang; Chen, Yi-Huei; Lin, Ching-Heng; Luo, Xun; Lin, Tseng-Hsi

2018-03-30

To evaluate whether hyperthyroidism or hypothyroidism increases the risk of subsequent breast cancer in an Asian population. Nationwide population-based case-control study. All healthcare facilities in Taiwan. A total of 103 466 women (mean age 53.3 years) were enrolled. 51 733 adult women with newly diagnosed primary breast cancer without a previous cancer history between 2006 and 2011 were identified and included in our study. 51 733 women with no cancer diagnosis prior to the index date were age matched as controls. Diagnosis of hyperthyroidism or hypothyroidism prior to the diagnosis of breast cancer or the same index date was identified, age, histories of thyroid disease treatment, oestrogen use and radioactive iodine treatment were adjusted. To identify risk differences in developing breast cancer among patients with a medical history of hyperthyroidism or hypothyroidism. There was a significantly increased risk of breast cancer in women with hyperthyroidism under the age of 55 years (age <45: OR 1.16, P=0.049; age 45-55: OR 1.15, P=0.019). Patients with hypothyroidism also showed an increased risk of breast cancer (OR 1.19, P=0.029) without statistical significance after stratification by age group (age <45, 45-55, >55 years). Treatment for thyroid disorders did not alter the association in subgroup analyses (P=0.857; 0.262, respectively). Asian women under 55 years of age with history of hyperthyroidism have a significantly increased risk of breast cancer regardless of treatment. Women with history of hypothyroidism may also have an increased risk. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Transcriptomic alterations during ageing reflect the shift from cancer to degenerative diseases in the elderly.

PubMed

Aramillo Irizar, Peer; Schäuble, Sascha; Esser, Daniela; Groth, Marco; Frahm, Christiane; Priebe, Steffen; Baumgart, Mario; Hartmann, Nils; Marthandan, Shiva; Menzel, Uwe; Müller, Julia; Schmidt, Silvio; Ast, Volker; Caliebe, Amke; König, Rainer; Krawczak, Michael; Ristow, Michael; Schuster, Stefan; Cellerino, Alessandro; Diekmann, Stephan; Englert, Christoph; Hemmerich, Peter; Sühnel, Jürgen; Guthke, Reinhard; Witte, Otto W; Platzer, Matthias; Ruppin, Eytan; Kaleta, Christoph

2018-01-30

Disease epidemiology during ageing shows a transition from cancer to degenerative chronic disorders as dominant contributors to mortality in the old. Nevertheless, it has remained unclear to what extent molecular signatures of ageing reflect this phenomenon. Here we report on the identification of a conserved transcriptomic signature of ageing based on gene expression data from four vertebrate species across four tissues. We find that ageing-associated transcriptomic changes follow trajectories similar to the transcriptional alterations observed in degenerative ageing diseases but are in opposite direction to the transcriptomic alterations observed in cancer. We confirm the existence of a similar antagonism on the genomic level, where a majority of shared risk alleles which increase the risk of cancer decrease the risk of chronic degenerative disorders and vice versa. These results reveal a fundamental trade-off between cancer and degenerative ageing diseases that sheds light on the pronounced shift in their epidemiology during ageing.

Blood count and C-reactive protein evolution in gastric cancer patients with total gastrectomy surgery

PubMed Central

CSENDES J., Attila; MUÑOZ Ch., Andrea; BURGOS L., Ana María

2014-01-01

Background The complete blood count (CBC) and C-reactive protein (CRP) are useful inflammatory parameters for ruling out acute postoperative inflammatory complications. Aim To determine their changes in gastric cancer patients submitted to total gastrectomy. Methods This is a prospective study, with 36 patients with gastric cancer who were submitted to elective total gastrectomy. On the first, third and fifth postoperative day (POD), blood count and CRP changes were assessed. Patients with postoperative complications were excluded. Results Twenty-one (58%) were men and 15 (42%) women. The mean age was 65 years. The leukocytes peaked on the 1st POD with a mean of 13,826 u/mm³, and decreased to 8,266 u/mm³ by the 5th POD. The bacilliforms peaked on the 1st POD with a maximum value of 1.48%. CRP reached its maximum level on the 3rd POD with a mean of 144.64 mg/l±44.84. Preoperative hematocrit (HCT) was 35% and 33.67% by the 5th POD. Hemoglobin, showed similar values. Conclusions Leukocytes increased during the 1st POD but reached normal values by the 5th POD. CRP peaked on the 3rd POD but did not reach normal values by the 5th POD. PMID:25626929

Breast Cancer Brain Metastases: Clonal Evolution in Clinical Context.

PubMed

Saunus, Jodi M; McCart Reed, Amy E; Lim, Zhun Leong; Lakhani, Sunil R

2017-01-13

Brain metastases are highly-evolved manifestations of breast cancer arising in a unique microenvironment, giving them exceptional adaptability in the face of new extrinsic pressures. The incidence is rising in line with population ageing, and use of newer therapies that stabilise metastatic disease burden with variable efficacy throughout the body. Historically, there has been a widely-held view that brain metastases do not respond to circulating therapeutics because the blood-brain-barrier (BBB) restricts their uptake. However, emerging data are beginning to paint a more complex picture where the brain acts as a sanctuary for dormant, subclinical proliferations that are initially protected by the BBB, but then exposed to dynamic selection pressures as tumours mature and vascular permeability increases. Here, we review key experimental approaches and landmark studies that have charted the genomic landscape of breast cancer brain metastases. These findings are contextualised with the factors impacting on clonal outgrowth in the brain: intrinsic breast tumour cell capabilities required for brain metastatic fitness, and the neural niche, which is initially hostile to invading cells but then engineered into a tumour-support vehicle by the successful minority. We also discuss how late detection, abnormal vascular perfusion and interstitial fluid dynamics underpin the recalcitrant clinical behaviour of brain metastases, and outline active clinical trials in the context of precision management.

Is the current public health message on UV exposure correct?

PubMed Central

Lucas, Robyn M.; Repacholi, Mike H.; McMichael, Anthony J.

2006-01-01

Current sun safety messages stress the importance of sun protection in avoiding the consequences of excessive exposure to ultraviolet radiation (UVR), such as skin cancers, cataracts and other eye diseases, and viral infections caused by UV-induced immunosuppression. However, adequate exposure to UVR has an important role in human health, primarily through UV-induced production of vitamin D, a hormone essential to bone health. Vitamin D insufficiency may be associated with increased risks of some cancers, autoimmune diseases and mental health disorders such as schizophrenia. Here, we review the evolution of current sun exposure practices and sun-safe messages and consider not only the benefits, but also the detrimental effects that such messages may have. UVR-induced vitamin D production can be inhibited by factors such as deep skin pigmentation, indoor lifestyles, older age, sun avoidance behaviours and clothing habits that limit skin exposure, with deleterious consequences for health. There is some early evidence that sun-safe messages are beginning to cause a decrease in skin cancer rates in young people. After the widespread promotion of sun safety, it may now be appropriate to refine public health messages to take better account of variations between groups and their susceptibility to the dangers and benefits of sun exposure. PMID:16799733

Declines in Cancer Death Rates Among Children and Adolescents in the United States, 1999-2014.

PubMed

Curtin, Sally C; Minino, Arialdi M; Anderson, Robert N

2016-09-01

Data from the National Vital Statistics System •During 1999-2014, the cancer death rate for children and adolescents aged 1-19 years in the United States declined 20%, from 2.85 to 2.28 per 100,000 population. •The cancer death rate for males aged 1-19 years in 2014 was 30% higher than for females. •Declines in cancer death rates during 1999-2014 were experienced among both white and black persons aged 1-19 years and for all 5-year age groups. •During 1999-2014, brain cancer replaced leukemia as the most common cancer causing death among children and adolescents aged 1-19 years, accounting for 3 out of 10 cancer deaths in 2014. Since the mid-1970s, cancer death rates among children and adolescents in the United States showed marked declines despite a slow increase in incidence for some of the major types (1-3). These trends have previously been shown through 2012. This data brief extends previous research by showing trends in cancer death rates through 2014 among children and adolescents aged 1-19 years in the United States. Cancer death rates for 1999-2014 are presented and trends are compared for both females and males, by 5-year age group, and for white and black children and adolescents. Percent distributions of cancer deaths among children and adolescents aged 1-19 years are shown by anatomical site for 1999 and 2014. All material appearing in this report is in the public domain and may be reproduced or copied without permission; citation as to source, however, is appreciated.

[Incidence and mortality of female breast cancer in China, 2014].

PubMed

Li, H; Zheng, R S; Zhang, S W; Zeng, H M; Sun, K X; Xia, C F; Yang, Z X; Chen, W Q; He, J

2018-03-23

Objective: To estimate the incidence and mortality of female breast cancer in China based on the cancer registration data in 2014, collected by the National Central Cancer Registry (NCCR), and to provide support data for breast cancer prevention and control in China. Methods: There were 449 cancer registries submitting female breast cancer incidence and deaths data occurred in 2014 to NCCR. After evaluating the data quality, 339 registries' data were accepted for analysis and stratified by areas (urban/rural) and age group. Combined with data on national population in 2014, the nationwide incidence and mortality of female breast cancer were estimated. Chinese population census in 2000 and Segi's population were used for age-standardized incidence/mortality rates. Results: Qualified 339 cancer registries covered a total of 288 243 347 populations (144 061 915 in urban and 144 181 432 in rural areas) in 2014. The morphology verified cases (MV%) accounted for 87.42% and 0.59% of incident cases were identified through death certifications only (DCO%), with mortality to incidence ratio of 0.24. The estimates of new breast cancer cases were about 278 900 in China in 2014, accounting for 16.51% of all new cases in female. The crude incidence rate, age-standardized rate of incidence by Chinese standard population (ASRIC), and age-standardized rate of incidence by world standard population (ASRIW) of breast cancer were 41.82/100 000, 30.69/100 000, and 28.77/100 000, respectively, with a cumulative incidence rate (0-74 age years old) of 3.12%. The crude incidence rates and ASRIC in urban areas were 49.94 per 100 000 and 34.85 per 100 000, respectively, whereas those were 31.72 per 100 000 and 24.89 per 100 000 in rural areas. The estimates of breast cancer deaths were about 66 000 in China in 2014, accounting for 7.82% of all the cancer-related deaths in female. The crude mortality rate, age-standardized rate of mortality by Chinese standard population(ASRMC) and age-standardized rate of mortality by world standard population (ASRMW) of breast cancer were 9.90/100 000, 6.53/100 000, and 6.35/100 000, respectively, with a cumulative mortality rate of 0.69%. The crude mortality rates and ASRMC in urban areas were 11.48 per 100 000 and 7.04 per 100 000, respectively, whereas those were 7.93 per 100 000 and 5.79 per 100 000 in rural areas. The incidence and mortality rates of breast cancer were higher in areas than those in rural areas. The age-specific incidence rates of breast cancer increased greatly after 20 years old and peaked at the age group of 55-60. The age-specific mortality rates increased rapidly with age, particularly after 25 years old. They remained at a relative stable level from 55 to 65 years of age, and then increased dramatically and peaked in the age group of 85 and above. Conclusions: Breast cancer is still one of the most common malignant tumor threatening to famale health in China. The disease is more prevalent in urban areas at the age group of 55-60. Comprehensive prevention and control strategies referring to local status and age groups should be carried out to reduce the burden of breast cancer.

Spatial structure increases the waiting time for cancer

PubMed Central

Martens, Erik A.; Kostadinov, Rumen; Maley, Carlo C.; Hallatschek, Oskar

2012-01-01

Cancer results from a sequence of genetic and epigenetic changes which lead to a variety of abnormal phenotypes including increased proliferation and survival of somatic cells, and thus, to a selective advantage of pre-cancerous cells. The notion of cancer progression as an evolutionary process has been experiencing increasing interest in recent years. Many efforts have been made to better understand and predict the progression to cancer using mathematical models; these mostly consider the evolution of a well-mixed cell population, even though pre-cancerous cells often evolve in highly structured epithelial tissues. In this study, we propose a novel model of cancer progression that considers a spatially structured cell population where clones expand via adaptive waves. This model is used to assess two different paradigms of asexual evolution that have been suggested to delineate the process of cancer progression. The standard scenario of periodic selection assumes that driver mutations are accumulated strictly sequentially over time. However, when the mutation supply is sufficiently high, clones may arise simultaneously on distinct genetic backgrounds, and clonal adaptation waves interfere with each other. We find that in the presence of clonal interference, spatial structure increases the waiting time for cancer, leads to a patchwork structure of non-uniformly sized clones, decreases the survival probability of virtually neutral (passenger) mutations, and that genetic distance begins to increase over a characteristic length scale Lc. These characteristic features of clonal interference may help to predict the onset of cancers with pronounced spatial structure and to interpret spatially-sampled genetic data obtained from biopsies. Our estimates suggest that clonal interference likely occurs in the progression of colon cancer, and possibly other cancers where spatial structure matters. PMID:22707911

Spatial structure increases the waiting time for cancer

NASA Astrophysics Data System (ADS)

Martens, Erik A.; Kostadinov, Rumen; Maley, Carlo C.; Hallatschek, Oskar

2011-11-01

Cancer results from a sequence of genetic and epigenetic changes that lead to a variety of abnormal phenotypes including increased proliferation and survival of somatic cells and thus to a selective advantage of pre-cancerous cells. The notion of cancer progression as an evolutionary process has been attracting increasing interest in recent years. A great deal of effort has been made to better understand and predict the progression to cancer using mathematical models; these mostly consider the evolution of a well-mixed cell population, even though pre-cancerous cells often evolve in highly structured epithelial tissues. In this study, we propose a novel model of cancer progression that considers a spatially structured cell population where clones expand via adaptive waves. This model is used to assess two different paradigms of asexual evolution that have been suggested to delineate the process of cancer progression. The standard scenario of periodic selection assumes that driver mutations are accumulated strictly sequentially over time. However, when the mutation supply is sufficiently high, clones may arise simultaneously on distinct genetic backgrounds, and clonal adaptation waves interfere with each other. We find that in the presence of clonal interference, spatial structure increases the waiting time for cancer, leads to a patchwork structure of non-uniformly sized clones and decreases the survival probability of virtually neutral (passenger) mutations, and that genetic distance begins to increase over a characteristic length scale Lc. These characteristic features of clonal interference may help us to predict the onset of cancers with pronounced spatial structure and to interpret spatially sampled genetic data obtained from biopsies. Our estimates suggest that clonal interference likely occurs in the progression of colon cancer and possibly other cancers where spatial structure matters.

Age at exposure and attained age variations of cancer risk in the Japanese A-bomb and radiotherapy cohorts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schneider, Uwe, E-mail: uwe.schneider@uzh.ch; Walsh, Linda

Purpose: Phenomenological risk models for radiation-induced cancer are frequently applied to estimate the risk of radiation-induced cancers at radiotherapy doses. Such models often include the effect modification, of the main risk to radiation dose response, by age at exposure and attained age. The aim of this paper is to compare the patterns in risk effect modification by age, between models obtained from the Japanese atomic-bomb (A-bomb) survivor data and models for cancer risks previously reported for radiotherapy patients. Patterns in risk effect modification by age from the epidemiological studies of radiotherapy patients were also used to refine and extend themore » risk effect modification by age obtained from the A-bomb survivor data, so that more universal models can be presented here. Methods: Simple log-linear and power functions of age for the risk effect modification applied in models of the A-bomb survivor data are compared to risks from epidemiological studies of second cancers after radiotherapy. These functions of age were also refined and fitted to radiotherapy risks. The resulting age models provide a refined and extended functional dependence of risk with age at exposure and attained age especially beyond 40 and 65 yr, respectively, and provide a better representation than the currently available simple age functions. Results: It was found that the A-bomb models predict risk similarly to the outcomes of testicular cancer survivors. The survivors of Hodgkin’s disease show steeper variations of risk with both age at exposure and attained age. The extended models predict solid cancer risk increase as a function of age at exposure beyond 40 yr and the risk decrease as a function of attained age beyond 65 yr better than the simple models. Conclusions: The standard functions for risk effect modification by age, based on the A-bomb survivor data, predict second cancer risk in radiotherapy patients for ages at exposure prior to 40 yr and attained ages before 55 yr reasonably well. However, for larger ages, the refined and extended models can be applied to predict the risk as a function of age.« less

Age at exposure and attained age variations of cancer risk in the Japanese A-bomb and radiotherapy cohorts.

PubMed

Schneider, Uwe; Walsh, Linda

2015-08-01

Phenomenological risk models for radiation-induced cancer are frequently applied to estimate the risk of radiation-induced cancers at radiotherapy doses. Such models often include the effect modification, of the main risk to radiation dose response, by age at exposure and attained age. The aim of this paper is to compare the patterns in risk effect modification by age, between models obtained from the Japanese atomic-bomb (A-bomb) survivor data and models for cancer risks previously reported for radiotherapy patients. Patterns in risk effect modification by age from the epidemiological studies of radiotherapy patients were also used to refine and extend the risk effect modification by age obtained from the A-bomb survivor data, so that more universal models can be presented here. Simple log-linear and power functions of age for the risk effect modification applied in models of the A-bomb survivor data are compared to risks from epidemiological studies of second cancers after radiotherapy. These functions of age were also refined and fitted to radiotherapy risks. The resulting age models provide a refined and extended functional dependence of risk with age at exposure and attained age especially beyond 40 and 65 yr, respectively, and provide a better representation than the currently available simple age functions. It was found that the A-bomb models predict risk similarly to the outcomes of testicular cancer survivors. The survivors of Hodgkin's disease show steeper variations of risk with both age at exposure and attained age. The extended models predict solid cancer risk increase as a function of age at exposure beyond 40 yr and the risk decrease as a function of attained age beyond 65 yr better than the simple models. The standard functions for risk effect modification by age, based on the A-bomb survivor data, predict second cancer risk in radiotherapy patients for ages at exposure prior to 40 yr and attained ages before 55 yr reasonably well. However, for larger ages, the refined and extended models can be applied to predict the risk as a function of age.

Indicators of malnutrition in children with cancer: A study of 690 patients from a tertiary care cancer center.

PubMed

Srivastava, R; Pushpam, D; Dhawan, D; Bakhshi, S

2015-01-01

Large data pertaining to indicators of malnutrition in children with cancer is lacking from India. In view of this, we prospectively analyzed consecutive de novo childhood patients with cancer presenting at a tertiary care center. Height and weight of each child (n = 690) were compared with World Health Organization child growth standards-2006 for that particular age and sex to get weight-for-age, height-for-age, and weight-for-height indices and below 2SD of the reference median on these indices were considered as underweight, stunted, and wasted, respectively. Body mass index (BMI) for age was also analyzed for thinness and obesity. Prevalence of malnutrition based on Z-score for weight-for-age, height-for-age, weight-for-height, and BMI-for-age was 30%, 31%, 35%, and 41%, respectively. Weight-for-age (underweight) was significantly associated (P = 0.018) with solid tumors. Height-for-age, weight-for-age, and BMI-for-age were significantly associated (P = 0.007, P = 0.016, and P ≤ 0.001, respectively) with rural community. Malnutrition was observed in approximately one-third of children with cancer. Malnutrition is associated with solid tumors and those coming from rural community. Wasting has a higher prevalence in children with cancer in <5 years of age group.

[Mortality in early-stage, surgically resected non-small cell lung cancer less than 3 cm of size: Competing risk analysis].

PubMed

Jordá Aragón, Carlos; Peñalver Cuesta, Juan Carlos; Mancheño Franch, Nuria; de Aguiar Quevedo, Karol; Vera Sempere, Francisco; Padilla Alarcón, José

2015-09-07

Survival studies of non-small cell lung cancer (NSCLC) are usually based on the Kaplan-Meier method. However, other factors not covered by this method may modify the observation of the event of interest. There are models of cumulative incidence (CI), that take into account these competing risks, enabling more accurate survival estimates and evaluation of the risk of death from other causes. We aimed to evaluate these models in resected early-stage NSCLC patients. This study included 263 patients with resected NSCLC whose diameter was ≤ 3 cm without node involvement (N0). Demographic, clinical, morphopathological and surgical variables, TNM classification and long-term evolution were analysed. To analyse CI, death by another cause was considered to be competitive event. For the univariate analysis, Gray's method was used, while Fine and Gray's method was employed for the multivariate analysis. Mortality by NSCLC was 19.4% at 5 years and 14.3% by another cause. Both curves crossed at 6.3 years, and probability of death by another cause became greater from this point. In multivariate analysis, cancer mortality was conditioned by visceral pleural invasion (VPI) (P=.001) and vascular invasion (P=.020), with age>50 years (P=.034), smoking (P=.009) and the Charlson index ≥ 2 (P=.000) being by no cancer. By the method of CI, VPI and vascular invasion conditioned cancer death in NSCLC >3 cm, while non-tumor causes of long-term death were determined. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Evolution in the profile of thyroid cancer cases treated in an oncology reference service: what changed in the last 20 years.

PubMed

Lira, Renan Bezerra; Carvalho, Genival Barbosa de; Gonçalves Filho, João; Kowalski, Luiz Paulo

2014-01-01

To evaluate the characteristics of thyroid carcinoma cases treated at a reference hospital for cancer between 2008 and 2010. we studied 807 cases and analyzed the following clinicopathologic variables: symptoms, risk factors, diagnostic tests, staging, histological type, treatment performed and complications. Females were more affected, with 660 cases (82%). The average age at diagnosis was 44.5 years. Prior exposure to ionizing radiation was reported by 22 (3%) patients, a family history of thyroid cancer by 89 (11%), and 289 (36%) individuals reported other types of cancer in the family. The fine needle aspiration biopsy was the main parameter for surgical indication and was suggestive of carcinoma in 463 patients (57%). Papillary carcinoma was the most common histological type, with 780 cases (96.6%). There were 728 (90%) total thyroidectomies, 43 (5.3%) reoperations or partial thyroidectomies followed by totalization, 23 (2.8%) extended thyroidectomies and only 13 (1.6%) partial thyroidectomies (lobectomy with isthmectomy). Neck dissection associated with thyroidectomy was done in 158 patients (19.5%). We observed a predominance of tumors classified as T1 in 602 (74.6%) patients. Transient hypocalcemia was the most frequent complication. The results show that the worldwide increase in the incidence of thyroid cancer has changed the profile of patients seen at a referral service. In addition, there were changes in the type of surgical treatment used, with increased use of total thyroidectomy in relation to partial and subtotal ones, and decreased use of elective neck dissections.

The impact of age at diagnosis on socioeconomic inequalities in adult cancer survival in England.

PubMed

Nur, Ula; Lyratzopoulos, Georgios; Rachet, Bernard; Coleman, Michel P

2015-08-01

Understanding the age at which persistent socioeconomic inequalities in cancer survival become apparent may help motivate and support targeting of cancer site-specific interventions, and tailoring guidelines to patients at higher risk. We analysed data on more than 40,000 patients diagnosed in England with one of three common cancers in men and women, breast, colon and lung, 2001-2005 with follow-up to the end of 2011. We estimated net survival for each of the five deprivation categories (affluent, 2, 3, 4, deprived), cancer site, sex and age group (15-44, 45-54, 55-64, and 65-74 and 75-99 years). The magnitude and pattern of the age specific socioeconomic inequalities in survival was different for breast, colon and lung. For breast cancer the deprivation gap in 1-year survival widened with increasing age at diagnosis, whereas the opposite was true for lung cancer, with colon cancer having an intermediate pattern. The 'deprivation gap' in 1-year breast cancer survival widened steadily from -0.8% for women diagnosed at 15-44 years to -4.8% for women diagnosed at 75-99 years, and was the widest for women diagnosed at 65-74 years for 5- and 10-year survival. For colon cancer in men, the gap was widest in patients diagnosed aged 55-64 for 1-, 5- and 10-year survival. For lung cancer, the 'deprivation gap' in survival in patients diagnoses aged 15-44 years was more than 10% for 1-year survival in men and for 1- and 5-year survival in women. Our findings suggest that reduction of socioeconomic inequalities in survival will require updating of current guidelines to ensure the availability of optimal treatment and appropriate management of lung cancer patients in all age groups and older patients in deprived groups with breast or colon cancer. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

[Cost-effectiveness analysis on colorectal cancer screening program].

PubMed

Huang, Q C; Ye, D; Jiang, X Y; Li, Q L; Yao, K Y; Wang, J B; Jin, M J; Chen, K

2017-01-10

Objective: To evaluate the cost-effectiveness of colorectal cancer screening program in different age groups from the view of health economics. Methods: The screening compliance rates, detection rates in different age groups were calculated by using the data from colorectal cancer screening program in Jiashan county, Zhejiang province. The differences in indicator among age groups were analyzed with χ (2) test or trend χ (2) test. The ratios of cost to the number of case were calculated according to cost statistics. Results: The detection rates of immunochemical fecal occult blood test (iFOBT) positivity, advanced adenoma and colorectal cancer and early stage cancer increased with age, while the early diagnosis rates were negatively associated with age. After exclusion the younger counterpart, the cost-effectiveness of individuals aged >50 years could be reduced by 15 %- 30 % . Conclusion: From health economic perspective, it is beneficial to start colorectal cancer screening at age of 50 years to improve the efficiency of the screening.

[Association between obstetric factors, hormone levels and nutritional status with the development of breast cancer].

PubMed

González-Jiménez, Emilio; Montero-Alonso, Miguel Ángel; Schmidt Riovalle, Jacqueline

2013-12-01

Recent studies suggest that the age at first pregnancy, number of children and the lapse between births may protect against breast cancer. Furthermore, serum levels of estrogen, prolactin and progesterone appear to contribute to the development of this tumors in obese women. To verify whether the variables age at first pregnancy, number of children, birth interval, hormone levels and nutritional status are associated with the age at diagnosis of breast cancer. Retrospective analysis of medical records of 550 female patients, diagnosed and treated for breast cancer at a hospital in Spain between 2009 and 2012. We found a significant and positive association between age at diagnosis of cancer and the variables age at first pregnancy, parity and interval between pregnancies. There was also a significant correlation (p < 0.000) between serum levels of estrogen, prolactin and progesterone and nutritional status of patients. In this sample, age at first pregnancy or number of children, hormone levels and nutritional status are related to the age of onset of cancer.

Cancer incidence and mortality in China, 2013.

PubMed

Chen, Wanqing; Zheng, Rongshou; Zhang, Siwei; Zeng, Hongmei; Xia, Changfa; Zuo, Tingting; Yang, Zhixun; Zou, Xiaonong; He, Jie

2017-08-10

National Central Cancer Registry of China (NCCRC) updated nationwide statistics of cancer incidence and mortality in China using population-based cancer registration data in 2013 from all available cancer registries. In 2016, 255 registries' data were qualified and included in this analysis. We estimated numbers of new cancer cases and deaths in China in 2013 using age-specific rates and corresponding national population stratified by area, sex, age group (0, 1-4, 5-9, 10-14…85+) and cancer type. The world Segi's population was applied for age-standardized rates. All rates were expressed per 100,000 person-year. A total of 3,682,000 new cancer cases and 2,229,300 cancer deaths were estimated in China in 2013. Cancers of lung, female breast, stomach, liver, colon-rectum and esophagus were the most common cancers, accounting for about half of all cancer new cases. Lung cancer, liver cancer, stomach cancer, esophageal cancer, colorectal cancer were the five leading causes of cancer death, accounting for about 60% of all cancer deaths. The cancer patterns showed differences not only between male and female, but also among different geographic regions in China. For overall cancers, the age-standardized incidence rates were stable during the past decades in male, but significantly increased by 2.2% per year in female. Cancer poses a major threat to public health and the cancer burden keep raising in China. The annual updated cancer statistics can provide scientific basis for cancer prevention and control. Copyright © 2017. Published by Elsevier B.V.

A guide to help children understand cancer

MedlinePlus

... approach will depend on your child's age and maturity. Here is a general guide. CHILDREN AGES 0 ... child understands cancer. www.cancer.net/coping-and-emotions/communicating-loved-ones/how-child-understands-cancer . Updated ...

Break Breast Cancer Addiction by CRISPR/Cas9 Genome Editing

PubMed Central

Yang, Haitao; Jaeger, MariaLynn; Walker, Averi; Wei, Daniel; Leiker, Katie; Weitao, Tao

2018-01-01

Breast cancer is the leading diagnosed cancer for women globally. Evolution of breast cancer in tumorigenesis, metastasis and treatment resistance appears to be driven by the aberrant gene expression and protein degradation encoded by the cancer genomes. The uncontrolled cancer growth relies on these cellular events, thus constituting the cancerous programs and rendering the addiction towards them. These programs are likely the potential anticancer biomarkers for Personalized Medicine of breast cancer. This review intends to delineate the impact of the CRSPR/Cas-mediated genome editing in identification and validation of these anticancer biomarkers. It reviews the progress in three aspects of CRISPR/Cas9-mediated editing of the breast cancer genomes: Somatic genome editing, transcription and protein degradation addictions. PMID:29344267

Break Breast Cancer Addiction by CRISPR/Cas9 Genome Editing.

PubMed

Yang, Haitao; Jaeger, MariaLynn; Walker, Averi; Wei, Daniel; Leiker, Katie; Weitao, Tao

2018-01-01

Breast cancer is the leading diagnosed cancer for women globally. Evolution of breast cancer in tumorigenesis, metastasis and treatment resistance appears to be driven by the aberrant gene expression and protein degradation encoded by the cancer genomes. The uncontrolled cancer growth relies on these cellular events, thus constituting the cancerous programs and rendering the addiction towards them. These programs are likely the potential anticancer biomarkers for Personalized Medicine of breast cancer. This review intends to delineate the impact of the CRSPR/Cas-mediated genome editing in identification and validation of these anticancer biomarkers. It reviews the progress in three aspects of CRISPR/Cas9-mediated editing of the breast cancer genomes: Somatic genome editing, transcription and protein degradation addictions.

The biological age linked to oxidative stress modifies breast cancer aggressiveness.

PubMed

Sáez-Freire, María Del Mar; Blanco-Gómez, Adrián; Castillo-Lluva, Sonia; Gómez-Vecino, Aurora; Galvis-Jiménez, Julie Milena; Martín-Seisdedos, Carmen; Isidoro-García, María; Hontecillas-Prieto, Lourdes; García-Cenador, María Begoña; García-Criado, Francisco Javier; Patino-Alonso, María Carmen; Galindo-Villardón, Purificación; Mao, Jian-Hua; Prieto, Carlos; Castellanos-Martín, Andrés; Kaderali, Lars; Pérez-Losada, Jesús

2018-05-20

The incidence of breast cancer increases with age until menopause, and breast cancer is more aggressive in younger women. The existence of epidemiological links between breast cancer and aging indicates that both processes share some common mechanisms of development. Oxidative stress is associated with both cancer susceptibility and aging. Here we observed that ERBB2-positive breast cancer, which developed in genetically heterogeneous ERBB2-positive transgenic mice generated by a backcross, is more aggressive in chronologically younger than in older mice (differentiated by the median survival of the cohort that was 79 weeks), similar to what occurs in humans. In this cohort, we estimated the oxidative biological age using a mathematical model that integrated several subphenotypes directly or indirectly related to oxidative stress. The model selected the serum levels of HDL-cholesterol and magnesium and total AKT1 and glutathione concentrations in the liver. The grade of aging was calculated as the difference between the predicted biological age and the chronological age. This comparison permitted the identification of biologically younger and older mice compared with their chronological age. Interestingly, biologically older mice developed more aggressive breast cancer than the biologically younger mice. Genomic regions on chromosomes 2 and 15 linked to the grade of oxidative aging were identified. The levels of expression of Zbp1 located on chromosome 2, a gene related to necroptosis and inflammation, positively correlated with the grade of aging and tumour aggressiveness. Moreover, the pattern of gene expression of genes linked to the inflammation and the response to infection pathways was enriched in the livers of biologically old mice. This study shows part of the complex interactions between breast cancer and aging. Copyright © 2018 Elsevier Inc. All rights reserved.

Age of diagnosis of breast cancer in china: almost 10 years earlier than in the United States and the European union.

PubMed

Song, Qing-Kun; Li, Jing; Huang, Rong; Fan, Jin-Hu; Zheng, Rong-Shou; Zhang, Bao-Ning; Zhang, Bin; Tang, Zhong-Hua; Xie, Xiao-Ming; Yang, Hong-Jian; He, Jian-Jun; Li, Hui; Li, Jia-Yuan; Qiao, You-Lin; Chen, Wan-Qing

2014-01-01

The study aimed to describe the age distribution of breast cancer diagnosis among Chinese females for comparison with the United States and the European Union, and provide evidence for the screening target population in China. Median age was estimated from hospital databases from 7 tertiary hospitals in China. Population-based data in China, United States and European Union was extracted from the National Central Cancer Registry, SEER program and GLOBOCAN 2008, respectively. Age-standardized distribution of breast cancer at diagnosis in the 3 areas was estimated based on the World Standard Population 2000. The median age of breast cancer at diagnosis was around 50 in China, nearly 10 years earlier than United States and European Union. The diagnosis age in China did not vary between subgroups of calendar year, region and pathological characteristics. With adjustment for population structure, median age of breast cancer at diagnosis was 50~54 in China, but 55~59 in United States and European Union. The median diagnosis age of female breast cancer is much earlier in China than in the United States and the European Union pointing to racial differences in genetics and lifestyle. Screening programs should start at an earlier age for Chinese women and age disparities between Chinese and Western women warrant further studies.

Heart Disease and Cancer Deaths - Trends and Projections in the United States, 1969-2020.

PubMed

Weir, Hannah K; Anderson, Robert N; Coleman King, Sallyann M; Soman, Ashwini; Thompson, Trevor D; Hong, Yuling; Moller, Bjorn; Leadbetter, Steven

2016-11-17

Heart disease and cancer are the first and second leading causes of death in the United States. Age-standardized death rates (risk) have declined since the 1960s for heart disease and for cancer since the 1990s, whereas the overall number of heart disease deaths declined and cancer deaths increased. We analyzed mortality data to evaluate and project the effect of risk reduction, population growth, and aging on the number of heart disease and cancer deaths to the year 2020. We used mortality data, population estimates, and population projections to estimate and predict heart disease and cancer deaths from 1969 through 2020 and to apportion changes in deaths resulting from population risk, growth, and aging. We predicted that from 1969 through 2020, the number of heart disease deaths would decrease 21.3% among men (-73.9% risk, 17.9% growth, 34.7% aging) and 13.4% among women (-73.3% risk, 17.1% growth, 42.8% aging) while the number of cancer deaths would increase 91.1% among men (-33.5% risk, 45.6% growth, 79.0% aging) and 101.1% among women (-23.8% risk, 48.8% growth, 76.0% aging). We predicted that cancer would become the leading cause of death around 2016, although sex-specific crossover years varied. Risk of death declined more steeply for heart disease than cancer, offset the increase in heart disease deaths, and partially offset the increase in cancer deaths resulting from demographic changes over the past 4 decades. If current trends continue, cancer will become the leading cause of death by 2020.

[The incidence differences among sex, geographical areas and mean age of diagnosis for liver cancer in China, 1989-2008].

PubMed

Zhang, Siwei; Zheng, Rongshou; Zeng, Hongmei; Chen, Wanqing

2014-05-01

Using the incidence data from 1989 to 2008 of liver cancer from population in cancer registration areas in China, the differences and changes of gender, urban and rural areas for liver cancer incidence in different years were studied, and the mean age of incidence was analyzed. The incidence data of liver cancer from National Cancer Registration database were sorted and checked. A total of 181 097 new liver cancer cases were collected, covering 711 843 051 person years from 1989 to 2008.Using Poisson regression model, Stratified by gender and areas, changes of incidence gender ratio, ratio of urban and rural, and mean age were analyzed. After adjusting the age, the liver cancer incidence in male was about 3 times higher than that in females (ranging from 2.64-3.54), and the ratio change between male and female for the 20 years did not have statistically significant (P = 0.150). The incidence ratio between urban and rural areas has increased from 0.51 in 1989 to 0.61 in 2008 (P < 0.01). The mean ages of diagnosis for male and female increased from 57.14 years to 60.34 years, 61.69 years to 66.47 years, respectively from 1989 to 2008. The mean age of liver cancer diagnosis has increased in the 20 years (P < 0.01). The liver cancer incidence between male and female did not change significantly among 20 years. The difference of liver cancer incidence between urban and rural areas has reduced, and the mean age of diagnosis was deferred.

Long-term trend of thyroid cancer risk among Japanese atomic-bomb survivors: 60 years after exposure

PubMed Central

Furukawa, Kyoji; Preston, Dale; Funamoto, Sachiyo; Yonehara, Shuji; Ito, Masahiro; Tokuoka, Shoji; Sugiyama, Hiromi; Soda, Midori; Ozasa, Kotaro; Mabuchi, Kiyohiko

2014-01-01

Thyroid cancer risk following exposure to ionizing radiation in childhood and adolescence is a topic of public concern. To characterize the long-term temporal trend and age-at-exposure variation in the radiation-induced risk of thyroid cancer, we analyzed thyroid cancer incidence data for the period from 1958 through 2005 among 105,401 members of the Life Span Study cohort of Japanese atomic-bomb survivors. During the follow-up period, 371 thyroid cancer cases (excluding those with microcarcinoma with a diameter <10 mm) were identified as a first primary among the eligible subjects. Using a linear dose–response model, the excess relative risk of thyroid cancer at 1 Gy of radiation exposure was estimated as 1.28 (95% confidence interval: 0.59–2.70) at age 60 after acute exposure at age 10. The risk decreased sharply with increasing age-at-exposure and there was little evidence of increased thyroid cancer rates for those exposed after age 20. About 36% of the thyroid cancer cases among those exposed before age 20 were estimated to be attributable to radiation exposure. While the magnitude of the excess risk has decreased with increasing attained age or time since exposure, the excess thyroid cancer risk associated with childhood exposure has persisted for >50 years after exposure PMID:22847218

Impact of extending screening mammography to older women: Information to support informed choices.

PubMed

Jacklyn, Gemma; Howard, Kirsten; Irwig, Les; Houssami, Nehmat; Hersch, Jolyn; Barratt, Alexandra

2017-10-15

From 2013 through 2017, the Australian national breast cancer screening programme is gradually inviting women aged 70-74 years to attend screening, following a policy decision to extend invitations to older women. We estimate the benefits and harms of the new package of biennial screening from age 50-74 compared with the previous programme of screening from age 50-69. Using a Markov model, we applied estimates of the relative risk reduction for breast cancer mortality and the risk of overdiagnosis from the Independent UK Panel on Breast Cancer Screening review to Australian breast cancer incidence and mortality data. We estimated screening specific outcomes (recalls for further imaging, biopsies, false positives, and interval cancer rates) from data published by BreastScreen Australia. When compared with stopping at age 69, screening 1,000 women to age 74 is likely to avert one more breast cancer death, with an additional 78 women receiving a false positive result and another 28 women diagnosed with breast cancer, of whom eight will be overdiagnosed and overtreated. The extra 5 years of screening results in approximately 7 more overdiagnosed cancers to avert one more breast cancer death. Thus extending screening mammography in Australia to older women results in a less favourable harm to benefit ratio than stopping at age 69. Supporting informed decision making for this age group should be a public health priority. © 2017 UICC.

Breast Cancer Epidemiology of the Working-Age Female Population Reveals Significant Implications for the South Korean Economy.

PubMed

Park, Jeong Hyun; Lee, Se Kyung; Lee, Jeong Eon; Kim, Seok Won; Nam, Seok Jin; Kim, Ji-Yeon; Ahn, Jin-Seok; Park, Won; Yu, Jonghan; Park, Yeon Hee

2018-03-01

In this study, we aimed to evaluate the economic loss due to the diagnosis of breast cancer within the female South Korean working-age population. A population-based cost analysis was performed for cancer-related diagnoses between 1999 and 2014, using respective public government funded databases. Among the five most common cancers, breast cancer mortality was strongly associated with the growth in gross domestic product between 1999 and 2014 (R=0.98). In the female population, breast cancer represented the greatest productivity loss among all cancers, which was a consequence of the peak in the incidence of breast cancer during mid-working age in the working-age population, in addition to being the most common and fastest growing cancer among South Korean women. Our study shows that breast cancer not only represents a significant disease burden for individual patients, but also contributes a real, nonnegligible loss in productivity in the South Korean economy.

Useful indicators to interpret the cancer burden in Italy.

PubMed

Vercelli, Marina; Quaglia, Alberto; Lillini, Roberto

2013-01-01

In the last decades the demographics of most Western countries have undergone a deep transformation, which has caused a steady increase in degenerative chronic diseases and has made maintaining health and social support by the welfare system difficult. This paper aims to present a set of indicators pertaining to the health status of the Italian population and to the national economic and social systems, as an aid to a better interpretation of the cancer burden impact and of its future tendencies. All indicators were derived from the ISTAT Health for All database. They were presented by region or macro area, globally or by gender, considering the most recent regional distribution and their time trends. The following features of the Italian population were chosen: percent of people aged over 65 years; life expectancy at birth; birth rate; crude and age-standardized overall mortality rates; dependency ratio; percent of single persons; percent of people with no more than a junior high school diploma; percent of people attaining at least the short first university degree; percent of people employed in the service and tertiary sectors; unemployment rate; incidence of poverty; total health expenditure (THE) as an absolute value and as percent of GDP; percent of public THE; percent of out-of-pocket THE of households; percent of smokers; proportion of overweight and obese people aged ≥18 years. Italy presented an unbalanced demographic situation with an increasingly old population, a decreasing middle-aged age group, a low birth rate, high crude overall mortality rates, and decreasing standardized overall mortality rates. The Italian population is characterized by a constant increase in the dependency ratio and in the percentage of people living alone, together with increasing expenses for health care, both at the public and households levels. Smoking has reduced its impact in men but not yet in women. The increasing proportion of overweight and obese people may explain the convergence in time of the mortality rates of the different Italian macro areas. The Italian situation seems to be not well fitted to face the expected growing cancer burden. Along with the aging of the population, the corresponding lowering of the national GDP due to the persisting global economic crisis will lead the public sector and families to reduce health expenditure, while the number of people affected by cancer is bound to increase. Moreover, the social support provided by family members and the advantages of the Mediterranean dietary habits are declining. The strategies for facing the challenging evolution of the future should focus on successful primary prevention and a wider application of evidence-based medicine to optimize the choice of diagnostic and therapeutic procedures offered to citizens.

Evolution in Stage-Structured Populations

PubMed Central

Barfield, Michael; Holt, Robert D.; Gomulkiewicz, Richard

2016-01-01

For many organisms, stage is a better predictor of demographic rates than age. Yet no general theoretical framework exists for understanding or predicting evolution in stage-structured populations. Here, we provide a general modeling approach that can be used to predict evolution and demography of stage-structured populations. This advances our ability to understand evolution in stage-structured populations to a level previously available only for populations structured by age. We use this framework to provide the first rigorous proof that Lande’s theorem, which relates adaptive evolution to population growth, applies to stage-classified populations, assuming only normality and that evolution is slow relative to population dynamics. We extend this theorem to allow for different means or variances among stages. Our next major result is the formulation of Price’s theorem, a fundamental law of evolution, for stage-structured populations. In addition, we use data from Trillium grandiflorum to demonstrate how our models can be applied to a real-world population and thereby show their practical potential to generate accurate projections of evolutionary and population dynamics. Finally, we use our framework to compare rates of evolution in age- versus stage-structured populations, which shows how our methods can yield biological insights about evolution in stage-structured populations. PMID:21460563

Social Media and the Adolescent and Young Adult (AYA) patient with Cancer

PubMed Central

Perales, Miguel-Angel; Drake, Emily K; Pemmaraju, Naveen; Wood, William A

2016-01-01

Over 70,000 adolescent and young adults aged 15 to 39 years (AYA) are diagnosed with cancer each year in the US. The National Cancer Institute (NCI) has identified AYA cancer patients as a unique population. The most common cancers in this age group include tumors typically seen in pediatric patients such as acute lymphoblastic leukemia (ALL) and brain tumors, as well as cancers more typically seen in adult patients such as breast cancer and melanoma. In addition, some cancers have their highest incidence in AYA patients, such as Hodgkin Lymphoma, testicular cancer and bone tumors. AYA patients face additional unique issues due to their age, not just questions about treatment choices due to lack of data, but also questions about fertility, relationships, loss of autonomy, and interruptions in school/work with potentially significant financial complications. This age group also has very high rates of social media usage with up to 90% of adults aged 18 to 29 using social networking sites. In this review, we will describe the use of social media in AYAs with cancer and highlight some of the online resources for AYAs. PMID:26893061

Social Media and the Adolescent and Young Adult (AYA) Patient with Cancer.

PubMed

Perales, Miguel-Angel; Drake, Emily K; Pemmaraju, Naveen; Wood, William A

2016-12-01

Over 70,000 adolescent and young adults (AYA) aged 15 to 39 years are diagnosed with cancer each year in the US. The National Cancer Institute (NCI) has identified AYA cancer patients as a unique population. The most common cancers in this age group include tumors typically seen in pediatric patients such as acute lymphoblastic leukemia (ALL) and brain tumors, as well as cancers more typically seen in adult patients such as breast cancer and melanoma. In addition, some cancers have their highest incidence in AYA patients, such as Hodgkin Lymphoma, testicular cancer, and bone tumors. AYA patients face additional unique issues due to their age, not just questions about treatment choices due to lack of data but also questions about fertility, relationships, loss of autonomy, and interruptions in school/work with potentially significant financial complications. This age group also has very high rates of social media usage with up to 90 % of adults aged 18 to 29 using social networking sites. In this review, we will describe the use of social media in AYAs with cancer and highlight some of the online resources for AYAs.

Lung Cancer: Posttreatment Imaging: Radiation Therapy and Imaging Findings.

PubMed

Benveniste, Marcelo F; Welsh, James; Viswanathan, Chitra; Shroff, Girish S; Betancourt Cuellar, Sonia L; Carter, Brett W; Marom, Edith M

2018-05-01

In this review, we discuss the different radiation delivery techniques available to treat non-small cell lung cancer, typical radiologic manifestations of conventional radiotherapy, and different patterns of lung injury and temporal evolution of the newer radiotherapy techniques. More sophisticated techniques include intensity-modulated radiotherapy, stereotactic body radiotherapy, proton therapy, and respiration-correlated computed tomography or 4-dimensional computed tomography for radiotherapy planning. Knowledge of the radiation treatment plan and technique, the completion date of radiotherapy, and the temporal evolution of radiation-induced lung injury is important to identify expected manifestations of radiation-induced lung injury and differentiate them from tumor recurrence or infection. Published by Elsevier Inc.

Evolution of breast cancer screening in the Medicare population: clinical and economic implications.

PubMed

Killelea, Brigid K; Long, Jessica B; Chagpar, Anees B; Ma, Xiaomei; Wang, Rong; Ross, Joseph S; Gross, Cary P

2014-08-01

Newer approaches to mammography, including digital image acquisition and computer-aided detection (CAD), and adjunct imaging (e.g., magnetic resonance imaging [MRI]) have diffused into clinical practice. The impact of these technologies on screening-related cost and outcomes remains undefined, particularly among older women. Using the Surveillance, Epidemiology, and End Results-Medicare linked database, we constructed two cohorts of women without a history of breast cancer and followed each cohort for 2 years. We compared the use and cost of screening mammography including digital mammography and CAD, adjunct procedures including breast ultrasound, MRI, and biopsy between the period of 2001 and 2002 and the period of 2008 and 2009 using χ(2) and t test. We also assessed the change in breast cancer stage and incidence rates using χ(2) and Poisson regression. All statistical tests were two-sided. There were 137150 women (mean age = 76.0 years) in the early cohort (2001-2002) and 133097 women (mean age = 77.3 years) in the later cohort (2008-2009). The use of digital image acquisition for screening mammography increased from 2.0% in 2001 and 2002 to 29.8% in 2008 and 2009 (P < .001). CAD use increased from 3.2% to 33.1% (P < .001). Average screening-related cost per capita increased from $76 to $112 (P < .001), with annual national fee-for-service Medicare spending increasing from $666 million to $962 million. There was no statistically significant change in detection rates of early-stage tumors (2.45 vs 2.57 per 1000 person-years; P = .41). Although breast cancer screening-related costs increased substantially from 2001 through 2009 among Medicare beneficiaries, a clinically significant change in stage at diagnosis was not observed. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

The future of smoking-attributable mortality: the case of England & Wales, Denmark and the Netherlands.

PubMed

Stoeldraijer, Lenny; Bonneux, Luc; van Duin, Coen; van Wissen, Leo; Janssen, Fanny

2015-02-01

We formally estimate future smoking-attributable mortality up to 2050 for the total national populations of England & Wales, Denmark and the Netherlands, providing an update and extension of the descriptive smoking-epidemic model. We used smoking prevalence and population-level lung cancer mortality data for England & Wales, Denmark and the Netherlands, covering the period 1950-2009. To estimate the future smoking-attributable mortality fraction (SAF) we: (i) project lung cancer mortality by extrapolating age-period-cohort trends, using the observed convergence of smoking prevalence and similarities in past lung cancer mortality between men and women as input; and (ii) add other causes of death attributable to smoking by applying a simplified version of the indirect Peto-Lopez method to the projected lung cancer mortality. The SAF for men in 2009 was 19% (44 872 deaths) in England & Wales, 22% (5861 deaths) in Denmark and 25% (16 385 deaths) in the Netherlands. In our projections, these fractions decline to 6, 12 and 14%, respectively, in 2050. The SAF for women peaked at 14% (38 883 deaths) in 2008 in England & Wales, and is expected to peak in 2028 in Denmark (22%) and in 2033 in the Netherlands (23%). By 2050, a decline to 9, 17 and 19%, respectively, is foreseen. Different indirect estimation methods of the SAF in 2050 yield a range of 1-8% (England & Wales), 8-13% (Denmark) and 11-16% (the Netherlands) for men, and 7-16, 12-26 and 13-31% for women. From northern European data we project that smoking-attributable mortality will remain important for the future, especially for women. Whereas substantial differences between countries remain, the age-specific evolution of smoking-attributable mortality remains similar across countries and between sexes. © 2014 Society for the Study of Addiction.

Anthropogenic selection enhances cancer evolution in Tasmanian devil tumours.

PubMed

Ujvari, Beata; Pearse, Anne-Maree; Swift, Kate; Hodson, Pamela; Hua, Bobby; Pyecroft, Stephen; Taylor, Robyn; Hamede, Rodrigo; Jones, Menna; Belov, Katherine; Madsen, Thomas

2014-02-01

The Tasmanian Devil Facial Tumour Disease (DFTD) provides a unique opportunity to elucidate the long-term effects of natural and anthropogenic selection on cancer evolution. Since first observed in 1996, this transmissible cancer has caused local population declines by >90%. So far, four chromosomal DFTD variants (strains) have been described and karyotypic analyses of 253 tumours showed higher levels of tetraploidy in the oldest strain. We propose that increased ploidy in the oldest strain may have evolved in response to effects of genomic decay observed in asexually reproducing organisms. In this study, we focus on the evolutionary response of DFTD to a disease suppression trial. Tumours collected from devils subjected to the removal programme showed accelerated temporal evolution of tetraploidy compared with tumours from other populations where no increase in tetraploid tumours were observed. As ploidy significantly reduces tumour growth rate, we suggest that the disease suppression trial resulted in selection favouring slower growing tumours mediated by an increased level of tetraploidy. Our study reveals that DFTD has the capacity to rapidly respond to novel selective regimes and that disease eradication may result in novel tumour adaptations, which may further imperil the long-term survival of the world's largest carnivorous marsupial.

Anthropogenic selection enhances cancer evolution in Tasmanian devil tumours

PubMed Central

Ujvari, Beata; Pearse, Anne-Maree; Swift, Kate; Hodson, Pamela; Hua, Bobby; Pyecroft, Stephen; Taylor, Robyn; Hamede, Rodrigo; Jones, Menna; Belov, Katherine; Madsen, Thomas

2014-01-01

The Tasmanian Devil Facial Tumour Disease (DFTD) provides a unique opportunity to elucidate the long-term effects of natural and anthropogenic selection on cancer evolution. Since first observed in 1996, this transmissible cancer has caused local population declines by >90%. So far, four chromosomal DFTD variants (strains) have been described and karyotypic analyses of 253 tumours showed higher levels of tetraploidy in the oldest strain. We propose that increased ploidy in the oldest strain may have evolved in response to effects of genomic decay observed in asexually reproducing organisms. In this study, we focus on the evolutionary response of DFTD to a disease suppression trial. Tumours collected from devils subjected to the removal programme showed accelerated temporal evolution of tetraploidy compared with tumours from other populations where no increase in tetraploid tumours were observed. As ploidy significantly reduces tumour growth rate, we suggest that the disease suppression trial resulted in selection favouring slower growing tumours mediated by an increased level of tetraploidy. Our study reveals that DFTD has the capacity to rapidly respond to novel selective regimes and that disease eradication may result in novel tumour adaptations, which may further imperil the long-term survival of the world's largest carnivorous marsupial. PMID:24567746

Aging and cancer: are sirtuins the link?

PubMed

Rodriguez, Ramon M; Fraga, Mario F

2010-06-01

Classically, aging has been defined as a general degeneration process that leads to the loss of corporal function. The loss of function caused by degeneration limits the maximum lifespan of all organisms and is linked to disease and cancer. Nevertheless, the molecular mechanisms behind aging and their connection to cancer are not well understood. NAD-dependent protein deacetylase enzymes, sirtuins, are emerging as a novel molecular link between aging and cancer due to their specific role in cell cycle regulation, antistress response and cell survival. This article reviews the contribution of sirtuins and environmental factors to ontogenic development, senescence and cancer.

Clonal evolution in hematologic malignancies and therapeutic implications

PubMed Central

Landau, Dan A.; Carter, Scott L.; Getz, Gad; Wu, Catherine J.

2014-01-01

The ability of cancer to evolve and adapt is a principal challenge to therapy in general, and to the paradigm of targeted therapy in particular. This ability is fueled by the co-existence of multiple, genetically heterogeneous subpopulations within the cancer cell population. Increasing evidence has supported the idea that these subpopulations are selected in a Darwinian fashion, by which the genetic landscape of the tumor is continuously reshaped. Massively parallel sequencing has enabled a recent surge in our ability to study this process, adding to previous efforts using cytogenetic methods and targeted sequencing. Altogether, these studies reveal the complex evolutionary trajectories occurring across individual hematological malignancies. They also suggest that while clonal evolution may contribute to resistance to therapy, treatment may also hasten the evolutionary process. New insights into this process challenge us to understand the impact of treatment on clonal evolution, and inspire the development of novel prognostic and therapeutic strategies. PMID:23979521

Vital Signs: Trends in Incidence of Cancers Associated with Overweight and Obesity — United States, 2005–2014

PubMed Central

Thomas, Cheryll C.; Henley, S. Jane; Massetti, Greta M.; Galuska, Deborah A.; Agurs-Collins, Tanya; Puckett, Mary; Richardson, Lisa C.

2017-01-01

Background Overweight and obesity are associated with increased risk of at least 13 different types of cancer. Methods Data from the United States Cancer Statistics for 2014 were used to assess incidence rates, and data from 2005 to 2014 were used to assess trends for cancers associated with overweight and obesity (adenocarcinoma of the esophagus; cancers of the breast [in postmenopausal women], colon and rectum, endometrium, gallbladder, gastric cardia, kidney, liver, ovary, pancreas, and thyroid; meningioma; and multiple myeloma) by sex, age, race/ethnicity, state, geographic region, and cancer site. Because screening for colorectal cancer can reduce colorectal cancer incidence through detection of precancerous polyps before they become cancerous, trends with and without colorectal cancer were analyzed. Results In 2014, approximately 631,000 persons in the United States received a diagnosis of a cancer associated with overweight and obesity, representing 40% of all cancers diagnosed. Overweight- and obesity-related cancer incidence rates were higher among older persons (ages ≥50 years) than younger persons; higher among females than males; and higher among non-Hispanic black and non-Hispanic white adults compared with other groups. Incidence rates for overweight- and obesity-related cancers during 2005–2014 varied by age, cancer site, and state. Excluding colorectal cancer, incidence rates increased significantly among persons aged 20–74 years; decreased among those aged ≥75 years; increased in 32 states; and were stable in 16 states and the District of Columbia. Conclusions The burden of overweight- and obesity-related cancer is high in the United States. Incidence rates of overweight- and obesity-related cancers except colorectal cancer have increased in some age groups and states. Implications for Public Health Practice The burden of overweight- and obesity-related cancers might be reduced through efforts to prevent and control overweight and obesity. Comprehensive cancer control strategies, including use of evidence-based interventions to promote healthy weight, could help decrease the incidence of these cancers in the United States. PMID:28981482

NAD+ Deficits in Age-Related Diseases and Cancer.

PubMed

Garrido, Amanda; Djouder, Nabil

2017-08-01

The phenomenon of aging has gained widespread attention in recent times. Although significant advances have been made to better understand aging and its related pathologies including cancer, there is not yet a clear mechanism explaining why diseases and cancer are inherent parts of the aging process. Finding a unifying equation that could bridge aging and its related diseases would allow therapeutic development and solve an immense human health problem to live longer and better. In this review, we discuss NAD + reduction as the central mechanism that may connect aging to its related pathologies and cancer. NAD + boosters would ensure and ameliorate health quality during aging. Copyright © 2017 Elsevier Inc. All rights reserved.

Access to Preventive Health Care for Cancer Survivors

PubMed Central

Yabroff, K. Robin; Short, Pamela Farley; Machlin, Steven; Dowling, Emily; Rozjabek, Heather; Li, Chunyu; McNeel, Timothy; Ekwueme, Donatus U.; Virgo, Katherine S.

2013-01-01

Background Access to healthcare, particularly effective primary and secondary preventive care, is critical for cancer survivors, in order to minimize the adverse sequelae of cancer and its treatment. Purpose The goal of the study was to evaluate the association between cancer survivorship and access to primary and preventive health care. Methods Cancer survivors (n=4960) and individuals without a cancer history (n=64,431) aged ≥18 years, from the 2008–2010 Medical Expenditure Panel Survey (MEPS), were evaluated. Multiple measures of access and preventive services use were compared. The association between cancer survivorship and access and preventive services was evaluated with multivariate logistic regression models, stratified by age group (18–64 years and ≥65 years), controlling for the effects of age, gender, race/ethnicity, education, marital status, and comorbidities. Data were analyzed in 2013. Results Cancer survivors aged ≥65 years had equivalent or greater access and preventive services use than individuals without a cancer history, in adjusted analyses. However, among those aged 18–64 years with private health insurance, cancer survivors were more likely than other individuals to have a usual source of care and to use preventive services, whereas uninsured or publicly insured cancer survivors were generally less likely to have a usual source of care and to use preventive services than were uninsured or publicly insured adults without a cancer history. Conclusions Although access and preventive care use in cancer survivors is generally equivalent or greater compared to that of other individuals, disparities for uninsured and publicly insured cancer survivors aged 18–64 years suggest that improvements in survivor care are needed. PMID:23953357

Health State Utility Impact of Breast Cancer in U.S. Women Aged 18-44 Years.

PubMed

Brown, Derek S; Trogdon, Justin G; Ekwueme, Donatus U; Chamiec-Case, Linda; Guy, Gery P; Tangka, Florence K; Li, Chunyu; Trivers, Katrina F; Rodriguez, Juan L

2016-02-01

Breast cancer affects women's health-related quality of life negatively, but little is known about how breast cancer affects this in younger women aged 18-44 years. This study measures preference-based health state utility (HSU) values, a scaled index of health-related quality of life for economic evaluation, for younger women with breast cancer and compares these values with same-age women with other cancers and older women (aged ≥45 years) with breast cancer. Data from the 2009 and 2010 Behavioral Risk Factor Surveillance System were analyzed in 2014. The sample included 218,852 women; 7,433 and 18,577 had histories of breast and other cancers. HSU values were estimated using Healthy Days survey questions and a published mapping algorithm. Linear regression models for HSU were estimated by age group (18-44 and ≥45 years). The adjusted breast cancer HSU impact was four times larger for younger women than for older women (-0.097 vs -0.024, p<0.001). For younger women, the effect of breast cancer on HSU was 70% larger than that of other cancers (-0.097 vs -0.057, p=0.024). Younger breast cancer survivors reported lower HSU values than older survivors, highlighting the impact of breast cancer on the physical and mental health of younger women. The estimates may be used to evaluate quality-adjusted life-years or expectancy for prevention or treatment of breast cancer. This study also indicates that separate quality of life adjustments for women by age group are important for economic analysis of public health breast cancer interventions. Copyright © 2016 American Journal of Preventive Medicine. All rights reserved.

Cancer mortality in central Serbia.

PubMed

Markovic-Denic, Ljiljana; Cirkovic, Andia; Zivkovic, Snezana; Stanic, Danica; Skodric-Trifunovic, Vesna

2014-01-01

Cancer is the one of the leading cause of death worldwide. The aim of this study was to examine cancer mortality trends in the population of central Serbia in the period from 2002 to 2011. The descriptive epidemiological method was used. The mortality from all malignant tumors (code C00-C96 of the International Disease Classification) was registered. The source of mortality data was the published material of the Cancer Registry of Serbia. The source of population data was the census of 2002 and 2011 and the estimates for inter-census years. Non-standardized, age-adjusted and age-specific mortality rates were calculated. Age adjustment of mortality rates was performed by the direct method of standardization. Trend lines were estimated using linear regression. During 2002-2011, cancer caused about 20% of all deaths each year in central Serbia. More men (56.9%) than women (43.1%) died of cancer. The average mortality rate for men was 1.3 times higher compared to women. A significant trend of increase of the age-adjusted mortality rates was recorded both for males (p<0.001) and for females (p=0.02). Except gastric cancer, the age-adjusted mortality rates in men were significantly increased for lung cancer (p=0.02), colorectal cancer (p<0.05), prostate cancer (p=0.01) and pancreatic cancer (p=0.01). Age-adjusted mortality rates for breast cancer in females were remarkably increased (p=0.01), especially after 2007. In central Serbia during the period from 2002 to 2011, there was an increasing trend in mortality rates due to cancers in both sexes. Cancer mortality in males was 1.3-fold higher compared to females.

Advanced glycation end products influence oral cancer cell survival via Bcl-xl and Nrf-2 regulation in vitro.

PubMed

Ko, Shun-Yao; Ko, Hshin-An; Shieh, Tzong-Ming; Chi, Tzong-Cherng; Chen, Hong-I; Chen, Yi-Ting; Yu, Ya-Hui; Yang, Shu-Han; Chang, Shu-Shing

2017-05-01

An irreversible non-enzymatic reaction between carbohydrates and proteins results in the formation of advanced glycation end products (AGEs). AGEs have been demonstrated to be a risk factor of complications in patients with diabetes mellitus (DM). Previous studies have suggested that patients with DM exhibit a higher rate of metastasis of oral cancer and a lower cancer-associated survival rate. The receptor for AGEs (RAGE) has been associated with angiogenesis and an increase in cancer malignancy. Previous studies have suggested that AGE-RAGE regulates cell migration via extracellular signal-regulated kinase (ERK) phosphorylation. Nuclear factor-erythroid 2-related factor 2 (Nrf-2) is associated with the regulation of tumor protein p53 (p53) and the apoptotic response of oral cancer cells. AGEs are associated with oral cancer; however, the mechanism underlying this association remains to be elucidated. The present study hypothesized that AGEs regulate Nrf-2 and downstream pathways through ERK phosphorylation. The results of the current study demonstrated that AGEs inhibit the expression of Nrf-2, p53 and Bcl-2 associated × apoptosis regulator, and increase the expression of apoptosis regulator Bcl-x protein. The effect of AGEs was inhibited through the use of the PD98059. The present study demonstrated that AGEs regulate the downstream pathways Nrf-2 and Bcl-xl via ERK phosphorylation. It is suggested that AGEs regulate the survival of oral cancer cells via Nrf-2 and Bcl-xl through p53 regulation, which explains the poor prognosis of patients with DM who have oral cancer.

Characteristics of invasive breast cancer and overall survival of patients eligible for mass breast cancer screening in Guadeloupe compared to those of the preceding age group.

PubMed

Kadhel, Philippe; Borja De Mozota, Daphné; Gaumond, Stéphanie; Deloumeaux, Jacqueline

2017-10-01

Mass breast cancer screening is offered to French women between the ages of 50 and 74. In the French overseas department of Guadeloupe, where the population is of mostly African ancestry, a low age at diagnosis of breast cancer has been reported, as for African-Americans. This raises the question of whether breast cancer is more aggressive in the age group preceding that eligible for mass screening (40-49) in Guadeloupe. We compared the tumor-related prognostic factors, first line therapy and overall survival rates of breast cancer cases diagnosed between the 40-49 and 50-74 age groups, based on reports of the cancer registry of Guadeloupe for the period 2008-2013. The characteristics studied, risk of death after breast cancer (HR 0.84 [95% CI: 0.58-1.22] and overall survival, did not differ significantly between the two groups, except for higher tumor size (28.8 vs 24.0; p=0.004) in the younger group. These results do not show a pattern of more aggressive breast cancer in the age group preceding that eligible for mass screening in Guadeloupe. Copyright © 2017 Elsevier Ltd. All rights reserved.

Squamous Cell Carcinoma in African Children with Xeroderma Pigmentosum: Three Case Reports.

PubMed

Kaloga, Mamadou; Dioussé, Pauline; Diatta, Boubacar Ahy; Bammo, Mariama; Kourouma, Sarah; Diabate, Almamy; Gueye, Ndiaga; Dione, Haby; Diallo, Moussa; Diop, Bernard Marcel

2016-01-01

Xeroderma pigmentosum is a rare autosomal recessive genetic disease. This disease predisposes patients to early-onset skin cancers, particularly squamous cell carcinoma. Here, we report 3 pediatric cases, including 2 deaths. The subjects included 2 boys and 1 girl with skin type VI. All subjects were from consanguineous marriages, and the average age was 7.6 years. The patients all had ulcerative budding tumor lesions in the cephalic region, and the mean disease duration was 18 months. In all 3 cases, the diagnosis of xeroderma pigmentosum was made before the poikilodermal appearance of sun-exposed areas and photophobia. Neurological-type mental retardation was noted in 1 case. Histology confirmed squamous cell carcinoma in all 3 cases. The evolutions were marked by the death of 2 children (cases 1 and 3). In one case, the outcome was favorable following cancer excision and subsequent chemotherapy with adjuvant radiotherapy. Squamous cell carcinoma is a serious complication related to xeroderma pigmentosum in Sub-Saharan Africa. Prevention is based on the early diagnosis of xeroderma pigmentosum, black skin photoprotection, screening and early treatment of lesions, and genetic counseling.

Colorectal cancer is a leading cause of cancer incidence and mortality among adults younger than 50 years in the USA: a SEER-based analysis with comparison to other young-onset cancers.

PubMed

Bhandari, Abhishek; Woodhouse, Melissa; Gupta, Samir

2017-02-01

Colorectal cancer (CRC) incidence and mortality are rising among young adults. Our aim was to contrast the relative incidence and mortality of CRC to other common cancers among young adults in the USA. We used Surveillance, Epidemiology, and End Results registry data to compare cancer site-specific and age-specific mortality and incident rates for adults younger than age 50. We summarized extracted data, both overall, and stratified by sex. We found CRC was the third leading cause of cancer death among adults younger than age 50, after breast and lung cancer (1.67 cases per 100,000). Among young women, CRC was the fourth leading cause of cancer death (1.51 per 100,000). Among young men, CRC was the second leading cause of cancer death (1.82 cases per 100,000). CRC was the second most incident cancer among young adults for men and women combined. Among men, CRC was the second most incident cancer after age 30, with 4.9, 9.0, 16.4, and 30.8 cases per 100,000 for ages 30-34, 35-39, 40-44, and 45-49 years, respectively. Among women, CRC incidence was similar with 4.2, 7.6, 15.3, and 25.9 cases per 100,000 for ages 30-34, 35-39, 40-44, and 45-49 years, respectively. These results show that CRC is a leading cause of cancer incidence and mortality among young adults in the USA, relative to other cancers. Given trends toward increasing rates of CRC among young adults, strategies for identifying individuals at risk for young-onset CRC who might benefit from early age of screening initiation merit investigation. Copyright © 2016 American Federation for Medical Research.

Glucose-derived AGEs enhance human gastric cancer metastasis through RAGE/ERK/Sp1/MMP2 cascade.

PubMed

Deng, Ruyuan; Mo, Fengbo; Chang, Bowen; Zhang, Qi; Ran, Hui; Yang, Shuhua; Zhu, Zhiqiang; Hu, Lei; Su, Qing

2017-11-28

Advanced glycation end products (AGEs) have been reported to take part in many cancer processes. Whether AGEs contribute to gastric cancer (GC) course and the underlying mechanism are still unclear. Here, glucose-derived AGEs are detected to be accumulated in tumor tissues and blood of patients with GC. As the receptor for AGEs, RAGE is highly expressed in cancer tissues, and closely associated with the depth of cancer invasion, lymph node metastasis and TNM stage. Both in vivo and in vitro treatment of AGEs accelerate the tumor invasion and metastasis, with upregualtion of RAGE, Specificity Protein 1 (Sp1), and MMP2 protein expression, as well as enhancement of MMP2 activity. Either RAGE-blocking antibody or Sp1-knockdown can partially block the AGEs-induced effects. Moreover, AGEs increased the phosphorylation of ERK, and reducing the phosphorylation level of ERK by MEK1/2 inhibitor decreased the expression of Sp1. These results indicate that accumulation of glucose-derived AGEs may act as one of potential risk factors for GC progression and promote the invasion and metastasis of gastric cancer partially through the activation of RAGE/ERK/Sp1/MMP2 pathway.

Glucose-derived AGEs enhance human gastric cancer metastasis through RAGE/ERK/Sp1/MMP2 cascade

PubMed Central

Deng, Ruyuan; Mo, Fengbo; Chang, Bowen; Zhang, Qi; Ran, Hui; Yang, Shuhua; Zhu, Zhiqiang; Hu, Lei; Su, Qing

2017-01-01

Advanced glycation end products (AGEs) have been reported to take part in many cancer processes. Whether AGEs contribute to gastric cancer (GC) course and the underlying mechanism are still unclear. Here, glucose-derived AGEs are detected to be accumulated in tumor tissues and blood of patients with GC. As the receptor for AGEs, RAGE is highly expressed in cancer tissues, and closely associated with the depth of cancer invasion, lymph node metastasis and TNM stage. Both in vivo and in vitro treatment of AGEs accelerate the tumor invasion and metastasis, with upregualtion of RAGE, Specificity Protein 1 (Sp1), and MMP2 protein expression, as well as enhancement of MMP2 activity. Either RAGE-blocking antibody or Sp1-knockdown can partially block the AGEs-induced effects. Moreover, AGEs increased the phosphorylation of ERK, and reducing the phosphorylation level of ERK by MEK1/2 inhibitor decreased the expression of Sp1. These results indicate that accumulation of glucose-derived AGEs may act as one of potential risk factors for GC progression and promote the invasion and metastasis of gastric cancer partially through the activation of RAGE/ERK/Sp1/MMP2 pathway. PMID:29262634

Use of National Comprehensive Cancer Network and Other Guidelines and Biomarkers for Colorectal Cancer Screening

PubMed Central

Williams, Christina D.; Grady, William M.; Zullig, Leah L.

2016-01-01

Colorectal cancer (CRC) remains a common cancer and significant public health burden. CRC-related mortality is declining, in part due to the early detection of CRC through robust screening. The National Comprehensive Cancer Network (NCCN) has established CRC screening guidelines to aid healthcare providers in making appropriate recommendations for screening according to a patient’s risk of developing CRC. The purpose of this review is to describe the evolution of CRC screening guidelines for average risk individuals, discuss the role of NCCN CRC screening guidelines in cancer prevention, and comment on the current and emerging use of biomarkers for CRC screening. PMID:27799515

Liver cancer mortality rate model in Thailand

NASA Astrophysics Data System (ADS)

Sriwattanapongse, Wattanavadee; Prasitwattanaseree, Sukon

2013-09-01

Liver Cancer has been a leading cause of death in Thailand. The purpose of this study was to model and forecast liver cancer mortality rate in Thailand using death certificate reports. A retrospective analysis of the liver cancer mortality rate was conducted. Numbering of 123,280 liver cancer causes of death cases were obtained from the national vital registration database for the 10-year period from 2000 to 2009, provided by the Ministry of Interior and coded as cause-of-death using ICD-10 by the Ministry of Public Health. Multivariate regression model was used for modeling and forecasting age-specific liver cancer mortality rates in Thailand. Liver cancer mortality increased with increasing age for each sex and was also higher in the North East provinces. The trends of liver cancer mortality remained stable in most age groups with increases during ten-year period (2000 to 2009) in the Northern and Southern. Liver cancer mortality was higher in males and increase with increasing age. There is need of liver cancer control measures to remain on a sustained and long-term basis for the high liver cancer burden rate of Thailand.

Impact of Age and Comorbidity on Cervical and Breast Cancer Literacy of African Americans, Latina, and Arab women

PubMed Central

Talley, Costellia H.; Williams, Karen Patricia

2015-01-01

Background Appropriate and timely screening can significantly reduce breast and cervical cancer morbidity and mortality. Racial/ethnic minorities and immigrant populations have lower screening rates and delays in follow-up after abnormal tests. Purpose In this study, we examined the relationship between age, comorbidity, breast and cervical cancer literacy in a sample of African American, Latina, and Arab women (N=371) from Detroit, Michigan. Methods Age-adjusted Charlson Comorbidity Index (ACC) was used characterize the impact of age and comorbidity has on breast and cervical cancer literacy; Breast Cancer Literacy Assessment Tool was used to assess breast cancer literacy; Cervical Cancer Literacy Assessment Tool was used to assess cervical cancer literacy. ANOVA was used to assess the relationship between ACC, breast and cervical cancer screening and group differences. Results There was a statistically significant difference between breast cancer literacy (Breast-CLAT total scores) scores (F(2,367)= 17.31, p= < 0.01). ACC had a greater impact on breast cancer literacy for African American F(2,214) =11, p = <0.01. PMID:26333609

Mutational landscape of gastric adenocarcinoma in Chinese: implications for prognosis and therapy.

PubMed

Chen, Kexin; Yang, Da; Li, Xiangchun; Sun, Baocun; Song, Fengju; Cao, Wenfeng; Brat, Daniel J; Gao, Zhibo; Li, Haixin; Liang, Han; Zhao, Yanrui; Zheng, Hong; Li, Miao; Buckner, Jan; Patterson, Scott D; Ye, Xiang; Reinhard, Christoph; Bhathena, Anahita; Joshi, Deepa; Mischel, Paul S; Croce, Carlo M; Wang, Yi Michael; Raghavakaimal, Sreekumar; Li, Hui; Lu, Xin; Pan, Yang; Chang, Han; Ba, Sujuan; Luo, Longhai; Cavenee, Webster K; Zhang, Wei; Hao, Xishan

2015-01-27

Gastric cancer (GC) is a highly heterogeneous disease. To identify potential clinically actionable therapeutic targets that may inform individualized treatment strategies, we performed whole-exome sequencing on 78 GCs of differing histologies and anatomic locations, as well as whole-genome sequencing on two GC cases, each with three primary tumors and two matching lymph node metastases. The data showed two distinct GC subtypes with either high-clonality (HiC) or low-clonality (LoC). The HiC subtype of intratumoral heterogeneity was associated with older age, TP53 (tumor protein P53) mutation, enriched C > G transition, and significantly shorter survival, whereas the LoC subtype was associated with younger age, ARID1A (AT rich interactive domain 1A) mutation, and significantly longer survival. Phylogenetic tree analysis of whole-genome sequencing data from multiple samples of two patients supported the clonal evolution of GC metastasis and revealed the accumulation of genetic defects that necessitate combination therapeutics. The most recurrently mutated genes, which were validated in a separate cohort of 216 cases by targeted sequencing, were members of the homologous recombination DNA repair, Wnt, and PI3K-ERBB pathways. Notably, the drugable NRG1 (neuregulin-1) and ERBB4 (V-Erb-B2 avian erythroblastic leukemia viral oncogene homolog 4) ligand-receptor pair were mutated in 10% of GC cases. Mutations of the BRCA2 (breast cancer 2, early onset) gene, found in 8% of our cohort and validated in The Cancer Genome Atlas GC cohort, were associated with significantly longer survivals. These data define distinct clinicogenetic forms of GC in the Chinese population that are characterized by specific mutation sets that can be investigated for efficacy of single and combination therapies.

Acceleration of leukocytes' epigenetic age as an early tumor and sex-specific marker of breast and colorectal cancer.

PubMed

Durso, Danielle Fernandes; Bacalini, Maria Giulia; Sala, Claudia; Pirazzini, Chiara; Marasco, Elena; Bonafé, Massimiliano; do Valle, Ítalo Faria; Gentilini, Davide; Castellani, Gastone; Faria, Ana Maria Caetano; Franceschi, Claudio; Garagnani, Paolo; Nardini, Christine

2017-04-04

Changes in blood epigenetic age have been associated with several pathological conditions and have recently been described to anticipate cancer development. In this work, we analyze a publicly available leukocytes methylation dataset to evaluate the relation between DNA methylation age and the prospective development of specific types of cancer. We calculated DNA methylation age acceleration using five state-of-the-art estimators (three multi-site: Horvath, Hannum, Weidner; and two CpG specific: ELOV2 and FHL2) in a cohort including 845 subjects from the EPIC-Italy project and we compared 424 samples that remained cancer-free over the approximately ten years of follow-up with 235 and 166 subjects who developed breast and colorectal cancer, respectively. We show that the epigenetic age estimated from blood DNA methylation data is statistically significantly associated to future breast and male colorectal cancer development. These results are corroborated by survival analysis that shows significant association between age acceleration and cancer incidence suggesting that the chance of developing age-related diseases may be predicted by circulating epigenetic markers, with a dependence upon tumor type, sex and age estimator. These are encouraging results towards the non-invasive and perspective usage of epigenetic biomarkers.

Correlation of nucleotides and carbohydrates metabolism with pro-oxidant and antioxidant systems of erythrocytes depending on age in patients with colorectal cancer.

PubMed

Zuikov, S A; Borzenko, B G; Shatova, O P; Bakurova, E M; Polunin, G E

2014-06-01

To examine the relationship between metabolic features of purine nucleotides and antioxidant system depending on the age of patients with colorectal cancer. The activity of adenosine deaminase, xanthine oxidase, glutathione peroxidase, superoxide dismutase and glucose-6-phosphate dehydrogenase, the NOx concentration and the oxidative modification of proteins were determined spectrophotometricaly in 50 apparently healthy people and 26 patients with colorectal cancer stage -III---IV, aged 40 to 79 years. Increase of pro-oxidant system of erythrocytes with the age against decrease in level of antioxidant protection in both healthy individuals and colorectal cancer patients was determined. A significant increase of pro-ducts of oxidative proteins modification in erythrocytes with ageing was shown. Statistically significant correlation between enzymatic and non enzymatic markers pro-oxidant system and the activity of antioxidant defense enzymes in erythrocytes of patient with colorectal cancer was determined. Obtained results have demonstrated the imbalance in the antioxidant system of erythrocytes in colorectal cancer patients that improve the survival of cancer cells that is more distinctly manifested in ageing.

Screening for Prostate Cancer Starting at Age 50-54. A Population-based Cohort Study

PubMed Central

Carlsson, Sigrid; Assel, Melissa; Ulmert, David; Gerdtsson, Axel; Hugosson, Jonas; Vickers, Andrew; Lilja, Hans

2016-01-01

Background Current prostate cancer screening guidelines conflict with respect to the age at which to initiate screening. Objective To evaluate the effect of prostate-specific antigen (PSA) screening, versus zero screening, starting at age 50-54, on prostate cancer mortality. Design, Setting, and Participants This is a population-based cohort study comparing 3,479 men aged 50 through 54 randomized to PSA-screening in the Göteborg population-based prostate cancer screening trial, initiated in 1995, versus 4,060 unscreened men aged 51 to 55 providing cryopreserved blood in the population-based Malmö Preventive Project in the pre-PSA era, during 1982-1985. Outcome measures and Statistical Analysis Cumulative incidence and incidence rate ratios of prostate cancer diagnosis, metastasis, and prostate cancer death. Results and Limitation At 17 years, regular PSA-screening in Göteborg of men in their early 50s carried a more than 2-fold higher risk of prostate cancer diagnosis compared to the unscreened men in Malmö (IRR 2.56, 95% CI 2.18, 3.02), but resulted in a substantial decrease in risk of metastases (IRR 0.43, 95% CI 0.22, 0.79) and prostate cancer death (IRR 0.29, 95% CI 0.11, 0.67). There were 57 fewer prostate cancer deaths per 10,000 men (95% CI 22, 92) in the screened group. At 17 years, the number needed to invite to PSA-screening and the number needed to diagnose to prevent one prostate cancer death was 176 and 16, respectively. The study is limited by lack of treatment information and the comparison of two different birth cohorts. Conclusions PSA screening for prostate cancer can decrease prostate cancer mortality among men aged 50–54, with NNI and NND comparable to those previously reported from the European Randomized Study of Screening for Prostate Cancer for men aged 55-69 years, at similar follow-up. Guideline groups could consider whether guidelines for PSA screening should recommend starting no later than at ages 50-54. Trial registration The Göteborg randomized population-based prostate cancer screening trial is registered with the ISRCTN registry (isrctn.com). Identifier: ISRCTN54449243. PMID:27084245

Sociodemographic Disparities in Quality of Life for Survivors of Adolescent and Young Adult Cancers in the Behavioral Risk Factor Surveillance System

PubMed Central

Spraker-Perlman, Holly L.; McFadden, Molly; Warner, Echo L.; Oeffinger, Kevin C.; Wright, Jennifer; Kinney, Anita Y.

2014-01-01

Purpose: Survivors of cancer diagnosed during adolescence and young adulthood (AYA; aged 15–39) may experience quality of life (QOL) limitations; however, little is known about QOL for AYA survivors who are now middle-aged or among racial/ethnic minority survivors. We evaluated QOL outcomes for AYA cancer survivors relative to a non-cancer comparison group by gender, race/ethnicity, and current age. Methods: Using the 2009 Behavioral Risk Factor Surveillance System (BRFSS) data, we identified 8375 individuals diagnosed with cancer while aged 15–39 years old and 334,759 controls. Participants were currently ≥20 years of age. QOL was measured using four items from the Center for Disease Control's Healthy Days Measure (general health, number of days of poor physical and mental health, and activity limitation days). Multivariable regressions compared these measures for survivors and controls by gender, race/ethnicity, and age, and among survivors to determine cancer-related factors associated with poor QOL. Results: Survivors were more likely to report fair/poor general health than controls (relative risk=1.92; 95% confidence interval: 1.77–2.10; p<0.001). QOL limitations existed by gender and race/ethnicity for survivors. Approximately 30% of survivors currently in their 40s, 50s, and early 60s were in poor health, compared to less than 20% of same-aged controls (both p<0.001). Of survivors with two or more cancers, 41.0% reported poor health, compared to 26.2% with one cancer (p<0.001). Conclusion: AYA cancer survivors have worse QOL compared to the general population and these limitations persist across gender, race/ethnicity, and age. Targeted interventions are essential for improving AYA cancer survivors' health status. PMID:24940530

Normal breast tissue DNA methylation differences at regulatory elements are associated with the cancer risk factor age.

PubMed

Johnson, Kevin C; Houseman, E Andres; King, Jessica E; Christensen, Brock C

2017-07-10

The underlying biological mechanisms through which epidemiologically defined breast cancer risk factors contribute to disease risk remain poorly understood. Identification of the molecular changes associated with cancer risk factors in normal tissues may aid in determining the earliest events of carcinogenesis and informing cancer prevention strategies. Here we investigated the impact cancer risk factors have on the normal breast epigenome by analyzing DNA methylation genome-wide (Infinium 450 K array) in cancer-free women from the Susan G. Komen Tissue Bank (n = 100). We tested the relation of established breast cancer risk factors, age, body mass index, parity, and family history of disease, with DNA methylation adjusting for potential variation in cell-type proportions. We identified 787 cytosine-guanine dinucleotide (CpG) sites that demonstrated significant associations (Q value <0.01) with subject age. Notably, DNA methylation was not strongly associated with the other evaluated breast cancer risk factors. Age-related DNA methylation changes are primarily increases in methylation enriched at breast epithelial cell enhancer regions (P = 7.1E-20), and binding sites of chromatin remodelers (MYC and CTCF). We validated the age-related associations in two independent populations, using normal breast tissue samples (n = 18) and samples of normal tissue adjacent to tumor tissue (n = 97). The genomic regions classified as age-related were more likely to be regions altered in both pre-invasive (n = 40, P = 3.0E-03) and invasive breast tumors (n = 731, P = 1.1E-13). DNA methylation changes with age occur at regulatory regions, and are further exacerbated in cancer, suggesting that age influences breast cancer risk in part through its contribution to epigenetic dysregulation in normal breast tissue.

Reassessing the NTCTCS Staging Systems for Differentiated Thyroid Cancer, Including Age at Diagnosis

PubMed Central

McLeod, Donald S.A.; Jonklaas, Jacqueline; Brierley, James D.; Ain, Kenneth B.; Cooper, David S.; Fein, Henry G.; Haugen, Bryan R.; Ladenson, Paul W.; Magner, James; Ross, Douglas S.; Skarulis, Monica C.; Steward, David L.; Xing, Mingzhao; Litofsky, Danielle R.; Maxon, Harry R.

2015-01-01

Background: Thyroid cancer is unique for having age as a staging variable. Recently, the commonly used age cut-point of 45 years has been questioned. Objective: This study assessed alternate staging systems on the outcome of overall survival, and compared these with current National Thyroid Cancer Treatment Cooperative Study (NTCTCS) staging systems for papillary and follicular thyroid cancer. Methods: A total of 4721 patients with differentiated thyroid cancer were assessed. Five potential alternate staging systems were generated at age cut-points in five-year increments from 35 to 70 years, and tested for model discrimination (Harrell's C-statistic) and calibration (R2). The best five models for papillary and follicular cancer were further tested with bootstrap resampling and significance testing for discrimination. Results: The best five alternate papillary cancer systems had age cut-points of 45–50 years, with the highest scoring model using 50 years. No significant difference in C-statistic was found between the best alternate and current NTCTCS systems (p = 0.200). The best five alternate follicular cancer systems had age cut-points of 50–55 years, with the highest scoring model using 50 years. All five best alternate staging systems performed better compared with the current system (p = 0.003–0.035). There was no significant difference in discrimination between the best alternate system (cut-point age 50 years) and the best system of cut-point age 45 years (p = 0.197). Conclusions: No alternate papillary cancer systems assessed were significantly better than the current system. New alternate staging systems for follicular cancer appear to be better than the current NTCTCS system, although they require external validation. PMID:26203804

Nutritional Status After Total Gastrectomy for Gastric Cancer.

PubMed

Cidon, Esther Una

2010-04-01

Gastric cancer is one of the most frequent causes of death secondary to cancer in the world. Surgery is the only potentially curative treatment but its clinical consequences are significant. The objective of this study is to evaluate the nutritional state of patients with a total gastrectomy secondary to gastric adenocarcinoma. We designed a descriptive study with a transversal cut in our institution. We included 22 patients which had a minimum evolution time of six months after total gastrectomy secondary to gastric cancer surgery was performed. Neither of them had metastasis. The nutritional analysis included only biochemical data. Descriptive statistics were used for statistical analysis. Eight females and 14 males were included in the study. Median age was 57 years (34 - 69 years). The 74% of the patients were underweight and none of them was overweight. The average body mass index (BMI) was 16.88 kg/m 2 . Eleven patients suffered from mild anemia (10.5 - 12 g/dl) and 5 from moderate anemia (9 - 10.5 g/dl). Only two patients presented severe anemia (less than 9 g/dl). The 58% presented hypoproteinaemia and hypoalbuminaemia. The main post-surgery complication was nausea (46%). Seventy-eight percent of the patients had loss of appetite. Twenty-one patients were able to walk without help and leave their homes. The incidence of anemia in these patients was very high. In most of the patients, albumin and proteins levels were affected too. So malnutrition was a relevant consequence of a total gastrectomy.

Personalizing mammography by breast density and other risk factors for breast cancer: analysis of health benefits and cost-effectiveness.

PubMed

Schousboe, John T; Kerlikowske, Karla; Loh, Andrew; Cummings, Steven R

2011-07-05

Current guidelines recommend mammography every 1 or 2 years starting at age 40 or 50 years, regardless of individual risk for breast cancer. To estimate the cost-effectiveness of mammography by age, breast density, history of breast biopsy, family history of breast cancer, and screening interval. Markov microsimulation model. Surveillance, Epidemiology, and End Results program, Breast Cancer Surveillance Consortium, and the medical literature. U.S. women aged 40 to 49, 50 to 59, 60 to 69, and 70 to 79 years with initial mammography at age 40 years and breast density of Breast Imaging Reporting and Data System (BI-RADS) categories 1 to 4. Lifetime. National health payer. Mammography annually, biennially, or every 3 to 4 years or no mammography. Costs per quality-adjusted life-year (QALY) gained and number of women screened over 10 years to prevent 1 death from breast cancer. Biennial mammography cost less than $100,000 per QALY gained for women aged 40 to 79 years with BI-RADS category 3 or 4 breast density or aged 50 to 69 years with category 2 density; women aged 60 to 79 years with category 1 density and either a family history of breast cancer or a previous breast biopsy; and all women aged 40 to 79 years with both a family history of breast cancer and a previous breast biopsy, regardless of breast density. Biennial mammography cost less than $50,000 per QALY gained for women aged 40 to 49 years with category 3 or 4 breast density and either a previous breast biopsy or a family history of breast cancer. Annual mammography was not cost-effective for any group, regardless of age or breast density. Mammography is expensive if the disutility of false-positive mammography results and the costs of detecting nonprogressive and nonlethal invasive cancer are considered. Results are not applicable to carriers of BRCA1 or BRCA2 mutations. Mammography screening should be personalized on the basis of a woman's age, breast density, history of breast biopsy, family history of breast cancer, and beliefs about the potential benefit and harms of screening. Eli Lilly, Da Costa Family Foundation for Research in Breast Cancer Prevention of the California Pacific Medical Center, and Breast Cancer Surveillance Consortium.

A LINE-1 Component to Human Aging: Do LINE elements exact a longevity cost for evolutionary advantage?

PubMed Central

Laurent, Georges St.; Hammell, Neil; McCaffrey, Timothy A.

2010-01-01

Advancing age remains the largest risk factor for devastating diseases, such as heart disease, stroke, and cancer. The mechanisms by which advancing age predisposes to disease are now beginning to unfold, due in part, to genetic and environmental manipulations of longevity in lower organisms. Converging lines of evidence suggest that DNA damage may be a final common pathway linking several proposed mechanisms of aging. The present review forwards a theory for an additional aging pathway that involves modes of inherent genetic instability. Long interspersed nuclear elements (LINEs) are endogenous non-LTR retrotransposons that compose about 20% of the human genome. The LINE-1 (L1) gene products, ORF1p and ORF2p, possess mRNA binding, endonuclease, and reverse transcriptase activity that enable retrotransposition. While principally active only during embryogenesis, L1 transcripts are detected in adult somatic cells under certain conditions. The present hypothesis proposes that L1s act as an ‘endogenous clock’, slowly eroding genomic integrity by competing with the organism’s double-strand break repair mechanism. Thus, while L1s are an accepted mechanism of genetic variation fueling evolution, it is proposed that longevity is negatively impacted by somatic L1 activity. The theory predicts testable hypotheses about the relationship between L1 activity, DNA repair, healthy aging, and longevity. PMID:20346965

Demonstration of the need for cardiovascular and pulmonary normative data for cancer survivors.

PubMed

Schneider, C M; Repka, C P; Brown, J M; Lalonde, T L; Dallow, K T; Barlow, C E; Hayward, R

2014-12-01

Despite evidence that cancer and its treatments severely reduce cardiorespiratory fitness (CRF), normative data for cancer survivors do not exist. The present study identifies age and gender-specific CRF distributions in a cancer population. The use of cancer-specific normative CRF data may help stratify initial fitness status and assess improvements in response to exercise interventions in cancer survivors. Data from 703 cancer survivors were analyzed for this study. Quintiles were compiled for peak oxygen consumption (VO2peak), forced vital capacity (FVC), and forced expiratory volume (FEV1) for males and females in 5 age groups (19-39, 40-49, 50-59, 60-69, and ≥70 years of age). VO2peak values for the cancer population were significantly lower than the general US population. The cancer population average in each age group fell within the "very poor" classification of VO2peak values for the general population. FVC values in the cancer population were similar to the general population. Cancer survivors had very low age group-specific VO2peak values compared to the apparently healthy general US population. Previously, CRF values of cancer survivors were compared to normative values for the apparently healthy general population, which yielded imprecise classifications of initial fitness and changes in fitness, resulting in patient discouragement. © Georg Thieme Verlag KG Stuttgart · New York.

Cervical cancer in women under 25 years of age in Queensland, Australia: To what extent is the diagnosis made by screening cytology?

PubMed

Morgan, Edwina L; Sanday, Karen; Budd, Alison; Hammond, Ian G; Nicklin, James

2017-08-01

The current Australian National Cervical Screening Program (NCSP) involves biennial, cytology-based screening of women from the age of 18 years. From December, 2017 this will change to a five-yearly human papilloma virus-based screening commencing at age 25. There is some concern that the new program may delay the opportunistic detection of cervical cancers in women under 25 years. (1) To review all cases of invasive cervical cancer in Queensland women under the age of 25 over the last 28 years. (2) To determine symptoms and screening history prior to diagnosis. A retrospective cohort study was undertaken at the Queensland Centre for Gynaecological Cancer (QCGC) and the Queensland Cancer Registry (QCR) of all women aged between 13 and 25 years diagnosed with cervical cancer in Queensland between 1984 and 2012. Demographic data and symptoms prior to diagnosis were extracted from the QCGC and QCR databases. A total of 56 women aged 13-25, were diagnosed with cervical cancer and treated at the QCGC between 1984 and 2012. The commonest reason for the diagnosis of cancer was investigation of abnormal symptoms (n = 22, 39%) rather than routine Pap smear abnormalities (n = 15, 26%). Consistent with the world literature, there is a very low incidence of cervical cancer in women under 25 years of age, irrespective of the age of commencement of screening, or the screening interval. Our study lends some support to the proposed commencement age of 25 years in the new NCSP. © 2017 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

Phylogenetic analysis of eukaryotic NEET proteins uncovers a link between a key gene duplication event and the evolution of vertebrates.

PubMed

Inupakutika, Madhuri A; Sengupta, Soham; Nechushtai, Rachel; Jennings, Patricia A; Onuchic, Jose' N; Azad, Rajeev K; Padilla, Pamela; Mittler, Ron

2017-02-16

NEET proteins belong to a unique family of iron-sulfur proteins in which the 2Fe-2S cluster is coordinated by a CDGSH domain that is followed by the "NEET" motif. They are involved in the regulation of iron and reactive oxygen metabolism, and have been associated with the progression of diabetes, cancer, aging and neurodegenerative diseases. Despite their important biological functions, the evolution and diversification of eukaryotic NEET proteins are largely unknown. Here we used the three members of the human NEET protein family (CISD1, mitoNEET; CISD2, NAF-1 or Miner 1; and CISD3, Miner2) as our guides to conduct a phylogenetic analysis of eukaryotic NEET proteins and their evolution. Our findings identified the slime mold Dictyostelium discoideum's CISD proteins as the closest to the ancient archetype of eukaryotic NEET proteins. We further identified CISD3 homologs in fungi that were previously reported not to contain any NEET proteins, and revealed that plants lack homolog(s) of CISD3. Furthermore, our study suggests that the mammalian NEET proteins, mitoNEET (CISD1) and NAF-1 (CISD2), emerged via gene duplication around the origin of vertebrates. Our findings provide new insights into the classification and expansion of the NEET protein family, as well as offer clues to the diverged functions of the human mitoNEET and NAF-1 proteins.

Under-treatment of elderly patients with ovarian cancer: a population based study.

PubMed

Fourcadier, Elisabeth; Trétarre, Brigitte; Gras-Aygon, Claudine; Ecarnot, Fiona; Daurès, Jean-Pierre; Bessaoud, Faïza

2015-11-26

Ovarian cancer is the fourth most common cancer among women in France, and mainly affects the elderly. The primary objective of this study was to compare treatment of ovarian cancer according to age. All patients with invasive cancer (n=1151) diagnosed between 1997 and 2011 in the Herault Department of southern France were included. Demographic data (age, area of residence), cancer characteristics (stage, histology, grade) and treatment modality (type, period and location of treatment) were analysed. Univariate and multivariate logistic regression was used to compare treatment by age. Ovarian cancer was less treated in elderly compared to younger patients, regardless of the type of treatment. This difference was more pronounced for chemotherapy, and was maximal for surgery followed by chemotherapy (odds ratio (OR) for surgery for patients aged >70 vs those aged <70 years=0.47 [0.24-0.91], OR for chemotherapy, age>70 vs <70=0.30 [0.16-0.55] and OR for surgery plus chemotherapy, age>70 vs <70=0.14 [0.08-0.28]). This effect of age was independent of other variables, including stage and grade. The probability of receiving standard treatment, in accordance with recommendations, was reduced by 50% in elderly patients compared to their younger counterparts. Overall and net survival of elderly patients with standard treatment was similar to those of younger patients treated outside standard treatment. Elderly women with ovarian cancer were therapeutically disadvantaged compared to younger women. Further studies including co morbidities are necessary to refine these results and to improve therapeutic management of elderly patients with ovarian cancer.

Precancer Atlas to Drive Precision Prevention Trials

DOE PAGES

Spira, Avrum; Yurgelun, Matthew B.; Alexandrov, Ludmil B.; ...

2017-04-01

Cancer development is a complex process driven by inherited and acquired molecular and cellular alterations. Prevention is the holy grail of cancer elimination, but making this a reality will take a fundamental rethinking and deep understanding of premalignant biology. Here, we propose a national concerted effort to create a Precancer Atlas (PCA), integrating multi-omics and immunity – basic tenets of the neoplastic process. The biology of neoplasia caused by germline mutations has led to paradigm-changing precision prevention efforts, including: tumor testing for mismatch repair (MMR) deficiency in Lynch syndrome establishing a new paradigm, combinatorial chemoprevention efficacy in familial adenomatous polyposismore » (FAP), signal of benefit from imaging-based early detection research in high-germline risk for pancreatic neoplasia, elucidating early ontogeny in BRCA1-mutation carriers leading to an international breast cancer prevention trial, and insights into the intricate germline-somatic-immunity interaction landscape. Emerging genetic and pharmacologic (metformin) disruption of mitochondrial (mt) respiration increased autophagy to prevent cancer in a Li-Fraumeni mouse model (biology reproduced in clinical pilot) and revealed profound influences of subtle changes in mt DNA background variation on obesity, aging, and cancer risk. The elaborate communication between the immune system and neoplasia includes an increasingly complex cellular microenvironment and dynamic interactions between host genetics, environmental factors, and microbes in shaping the immune response. Cancer vaccines are in early murine and clinical precancer studies, building on the recent successes of immunotherapy and HPV vaccine immune prevention. Molecular monitoring in Barrett's esophagus to avoid overdiagnosis/treatment highlights an important PCA theme. Next generation sequencing (NGS) discovered age-related clonal hematopoiesis of indeterminate potential (CHIP). Ultra-deep NGS reports over the past year have redefined the premalignant landscape remarkably identifying tiny clones in the blood of up to 95% of women in their 50s, suggesting that potentially premalignant clones are ubiquitous. Similar data from eyelid skin and peritoneal and uterine lavage fluid provide unprecedented opportunities to dissect the earliest phases of stem/progenitor clonal (and microenvironment) evolution/diversity with new single-cell and liquid biopsy technologies. Cancer mutational signatures reflect exogenous or endogenous processes imprinted over time in precursors. In conclusion, accelerating the prevention of cancer will require a large-scale, longitudinal effort, leveraging diverse disciplines (from genetics, biochemistry, and immunology to mathematics, computational biology, and engineering), initiatives, technologies, and models in developing an integrated multi-omics and immunity PCA – an immense national resource to interrogate, target, and intercept events that drive oncogenesis.« less

Precancer Atlas to Drive Precision Prevention Trials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Spira, Avrum; Yurgelun, Matthew B.; Alexandrov, Ludmil B.

Cancer development is a complex process driven by inherited and acquired molecular and cellular alterations. Prevention is the holy grail of cancer elimination, but making this a reality will take a fundamental rethinking and deep understanding of premalignant biology. Here, we propose a national concerted effort to create a Precancer Atlas (PCA), integrating multi-omics and immunity – basic tenets of the neoplastic process. The biology of neoplasia caused by germline mutations has led to paradigm-changing precision prevention efforts, including: tumor testing for mismatch repair (MMR) deficiency in Lynch syndrome establishing a new paradigm, combinatorial chemoprevention efficacy in familial adenomatous polyposismore » (FAP), signal of benefit from imaging-based early detection research in high-germline risk for pancreatic neoplasia, elucidating early ontogeny in BRCA1-mutation carriers leading to an international breast cancer prevention trial, and insights into the intricate germline-somatic-immunity interaction landscape. Emerging genetic and pharmacologic (metformin) disruption of mitochondrial (mt) respiration increased autophagy to prevent cancer in a Li-Fraumeni mouse model (biology reproduced in clinical pilot) and revealed profound influences of subtle changes in mt DNA background variation on obesity, aging, and cancer risk. The elaborate communication between the immune system and neoplasia includes an increasingly complex cellular microenvironment and dynamic interactions between host genetics, environmental factors, and microbes in shaping the immune response. Cancer vaccines are in early murine and clinical precancer studies, building on the recent successes of immunotherapy and HPV vaccine immune prevention. Molecular monitoring in Barrett's esophagus to avoid overdiagnosis/treatment highlights an important PCA theme. Next generation sequencing (NGS) discovered age-related clonal hematopoiesis of indeterminate potential (CHIP). Ultra-deep NGS reports over the past year have redefined the premalignant landscape remarkably identifying tiny clones in the blood of up to 95% of women in their 50s, suggesting that potentially premalignant clones are ubiquitous. Similar data from eyelid skin and peritoneal and uterine lavage fluid provide unprecedented opportunities to dissect the earliest phases of stem/progenitor clonal (and microenvironment) evolution/diversity with new single-cell and liquid biopsy technologies. Cancer mutational signatures reflect exogenous or endogenous processes imprinted over time in precursors. In conclusion, accelerating the prevention of cancer will require a large-scale, longitudinal effort, leveraging diverse disciplines (from genetics, biochemistry, and immunology to mathematics, computational biology, and engineering), initiatives, technologies, and models in developing an integrated multi-omics and immunity PCA – an immense national resource to interrogate, target, and intercept events that drive oncogenesis.« less

Quantifying the Number of Independent Organelle DNA Insertions in Genome Evolution and Human Health.

PubMed

Hazkani-Covo, Einat; Martin, William F

2017-05-01

Fragments of organelle genomes are often found as insertions in nuclear DNA. These fragments of mitochondrial DNA (numts) and plastid DNA (nupts) are ubiquitous components of eukaryotic genomes. They are, however, often edited out during the genome assembly process, leading to systematic underestimation of their frequency. Numts and nupts, once inserted, can become further fragmented through subsequent insertion of mobile elements or other recombinational events that disrupt the continuity of the inserted sequence relative to the genuine organelle DNA copy. Because numts and nupts are typically identified through sequence comparison tools such as BLAST, disruption of insertions into smaller fragments can lead to systematic overestimation of numt and nupt frequencies. Accurate identification of numts and nupts is important, however, both for better understanding of their role during evolution, and for monitoring their increasingly evident role in human disease. Human populations are polymorphic for 141 numt loci, five numts are causal to genetic disease, and cancer genomic studies are revealing an abundance of numts associated with tumor progression. Here, we report investigation of salient parameters involved in obtaining accurate estimates of numt and nupt numbers in genome sequence data. Numts and nupts from 44 sequenced eukaryotic genomes reveal lineage-specific differences in the number, relative age and frequency of insertional events as well as lineage-specific dynamics of their postinsertional fragmentation. Our findings outline the main technical parameters influencing accurate identification and frequency estimation of numts in genomic studies pertinent to both evolution and human health. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Tumor morphology and phenotypic evolution driven by selective pressure from the microenvironment.

PubMed

Anderson, Alexander R A; Weaver, Alissa M; Cummings, Peter T; Quaranta, Vito

2006-12-01

Emergence of invasive behavior in cancer is life-threatening, yet ill-defined due to its multifactorial nature. We present a multiscale mathematical model of cancer invasion, which considers cellular and microenvironmental factors simultaneously and interactively. Unexpectedly, the model simulations predict that harsh tumor microenvironment conditions (e.g., hypoxia, heterogenous extracellular matrix) exert a dramatic selective force on the tumor, which grows as an invasive mass with fingering margins, dominated by a few clones with aggressive traits. In contrast, mild microenvironment conditions (e.g., normoxia, homogeneous matrix) allow clones with similar aggressive traits to coexist with less aggressive phenotypes in a heterogeneous tumor mass with smooth, noninvasive margins. Thus, the genetic make-up of a cancer cell may realize its invasive potential through a clonal evolution process driven by definable microenvironmental selective forces. Our mathematical model provides a theoretical/experimental framework to quantitatively characterize this selective pressure for invasion and test ways to eliminate it.

The statistical geometry of transcriptome divergence in cell-type evolution and cancer.

PubMed

Liang, Cong; Forrest, Alistair R R; Wagner, Günter P

2015-01-14

In evolution, body plan complexity increases due to an increase in the number of individualized cell types. Yet, there is very little understanding of the mechanisms that produce this form of organismal complexity. One model for the origin of novel cell types is the sister cell-type model. According to this model, each cell type arises together with a sister cell type through specialization from an ancestral cell type. A key prediction of the sister cell-type model is that gene expression profiles of cell types exhibit tree structure. Here we present a statistical model for detecting tree structure in transcriptomic data and apply it to transcriptomes from ENCODE and FANTOM5. We show that transcriptomes of normal cells harbour substantial amounts of hierarchical structure. In contrast, cancer cell lines have less tree structure, suggesting that the emergence of cancer cells follows different principles from that of evolutionary cell-type origination.

The moderating effect of age on the 12-month prevalence of anxiety and depressive disorders in adults with a lifetime history of cancer.

PubMed

Simning, Adam; Conwell, Yeates; Mohile, Supriya G; van Wijngaarden, Edwin

2014-12-01

To determine how age may modulate the association of a history of cancer with a 12-month history of anxiety and depressive disorders. The authors used population-based, cross-sectional surveys, the Collaborative Psychiatric Epidemiology Surveys. These surveys were conducted in the United States in 2001-2003 and included 16,423 adult participants, of whom 702 reported a cancer history. The Composite International Diagnostic Interview evaluated the presence of a 12-month history of anxiety and depressive disorders. Among those with a cancer history, older adults (≥60 years old) were less likely than younger adults (18-59 years old) to have a 12-month history of an anxiety or depressive disorder. Compared with their peers without cancer, younger adults with a cancer history had more anxiety (23.8% versus 13.9%) and depressive (16.0% versus 9.5%) disorders, whereas older adults with a cancer history had lower levels of anxiety (3.7% versus 6.3%) and depressive (1.9% versus 3.9%) disorders. In multivariable modeling, there was a statistically significant interaction between age group and cancer history, with the risk for anxiety and depressive disorders elevated in the younger age group with a cancer history (odds ratio: 5.84 and odds ratio: 6.13, respectively) but decreased in the older age group with a cancer history (odds ratio: 0.55 and odds ratio: 0.45, respectively). The authors' findings suggest a considerable age-dependent variation with regard to anxiety and depressive disorders in adults with a cancer history. Investigation of the mechanisms contributing to this apparent age differential in risk could have important mental illness treatment implications in this population. Copyright © 2014 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

The past, present, and future of cancer incidence in the United States: 1975 through 2020.

PubMed

Weir, Hannah K; Thompson, Trevor D; Soman, Ashwini; Møller, Bjørn; Leadbetter, Steven

2015-06-01

The overall age-standardized cancer incidence rate continues to decline whereas the number of cases diagnosed each year increases. Predicting cancer incidence can help to anticipate future resource needs, evaluate primary prevention strategies, and inform research. Surveillance, Epidemiology, and End Results data were used to estimate the number of cancers (all sites) resulting from changes in population risk, age, and size. The authors projected to 2020 nationwide age-standardized incidence rates and cases (including the top 23 cancers). Since 1975, incident cases increased among white individuals, primarily caused by an aging white population, and among black individuals, primarily caused by an increasing black population. Between 2010 and 2020, it is expected that overall incidence rates (proxy for risk) will decrease slightly among black men and stabilize in other groups. By 2020, the authors predict annual cancer cases (all races, all sites) to increase among men by 24.1% (-3.2% risk and 27.3% age/growth) to >1 million cases, and by 20.6% among women (1.2% risk and 19.4% age/growth) to >900,000 cases. The largest increases are expected for melanoma (white individuals); cancers of the prostate, kidney, liver, and urinary bladder in males; and the lung, breast, uterus, and thyroid in females. Overall, the authors predict cancer incidence rates/risk to stabilize for the majority of the population; however, they expect the number of cancer cases to increase by >20%. A greater emphasis on primary prevention and early detection is needed to counter the effect of an aging and growing population on the burden of cancer. © 2015 American Cancer Society.

Assessment of Risk Factors of Obesity and Diet on Breast Cancer in Ankara, Turkey.

PubMed

Alim, Nural Erzurum; Kiziltan, Gul

2016-01-01

To determine the risk factors of obesity and diet on breast cancer in Ankara, Turkey. A case-controlled study was carried out on newly diagnosed 40 breast cancer patients [patient group (PC)] and 40 volunteer individuals [control group (CG)] with no diagnosis of cancer and history of cancer in the family with similar characteristics to the age and gender-matched patient group between March and July 2016. All the individuals were administered a questionnaire by face-to-face interview method. The mean menarche age, age at first birth and menopause age were 13.0±1.17, 22.6±3.78 and 44.33±2.39 years in PG and 12.3±0.95, 21.6±2.99, 46.71±2.41 years in CG, respectively. The mean BMI values were determined as 28.1±6.75 kg/m 2 in PG and 30.1±6.18 kg/m 2 in CG (p>0.05). It was determined that intake of vitamin C and fiber decreases the risk of breast cancer. Also, eating quickly and smoking were risk factors for breast cancer (p<0.05). This study indicated that there are relationships between menarche age, menopause age, and age at first birth, eating quickly, smoking and breast cancer. Conversely, there are significant negative relationships between dietary fiber, vitamin C intake and breast cancer. As a result, it can be said that there is a link between breast cancer and lifestyle factors and a reduction in the risk of developing breast cancer can be achieved through changes in diet, one of the lifestyle factors.

Assessment of Risk Factors of Obesity and Diet on Breast Cancer in Ankara, Turkey

PubMed Central

Alim, Nural Erzurum; Kiziltan, Gul

2016-01-01

Objective: To determine the risk factors of obesity and diet on breast cancer in Ankara, Turkey. Methods: A case-controlled study was carried out on newly diagnosed 40 breast cancer patients [patient group (PC)] and 40 volunteer individuals [control group (CG)] with no diagnosis of cancer and history of cancer in the family with similar characteristics to the age and gender-matched patient group between March and July 2016. All the individuals were administered a questionnaire by face-to-face interview method. Results: The mean menarche age, age at first birth and menopause age were 13.0±1.17, 22.6±3.78 and 44.33±2.39 years in PG and 12.3±0.95, 21.6±2.99, 46.71±2.41 years in CG, respectively. The mean BMI values were determined as 28.1±6.75 kg/m2 in PG and 30.1±6.18 kg/m2 in CG (p>0.05). It was determined that intake of vitamin C and fiber decreases the risk of breast cancer. Also, eating quickly and smoking were risk factors for breast cancer (p<0.05). Conclusion: This study indicated that there are relationships between menarche age, menopause age, and age at first birth, eating quickly, smoking and breast cancer. Conversely, there are significant negative relationships between dietary fiber, vitamin C intake and breast cancer. As a result, it can be said that there is a link between breast cancer and lifestyle factors and a reduction in the risk of developing breast cancer can be achieved through changes in diet, one of the lifestyle factors. PMID:28083060

Heart Disease and Cancer Deaths — Trends and Projections in the United States, 1969–2020

PubMed Central

Anderson, Robert N.; Coleman King, Sallyann M.; Soman, Ashwini; Thompson, Trevor D.; Hong, Yuling; Moller, Bjorn; Leadbetter, Steven

2016-01-01

Introduction Heart disease and cancer are the first and second leading causes of death in the United States. Age-standardized death rates (risk) have declined since the 1960s for heart disease and for cancer since the 1990s, whereas the overall number of heart disease deaths declined and cancer deaths increased. We analyzed mortality data to evaluate and project the effect of risk reduction, population growth, and aging on the number of heart disease and cancer deaths to the year 2020. Methods We used mortality data, population estimates, and population projections to estimate and predict heart disease and cancer deaths from 1969 through 2020 and to apportion changes in deaths resulting from population risk, growth, and aging. Results We predicted that from 1969 through 2020, the number of heart disease deaths would decrease 21.3% among men (–73.9% risk, 17.9% growth, 34.7% aging) and 13.4% among women (–73.3% risk, 17.1% growth, 42.8% aging) while the number of cancer deaths would increase 91.1% among men (–33.5% risk, 45.6% growth, 79.0% aging) and 101.1% among women (–23.8% risk, 48.8% growth, 76.0% aging). We predicted that cancer would become the leading cause of death around 2016, although sex-specific crossover years varied. Conclusion Risk of death declined more steeply for heart disease than cancer, offset the increase in heart disease deaths, and partially offset the increase in cancer deaths resulting from demographic changes over the past 4 decades. If current trends continue, cancer will become the leading cause of death by 2020. PMID:27854420

Ovary cancer incidence and mortality in China, 2011.

PubMed

Wei, Kuangrong; Li, Yuanming; Zheng, Rongshou; Zhang, Siwei; Liang, Zhiheng; Cen, Huishan; Chen, Wanqing

2015-02-01

To evaluate and analyze ovary cancer incidence and mortality in China in 2011 using ovary cancer data from population-based cancer registration in China, and to provide scientific information for its control and prevention. Invasive cases of ovary cancer were extracted and analyzed from the overall Chinese cancer database in 2011, which were based on data from 177 population-based cancer registries distributing in 28 provinces. The crude, standardized, and truncated incidences and mortalities et al. were calculated and new and deaths cases from ovary cancer throughout China and in different regions in 2011 were estimated using Chinese practical population. The estimates of new ovary cancer cases and deaths were 45,223 and 18,430, respectively, in China in 2011. The crude incidence rate, age-standardized rate by Chinese standard population (ASR-C) and age-standardized rate by world standard population (ASR-W) incidence were 6.89/100,000, 5.35/100,000 and 5.08/100,000, respectively; the crude, ASR-C and ASR-W mortalities were 2.81/100,000, 2.01/100,000 and 1.99/100,000, respectively. The incidence and mortality in urban areas were higher than those in rural areas. The age-specific incidence and mortality increased rapidly from age 35-39 and peaked at age 60-64 or 75-79 years. After age 45 or 55, the age-specific incidence and death rates in urban were much higher than those in rural areas. Compared with GLOBOCAN 2012 data, the ovary cancer incidence in China in 2011 was at middle level, but its mortality was at low level worldwide.

Radiation-Induced Breast Cancer Incidence and Mortality From Digital Mammography Screening: A Modeling Study.

PubMed

Miglioretti, Diana L; Lange, Jane; van den Broek, Jeroen J; Lee, Christoph I; van Ravesteyn, Nicolien T; Ritley, Dominique; Kerlikowske, Karla; Fenton, Joshua J; Melnikow, Joy; de Koning, Harry J; Hubbard, Rebecca A

2016-02-16

Estimates of risk for radiation-induced breast cancer from mammography screening have not considered variation in dose exposure or diagnostic work-up after abnormal screening results. To estimate distributions of radiation-induced breast cancer incidence and mortality from digital mammography screening while considering exposure from screening and diagnostic mammography and dose variation among women. 2 simulation-modeling approaches. U.S. population. Women aged 40 to 74 years. Annual or biennial digital mammography screening from age 40, 45, or 50 years until age 74 years. Lifetime breast cancer deaths averted (benefits) and radiation-induced breast cancer incidence and mortality (harms) per 100,000 women screened. Annual screening of 100,000 women aged 40 to 74 years was projected to induce 125 breast cancer cases (95% CI, 88 to 178) leading to 16 deaths (CI, 11 to 23), relative to 968 breast cancer deaths averted by early detection from screening. Women exposed at the 95th percentile were projected to develop 246 cases of radiation-induced breast cancer leading to 32 deaths per 100,000 women. Women with large breasts requiring extra views for complete examination (8% of population) were projected to have greater radiation-induced breast cancer risk (266 cancer cases and 35 deaths per 100,000 women) than other women (113 cancer cases and 15 deaths per 100,000 women). Biennial screening starting at age 50 years reduced risk for radiation-induced cancer 5-fold. Life-years lost from radiation-induced breast cancer could not be estimated. Radiation-induced breast cancer incidence and mortality from digital mammography screening are affected by dose variability from screening, resultant diagnostic work-up, initiation age, and screening frequency. Women with large breasts may have a greater risk for radiation-induced breast cancer. Agency for Healthcare Research and Quality, U.S. Preventive Services Task Force, National Cancer Institute.

Age- and Sex-Specific Trends in Lung Cancer Mortality over 62 Years in a Nation with a Low Effort in Cancer Prevention

PubMed Central

John, Ulrich; Hanke, Monika

2016-01-01

Background: A decrease in lung cancer mortality among females below 50 years of age has been reported for countries with significant tobacco control efforts. The aim of this study was to describe the lung cancer deaths, including the mortality rates and proportions among total deaths, for females and males by age at death in a country with a high smoking prevalence (Germany) over a time period of 62 years. Methods: The vital statistics data were analyzed using a joinpoint regression analysis stratified by age and sex. An age-period-cohort analysis was used to estimate the potential effects of sex and school education on mortality. Results: After an increase, lung cancer mortality among women aged 35–44 years remained stable from 1989 to 2009 and decreased by 10.8% per year from 2009 to 2013. Conclusions: Lung cancer mortality among females aged 35–44 years has decreased. The potential reasons include an increase in the number of never smokers, following significant increases in school education since 1950, particularly among females. PMID:27023582

[Proportion of breast cancer in women aged 50 to 69 years from Girona, Spain, according to detection method].

PubMed

Puig-Vives, Montse; Osca-Gelis, Gemma; Camprubí-Font, Carla; Vilardell, M Loreto; Izquierdo, Angel; Marcos-Gragera, Rafael

2014-10-07

The aim of this study was to determine the tumor stage, the proportion of cases and the age specific rate of breast cancer (BC) cases according to detection method. Cases of women aged 50 to 69 years diagnosed with BC in the Girona province during 1999-2006 were extracted from the population-based Girona Cancer Registry (n=1,254). BC was classified by detection method: screen-detected cancer, interval cancer and others. Proportion of cases and age-specific incidence were calculated according to detection method. During the period 2002-2006, the proportion of screen-detected cancers, interval cancers and other cancers were 42.2%, 5.8% and 52.2%, respectively. After implementation of the early detection of breast cancer program (PDPCM), the incidence of screen-detected cases raised; thereafter, interval cancers also increased and the rate of other cancers decreased. In the Girona province during the fully implemented PDPCM period (2002-2006), interval cancers represented a low proportion (5.8%) of women diagnosed with BC at 50 to 69 years old. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

Life expectancy of colon, breast, and testicular cancer patients: an analysis of US-SEER population-based data.

PubMed

Capocaccia, R; Gatta, G; Dal Maso, L

2015-06-01

Cancer survivorship is an increasingly important issue in cancer control. Life expectancy of patients diagnosed with breast, colon, and testicular cancers, stratified by age at diagnosis and time since diagnosis, is provided as an indicator to evaluate future mortality risks and health care needs of cancer survivors. The standard period life table methodology was applied to estimate excess mortality risk for cancer patients diagnosed in 1985-2011 from SEER registries and mortality data of the general US population. The sensitivity of life expectancy estimates on different assumptions was evaluated. Younger patients with colon cancer showed wider differences in life expectancy compared with that of the general population (11.2 years in women and 10.7 in men at age 45-49 years) than older patients (6.3 and 5.8 at age 60-64 years, respectively). Life expectancy progressively increases in patients surviving the first years, up to 4 years from diagnosis, and then starts to decrease again, approaching that of the general population. For breast cancer, the initial drop in life expectancy is less marked, and again with wider differences in younger patients, varying from 8.7 at age 40-44 years to 2.4 at ages 70-74 years. After diagnosis, life expectancy still decreases with time, but less than that in the general population, slowly approaching that of cancer-free women. Life expectancy of men diagnosed with testicular cancer at age 30 years is estimated as 45.2 years, 2 years less than cancer-free men of the same age. The difference becomes 1.3 years for patients surviving the first year, and then slowly approaches zero with increasing survival time. Life expectancy provides meaningful information on cancer patients, and can help in assessing when a cancer survivor can be considered as cured. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Heat Shock Proteins Promote Cancer: It's a Protection Racket.

PubMed

Calderwood, Stuart K; Gong, Jianlin

2016-04-01

Heat shock proteins (HSP) are expressed at high levels in cancer and form a fostering environment that is essential for tumor development. Here, we review the recent data in this area, concentrating mainly on Hsp27, Hsp70, and Hsp90. The overriding role of HSPs in cancer is to stabilize the active functions of overexpressed and mutated cancer genes. Thus, elevated HSPs are required for many of the traits that underlie the morbidity of cancer, including increased growth, survival, and formation of secondary cancers. In addition, HSPs participate in the evolution of cancer treatment resistance. HSPs are also released from cancer cells and influence malignant properties by receptor-mediated signaling. Current data strongly support efforts to target HSPs in cancer treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Is age a risk factor for depression among the oldest old with cancer?

PubMed

Goldzweig, Gil; Baider, Lea; Rottenberg, Yakir; Andritsch, Elisabeth; Jacobs, Jeremy M

2018-04-09

Age is negatively related to depression among young and middle age patients with cancer. Nevertheless the relationship between age and depression among older patients with cancer is unclear. The goal of the current study is to assess the association of depression with increasing age among older patients with cancer. Participants were 243 oncology out-patients, aged ≥65, either receiving treatment for active disease or within 6 months of completing treatment for active disease, with a Karnofsky score ≥70. Participants were grouped by age: "Younger-Old" - age 65-74 (N = 125); "Old" - age 75-84 (N = 49); and "Oldest-Old" -age ≥ 85 years (N = 69). Background data included: socio-demography; cancer type/staging/treatment; Charlson comorbidity index (CCI); Eastern Cooperative Oncology Group (ECOG) performance. Psychological data included: the 5-item Geriatric Depression Scale (GDS); "Distress Thermometer" (single item); and Cancer Perceived Agents of Social Support (12-item). Depression levels were significantly higher among oldest-old participants in comparison to the old and younger-old groups: mean GDS scores were 0.93 ± 1.13, 1.27 ± 1.41 and 3.91 ± 1.35 respectively. After controlling for all potential confounders in a hierarchical logistic regression model, age-group significantly predicted both depression and distress. Receiver operating characteristic (ROC) analysis determined age 86 as the optimal cutoff for both clinical depression and distress. Depression among older patients with cancer rises with increasing age, being extremely common among the oldest old. Age independently predicted depression, irrespective of medical variables, social support, or functional status. Findings highlight the importance of addressing the potentially unmet psychological needs of this rapidly growing patient population. Copyright © 2018. Published by Elsevier Ltd.

Incidence, management, and course of cancer in patients with inflammatory bowel disease.

PubMed

Algaba, Alicia; Guerra, Iván; Marín-Jiménez, Ignacio; Quintanilla, Elvira; López-Serrano, Pilar; García-Sánchez, María Concepción; Casis, Begoña; Taxonera, Carlos; Moral, Ignacio; Chaparro, María; Martín-Rodríguez, Daniel; Martín-Arranz, María Dolores; Manceñido, Noemí; Menchén, Luis; López-Sanromán, Antonio; Castaño, Ángel; Bermejo, Fernando

2015-04-01

Patients with inflammatory bowel disease [IBD] are at increased risk for developing some types of neoplasia. Our aims were to determin the risk for cancer in patients with IBD and to describe the relationship with immunosuppressive therapies and clinical management after tumor diagnosis. Retrospective, multicenter, observational, 5-year follow-up, cohort study. Relative risk [RR] of cancer in the IBD cohort and the background population, therapeutic strategies, and cancer evolution were analyzed. A total of 145 cancers were diagnosed in 133 of 9100 patients with IBD (global cumulative incidence 1.6% vs 2.4% in local population; RR = 0.67; 95% confidence interval [CI]: 0.57-0.78). Patients with IBD had a significantly increased RR of non-melanoma skin cancer [RR = 3.85; 2.53-5.80] and small bowel cancer [RR = 3.70; 1.23-11.13]. After cancer diagnosis, IBD treatment was maintained in 13 of 27 [48.1%] patients on thiopurines, in 2 of 3 on methotrexate [66.6%], none on anti-TNF-α monotherapy [n = 6] and 4 of 12 [33.3%] patients on combined therapy. Rate of death and cancer remission during follow-up did not differ [p > 0.05] between patients who maintained the treatment compared with patients who withdrew [5% vs 8% and 95% vs 74%, respectively]. An association between thiopurines [p = 0.20] or anti-TNF-α drugs [p = 0.77] and cancer was not found. Patients with IBD have an increased risk for non-melanoma skin cancer and small bowel cancer. Immunosuppresive therapy is not related to a higher overall risk for cancer or worse tumor evolution in patients who maintain these drugs after cancer diagnosis. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

TP53 copy number expansion is associated with the evolution of increased body size and an enhanced DNA damage response in elephants

PubMed Central

Sulak, Michael; Fong, Lindsey; Mika, Katelyn; Chigurupati, Sravanthi; Yon, Lisa; Mongan, Nigel P; Emes, Richard D; Lynch, Vincent J

2016-01-01

A major constraint on the evolution of large body sizes in animals is an increased risk of developing cancer. There is no correlation, however, between body size and cancer risk. This lack of correlation is often referred to as 'Peto's Paradox'. Here, we show that the elephant genome encodes 20 copies of the tumor suppressor gene TP53 and that the increase in TP53 copy number occurred coincident with the evolution of large body sizes, the evolution of extreme sensitivity to genotoxic stress, and a hyperactive TP53 signaling pathway in the elephant (Proboscidean) lineage. Furthermore, we show that several of the TP53 retrogenes (TP53RTGs) are transcribed and likely translated. While TP53RTGs do not appear to directly function as transcription factors, they do contribute to the enhanced sensitivity of elephant cells to DNA damage and the induction of apoptosis by regulating activity of the TP53 signaling pathway. These results suggest that an increase in the copy number of TP53 may have played a direct role in the evolution of very large body sizes and the resolution of Peto's paradox in Proboscideans. DOI: http://dx.doi.org/10.7554/eLife.11994.001 PMID:27642012

The Genomic Evolution of Prostate Cancer

DTIC Science & Technology

2017-06-01

This study is supported by the AACI Fellowship for Trans- lational Cancer Research and DOD Prostate Cancer Research Program PRTA (DVW) and the...degraded during post -mor- tem time before fixation, which is supported by the low quality of RNA from matched frozen tissue. A limitation of this study ...is that a portion of the study used autopsy specimens, which have already undergone some degree of post -mor- tem degradation prior to PAXgene and

Temporal evolution of age data under transient pumping conditions

NASA Astrophysics Data System (ADS)

Leray, S.; De Dreuzy, J.; Aquilina, L.; Vergnaud, V.; Labasque, T.; Bour, O.; Le Borgne, T.

2013-12-01

While most age data derived from tracers have been analyzed in steady-state flow conditions, we determine their temporal evolution under transient pumping conditions. Starting pumping in a well modifies the natural flow patterns induced by the topographical gradient to a mainly convergent flow to the well. Our study is based on a set of models made up of a shallowly dipping aquifer overlain by a less permeable aquitard. These settings are characteristic of the crystalline aquifer of Plœmeur (Brittany, France) located in a highly fractured zone at the contact between a granite and micaschists. Under a pseudo steady-state flow assumption (instantaneous shift between two steady-state flow fields), we solve the transport equation with a backward particle-tracking method and determine the temporal evolution of the concentrations at the pumping well of the four atmospheric tracers CFC 11, CFC 12, CFC 113 and SF6. We show that apparent ages deduced from these concentrations evolve both because of the flow patterns modifications and because of the non-linear evolution of the atmospheric tracer concentrations. Flow patterns modifications only intervene just after the start of pumping, when the initially piston-like residence time distribution is transformed to a broader distribution mixing residence times from a wide variety of flow lines. Later, while flow patterns and the supplying volume of the pumping well still evolve, the residence time distributions are hardly modified and apparent ages are solely altered by the non-linear atmospheric tracer concentrations that progressively modifies the weighting of the residence time distribution. These results are confirmed by the observations at the site of Plœmeur in the pumping area. First, long term chloride observations confirm the quick evolution of the flow patterns after the start of pumping. Second, posterior and more recent evolutions of apparent ages derived from CFCs are consistent with the modeling results revealing in turn the marginal effect of the 20-year pumping on the first 70 years of the residence time distribution. We conclude that the temporal evolution of apparent ages should be used with great care for identifying the temporal evolution of the flow patterns as the apparent age evolution can have two sources - the transient flow patterns and transient tracer atmospheric concentrations. We argue that both evolutions either controlled by transient flow patterns or by transient tracer atmospheric concentrations provide key information that can be further used for the characterization of the hydrogeological system. This study illustrates that the temporal evolution of apparent ages could be used for models segregation and slightly compensate for the small number of tracers.

Trends in stage-specific incidence of prostate cancer in Norway, 1980-2010: a population-based study.

PubMed

Møller, Mette H; Kristiansen, Ivar S; Beisland, Christian; Rørvik, Jarle; Støvring, Henrik

2016-10-01

To estimate changes in the stage distribution of prostate cancer during the time period where opportunistic prostate-specific antigen (PSA) testing was introduced. Cancer stage, age, and year of diagnosis were obtained for all men aged >50 years diagnosed with prostate cancer in Norway during the period 1980-2010. Three calendar-time periods (1980-1989, 1990-2000, and 2001-2010) and three age groups (50-65, 66-74, and ≥75 years) were defined. Birth cohorts were categorised into four intervals: ≤1915, 1916-1925, 1926-1940 and ≥1941. We used Poisson regressions to conduct both a time period and cohort-based analysis of trends in the incidence of localised, regional, and distant cancer for each combination of age groups and calendar-time periods or birth cohorts, respectively. Additionally, we explored the effect of cohorts on the stage-specific incidence graphically with a Poisson regression using 5-year age groups, and by estimating cumulative incidence rates for each birth cohort. The annual incidence of localised cancers among men aged 50-65 and 66-74 years rose from 41.4 and 255.2 per 100 000, respectively, before the introduction of PSA testing to 137.9 and 418.7 in 2001-2010 afterwards, corresponding to 3.3 [95% confidence interval (CI) 3.1-3.5] and 1.6 (95% CI 1.6-1.7) fold increases. The incidence of regional cancers increased by a factor seven among men aged <75 years. The incidence of distant cancers in men aged ≥75 years decreased by 29% (95% CI 25-33%). These findings were confirmed in the cohort-based approach. Opportunistic PSA testing substantially increased the incidence of localised and regional prostate cancers among men aged 50-74 years, which was not fully compensated by the 30% decrease in incidence of distant prostate cancers in older men. © 2015 The Authors BJU International © 2015 BJU International Published by John Wiley & Sons Ltd.

Is Heart Disease or Cancer the Leading Cause of Death in United States Women?

PubMed

Pathak, Elizabeth B

This paper compares the mortality burden of heart disease versus cancer among women by age, race, and ethnicity. U.S. death and population data for the years 2000 through 2013 were used to calculate heart disease and cancer death rates. Detailed analyses focused on age (15-19 years old to ≥100 years old) and race and ethnicity (Whites, Blacks, Hispanics, Asians and Pacific Islanders (A/PIs), and American Indians and Alaska Natives (AI/ANs)). Among women aged 15 years and older, there were 289,467 heart disease deaths and 276,716 cancer deaths in 2013. The majority of heart disease deaths (51.6%) occurred among women 85 years or older, compared with 18.9% of female cancer deaths. The age-adjusted death rates (per 100,000 population) were 171 (95% confidence interval [CI], 170-171) for heart disease versus 177 (95% CI, 176-178) for cancer. For all racial and ethnic groups, cancer mortality was significantly higher than heart disease mortality among women younger than 80 years of age. For all ages combined, cancer deaths exceeded heart disease deaths among Hispanics, A/PIs, and AI/ANs. Black non-Hispanic women were the only racial/ethnic group who had a higher age-adjusted death rate for heart disease than for cancer: 224 (95% CI, 222-226) versus 207 (95% CI, 205-209). Heart disease remains the leading cause of death among all women combined in the United States by a narrow margin. However, cancer predominantly kills middle-aged and young women, whereas heart disease predominantly kills the very old. New research on the overreporting of heart disease on death certificates for elderly women is needed. National summary statistics obscure the fact that cancer is already the overall leading cause of death for Hispanic women, Asian and Pacific Islander women, and American Indian and Alaska Native women. Copyright © 2016 Jacobs Institute of Women's Health. Published by Elsevier Inc. All rights reserved.

Cervical cancer incidence and mortality in Fiji 2003-2009.

PubMed

Kuehn, Rebecca; Fong, James; Taylor, Richard; Gyaneshwar, Rajanishwar; Carter, Karen

2012-08-01

Previous studies indicate that cervical cancer is the second most frequent cancer and most common cause of cancer mortality among women in Fiji. There is little published data on the epidemiology of cervical cancer in Pacific countries. To determine the incidence 2003-2009 of, and mortality 2003-2008 from, cervical cancer by ethnicity and period in Fiji, identify evidence of secular change and relate these data to other Pacific countries, Australia and New Zealand. Counts of incident cervical cancer cases (2003-2009) and unit record mortality data (2003-2008) from the Fiji Ministry of Health were used to calculate age-standardised (to the WHO World Population) cervical cancer incidence and mortality rates, and cervical or uterine cancer mortality rates, by ethnicity, with 95% confidence intervals. On the basis of comparison of cervical cancer mortality with cervical or uterine cancer mortality in Fiji with similar populations, misclassification of cervical cancer deaths is unlikely. There is no evidence of secular change in cervical cancer incidence and mortality rates for the study period. For women of all ages and ethnicities, the age-standardised incidence rate of cervical cancer (2003-2009) was 27.6 per 100,000 (95% CI 25.4-29.8) and the age-standardised mortality rate (2003-2008) was 23.9 per 100,000 (95% CI 21.5-26.4). The mortality/incidence ratio was 87%. Fijians had statistically significant higher age-standardised incidence and mortality rates than Indians. Fiji has one of the highest estimated rates of cervical cancer incidence and mortality in the Pacific region. Cervical cancer screening in Fiji needs to be expanded and strengthened. © 2012 The Authors ANZJOG © 2012 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

Cancer surgery in the elderly.

PubMed

Hoekstra, H J

2001-10-01

Surprisingly, cancer in the elderly is frequently treated in a poor manner, and the behaviour of the disease in elderly patients is often poorly understood. Cancer treatment varies significantly with age, the percentage of patients receiving definitive treatment declines with increasing age, and there is a decline in survival of cancer with age. One of the contributing factors may be that physicians are less likely to recommend specialist consultation for elderly patients. One has to keep in mind that cancer surgery in the elderly, without any co-morbidity, is safe, and that, nowadays, the morbidity and mortality increases minimally with the age of the patient. In contrast, the morbidity and mortality is 2-3 fold as high in the elderly cancer patients with co-morbidity compared with younger cancer patients. A better public education of the elderly may increase cancer awareness, and therefore decrease the risk of developing symptoms that require emergency surgery, with a subsequent three times increase in the mortality rate. Surgeons treating elderly cancer patients should realise that performance status is more important than age, and should always keep in mind the three major questions as recently formulated by Balducci; (1) is the patient going to die of cancer or with cancer, (2) is the patient able to tolerate the surgery and possible surgical-related complications, and (3) is the patient likely to suffer the complications of cancer during her/his life? The increased number of surgical treatment options in elderly cancer patients will lead to an increase in overall cancer survival in elderly cancer patients, and contribute to an improvement in their quality of life. Surgical oncologists should focus on how to manage the most common cancers in elderly people such as breast, colorectal, lung and prostate, as well as take an active part in palliative treatments.

Personalized Cancer Medicine: Molecular Diagnostics, Predictive biomarkers, and Drug Resistance

PubMed Central

Gonzalez de Castro, D; Clarke, P A; Al-Lazikani, B; Workman, P

2013-01-01

The progressive elucidation of the molecular pathogenesis of cancer has fueled the rational development of targeted drugs for patient populations stratified by genetic characteristics. Here we discuss general challenges relating to molecular diagnostics and describe predictive biomarkers for personalized cancer medicine. We also highlight resistance mechanisms for epidermal growth factor receptor (EGFR) kinase inhibitors in lung cancer. We envisage a future requiring the use of longitudinal genome sequencing and other omics technologies alongside combinatorial treatment to overcome cellular and molecular heterogeneity and prevent resistance caused by clonal evolution. PMID:23361103

EXPRESSION OF INDUCIBLE HSP70 ENHANCES THE PROLIFERATION OF MCF-7 BREAST CANCER CELLS AND PROTECTS AGAINST THE CYTOTOXIC EFFECTS OF HYPERTHERMIA

EPA Science Inventory

Heat shock proteins (HSPs) are ubiquitous proteins that are induced following exposure to sub-lethal heat shock, are highly conserved during evolution and protect cells from damage through their function as molecular chaperones. Some cancers demonstrate elevated levels of Hsp70 ...

Identification and Characterization of MYC Regulatory Elements: Links to Prostate Cancer

DTIC Science & Technology

2011-06-01

cell proliferation and growth,MYC is up-regulated at both the mRNA and protein levels in aggressive prostate cancers ( DeMarzo et al. 2003). In...evolutionary synthesis: A genetic theory of morphological evolution. Cell 134: 25–36. DeMarzo AM, Nelson WG, Isaacs WB, Epstein JI. 2003. Pathological and

Experimental evolution of slowed cognitive aging in Drosophila melanogaster.

PubMed

Zwoinska, Martyna K; Maklakov, Alexei A; Kawecki, Tadeusz J; Hollis, Brian

2017-03-01

Reproductive output and cognitive performance decline in parallel during aging, but it is unknown whether this reflects a shared genetic architecture or merely the declining force of natural selection acting independently on both traits. We used experimental evolution in Drosophila melanogaster to test for the presence of genetic variation for slowed cognitive aging, and assess its independence from that responsible for other traits' decline with age. Replicate experimental populations experienced either joint selection on learning and reproduction at old age (Old + Learning), selection on late-life reproduction alone (Old), or a standard two-week culture regime (Young). Within 20 generations, the Old + Learning populations evolved a slower decline in learning with age than both the Old and Young populations, revealing genetic variation for cognitive aging. We found little evidence for a genetic correlation between cognitive and demographic aging: although the Old + Learning populations tended to show higher late-life fecundity than Old populations, they did not live longer. Likewise, selection for late reproduction alone did not result in improved late-life learning. Our results demonstrate that Drosophila harbor genetic variation for cognitive aging that is largely independent from genetic variation for demographic aging and suggest that these two aspects of aging may not necessarily follow the same trajectories. © 2016 The Author(s). Evolution published by Wiley Periodicals, Inc. on behalf of The Society for the Study of Evolution.

International incidence of childhood cancer, 2001-10: a population-based registry study.

PubMed

Steliarova-Foucher, Eva; Colombet, Murielle; Ries, Lynn A G; Moreno, Florencia; Dolya, Anastasia; Bray, Freddie; Hesseling, Peter; Shin, Hee Young; Stiller, Charles A

2017-06-01

Cancer is a major cause of death in children worldwide, and the recorded incidence tends to increase with time. Internationally comparable data on childhood cancer incidence in the past two decades are scarce. This study aimed to provide internationally comparable local data on the incidence of childhood cancer to promote research of causes and implementation of childhood cancer control. This population-based registry study, devised by the International Agency for Research on Cancer in collaboration with the International Association of Cancer Registries, collected data on all malignancies and non-malignant neoplasms of the CNS diagnosed before age 20 years in populations covered by high-quality cancer registries with complete data for 2001-10. Incidence rates per million person-years for the 0-14 years and 0-19 years age groups were age-adjusted using the world standard population to provide age-standardised incidence rates (WSRs), using the age-specific incidence rates (ASR) for individual age groups (0-4 years, 5-9 years, 10-14 years, and 15-19 years). All rates were reported for 19 geographical areas or ethnicities by sex, age group, and cancer type. The regional WSRs for children aged 0-14 years were compared with comparable data obtained in the 1980s. Of 532 invited cancer registries, 153 registries from 62 countries, departments, and territories met quality standards, and contributed data for the entire decade of 2001-10. 385 509 incident cases in children aged 0-19 years occurring in 2·64 billion person-years were included. The overall WSR was 140·6 per million person-years in children aged 0-14 years (based on 284 649 cases), and the most common cancers were leukaemia (WSR 46·4), followed by CNS tumours (WSR 28·2), and lymphomas (WSR 15·2). In children aged 15-19 years (based on 100 860 cases), the ASR was 185·3 per million person-years, the most common being lymphomas (ASR 41·8) and the group of epithelial tumours and melanoma (ASR 39·5). Incidence varied considerably between and within the described regions, and by cancer type, sex, age, and racial and ethnic group. Since the 1980s, the global WSR of registered cancers in children aged 0-14 years has increased from 124·0 (95% CI 123·3-124·7) to 140·6 (140·1-141·1) per million person-years. This unique global source of childhood cancer incidence will be used for aetiological research and to inform public health policy, potentially contributing towards attaining several targets of the Sustainable Development Goals. The observed geographical, racial and ethnic, age, sex, and temporal variations require constant monitoring and research. International Agency for Research on Cancer and the Union for International Cancer Control. Copyright © 2017 World Health Organization; licensee Elsevier. This is an Open Access article published under the CC BY-NC-ND 3.0 IGO license which permits users to download and share the article for non-commercial purposes, so long as the article is reproduced in the whole without changes, and provided the original source is properly cited. This article shall not be used or reproduced in association with the promotion of commercial products, services or any entity. There should be no suggestion that WHO endorses any specific organisation, products, or services. The use of the WHO logo is not permitted. This notice should be preserved along with the article's original URL.

Nutrigenomics at the Interface of Aging, Lifespan, and Cancer Prevention123

PubMed Central

Riscuta, Gabriela

2016-01-01

The percentage of elderly people with associated age-related health deterioration, including cancer, has been increasing for decades. Among age-related diseases, the incidence of cancer has grown substantially, in part because of the overlap of some molecular pathways between cancer and aging. Studies with model organisms suggest that aging and age-related conditions are manipulable processes that can be modified by both genetic and environmental factors, including dietary habits. Variations in genetic backgrounds likely lead to differential responses to dietary changes and account for some of the inconsistencies found in the literature. The intricacies of the aging process, coupled with the interrelational role of bioactive food components on gene expression, make this review a complex undertaking. Nevertheless, intriguing evidence suggests that dietary habits can manipulate the aging process and/or its consequences and potentially may have unprecedented health benefits. The present review focuses on 4 cellular events: telomerase activity, bioenergetics, DNA repair, and oxidative stress. These processes are linked to both aging and cancer risk, and their alteration in animal models by selected food components is evident. PMID:27558581

Nutrigenomics at the Interface of Aging, Lifespan, and Cancer Prevention.

PubMed

Riscuta, Gabriela

2016-10-01

The percentage of elderly people with associated age-related health deterioration, including cancer, has been increasing for decades. Among age-related diseases, the incidence of cancer has grown substantially, in part because of the overlap of some molecular pathways between cancer and aging. Studies with model organisms suggest that aging and age-related conditions are manipulable processes that can be modified by both genetic and environmental factors, including dietary habits. Variations in genetic backgrounds likely lead to differential responses to dietary changes and account for some of the inconsistencies found in the literature. The intricacies of the aging process, coupled with the interrelational role of bioactive food components on gene expression, make this review a complex undertaking. Nevertheless, intriguing evidence suggests that dietary habits can manipulate the aging process and/or its consequences and potentially may have unprecedented health benefits. The present review focuses on 4 cellular events: telomerase activity, bioenergetics, DNA repair, and oxidative stress. These processes are linked to both aging and cancer risk, and their alteration in animal models by selected food components is evident. © 2016 American Society for Nutrition.

Breast cancer correlates in a cohort of breast screening program participants in Riyadh, KSA.

PubMed

Al-Amri, Fahad A; Saeedi, Mohammed Y; Al-Tahan, Fatina M; Ali, Arwa M; Alomary, Shaker A; Arafa, Mostafa; Ibrahim, Ahmed K; Kassim, Kassim A

2015-06-01

Breast cancer is the first cancer among females in the Kingdom of Saudi Arabia, accounting for 27.4% of all newly diagnosed female cancers in 2010. There are several risk factors affecting the incidence of breast cancer where some factors influence the risk more than the others. We aimed to identify the different risk factors related to breast cancer among females participating in the breast-screening program in Riyadh, KSA. Based on data from phase-I of the breast-screening program, a case-control study was conducted on women living in Riyadh, KSA. A sample of 349 women (58 cases and 290 controls) was recruited to examine the different breast cancer correlates. Multivariate regression model was built to investigate the most important risk factors. The mean age of cases was 48.5±7.1 years. Age at marriage, number of pregnancy, age at menopause, oral contraceptive pills, breast feeding and family history of breast cancer in first-degree relative were identified as the most important correlates among the studied cohort. The findings of the current work suggested that age at marriage, age at menopause ⩾50 years and 1st degree family history of breast cancer were risk factors for breast cancer, while, age at menopause <50 years, number of pregnancies and practicing breast feeding were protective factors against breast cancer. There was no effect of body mass index or physical inactivity. Further studies are needed to explore the hereditary, familial and genetic background risk factors in Saudi population. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

[Risk factors associated with breast cancer women's in Durango, Mexico].

PubMed

Sifuentes-Álvarez, Antonio; Castañeda-Martínez, Lucy Yolanda; Lugo-Nevares, Mario; Reyes-Romero, Miguel Arturo

2015-11-01

Breast cancer is a public health problem worldwide and is a priority for developing countries like ours, to establish preventive and early detection measures. In Mexico since 2006 breast cancer than cervical cancer as a cause of death in women aged 30-54 years and threatens all socioeconomic groups. The known risk factors for the occurrence of this neoplasm are early menarche, nulliparity, late age parity and late menopause and family history of breast cancer. To determine the risk factors associated with breast cancer in women in the State of Durango. Epidemiological study of 50 cases and 100 con- trols aged between 35 and 69 years old. For the calculation of sample size Schlesselman tables were used. The data was collected and analyzed in SPSS V15. We used descriptive statistics and odds ratio was calculated. Age had a mean of 50.60 years and a deviation ±9,599 for cases and 50.73 (SD ± 10.08) for controls. The hereditary familial history of breast cancer OR = 5.182 (Cl 1694-15855), higher age at first pregnancy at 30 years of age OR = 3.582 (95% CI .1.121-11.439). The results of this study suggest that reproductive and hereditary familial history may influence the development of breast cancer, which is a multifactorial disease.

Prostate cancer characteristics in the World Trade Center cohort, 2002-2013.

PubMed

Hashim, Dana; Boffetta, Paolo; Galsky, Matthew; Oh, William; Lucchini, Roberto; Crane, Michael; Luft, Benjamin; Moline, Jaqueline; Udasin, Iris; Harrison, Denise; Taioli, Emanuela

2018-07-01

An increased incidence of prostate cancer was reported in three cohorts of World Trade Center (WTC) respondents. It is uncertain whether this increase is because of WTC-related exposures or enhanced surveillance. Prostate cancer cases (2002-2013) were obtained from the WTC Health Program. Age, race, and Gleason score distribution were compared with New York State Cancer Registry cases from the same time period. Multivariate models were adjusted for age and race. Analyses of clinical characteristics of prostate cancer cases within the cohort were also carried out, adjusting for age, race, and WTC exposure categories. WTC respondents had a prostate cancer age-standardized rate ratio of 1.65 [95% confidence interval (CI): 1.37-1.93] compared with New York State; age-specific ratios were highest for ages 30-49 (2.28; 95% CI: 1.51-3.43), 70-74 (2.05; 95% CI: 1.03-4.10), and 80-84 years (5.65; 95% CI: 1.41-22.58). High WTC exposure was associated with advanced clinical stage (5.58; 95% CI: 1.05-29.76; Ptrend=0.03). WTC respondents continue to have a higher prostate cancer rate compared with New York State as a whole. Respondents with a higher WTC exposure level may have had more advanced clinical stage of prostate cancer.

The burden of cancer in Mexico, 1990-2013.

PubMed

Gómez-Dantés, Héctor; Lamadrid-Figueroa, Héctor; Cahuana-Hurtado, Lucero; Silverman-Retana, Omar; Montero, Pablo; González-Robledo, María Cecilia; Fitzmaurice, Christina; Pain, Amanda; Allen, Christine; Dicker, Daniel J; Hamavid, Hannah; López, Alan; Murray, Christopher; Naghavi, Mohsen; Lozano, Rafael

2016-04-01

To analyze mortality and incidence for 28 cancers by deprivation status, age and sex from 1990 to 2013. The data and methodological approaches provided by the Global Burden of Disease (GBD 2013) were used. Trends from 1990 to 2013 show important changes in cancer epidemiology in Mexico. While some cancers show a decreasing trend in incidence and mortality (lung, cervical) others emerge as relevant health priorities (prostate, breast, stomach, colorectal and liver cancer). Age standardized incidence and mortality rates for all cancers are higher in the northern states while the central states show a decreasing trend in the mortality rate. The analysis show that infection related cancers like cervical or liver cancer play a bigger role in more deprived states and that cancers with risk factors related to lifestyle like colorectal cancer are more common in less marginalized states. The burden of cancer in Mexico shows complex regional patterns by age, sex, types of cancer and deprivation status. Creation of a national cancer registry is crucial.

Age at Last Birth in Relation to Risk of Endometrial Cancer: Pooled Analysis in the Epidemiology of Endometrial Cancer Consortium

PubMed Central

Setiawan, Veronica Wendy; Pike, Malcolm C.; Karageorgi, Stalo; Deming, Sandra L.; Anderson, Kristin; Bernstein, Leslie; Brinton, Louise A.; Cai, Hui; Cerhan, James R.; Cozen, Wendy; Chen, Chu; Doherty, Jennifer; Freudenheim, Jo L.; Goodman, Marc T.; Hankinson, Susan E.; Lacey, James V.; Liang, Xiaolin; Lissowska, Jolanta; Lu, Lingeng; Lurie, Galina; Mack, Thomas; Matsuno, Rayna K.; McCann, Susan; Moysich, Kirsten B.; Olson, Sara H.; Rastogi, Radhai; Rebbeck, Timothy R.; Risch, Harvey; Robien, Kim; Schairer, Catherine; Shu, Xiao-Ou; Spurdle, Amanda B.; Strom, Brian L.; Thompson, Pamela J.; Ursin, Giske; Webb, Penelope M.; Weiss, Noel S.; Wentzensen, Nicolas; Xiang, Yong-Bing; Yang, Hannah P.; Yu, Herbert; Horn-Ross, Pamela L.; De Vivo, Immaculata

2012-01-01

Childbearing at an older age has been associated with a lower risk of endometrial cancer, but whether the association is independent of the number of births or other factors remains unclear. Individual-level data from 4 cohort and 13 case-control studies in the Epidemiology of Endometrial Cancer Consortium were pooled. A total of 8,671 cases of endometrial cancer and 16,562 controls were included in the analysis. After adjustment for known risk factors, endometrial cancer risk declined with increasing age at last birth (Ptrend < 0.0001). The pooled odds ratio per 5-year increase in age at last birth was 0.87 (95% confidence interval: 0.85, 0.90). Women who last gave birth at 40 years of age or older had a 44% decreased risk compared with women who had their last birth under the age of 25 years (95% confidence interval: 47, 66). The protective association was similar across the different age-at-diagnosis groups and for the 2 major tumor histologic subtypes (type I and type II). No effect modification was observed by body mass index, parity, or exogenous hormone use. In this large pooled analysis, late age at last birth was independently associated with a reduced risk of endometrial cancer, and the reduced risk persisted for many years. PMID:22831825

Secular trend analysis of lung cancer incidence in Sihui city, China between 1987 and 2011.

PubMed

Du, Jin-Lin; Lin, Xiao; Zhang, Li-Fang; Li, Yan-Hua; Xie, Shang-Hang; Yang, Meng-Jie; Guo, Jie; Lin, Er-Hong; Liu, Qing; Hong, Ming-Huang; Huang, Qi-Hong; Liao, Zheng-Er; Cao, Su-Mei

2015-07-31

With industrial and econom ic development in recent decades in South China, cancer incidence may have changed due to the changing lifestyle and environment. However, the trends of lung cancer and the roles of smoking and other environmental risk factors in the development of lung cancer in rural areas of South China remain unclear. The purpose of this study was to explore the lung cancer incidence trends and the possible causes of these trends. Joinpoint regression analysis and the age-period-cohort (APC) model were used to analyze the lung cancer incidence trends in Sihui, Guangdong province, China between 1987 and 2011, and explore the possible causes of these trends. A total of 2,397 lung cancer patients were involved in this study. A 3-fold increase in the incidence of lung cancer in both sexes was observed over the 25-year period. Joinpoint regression analysis showed that while the incidence continued to increase steadily in females during the entire period, a sharp acceleration was observed in males starting in 2005. The full APC model was selected to describe age, period, and birth cohort effects on lung cancer incidence trends in Sihui. The age cohorts in both sexes showed a continuously significant increase in the relative risk (RR) of lung cancer, with a peak in the eldest age group (80-84 years). The RR of lung cancer showed a fluctuating curve in both sexes. The birth cohorts identified an increased trend in both males and females; however, males had a plateau in the youngest cohorts who were born during 1955-1969. Increasing trends of the incidence of lung cancer in Sihui were dominated by the effects of age and birth cohorts. Social aging, smoking, and environmental changes may play important roles in such trends.

Fertility preservation and cancer: How many persons are concerned?

PubMed

Le Bihan-Benjamin, Christine; Hoog-Labouret, Natalie; Lefeuvre, Delphine; Carré-Pigeon, Frédérique; Bousquet, Philippe Jean

2018-06-01

A significant proportion of cancer survivors experience chronic health sequelae, one of them being fertility impairment. However, even if many reports, guidelines and positions papers focus on fertility preservation and its needs, access to fertility preservation is not currently offered to all the patients concerned, and the targeted population is not well counted. A cross sectional study was conducted using the French cancer cohort, a cohort covering the whole French population and including around 7 million of cancer patients. Women under the age of 40 and men under the age of 60 included in the cancer cohort in 2013 who had, in the first year, cancer surgery, chemotherapy or radiotherapy were considered. Patients treated by surgery alone for cancers in locations distant from the reproductive organs, or being treated for a cancer the past 3 years were excluded. The number of patients concerned by fertility preservation was estimated at a national and regional level, and by cancer types. 40,000 patients - 30,000 men under the age of 60 years and 10,000 women under the age of 40 years - were identified. A second estimation concerning women under the age of 35 and men under 50 reduced the number of patients to 17,200-10,400 men and 6800 women. The most frequent locations were malignant neoplasm of lymphoid and hematopoietic tissue, lung cancer, cervix uteri, prostate and colorectal cancer. In 2014, around 5 400 persons had a preservation. Around 17,200 cancer patients of reproductive age should be informed about the fertility preservation options available. Medical professionals have to better integrate in their daily practice fertility preservation. Copyright © 2018 Elsevier B.V. All rights reserved.

A case-control study to assess the impact of mammographic density on breast cancer risk in women aged 40-49 at intermediate familial risk.

PubMed

Assi, Valentina; Massat, Nathalie J; Thomas, Susan; MacKay, James; Warwick, Jane; Kataoka, Masako; Warsi, Iqbal; Brentnall, Adam; Warren, Ruth; Duffy, Stephen W

2015-05-15

Mammographic density is a strong risk factor for breast cancer, but its potential application in risk management is not clear, partly due to uncertainties about its interaction with other breast cancer risk factors. We aimed to quantify the impact of mammographic density on breast cancer risk in women aged 40-49 at intermediate familial risk of breast cancer (average lifetime risk of 23%), in particular in premenopausal women, and to investigate its relationship with other breast cancer risk factors in this population. We present the results from a case-control study nested with the FH01 cohort study of 6,710 women mostly aged 40-49 at intermediate familial risk of breast cancer. One hundred and three cases of breast cancer were age-matched to one or two controls. Density was measured by semiautomated interactive thresholding. Absolute density, but not percent density, was a significant risk factor for breast cancer in this population after adjusting for area of nondense tissue (OR per 10 cm(2) = 1.07, 95% CI 1.00-1.15, p = 0.04). The effect was stronger in premenopausal women, who made up the majority of the study population. Absolute density remained a significant predictor of breast cancer risk after adjusting for age at menarche, age at first live birth, parity, past or present hormone replacement therapy, and the Tyrer-Cuzick 10-year relative risk estimate of breast cancer. Absolute density can improve breast cancer risk stratification and delineation of high-risk groups alongside the Tyrer-Cuzick 10-year relative risk estimate. © 2014 UICC.

Proposing an Interdisciplinary, Communication-Focused Agenda for Cancer and Aging Researchers

PubMed Central

Friedman, Daniela B.; Wilcox, Sara; Hebert, James R.

2015-01-01

Cancer is mainly a disease of older people. Costs for cancer prevention and control are rising due to increased life expectancy and the large cohort of aging “baby boomers.” An effective strategy for better understanding processes related to cancer and aging across the entire cancer continuum (i.e., from prevention through to end-of-life care) is to approach this challenge collaboratively. Communication-focused research is an area of collaborative study for cancer and aging researchers that would provide evidence regarding the most effective means for reaching older adults with messages about cancer prevention, control, and quality of life issues. Specifically we recommend research that is guided by multidisciplinary communication frameworks, involves health care providers, incorporates an intergenerational and family-centered approach into designing and implementing empirical studies, and creates culturally appropriate messaging through community-engaged research. PMID:25893924

Is early-onset microsatellite and chromosomally stable colorectal cancer a hallmark of a genetic susceptibility syndrome?

PubMed

Kets, C M; van Krieken, J H J M; van Erp, P E J; Feuth, T; Jacobs, Y H A; Brunner, H G; Ligtenberg, M J L; Hoogerbrugge, N

2008-02-15

Most colorectal cancers show either microsatellite or chromosomal instability. A subset of colorectal cancers, especially those diagnosed at young age, is known to show neither of these forms of genetic instability and thus might have a distinct pathogenesis. Colorectal cancers diagnosed at young age are suggestive for hereditary predisposition. We investigate whether such early-onset microsatellite and chromosomally stable colorectal cancers are a hallmark of a genetic susceptibility syndrome. The ploidy status of microsatellite stable (familial) colorectal cancers of patients diagnosed before age 50 (n = 127) was analyzed in relation to the histopathological characteristics and family history. As a control the ploidy status of sporadic colorectal cancer, with normal staining of mismatch repair proteins, diagnosed at the age of 69 years or above (n = 70) was determined. A diploid DNA content was used as a marker for chromosomal stability. Within the group of patients with (familial) early onset microsatellite stable colorectal cancer the chromosomally stable tumors did not differ from chromosomally unstable tumors with respect to mean age at diagnosis, fulfillment of Amsterdam criteria or pathological characteristics. Segregation analysis did not reveal any family with microsatellite and chromosomally stable colorectal cancer in 2 relatives. The prevalence of microsatellite and chromosomally stable colorectal cancer was not significantly different for the early and late onset group (28 and 21%, respectively). We find no evidence that early-onset microsatellite and chromosomally stable colorectal cancer is a hallmark of a hereditary colorectal cancer syndrome. (c) 2007 Wiley-Liss, Inc.

Cancer incidence and mortality among young adults aged 20-39 years worldwide in 2012: a population-based study.

PubMed

Fidler, Miranda M; Gupta, Sumit; Soerjomataram, Isabelle; Ferlay, Jacques; Steliarova-Foucher, Eva; Bray, Freddie

2017-12-01

To date, the burden of cancer among young adults has rarely been studied in depth. Our aim was to describe the scale and profile of cancer incidence and mortality worldwide among 20-39 year-olds, highlighting major patterns by age, sex, development level, and geographical region. We did a population-based study to quantify the burden of young adult cancers worldwide. We defined young adult cancers as those occurring between the ages of 20 and 39 years because these individuals will have passed puberty and adolescence, but not yet experienced the effects of hormonal decline, immune response deterioration, or organ dysfunction associated with chronic health conditions. Global, regional, and country-specific (n=184) data estimates of the number of new cancer cases and cancer-associated deaths that occurred in 2012 among young adults were extracted in four 5-year bands from the International Agency for Research on Cancer's GLOBOCAN 2012 for all cancers combined and for 27 major types as defined by the International Classification of Disease, tenth revision. We report the number of new cancer cases and cancer-associated deaths overall and by sex alongside corresponding age-standardised rates (ASR) per 100 000 people per year. We also present results using four levels of the Human Development Index (HDI; low [least developed], medium, high, and very high [most developed]), which is a composite indicator for socioeconomic development comprising life expectancy, education, and gross national income. 975 396 new cancer cases and 358 392 cancer-associated deaths occurred among young adults worldwide in 2012, which equated to an ASR of 43·3 new cancer cases per 100 000 people per year and 15·9 cancer-associated deaths per 100 000 people per year. The burden was disproportionally greater among women and the most common cancer types overall in terms of new cases were female breast cancer, cervical cancer, thyroid cancer, leukaemia, and colorectal cancer; in terms of deaths, female breast cancer, liver cancer, leukaemia, and cervical cancer were the main contributors. When assessed by development level and geographical region, the cancer profile varied substantially; generally, the burden of infection-associated cancers was greater in regions under transition. Cancer incidence was elevated in very high-HDI regions compared with low-HDI regions (ASR 64·5 vs 46·2 cancer cases per 100 000 people per year); however, the mortality burden was 3 times higher in low-HDI regions (ASR 25·4 vs 9·2 cancer-associated deaths per 100 000 people per year), reflecting differences in cancer profiles and inferior outcomes. The global cancer burden among 20-39 year-olds differs from that seen in younger or older ages and varies substantially by age, sex, development level, and geographical region. Although the cancer burden is lower in this age group than that observed in older ages, the societal and economic effects remain great given the major effects of premature morbidity and mortality. Targeted surveillance, prevention, and treatment are needed to reduce the cancer burden in this underserved age group. International Agency for Research on Cancer (IARC) and European Commission's FP-7 Marie Curie Actions-People-COFUND. Copyright © The Author(s). Published by Elsevier Ltd. This is an Open Access article published under the CC BY 3.0 IGO license which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. In any use of this article, there should be no suggestion that WHO endorses any specific organisation, products, or services. The use of the WHO logo is not permitted. This notice should be preserved along with the article's original URL.

[Feature extraction for breast cancer data based on geometric algebra theory and feature selection using differential evolution].

PubMed

Li, Jing; Hong, Wenxue

2014-12-01

The feature extraction and feature selection are the important issues in pattern recognition. Based on the geometric algebra representation of vector, a new feature extraction method using blade coefficient of geometric algebra was proposed in this study. At the same time, an improved differential evolution (DE) feature selection method was proposed to solve the elevated high dimension issue. The simple linear discriminant analysis was used as the classifier. The result of the 10-fold cross-validation (10 CV) classification of public breast cancer biomedical dataset was more than 96% and proved superior to that of the original features and traditional feature extraction method.

Sperm competition, immunity, selfish genes and cancer.

PubMed

Lewis, Z; Price, T A R; Wedell, N

2008-10-01

Sperm competition is widespread and has played an important role in shaping male reproductive characters such as testis size and numbers of sperm produced, and this is reflected in the rapid evolution of many reproductive genes. Additionally, sperm competition has been implicated in the rapid evolution of seminal fluids. However, our understanding of the molecular basis of many traits thought to be important in sperm competition is rudimentary. Furthermore, links between sperm competition and a range of issues not directly related to reproduction are only just beginning to be explored. These include associations between sperm competition and selfish genes, immunity and diseases such as cancer.We briefly review these topics and suggest areas we consider worthy of additional research.

Dietary Epigenetics in Cancer and Aging

PubMed Central

Tollefsbol, Trygve O.

2013-01-01

Although epigenetic aberrations frequently occur in aging and cancer and form a core component of these conditions, perhaps the most useful aspect of epigenetic processes is that they are readily reversible. Unlike genetic effects that also play a role in cancer and aging, epigenetic aberrations can be relatively easily corrected. One of the most widespread approaches to the epigenetic alterations in cancer and aging is dietary control. This can be achieved not only through the quality of the diet, but also through the quantity of calories that are consumed. Many phytochemicals such as sulforaphane from cruciferous vegetables and green tea have anticancer epigenetic effects and are also efficacious for preventing or treating the epigenetic aberrations of other age-associated diseases besides cancer. Likewise, the quantity of calories that are consumed have proven to be advantageous in preventing cancer and extending the lifespan through control of epigenetic mediators. The purpose of this chapter is to review some of the most recent advances in the epigenetics of cancer and aging and to provide insights into advances being made with respect to dietary intervention into these biological processes that have vast health implications and high translational potential. PMID:24114485

Screening for Colorectal Cancer: US Preventive Services Task Force Recommendation Statement.

PubMed

Bibbins-Domingo, Kirsten; Grossman, David C; Curry, Susan J; Davidson, Karina W; Epling, John W; García, Francisco A R; Gillman, Matthew W; Harper, Diane M; Kemper, Alex R; Krist, Alex H; Kurth, Ann E; Landefeld, C Seth; Mangione, Carol M; Owens, Douglas K; Phillips, William R; Phipps, Maureen G; Pignone, Michael P; Siu, Albert L

2016-06-21

Colorectal cancer is the second leading cause of cancer death in the United States. In 2016, an estimated 134,000 persons will be diagnosed with the disease, and about 49,000 will die from it. Colorectal cancer is most frequently diagnosed among adults aged 65 to 74 years; the median age at death from colorectal cancer is 68 years. To update the 2008 US Preventive Services Task Force (USPSTF) recommendation on screening for colorectal cancer. The USPSTF reviewed the evidence on the effectiveness of screening with colonoscopy, flexible sigmoidoscopy, computed tomography colonography, the guaiac-based fecal occult blood test, the fecal immunochemical test, the multitargeted stool DNA test, and the methylated SEPT9 DNA test in reducing the incidence of and mortality from colorectal cancer or all-cause mortality; the harms of these screening tests; and the test performance characteristics of these tests for detecting adenomatous polyps, advanced adenomas based on size, or both, as well as colorectal cancer. The USPSTF also commissioned a comparative modeling study to provide information on optimal starting and stopping ages and screening intervals across the different available screening methods. The USPSTF concludes with high certainty that screening for colorectal cancer in average-risk, asymptomatic adults aged 50 to 75 years is of substantial net benefit. Multiple screening strategies are available to choose from, with different levels of evidence to support their effectiveness, as well as unique advantages and limitations, although there are no empirical data to demonstrate that any of the reviewed strategies provide a greater net benefit. Screening for colorectal cancer is a substantially underused preventive health strategy in the United States. The USPSTF recommends screening for colorectal cancer starting at age 50 years and continuing until age 75 years (A recommendation). The decision to screen for colorectal cancer in adults aged 76 to 85 years should be an individual one, taking into account the patient's overall health and prior screening history (C recommendation).

Epidemiology of cervical cancer and human papilloma virus infection among Iranian women - analyses of national data and systematic review of the literature.

PubMed

Khorasanizadeh, Faezeh; Hassanloo, Jaleh; Khaksar, Nafiseh; Mohammad Taheri, Somayeh; Marzaban, Maryam; H Rashidi, Batool; Akbari Sari, Ali; Zendehdel, Kazem

2013-02-01

Few studies have evaluated the epidemiology of cervical cancer in low risk Muslim countries, where the prognosis of cervical cancer is poor and which lack an organized cervical screening program. We studied incidence and mortality rates of cervical cancer and the prevalence of high risk human papilloma virus (HPV) infection in the Islamic Republic (I.R.) of Iran. We analyzed national cancer and mortality registration data and estimated age-standardized incidence (ASR) and mortality (ASMR) rates and age-specific patterns of cervical cancer. Furthermore, based on a systematic review we estimated prevalence of HPV infection in Iran. The mean cervical cancer ASR was 2.5 per 100,000 in pathology-based cancer registries. However, ASRs were almost double in the population-based cancer registry and reached 6 per 100,000. The mean cervical cancer ASMR for Iran was 1.04 per 100,000. The mortality to incidence ratio was 42%. The cervical cancer incidence rate increased after age 30 and peaked between ages 55 and 65. The prevalence of HPV infection was 76% in cervical cancer patients and 7% among healthy Iranian women. Of the HPV types isolated, HPV 16 (54%), 18 (14%), and 31 (6%) were the most commonly detected in Iranian cervical cancer patients. An organized prevention program is needed to fight against cervical cancer in Iran and other low incidence countries. We suggest a screening program starting after age 30 and with at least three screenings tests over each woman's lifetime. With a reservation on cost-effectiveness issue, available HPV vaccine will prevent HPV infection and cervical cancer in Iran. Copyright © 2012 Elsevier Inc. All rights reserved.

Is there a genetic anticipation in breast and/or ovarian cancer families with the germline c.3481_3491del11 mutation?

PubMed

El Tannouri, R; Albuisson, E; Jonveaux, P; Luporsi, E

2018-01-01

The aim of the current analysis is to evaluate any differences of breast or ovarian cancer age at diagnosis between mothers and daughters carrying the c.3481_3491del11 mutation in the BRCA1 gene. A study cohort of 38 women carrying the c.3481_3491del11 mutation and affected by first breast or ovarian cancer who reported a first breast or ovarian cancer in their mother carrying the c.3481_3491del11 mutation, was identified in 37 different families including members with breast and/or ovarian cancer at the Oncology Institute of Lorraine. Twelve mothers underwent genetic testing. Twenty-five pairs of the 38 mothers-daughters pairs with c.3481_3491del11 mutation were affected by breast cancer and 13 pairs by ovarian cancer. Clinical and genetic data were collected from medical files and family pedigrees. Analyses were conducted for each cancer type. We investigated an early breast cancer detection effect due to early screening programs and also an increased breast tumor aggression. Since major improvements in breast cancer clinical management and imaging techniques appeared after 1980, we compared the age at breast cancer diagnosis and the age at death in mothers and daughters before and after 1980, first, in the group of women including mothers and daughters taken together and then in mothers and daughters separately. The mean age at breast cancer diagnosis was 45.28 ± 10.27 years in mothers and 39.80 ± 7.79 years in daughters (p = 0.026). The difference of age at ovarian cancer diagnosis in mother-daughter pairs was 8.62 ± 12.76 years (p = 0.032). When considering the group of women including mothers and daughters taken together, no significant difference of age at breast cancer diagnosis was found between women affected before 1980 and those affected after 1980 (p = 0.577). However, the age at death increased in these women after 1980 (p = 0.026). Comparison of age at breast cancer diagnosis in mothers and daughters separately, showed that daughters were affected at an earlier age after 1980 (p = 0.002). Daughters had a poor prognosis and died earlier than mothers after 1980. Our results may have reflected genetic anticipation in c.3481_3491del11 mutation breast and ovarian cancer families. In order to confirm our findings, a larger cohort would provide more precision to the difference of ages at breast or ovarian cancer diagnosis between mothers and daughters and more powerful statistical analyses. Increased aggression in daughters' tumors compared to those of mothers could be also considered as a parameter of genetic anticipation. Complete information on tumor profile and proliferation would allow us to study genetic anticipation by comparing the tumor phenotypes between mothers and daughters in the future.

Investigation of mammographic breast density as a risk factor for ovarian cancer.

PubMed

Wernli, Karen J; O'Meara, Ellen S; Kerlikowske, Karla; Miglioretti, Diana L; Muller, Carolyn Y; Onega, Tracy; Sprague, Brian L; Henderson, Louise M; Buist, Diana S M

2014-01-01

Endogenous hormones and growth factors that increase mammographic breast density could increase ovarian cancer risk. We examined whether high breast density is associated with ovarian cancer risk. We conducted a cohort study of 724,603 women aged 40 to 79 years with 2,506,732 mammograms participating in the Breast Cancer Surveillance Consortium from 1995 to 2009. Incident epithelial ovarian cancer was diagnosed in 1373 women. We used partly conditional Cox regression to estimate the association between breast density and 5-year risk of incident epithelial ovarian cancer overall and stratified by 10-year age group. All statistical tests were two-sided. Compared with women with scattered fibroglandular densities, women with heterogeneously dense and extremely dense breast tissue had 20% and 18% increased 5-year risk of incident epithelial ovarian cancer (hazard ratio [HR] = 1.20, 95% confidence interval [CI] = 1.06 to 1.36; HR = 1.18, 95% CI = 0.93 to 1.50, respectively; P(trend) = .01). Among women aged 50 to 59 years, we observed a trend in elevated risk associated with increased breast density (P(trend) = .02); women with heterogeneously and extremely dense breast tissue had 30% (HR = 1.30; 95% CI = 1.03 to 1.64) and 65% (HR = 1.65; 95% CI = 1.12 to 2.44) increased risk, respectively, compared with women with scattered fibroglandular densities. The pattern was similar but not statistically significant at age 40 to 49 years. There were no consistent patterns of breast density and ovarian cancer risk at age 60 to 79 years. Dense breast tissue was associated with a modest increase in 5-year ovarian cancer risk in women aged 50 to 59 years but was not associated with ovarian cancer at ages 40 to 49 or 60 to 79 years.

The Past, Present, and Future of Cancer Incidence in the United States: 1975 Through 2020

PubMed Central

Weir, Hannah K.; Thompson, Trevor D.; Soman, Ashwini; Møller, Bjørn; Leadbetter, Steven

2015-01-01

BACKGROUND The overall age-standardized cancer incidence rate continues to decline whereas the number of cases diagnosed each year increases. Predicting cancer incidence can help to anticipate future resource needs, evaluate primary prevention strategies, and inform research. METHODS Surveillance, Epidemiology, and End Results data were used to estimate the number of cancers (all sites) resulting from changes in population risk, age, and size. The authors projected to 2020 nationwide age-standardized incidence rates and cases (including the top 23 cancers). RESULTS Since 1975, incident cases increased among white individuals, primarily caused by an aging white population, and among black individuals, primarily caused by an increasing black population. Between 2010 and 2020, it is expected that overall incidence rates (proxy for risk) will decrease slightly among black men and stabilize in other groups. By 2020, the authors predict annual cancer cases (all races, all sites) to increase among men by 24.1% (−3.2% risk and 27.3% age/growth) to >1 million cases, and by 20.6% among women (1.2% risk and 19.4% age/growth) to >900,000 cases. The largest increases are expected for melanoma (white individuals); cancers of the prostate, kidney, liver, and urinary bladder in males; and the lung, breast, uterus, and thyroid in females. CONCLUSIONS Overall, the authors predict cancer incidence rates/risk to stabilize for the majority of the population; however, they expect the number of cancer cases to increase by >20%. A greater emphasis on primary prevention and early detection is needed to counter the effect of an aging and growing population on the burden of cancer. PMID:25649671

[Alterations of c-Myc and c-erbB-2 genes in ovarian tumours].

PubMed

Pastor, Tibor; Popović, Branka; Gvozdenović, Ana; Boro, Aleksandar; Petrović, Bojana; Novaković, Ivana; Puzović, Dragana; Luković, Ljiljana; Milasin, Jelena

2009-01-01

According to clinical and epidemiological studies, ovarian cancer ranks fifth in cancer deaths among women. The causes of ovarian cancer remain largely unknown but various factors may increase the risk of developing it, such as age, family history of cancer, childbearing status etc. This cancer results from a succession of genetic alterations involving oncogenes and tumour suppressor genes, which have a critical role in normal cell growth regulation. Mutations and/or overexpression of three oncogenes, c-erbB-2, c-Myc and K-ras, and of the tumour suppressor gene p53, have been frequently observed in a sporadic ovarian cancer. The aim of the present study was to analyse c-Myc and c-erbB-2 oncogene alterations, specifically amplification, as one of main mechanisms of their activation in ovarian cancers and to establish a possible association with the pathogenic process. DNA was isolated from 15 samples of malignant and 5 benign ovarian tumours, using proteinase K digestion, followed by phenol-chloroform isoamyl extraction and ethanol precipitation. C-Myc and c-erbB-2 amplification were detected by differential PCR. The level of gene copy increase was measured using the Scion image software. The amplification of both c-Myc and c-erbB-2 was detected in 26.7% of ovarian epithelial carcinoma specimens. Only one tumour specimen concomitantly showed increased gene copy number for both studied genes. Interestingly, besides amplification, gene deletion was also detected (26.7% for c-erbB-2). Most of the ovarian carcinomas with alterations in c-Myc and c-erbB-2 belonged to advanced FIGO stages. The amplification of c-Myc and c-erbB-2 oncogenes in ovarian epithelial carcinomas is most probably a late event in the pathogenesis conferring these tumours a more aggressive biological behaviour. Similarly, gene deletions point to genomic instability in epithelial carcinomas in higher clinical stages as the result of clonal evolution and selection.

Oral Cancer Facts

MedlinePlus

... biophysical processes of aging cells that allows malignant transformation, or perhaps, immune system competence diminishes with age. ... cancer develops We know that all cancers (neoplastic transformations) result from changes (mutations) in genes which control ...

Cardiac Mortality Among 200 000 Five-Year Survivors of Cancer Diagnosed at 15 to 39 Years of Age

PubMed Central

Henson, Katherine E.; Reulen, Raoul C.; Winter, David L.; Bright, Chloe J.; Fidler, Miranda M.; Frobisher, Clare; Guha, Joyeeta; Wong, Kwok F.; Kelly, Julie; Edgar, Angela B.; McCabe, Martin G.; Whelan, Jeremy; Cutter, David J.; Darby, Sarah C.

2016-01-01

Background: Survivors of teenage and young adult cancer are acknowledged as understudied. Little is known about their long-term adverse health risks, particularly of cardiac disease that is increased in other cancer populations where cardiotoxic treatments have been used. Methods: The Teenage and Young Adult Cancer Survivor Study cohort comprises 200 945 5-year survivors of cancer diagnosed at 15 to 39 years of age in England and Wales from 1971 to 2006, and followed to 2014. Standardized mortality ratios, absolute excess risks, and cumulative risks were calculated. Results: Two thousand sixteen survivors died of cardiac disease. For all cancers combined, the standardized mortality ratios for all cardiac diseases combined was greatest for individuals diagnosed at 15 to 19 years of age (4.2; 95% confidence interval, 3.4–5.2) decreasing to 1.2 (95% confidence interval, 1.1–1.3) for individuals aged 35 to 39 years (2P for trend <0.0001). Similar patterns were observed for both standardized mortality ratios and absolute excess risks for ischemic heart disease, valvular heart disease, and cardiomyopathy. Survivors of Hodgkin lymphoma, acute myeloid leukaemia, genitourinary cancers other than bladder cancer, non-Hodgkin lymphoma, lung cancer, leukaemia other than acute myeloid, central nervous system tumour, cervical cancer, and breast cancer experienced 3.8, 2.7, 2.0, 1.7, 1.7, 1.6, 1.4, 1.3 and 1.2 times the number of cardiac deaths expected from the general population, respectively. Among survivors of Hodgkin lymphoma aged over 60 years, almost 30% of the total excess number of deaths observed were due to heart disease. Conclusions: This study of over 200 000 cancer survivors shows that age at cancer diagnosis was critical in determining subsequent cardiac mortality risk. For the first time, risk estimates of cardiac death after each cancer diagnosed between the ages of 15 and 39 years have been derived from a large population-based cohort with prolonged follow-up. The evidence here provides an initial basis for developing evidence-based follow-up guidelines. PMID:27821538

[Thermodynamics of the origin of life, evolution and aging].

PubMed

Gladyshev, G P

2014-01-01

Briefly discusses the history of the search of thermodynamic approach to explain the origin of life, evolution and aging of living beings. The origin of life is the result of requirement by the quasi-equilibrium hierarchical thermodynamics, in particular, the supramolecular thermodynamics. The evolution and aging of living beings is accompanied with changes of chemical and supramolecular compositions of living bodies, as well as with changes in the composition and structure of all hierarchies of the living world. The thermodynamic principle of substance stability predicts the existence of a single genetic code in our universe. The thermodynamic theory optimizes physiology and medicine and recommends antiaging diets and medicines. Hierarchical thermodynamics forms the design diversity of culture and art. The thermodynamic theory of origin of life, evolution and aging is the development of Clausius-Gibbs thermodynamics. Hierarchical thermodynamics is the mirror of Darwin-Wallace's-theory.

HR+/Her2- breast cancer in pre-menopausal women: The impact of younger age on clinical characteristics at diagnosis, disease management and survival.

PubMed

De Camargo Cancela, Marianna; Comber, Harry; Sharp, Linda

2016-12-01

Young women (20-39 years-old) with breast cancer are diagnosed with more aggressive tumours and consequently have poorer survival. However, there is an evidence gap as to whether age has an independent effect on survival of pre-menopausal women diagnosed with HR+/Her2- tumours. The aim of this population-based study was to compare characteristics at diagnosis, determinants of treatment and survival in women aged 20-39 and 40-49 years diagnosed with HR+/Her2- tumours. From the National Cancer Registry Ireland, we identified women aged 20-49 diagnosed with a first invasive HR+/Her2- breast cancer during 2002-2008. Women aged 20-39 were compared to those aged 40-49 years. Poisson regression with robust error variance was used to explore the impact of age on treatment receipt. Associations between age and survival from all causes was investigated using Cox models. In multivariate models, women aged 20-39 significantly more often having no cancer-directed surgery (IRR=1.49, 95%CI 1.07, 2.08). In those having surgery, younger age was associated with significantly higher likelihood of receiving chemotherapy; age was not associated with receipt of adjuvant radiotherapy or endocrine therapy. Women aged 20-39 undergoing surgery were significantly more likely to die than women aged 40-49 (HR=1.84, 95%CI: 1.31, 2.59). Age is an independent prognostic factor in younger women diagnosed with HR+/Her2- breast cancer, supporting the hypothesis that breast cancer in women under 40 has more aggressive behaviour, even within HR+/Her2- tumours. Future research should explore the reasons for poorer survival in order to inform strategies to improve outcomes in this age group. Copyright © 2016 Elsevier Ltd. All rights reserved.

Early impact of the Patient Protection and Affordable Care Act on insurance among young adults with cancer: Analysis of the dependent insurance provision.

PubMed

Parsons, Helen M; Schmidt, Susanne; Tenner, Laura L; Bang, Heejung; Keegan, Theresa H M

2016-06-01

The Patient Protection and Affordable Care Act (ACA) included provisions to extend dependent health care coverage up to the age of 26 years in 2010. The authors examined the early impact of the ACA (before the implementation of insurance exchanges in 2014) on insurance rates in young adults with cancer, a historically underinsured group. Using National Cancer Institute Surveillance, Epidemiology, and End Results data for 18 cancer registries, the authors examined insurance rates before (pre) (January 2007-September 2010) versus after (post) (October 2010-December 2012) dependent insurance provisions among young adults aged 18 to 29 years when diagnosed with cancer during 2007 through 2012. Using multivariate generalized mixed effect models, the authors conducted difference-in-differences analysis to examine changes in overall and Medicaid insurance after the ACA among young adults who were eligible (those aged 18-25 years) and ineligible (those aged 26-29 years) for policy changes. Among 39,632 young adult cancer survivors, the authors found an increase in overall insurance rates in those aged 18 to 25 years after the dependent provisions (83.5% for pre-ACA vs 85.4% for post-ACA; P<.01), but not among individuals aged 26 to 29 years (83.4% for pre-ACA vs 82.9% for post-ACA; P = .38). After adjusting for patient sociodemographics and cancer characteristics, the authors found that those aged 18 to 25 years had a 3.1% increase in being insured compared with individuals aged 26 to 29 years (P<.01); however, there were no significant changes noted in Medicaid enrollment (P = .17). The findings of the current study identify an increase in insurance rates for young adults aged 18 to 25 years compared with those aged 26 to 29 years (1.9% vs -0.5%) that was not due to increases in Medicaid enrollment, thereby demonstrating a positive impact of the ACA dependent care provisions on insurance rates in this population. Cancer 2016;122:1766-73. © 2016 American Cancer Society. © 2016 American Cancer Society.

Cervical cancer risk levels in Turkey and compliance to the national cervical cancer screening standard.

PubMed

Açikgöz, Ayla; Ergör, Gül

2011-01-01

Cervical cancer screening with Pap smear test is a cost-effective method. The Ministry of Health in Turkey recommends that it be performed once every five years after age 35. The purpose of this study was to determine the cervical cancer risk levels of women between 35 and 69, and the intervals they have the Pap smear test, and to investigate the relation between the two. This study was performed on 227 women aged between 35 and 69 living in Balçova District of İzmir province. Using the cervical cancer risk index program of Harvard School of Public Health, the cervical cancer risk level of 70% of the women was found below average, 22.1% average, and 7.9% above average. Only 52% of the women have had Pap smear test at least once in their lives. The percentage screening regularly in conformity with the national screening standard was 39.2%. Women in the 40-49 age group, were married, conformed significantly more (p<0.05) to the national screening standard. Compliance also increased with the level of education and decreased with the cervical cancer risk level (p<0.05). A logistic regression model was constructed including age, education level, menstruation state of the women and the economic level of the family. Not having the Pap smear test in conformity with the national cervical cancer screening standard in 35-39 age group was 2.52 times more than 40-49 age group, while it was 3.26 times more in 60-69 age group (p< 0.05). Not having Pap smear test in 35-39 age group more than other groups might result from lack of information on the cervical cancer national screening standard and the necessity of having Pap smear test. As for 60-69 age group, the low education level might cause not having Pap smear test. Under these circumstances, the cervical cancer risk levels should be determined and the individuals should be informed. Providing Pap smear test screening service to individuals in the target group of national screening standard, as a public service may resolve the inequalities due to age and educational differences.

HAZMAT. I. The evolution of far-UV and near-UV emission from early M stars

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shkolnik, Evgenya L.; Barman, Travis S., E-mail: shkolnik@lowell.edu, E-mail: barman@lpl.arizona.edu

2014-10-01

The spectral energy distribution, variability, and evolution of the high-energy radiation from an M dwarf planet host is crucial in understanding the planet's atmospheric evolution and habitability and in interpreting the planet's spectrum. The star's extreme-UV (EUV), far-UV (FUV), and near-UV (NUV) emission can chemically modify, ionize, and erode the atmosphere over time. This makes determining the lifetime exposure of such planets to stellar UV radiation critical for both the evolution of a planet's atmosphere and our potential to characterize it. Using the early M star members of nearby young moving groups, which sample critical ages in planet formation andmore » evolution, we measure the evolution of the GALEX NUV and FUV flux as a function of age. The median UV flux remains at a 'saturated' level for a few hundred million years, analogous to that observed for X-ray emission. By the age of the Hyades Cluster (650 Myr), we measure a drop in UV flux by a factor of 2-3 followed by a steep drop from old (several Gyrs) field stars. This decline in activity beyond 300 Myr follows roughly t {sup –1}. Despite this clear evolution, there remains a wide range, of 1-2 orders of magnitude, in observed emission levels at every age. These UV data supply the much-needed constraints to M dwarf upper-atmosphere models, which will provide empirically motivated EUV predictions and more accurate age-dependent UV spectra as inputs to planetary photochemical models.« less

Reconstructing the evolution of first-row transition metal minerals by GeoDeepDive

NASA Astrophysics Data System (ADS)

Liu, C.; Peters, S. E.; Ross, I.; Golden, J. J.; Downs, R. T.; Hazen, R. M.

2016-12-01

Terrestrial mineralogy evolves as a consequence of a range of physical, chemical, and biological processes [1]. Evolution of the first-row transition metal minerals could mirror the evolution of Earth's oxidation state and life, since these elements mostly are redox-sensitive and/or play critical roles in biology. The fundamental building blocks to reconstruct mineral evolution are the mineral species, locality, and age data, which are typically dispersed in sentences in scientific and technical publications. These data can be tracked down in a brute-force way, i.e., human retrieval, reading, and recording all relevant literature. Alternatively, they can be extracted automatically by GeoDeepDive. In GeoDeepDive, scientific and technical articles from publishers, including Elsevier, Wiley, USGS, SEPM, GSA and Canada Science Publishing, have been parsed into a Javascript database with NLP tags. Sentences containing data of mineral names, locations, and ages can be recognized and extracted by user-developed applications. In a preliminary search for cobalt mineral ages, we successfully extracted 678 citations with >1000 mentions of cobalt minerals, their locations, and ages. The extracted results are in agreement with brute-force search results. What is more, GeoDeepDive provides 40 additional data points that were not recovered by the brute-force approach. The extracted mineral locality-age data suggest that the evolution of Co minerals is controlled by global supercontinent cycles, i.e., more Co minerals form during episodes of supercontinent assembly. Mineral evolution of other first-row transition elements is being investigated through GeoDeepDive. References: [1] Hazen et al. (2008) Mineral evolution. American Mineralogist, 93, 1693-1720

Circumcision and prostate cancer: a population-based case-control study in Montréal, Canada

PubMed Central

Spence, Andrea R; Rousseau, Marie-Claude; Karakiewicz, Pierre I; Parent, Marie-Élise

2014-01-01

Objectives To investigate the possible association between circumcision and prostate cancer risk, to examine whether age at circumcision influences prostate cancer risk, and to determine whether race modifies the circumcision–prostate cancer relationship. Subjects and Methods PROtEuS (Prostate Cancer and Environment Study), a population-based case-control study set amongst the mainly French-speaking population in Montréal, Canada, was used to address study objectives. The study included 1590 pathologically confirmed prostate cancer cases diagnosed in a Montréal French hospital between 2005 and 2009, and 1618 population controls ascertained from the French electoral list, frequency-matched to cases by age. In-person interviews elicited information on sociodemographic, lifestyle and environmental factors. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) between circumcision, age at circumcision and prostate cancer risk, adjusting for age, ancestry, family history of prostate cancer, prostate cancer screening history, education, and history of sexually transmitted infections. Results Circumcised men had a slightly lower risk, albeit not statistically significant, of developing prostate cancer than uncircumcised men (OR 0.89, 95% CI 0.76–1.04). Circumcision was found to be protective in men circumcised aged ≥36 years (OR 0.55, 95% CI 0.30–0.98). A weaker protective effect was seen among men circumcised within 1 year of birth (OR 0.86, 95% CI 0.72–1.04). The strongest protective effect of circumcision was recorded in Black men (OR 0.40, 95% CI 0.19–0.86, P-value for interaction 0.02) but no association was found with other ancestral groups. Conclusion Our findings provide novel evidence for a protective effect of circumcision against prostate cancer development, especially in those circumcised aged ≥36 years; although circumcision before the age of 1 year may also confer protection. Circumcision appeared to be protective only among Black men, a group that has the highest rate of disease. Further research into the differences in effect of circumcision on prostate cancer risk by ancestry is warranted, as is the influence of age at circumcision. PMID:24655933

Evaluating cytology for the detection of invasive cervical cancer.

PubMed

Landy, R; Castanon, A; Hamilton, W; Lim, A W W; Dudding, N; Hollingworth, A; Sasieni, P D

2016-06-01

To assess the sensitivity, the number needed to screen (NNS) and the positive predictive value (PPV) of cervical cytology for the diagnosis of cancer by age in a screening population. A retrospective cohort of women with invasive cervical cancer nested within a census of cervical cytology. All (c. 8 million) women aged 20-64 years with cervical cytology (excluding tests after an earlier abnormality). From April 2007 to March 2010, 3372 women had cervical cancer diagnosed within 12 months of such cytology in England. The sensitivity of cervical cytology to cancer, NNS to detect one cancer and predictive values of cytology were calculated for various 'referral' thresholds. These were calculated for ages 20-24, 25-34, 35-49 and 50-64 years. The sensitivity of at least moderate dyskaryosis [equivalent to a high-grade squamous intraepithelial lesion (HSIL) or worse] for cancer of 89.4% [95% confidence interval (CI) 88.3-90.4%] in women offered screening was independent of age. At all ages, women with borderline-early recall or mild dyskaryosis on cytology (equivalent to ASC-US and LSIL, respectively, in the Bethesda system) had a similar risk of cervical cancer to the risk in all women tested. The PPV of severe dyskaryosis/?invasive and ?glandular neoplasia cytology (equivalent to squamous cell carcinoma and adenocarcinoma/adenocarcinoma in situ, respectively, in the Bethesda System) were 34% and 12%, respectively; the PPV of severe dyskaryosis (HSIL: severe dysplasia) was 4%. The NNS was lowest when the incidence of cervical cancer was highest, at ages 25-39 years, but the proportion of those with abnormal cytology who have cancer was also lowest in younger women. The PPV of at least severe dyskaryosis (HSIL: severe dysplasia) for cancer was 4-10% of women aged 25-64 years, justifying a 2-week referral to colposcopy and demonstrating the importance of failsafe monitoring for such patients. The sensitivity of cytology for cervical cancer was excellent across all age groups. © 2015 The Authors Cytopathology Published by John Wiley & Sons Ltd.

QuickStats: Age-Adjusted Death Rates* for Top Five Causes of Cancer Death,(†) by Race/Hispanic Ethnicity - United States, 2014.

PubMed

2016-09-16

In 2014, the top five causes of cancer deaths for the total population were lung, colorectal, female breast, pancreatic, and prostate cancer. The non-Hispanic black population had the highest age-adjusted death rates for each of these five cancers, followed by non-Hispanic white and Hispanic groups. The age-adjusted death rate for lung cancer, the leading cause of cancer death in all groups, was 42.1 per 100,000 standard population for the total population, 45.4 for non-Hispanic white, 45.7 for non-Hispanic black, and 18.3 for Hispanic populations.

Evolution of prostate biopsy techniques. Looking back on a meaningful journey.

PubMed

Sivaraman, A; Sanchez-Salas, R; Castro-Marin, M; Barret, E; Guillot-Tantay, C; Prapotnich, D; Cathelineau, X

2016-10-01

The technique of prostate biopsy has evolved a long way since its inception to being a safe diagnostic procedure. The principles of the biopsy technique continue to improvise with the knowledge about prostate cancer and availability of newer treatment options like active surveillance and focal therapy. Currently, we depend on accurate cancer information from the biopsy more than ever for deciding the ideal treatment option. The aim of this review is to present the major milestones in prostate biopsy technique evolutions and its impact on the prostate cancer management. We performed a detailed non-systematic literature review to present the historical facts on the transformations in prostate biopsy techniques and also the direction of present research to improve accurate cancer detection. There is a clear change in trend in biopsy technique before and after the introduction of transrectal ultrasound and prostate specific antigen. In the earlier era, the biopsies were aimed at palpable nodules and obtaining adequate prostatic tissue for diagnosis while the later era has moved towards detection of non-palpable and early prostate cancer. Recently, there is an increasing trend towards image guided targeted biopsies to extract maximum cancer information from minimum biopsy cores. Prostate biopsy techniques have seen major changes since its inception and have a major impact on prostate cancer management. There is a great potential for research which can further support the newer treatment options like focal therapy. Copyright © 2016 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Reliability of recording uterine cancer in death certification in France and age-specific proportions of deaths from cervix and corpus uteri.

PubMed

Rogel, Agnès; Belot, Aurélien; Suzan, Florence; Bossard, Nadine; Boussac, Marjorie; Arveux, Patrick; Buémi, Antoine; Colonna, Marc; Danzon, Arlette; Ganry, Olivier; Guizard, Anne-Valérie; Grosclaude, Pascale; Velten, Michel; Jougla, Eric; Iwaz, Jean; Estève, Jacques; Chérié-Challine, Laurence; Remontet, Laurent

2011-06-01

French uterine cancer recordings in death certificates include 60% of "uterine cancer, Not Otherwise Specified (NOS)"; this hampers the estimation of mortalities from cervix and corpus uteri cancers. The aims of this work were to study the reliability of uterine cancer recordings in death certificates using a case matching with cancer registries and estimate age-specific proportions of deaths from cervix and corpus uteri cancers among all uterine cancer deaths by a statistical approach that uses incidence and survival data. Deaths from uterine cancer between 1989 and 2001 were extracted from the French National database of causes of death and case-to-case matched to women diagnosed with uterine cancer between 1989 and 1997 in 8 cancer registries. Registry data were considered as "gold-standard". Among the 1825 matched deaths, cancer registries recorded 830 cervix and 995 corpus uteri cancers. In death certificates, 5% and 40% of "true" cervix cancers were respectively coded "corpus" and "uterus, NOS" and 5% and 59% of "true" corpus cancers respectively coded "cervix" and "uterus, NOS". Miscoding cervix cancers was more frequent at advanced ages at death and in deaths at home or in small urban areas. Miscoding corpus cancers was more frequent in deaths at home or in small urban areas. From the statistical method, the estimated proportion of deaths from cervix cancer among all uterine cancer deaths was higher than 95% in women aged 30-40 years old but declined to 35% in women older than 70 years. The study clarifies the reason for poor encoding of uterus cancer mortality and refines the estimation of mortalities from cervix and corpus uteri cancers allowing future studies on the efficacy of cervical cancer screening. Copyright © 2010 Elsevier Ltd. All rights reserved.

AGEs, RAGEs and s-RAGE; friend or foe for cancer.

PubMed

Ahmad, Saheem; Khan, Hamda; Siddiqui, Zeba; Khan, Mohd Yasir; Rehman, Shahnawaz; Shahab, Uzma; Godovikova, Tatyana; Silnikov, Vladimir; Moinuddin

2018-04-01

Impaired awareness of glycation biology in cancer initiation and progression is one of the fundamental reasons for its meticulous investigation of the molecules involved in signalling pathway. Glycation of biological macromolecules results in the progression of advanced glycation end-products (AGEs) that proliferates the process of carcinogenesis by activation of transcription factors and release of cytokines. The receptor for advanced glycation end-products (RAGEs) with the binding of its different ligands like; AGEs, HMGB1 and S100 activate the signalling arrays. The activation of downstream signalling pathway ultimately leads to the pathophysiological conditions of diabetes, ageing, neurological disorders and cancers as well as a result of the activation of transcription factors which is discussed in the main body text of this review. However, there might be a likelihood of the positive effect of the HMGB1 and S100 proteins in cancer. Still, some untouched mechanisms might be responsible for the establishment of the function of AGE-RAGE or AGE-sRAGE axis activation that leads to the friend-foe association with the cancers. The levels of RAGE and s-RAGE may be a useful biomarker of ligand-RAGE pathway activation and cancer. Thus, the possibility of providing a potential complement to carcinogenesis is very high which might be an interesting target for therapeutic interventions. This article is an insightful assessment on AGE, RAGE and s-RAGE for its possible role in cancer onset and progression. The novel therapeutic targets for cancer prevention or inhibition are also explained in brief in relation to AGE and RAGE. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Report of Cancer Incidence and Mortality in China, 2014].

PubMed

Chen, W Q; Li, H; Sun, K X; Zheng, R S; Zhang, S W; Zeng, H M; Zou, X N; Gu, X Y; He, J

2018-01-23

Objective: The registration data of local cancer registries in 2014 were collected by National Central Cancer Registry (NCCR)in 2017 to estimate the cancer incidence and mortality in China. Methods: The data submitted from 449 registries were checked and evaluated, and the data of 339 registries out of them were qualified and selected for the final analysis. Cancer incidence and mortality were stratified by area, gender, age group and cancer type, and combined with the population data of 2014 to estimate cancer incidence and mortality in China. The age composition of standard population of Chinese census in 2000 and Segi's population were used for age-standardized incidence and mortality in China and worldwide, respectively. Results: Total covered population of 339 cancer registries (129 in urban and 210 in rural) in 2014 were 288 243 347 (144 061 915 in urban and 144 181 432 in rural areas). The mortality verified cases (MV%) were 68.01%. Among them, 2.19% cases were identified through death certifications only (DCO%), and the mortality to incidence ratio was 0.61. There were about 3, 804, 000 new cases diagnosed as malignant cancer and 2, 296, 000 cases dead in 2014 in the whole country. The incidence rate was 278.07/100, 000 (males 301.67/100, 000, females 253.29/100, 000) in China, age-standardized incidence rates by Chinese standard population (ASIRC) and by world standard population were 190.63/100, 000 and 186.53/100, 000, respectively, and the cumulative incidence rate (0-74 age years old) was 21.58%. The cancer incidence and ASIRC in urban areas were 302.13/100, 000 and 196.58/100, 000, respectively, whereas in rural areas, those were 248.94/100, 000 and 182.64/100, 000, respectively. The cancer mortality in China was 167.89/100, 000 (207.24/100, 000 in males and 126.54/100, 000 in females), age-standardized mortality rates by Chinese standard population (ASMRC) and by world standard population were 106.98/100, 000 and 106.09/100, 000, respectively. And the cumulative incidence rate (0-74 age years old) was 12.00%. The cancer mortality and ASMRC in urban areas were 174.34/100, 000 and 103.49/100, 000, respectively, whereas in rural areas, those were 160.07/100, 000 and 111.57/100, 000, respectively. Lung cancer, gastric cancer, colorectal cancer, liver cancer, female breast cancer, esophageal cancer, thyroid cancer, cervical cancer, encephala and pancreas cancer, were the most common cancers in China, accounting for about 77.00% of the new cancer cases. Lung cancer, liver cancer, gastric cancer, esophageal cancer, colorectal cancer, pancreatic cancer, breast cancer, encephala, leukemia and lymphoma were the leading causes of death and accounted for about 83.36% of cancer deaths. Conclusions: The progression of cancer registry in China develops rapidly in these years, with the coverage of registrations is expanded and the data quality was improved steadily year by year. As the basis of cancer prevention and control program, cancer registry plays an important role in making the medium and long term of anti-cancer strategies in China. As China is still facing the serious cancer burden and the cancer patterns varies differently according to the locations and genders, effective measures and strategies of cancer prevention and control should be implemented based on the practical situation.

Cancer and aging: Epidemiology and methodological challenges.

PubMed

Pedersen, Jacob K; Engholm, Gerda; Skytthe, Axel; Christensen, Kaare

2016-01-01

Epidemiological cancer data shed light on key questions within basic science, clinical medicine and public health. For decades, Denmark has had linkable health registers that contain individual level data on the entire population with virtually complete follow-up. This has enabled high quality studies of cancer epidemiology and minimized the challenges often faced in many countries, such as uncertain identification of the study base, age misreporting, and low validity of the cancer diagnoses. However, methodological challenges still remain to be addressed, especially in cancer epidemiology studies among the elderly and the oldest-old. For example, a characteristic pattern for many cancer types is that the incidence increases up to a maximum at about ages 75-90 years and is then followed by a decline or a leveling off at the oldest ages. It has been suggested that the oldest individuals may be asymptomatic, or even insusceptible to cancer. An alternative interpretation is that this pattern is an artifact due to lower diagnostic intensity among the elderly and oldest-old caused by higher levels of co-morbidities in this age group. Currently, the available cancer epidemiology data are not able to provide clear evidence for any of these hypotheses.

Advanced glycation end-products: a biological consequence of lifestyle contributing to cancer disparity.

PubMed

Turner, David P

2015-05-15

Low income, poor diet, obesity, and a lack of exercise are interrelated lifestyle factors that can profoundly alter our biologic make up to increase cancer risk, growth, and development. We recently reported a potential mechanistic link between carbohydrate-derived metabolites and cancer, which may provide a biologic consequence of lifestyle that can directly affect tumor biology. Advanced glycation end-products (AGE) are reactive metabolites produced as a by-product of sugar metabolism. Failure to remove these highly reactive metabolites can lead to protein damage, aberrant cell signaling, increased stress responses, and decreased genetic fidelity. Critically, AGE accumulation is also directly affected by our lifestyle choices and shows a race-specific, tumor-dependent pattern of accumulation in cancer patients. This review will discuss the contribution of AGEs to the cancer phenotype, with a particular emphasis on their biologic links with the socioeconomic and environmental risk factors that drive cancer disparity. Given the potential benefits of lifestyle changes and the potential biologic role of AGEs in promoting cancer, opportunities exist for collaborations affecting basic, translational, epidemiologic, and cancer prevention initiatives. ©2015 American Association for Cancer Research.

Risks of Breast, Ovarian, and Contralateral Breast Cancer for BRCA1 and BRCA2 Mutation Carriers.

PubMed

Kuchenbaecker, Karoline B; Hopper, John L; Barnes, Daniel R; Phillips, Kelly-Anne; Mooij, Thea M; Roos-Blom, Marie-José; Jervis, Sarah; van Leeuwen, Flora E; Milne, Roger L; Andrieu, Nadine; Goldgar, David E; Terry, Mary Beth; Rookus, Matti A; Easton, Douglas F; Antoniou, Antonis C; McGuffog, Lesley; Evans, D Gareth; Barrowdale, Daniel; Frost, Debra; Adlard, Julian; Ong, Kai-Ren; Izatt, Louise; Tischkowitz, Marc; Eeles, Ros; Davidson, Rosemarie; Hodgson, Shirley; Ellis, Steve; Nogues, Catherine; Lasset, Christine; Stoppa-Lyonnet, Dominique; Fricker, Jean-Pierre; Faivre, Laurence; Berthet, Pascaline; Hooning, Maartje J; van der Kolk, Lizet E; Kets, Carolien M; Adank, Muriel A; John, Esther M; Chung, Wendy K; Andrulis, Irene L; Southey, Melissa; Daly, Mary B; Buys, Saundra S; Osorio, Ana; Engel, Christoph; Kast, Karin; Schmutzler, Rita K; Caldes, Trinidad; Jakubowska, Anna; Simard, Jacques; Friedlander, Michael L; McLachlan, Sue-Anne; Machackova, Eva; Foretova, Lenka; Tan, Yen Y; Singer, Christian F; Olah, Edith; Gerdes, Anne-Marie; Arver, Brita; Olsson, Håkan

2017-06-20

The clinical management of BRCA1 and BRCA2 mutation carriers requires accurate, prospective cancer risk estimates. To estimate age-specific risks of breast, ovarian, and contralateral breast cancer for mutation carriers and to evaluate risk modification by family cancer history and mutation location. Prospective cohort study of 6036 BRCA1 and 3820 BRCA2 female carriers (5046 unaffected and 4810 with breast or ovarian cancer or both at baseline) recruited in 1997-2011 through the International BRCA1/2 Carrier Cohort Study, the Breast Cancer Family Registry and the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer, with ascertainment through family clinics (94%) and population-based studies (6%). The majority were from large national studies in the United Kingdom (EMBRACE), the Netherlands (HEBON), and France (GENEPSO). Follow-up ended December 2013; median follow-up was 5 years. BRCA1/2 mutations, family cancer history, and mutation location. Annual incidences, standardized incidence ratios, and cumulative risks of breast, ovarian, and contralateral breast cancer. Among 3886 women (median age, 38 years; interquartile range [IQR], 30-46 years) eligible for the breast cancer analysis, 5066 women (median age, 38 years; IQR, 31-47 years) eligible for the ovarian cancer analysis, and 2213 women (median age, 47 years; IQR, 40-55 years) eligible for the contralateral breast cancer analysis, 426 were diagnosed with breast cancer, 109 with ovarian cancer, and 245 with contralateral breast cancer during follow-up. The cumulative breast cancer risk to age 80 years was 72% (95% CI, 65%-79%) for BRCA1 and 69% (95% CI, 61%-77%) for BRCA2 carriers. Breast cancer incidences increased rapidly in early adulthood until ages 30 to 40 years for BRCA1 and until ages 40 to 50 years for BRCA2 carriers, then remained at a similar, constant incidence (20-30 per 1000 person-years) until age 80 years. The cumulative ovarian cancer risk to age 80 years was 44% (95% CI, 36%-53%) for BRCA1 and 17% (95% CI, 11%-25%) for BRCA2 carriers. For contralateral breast cancer, the cumulative risk 20 years after breast cancer diagnosis was 40% (95% CI, 35%-45%) for BRCA1 and 26% (95% CI, 20%-33%) for BRCA2 carriers (hazard ratio [HR] for comparing BRCA2 vs BRCA1, 0.62; 95% CI, 0.47-0.82; P=.001 for difference). Breast cancer risk increased with increasing number of first- and second-degree relatives diagnosed as having breast cancer for both BRCA1 (HR for ≥2 vs 0 affected relatives, 1.99; 95% CI, 1.41-2.82; P<.001 for trend) and BRCA2 carriers (HR, 1.91; 95% CI, 1.08-3.37; P=.02 for trend). Breast cancer risk was higher if mutations were located outside vs within the regions bounded by positions c.2282-c.4071 in BRCA1 (HR, 1.46; 95% CI, 1.11-1.93; P=.007) and c.2831-c.6401 in BRCA2 (HR, 1.93; 95% CI, 1.36-2.74; P<.001). These findings provide estimates of cancer risk based on BRCA1 and BRCA2 mutation carrier status using prospective data collection and demonstrate the potential importance of family history and mutation location in risk assessment.

Risk of breast cancer in young women in relation to body size and weight gain in adolescence and early adulthood.

PubMed

Coates, R J; Uhler, R J; Hall, H I; Potischman, N; Brinton, L A; Ballard-Barbash, R; Gammon, M D; Brogan, D R; Daling, J R; Malone, K E; Schoenberg, J B; Swanson, C A

1999-09-01

Findings have been inconsistent on effects of adolescent body size and adult weight gain on risk of breast cancer in young women. These relations were examined in a population-based case control study of 1590 women less than 45 years of age newly diagnosed with breast cancer during 1990-1992 in three areas of the US and an age-matched control group of 1390 women. Height and weight were measured at interview and participants asked to recall information about earlier body size. Logistic regression was used to estimate the relative risk of breast cancer adjusted for other risk factors. Women who were either much heavier or lighter than average in adolescence or at age 20 were at reduced risk. Weight gain after age 20 resulted in reduced risk, but the effect was confined to early-stage and, more specifically, lower grade breast cancer. Neither the risk reduction nor the variation by breast cancer stage or grade was explained by the method of cancer detection or by prior mammography history. These findings suggest that relations between breast cancer risk in young women and body weight at different ages is complex and that the risk reduction with adult weight gain is confined to less aggressive cancers.

Incidence of oral cavity and pharynx cancer in New Hampshire, 1990-2007.

PubMed

Cherala, Sai S; Kelley, Kristina

2012-01-01

The purpose of this study is to describe trends of the statewide cancer and treatment-related characteristics of oral cavity and pharynx (OCP) cancer and prevalence of risk factors in New Hampshire residents from 1990-2007. This is a descriptive study on oral cavity and pharynx cancer using a state cancer registry dataset for 1990- 2007. The age-adjusted rates with 95% confidence intervals for cancer incidence rates and standard proportions for stage, treatment, and risk factors were calculated. The Joinpoint regression model was used for assessing linear trends for cancer rates. The overall differences for the period under study between age, female and male rate, and stage were analyzed using the test. During 1990-2007, oral cavity and pharynx cancer incidence rates for New Hampshire residents have remained stable. The cancer incidence rates have decreased for older age groups (greater than 59) and the 50-59 age group has shown increase in incidence rate of OCP cancer since 1990. There is significant increase in the late-stage diagnoses from 1990-2007. Early detection through periodic medical and dental examinations can reduce the risk of these cancers. Public health strategies that address the gaps identified by this study can reduce OCP cancer and protect the health of the New Hampshire population.

Visual disturbances in advanced cancer patients: clinical observations.

PubMed

Saita, L; Polastri, D; De Conno, F

1999-03-01

Visual disturbances in advanced cancer patients are very rarely signaled, evaluated, or adequately treated. The main causes of sight disturbances are primary eye tumors, ocular metastases, and some paraneoplastic syndromes. Sight alteration can also be associated with asthenia, fatigue, anemia, and hypovitaminosis. These symptoms can be monocular or binocular, and their gravity and evolution can vary. Based on a survey of 156 patients, we estimate the prevalence of visual disturbances to be 12% in advanced cancer patients.

Use of NCCN Guidelines, Other Guidelines, and Biomarkers for Colorectal Cancer Screening.

PubMed

Williams, Christina D; Grady, William M; Zullig, Leah L

2016-11-01

Colorectal cancer (CRC) remains a common cancer and significant public health burden. CRC-related mortality is declining, partly due to the early detection of CRC through robust screening. NCCN has established the NCCN Guidelines for CRC Screening to help healthcare providers make appropriate screening recommendations according to the patient's risk of developing CRC. This review describes the evolution of CRC screening guidelines for average-risk individuals, discusses the role of NCCN Guidelines for CRC Screening in cancer prevention, and comments on the current and emerging use of biomarkers for CRC screening. Copyright © 2016 by the National Comprehensive Cancer Network.

Evolution of modern treatment of childhood acute leukemia and cancer: adventures and battles in the 1970s and 1980s.

PubMed

Ravindranath, Yaddanapudi

2015-02-01

This article summarizes the adventures and explorations in the 1970s and 1980s in the treatment of children with leukemia and cancer that paved the way for the current success in childhood cancers. Indeed, these were adventures and bold steps into unchartered waters. Because childhood leukemia the most common of the childhood cancers, success in childhood leukemia was pivotal in the push toward cure of all childhood cancers. The success in childhood leukemia illustrates how treatment programs were designed using clinical- and biology-based risk factors seen in the patients. Copyright © 2015. Published by Elsevier Inc.

The evolution of personalized cancer genetic counseling in the era of personalized medicine.

PubMed

Vig, Hetal S; Wang, Catharine

2012-09-01

Practice changes in cancer genetic counseling have occurred to meet the demand for cancer genetic services. As cancer genetics continues to impact not only prevention strategies but also treatment decisions, current cancer genetic counseling models will need to be tailored to accommodate emerging clinical indications. These clinical indications include: surgical prophylactic bilateral mastectomy candidates, PARP-inhibitor candidates, patients with abnormal tumor screening results for Lynch syndrome, and post-test counseling patients (after genetic testing is ordered by another healthcare provider). A more personalized, multidisciplinary approach to selecting the best framework, for a given clinical indication, may become increasingly necessary in this era of personalized medicine.

Efficacy of a film-forming medical device containing sunscreen (50+) and piroxicam 0.8% in actinic keratosis and field cancerization: a multicenter, assessor-blinded, 3 month trial.

PubMed

Puviani, Mario; Galloni, Chiara; Marchetti, Silvia; Sergio Pavone, Paolo; Lovati, Silvia; Pistone, Giuseppe; Caputo, Valentina; Tilotta, Giovanna; Scarcella, Giuseppe; Campione, Elena; Diluvio, Laura; Garofalo, Virginia; Bianchi, Luca; Milani, Massimo

2017-07-01

Sunscreen protection in subjects with actinic keratosis (AK) is highly recommended to prevent clinical evolution of this in situ skin cancer condition. Use of topical anti-cyclooxygenase drugs such as diclofenac and piroxicam reduces the number of lesions and improves the cancerization field. A film-forming medical device in a cream formulation containing organic and inorganic sun-filters (50+ SPF) and piroxicam 0.8% (ACTX) has shown in a pilot, single-center, open trial to reduce AK lesions improving the cancerization field. We evaluated in a multicenter, assessor-blinded, 3 month trial the efficacy of ACTX in AK. A total of 70 subjects with at least three AK lesions on the scalp or face were enrolled after written informed consent. Primary outcomes of the study were the clinical evolution of number of AK lesions on a target zone area and the evolution of dermoscopy features of the target lesion, assessing erythema, scaling, pigmentation, and follicular plug, using a 5 point score (from 0 to 4; maximum score: 16). Lesion count and dermoscopy score were evaluated in a blind fashion assessing digital color high definition coded images. A secondary outcome was the Investigator Global Score (IGS) of clinical evolution of the target area using a 7 point scale from -2 (significantly worse) to +4 (completely cured). IGS was evaluated in an open fashion. Subjects were instructed to apply the cream twice daily on the target area, using one finger-tip unit for the treatment of a 35 cm 2 area. All but one subject (40 men and 30 women, mean age 73 years) concluded the study period. At baseline the mean (±SD) number of AK lesions in the target area were 7.0 (5.9) with a median value of 5 and the dermoscopy score of the target lesion was 7.0 (2.3) with a median value of 7.0. ACTX treatment reduced AK lesions to 3.2 (2.9), (p = .0001; Wilcoxon Test), representing a 55% relative reduction. Dermoscopy score was reduced to 3.3 (2.6) (p = .0001) (a reduction of 53%). The IGS after ACTX treatment was +1.9 (1.1), with a median of 2.0. A total of 86% of subjects showed a clinical improvement of IGS (≥1) with a very significant/complete clearance (score +3 or +4) in 42% subjects. No change or a worsening of AK lesions was observed in 14% of the subjects. The product was well tolerated. No serious adverse events were reported during the duration of the trial. In this multicenter, assessor-blinded trial, the use of a film-forming medical device with sun protection and anti-inflammatory actions was effective in reducing AK lesions and improving the dermoscopy aspect of the target lesion in 86% of treated subjects. A head-to-head trial evaluating the efficacy of this medical device in comparison with diclofenac is warranted to establish whether this therapeutic approach could offer additional advantages in term of AK lesion reduction compared to an established topical treatment. (Trial ID: ISRCTN72020277).

All-Cause Mortality for Life Insurance Applicants with a History of Breast Cancer.

PubMed

Freitas, Stephen A; MacKenzie, Ross; Wylde, David N; Roudebush, Bradley T; Bergstrom, Richard L; Holowaty, J Carl; Hart, Anna; Rigatti, Steven J; Gill, Stacy

2017-01-01

Breast cancer is the most commonly diagnosed cancer worldwide. Breast cancer is also the second leading cause of cancer death among women in the United States after lung cancer with over 40,000 breast cancer deaths occurring each year. The purpose of this research was to determine the all-cause mortality of applicants diagnosed with breast cancer currently or at some time in the past. Life insurance applicants with reported breast cancer were extracted from data covering United States residents between November 2007 and November 2014. Information about these applicants was matched to the Social Security Death Master (SSDMF) file for deaths occurring from 2007 to 2011 and to another commercially available death source file (Other Death Source, ODS) for deaths occurring from 2007 to 2014 to determine vital status. If there was a death from the other death source, then the SSDMF was searched to verify the death. The study had approximately 561,000 person-years of exposure. Actual-to-expected (A/E) mortality ratios were calculated using the Society of Actuaries 2008 Valuation Basic Table (2008VBT), select and ultimate table (age last birthday) and the 2010 US population as expected mortality ratios. Since the A/Es presented in this paper were known to be an underestimate due to the exclusion of the recent SSDMF deaths, comparative analysis of the mortality ratios was done. Since there was no smoking status information in this study, all expected bases were not smoker distinct. Overall, the 35-44 age group had 6.3 times the relative mortality ratio than those in the 65-75 age group. The relative mortality ratio for the 35-44 age group applicants, when cancer severity was accounted for in combination with 3 or more nodes of cancer involvement, was 29.3 times that when compared to those in the 65-75 age group having localized cancer, where no nodes are involved. The 35-44 age group applicants who were diagnosed with cancer within the last year had over 10-fold increase in relative mortality ratios compared to the 65-75 age group, who were over 10 years from diagnosis. Taking the severity of cancer along with time from diagnosis showed over a 12 times relative mortality ratio between the low rate of over 10 years from diagnosis and localized involvement to those diagnosed within the last year having 3 or more nodes with cancer. Applicant age, time since diagnosis and cancer severity were the most significant variables to predict the relative mortality ratios.

The comet assay: Reflections on its development, evolution and applications.

PubMed

Singh, Narendra P

2016-01-01

The study of DNA damage and its repair is critical to our understanding of human aging and cancer. This review reflects on the development of a simple technique, now known as the comet assay, to study the accumulation of DNA damage and its repair. It describes my journey into aging research and the need for a method that sensitively quantifies DNA damage on a cell-by-cell basis and on a day-by-day basis. My inspirations, obstacles and successes on the path to developing this assay and improving its reliability and sensitivity are discussed. Recent modifications, applications, and the process of standardizing the technique are also described. What was once untried and unknown has become a technique used around the world for understanding and monitoring DNA damage. The comet assay's use has grown exponentially in the new millennium, as emphasis on studying biological phenomena at the single-cell level has increased. I and others have applied the technique across cell types (including germ cells) and species (including bacteria). As it enters new realms and gains clinical relevance, the comet assay may very well illuminate human aging and its prevention. Copyright © 2016. Published by Elsevier B.V.

Mortality of breast cancer in Taiwan, 1971–2010: Temporal changes and an age–period–cohort analysis

PubMed Central

Ho, M.-L.; Hsiao, Y.-H.; Su, S.-Y.

2015-01-01

The current paper describes the age, period and cohort effects on breast cancer mortality in Taiwan. Female breast cancer mortality data were collected from the Taiwan death registries for 1971–2010. The annual percentage changes, age- standardised mortality rates (ASMR) and age–period–cohort model were calculated. The mortality rates increased with advancing age groups when fixing the period. The percentage change in the breast cancer mortality rate increased from 54.79% at aged 20–44 years, to 149.78% in those aged 45–64 years (between 1971–75 and 2006–10). The mortality rates in the 45–64 age group increased steadily from 1971 to 1975 and 2006–10. The 1951 birth cohorts (actual birth cohort; 1947–55) showed peak mortalities in both the 50–54 and 45–49 age groups. We found that the 1951 birth cohorts had the greatest mortality risk from breast cancer. This might be attributed to the DDT that was used in large amounts to prevent deaths from malaria in Taiwan. However, future researches require DDT data to evaluate the association between breast cancer and DDT use. PMID:25020211

Biomolecular bases of the senescence process and cancer. A new approach to oncological treatment linked to ageing.

PubMed

Badiola, Iker; Santaolalla, Francisco; Garcia-Gallastegui, Patricia; Ana, Sánchez-Del Rey; Unda, Fernando; Ibarretxe, Gaskon

2015-09-01

Human ageing is associated with a gradual decline in the physiological functions of the body at multiple levels and it is a key risk factor for many diseases, including cancer. Ageing process is intimately related to widespread cellular senescence, characterised by an irreversible loss of proliferative capacity and altered functioning associated with telomere attrition, accumulation of DNA damage and compromised mitochondrial and metabolic function. Tumour and senescent cells may be generated in response to the same stimuli, where either cellular senescence or transformation would constitute two opposite outcomes of the same degenerative process. This paper aims to review the state of knowledge on the biomolecular relationship between cellular senescence, ageing and cancer. Importantly, many of the cell signalling pathways that are found to be altered during both cellular senescence and tumourigenesis are regulated through shared epigenetic mechanisms and, therefore, they are potentially reversible. MicroRNAs are emerging as pivotal players linking ageing and cancer. These small RNA molecules have generated great interest from the point of view of future clinical therapy for cancer because successful experimental results have been obtained in animal models. Micro-RNA therapies for cancer are already being tested in clinical phase trials. These findings have potential importance in cancer treatment in aged people although further research-based knowledge is needed to convert them into an effective molecular therapies for cancer linked to ageing. Copyright © 2015 Elsevier B.V. All rights reserved.

An earlier age of breast cancer diagnosis related to more frequent use of antiperspirants/deodorants and underarm shaving.

PubMed

McGrath, K G

2003-12-01

Breast cancer incidence suggests a lifestyle cause. A lifestyle factor used near the breast is the application of antiperspirants/deodorants accompanied by axillary shaving. A previous study did not support a link with breast cancer. If these habits have a role in breast cancer development, women using antiperspirants/deodorants and shaving their underarms frequently would be expected to have an earlier age of diagnosis than those doing so less often. An earlier age of diagnosis would also be expected in those starting to use deodorants and shaving at an earlier age. This is the first study to investigate the intensity of underarm exposure in a cohort of breast cancer survivors. Four hundred and thirty-seven females diagnosed with breast cancer were surveyed. Once grouped by their frequency of underarm hygiene habits, the mean age of diagnosis was the primary end point. Secondary end points included the overall frequency of these habits, and potential usage group confounding variables were evaluated. All statistical tests were two-sided. Frequency and earlier onset of antiperspirant/deodorant usage with underarm shaving were associated with an earlier age of breast cancer diagnosis. Combined habits are likely for this earlier age of diagnosis. In conclusion, underarm shaving with antiperspirant/deodorant use may play a role in breast cancer. It is not clear which of these components are involved. Reviewed literature insinuates absorption of aluminium salts facilitated by dermal barrier disruption. Case-controlled investigations are needed before alternative underarm hygiene habits are suggested.

Prostate cancer mortality in Serbia, 1991-2010: a joinpoint regression analysis.

PubMed

Ilic, Milena; Ilic, Irena

2016-06-01

The aim of this descriptive epidemiological study was to analyze the mortality trend of prostate cancer in Serbia (excluding the Kosovo and Metohia) from 1991 to 2010. The age-standardized prostate cancer mortality rates (per 100 000) were calculated by direct standardization, using the World Standard Population. Average annual percentage of change (AAPC) and the corresponding 95% confidence interval (CI) was computed for trend using the joinpoint regression analysis. Significantly increased trend in prostate cancer mortality was recorded in Serbia continuously from 1991 to 2010 (AAPC = +2.2, 95% CI = 1.6-2.9). Mortality rates for prostate cancer showed a significant upward trend in all men aged 50 and over: AAPC (95% CI) was +1.9% (0.1-3.8) in aged 50-59 years, +1.7% (0.9-2.6) in aged 60-69 years, +2.0% (1.2-2.9) in aged 70-79 years and +3.5% (2.4-4.6) in aged 80 years and over. According to comparability test, prostate cancer mortality trends in majority of age groups were parallel (final selected model failed to reject parallelism, P > 0.05). The increasing prostate cancer mortality trend implies the need for more effective measures of prevention, screening and early diagnosis, as well as prostate cancer treatment in Serbia. © The Author 2015. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Clinical decision making in cancer care: a review of current and future roles of patient age.

PubMed

Tranvåg, Eirik Joakim; Norheim, Ole Frithjof; Ottersen, Trygve

2018-05-09

Patient age is among the most controversial patient characteristics in clinical decision making. In personalized cancer medicine it is important to understand how individual characteristics do affect practice and how to appropriately incorporate such factors into decision making. Some argue that using age in decision making is unethical, and how patient age should guide cancer care is unsettled. This article provides an overview of the use of age in clinical decision making and discusses how age can be relevant in the context of personalized medicine. We conducted a scoping review, searching Pubmed for English references published between 1985 and May 2017. References concerning cancer, with patients above the age of 18 and that discussed age in relation to diagnostic or treatment decisions were included. References that were non-medical or concerning patients below the age of 18, and references that were case reports, ongoing studies or opinion pieces were excluded. Additional references were collected through snowballing and from selected reports, guidelines and articles. Three hundred and forty-seven relevant references were identified. Patient age can have many and diverse roles in clinical decision making: Contextual roles linked to access (age influences how fast patients are referred to specialized care) and incidence (association between increasing age and increasing incidence rates for cancer); patient-relevant roles linked to physiology (age-related changes in drug metabolism) and comorbidity (association between increasing age and increasing number of comorbidities); and roles related to interventions, such as treatment (older patients receive substandard care) and outcome (survival varies by age). Patient age is integrated into cancer care decision making in a range of ways that makes it difficult to claim age-neutrality. Acknowledging this and being more transparent about the use of age in decision making are likely to promote better clinical decisions, irrespective of one's normative viewpoint. This overview also provides a starting point for future discussions on the appropriate role of age in cancer care decision making, which we see as crucial for harnessing the full potential of personalized medicine.

The incidence, age at diagnosis of breast cancer in the Iraqi Kurdish population and comparison to some other countries of Middle-East and West.

PubMed

Molah Karim, Sherko Abdullah; Ali Ghalib, Hawar Hasan; Mohammed, Sangar Abdullah; Fattah, Fattah Hama Rahim

2015-01-01

Studies on breast cancer among Iraqi Kurdish are limited. The incidence of breast cancer is lower, more common in younger age and a significant proportion of cases occur in premenopausal women. The aims of this study are to estimate the age-standardized incidence rate, age-specific rates and their comparison with some countries of Middle-East and West, and clarify the association of family history and premenopausal status with breast cancer. This retrospective case control study was conducted in Sulaimanyah governorate (North of Iraq). Data were collected regarding demographical profile of 536 patients who were registered in Hewa Hematology and Oncology Hospital during 2011-2013, and 496 age-matched controls. There were 536 cases of breast cancer, 526 of them were female. The age range was 20-82 years. The mean age at diagnosis was 49.42±11.66 years compared to control 46.7±10.2 (p˂0.001, 95% CI: 1.7-3.7). The age-standardized rate was 17.9/100,000 Kurdish women population/year. Five year age-specific rates show the peak incidence for the age group 45-49 years (79.3/100,000). A significant percentage of patients were premenopausal at the time of diagnosis, which is account 55.52% of cases compared to control 59.67% (p=0.53). About 13.49% of cases have family history of breast cancer compared to control 3.2% (p=0.02). Among Kurdish people in Iraq, the incidence of breast cancer is less than Middle-East and Western countries with higher incidence in younger age group than western society, but similar to Middle-East countries. More than half of Kurdish women with breast cancer are premenopausal. Copyright © 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

Birth-order differences can drive natural selection on aging.

PubMed

Gillespie, Duncan O S; Trotter, Meredith V; Krishna-Kumar, Siddharth; Tuljapurkar, Shripad D

2014-03-01

Senescence-the deterioration of survival and reproductive capacity with increasing age-is generally held to be an evolutionary consequence of the declining strength of natural selection with increasing age. The diversity in rates of aging observed in nature suggests that the rate at which age-specific selection weakens is determined by species-specific ecological factors. We propose that, in iteroparous species, relationships between parental age, offspring birth order, and environment may affect selection on senescence. Later-born siblings have, on average, older parents than do first borns. Offspring born to older parents may experience different environments in terms of family support or inherited resources, factors often mediated by competition from siblings. Thus, age-specific selection on parents may change if the environment produces birth-order related gradients in reproductive success. We use an age-and-stage structured population model to investigate the impact of sibling environmental inequality on the expected evolution of senescence. We show that accelerated senescence evolves when later-born siblings are likely to experience an environment detrimental to lifetime reproduction. In general, sibling inequality is likely to be of particular importance for the evolution of senescence in species such as humans, where family interactions and resource inheritance have important roles in determining lifetime reproduction. © 2013 The Author(s). Evolution © 2013 The Society for the Study of Evolution.

Suicide and violent deaths in survivors of cancer in childhood, adolescence and young adulthood-A national cohort study.

PubMed

Gunnes, Maria W; Lie, Rolv T; Bjørge, Tone; Ghaderi, Sara; Syse, Astri; Ruud, Ellen; Wesenberg, Finn; Moster, Dag

2017-02-01

Suicide risk in adult cancer patients is found to be elevated, but limited information exists regarding risks of suicide and non-suicidal violent deaths when diagnosed with cancer in young age. We investigate suicide and violent deaths in a national cohort including individuals diagnosed with cancer before age 25. Through the linkage of different national registries (Cancer Registry of Norway, Norwegian Causes of Death Registry and the National Registry) a cohort of all live births in Norway during 1965-1985 was defined and followed up through 2008. Individuals diagnosed with cancer before age 25 and the cancer-free references were compared using an extended Cox proportional hazard regression model. The cohort comprised 1,218,013 individuals, including 5,440 diagnosed with cancer before age 25. We identified 24 suicides and 14 non-suicidal violent deaths in the cancer group. The hazard ratio (HR) of suicide in the cancer group was 2.5 (95% confidence interval (CI) 1.7-3.8), and was increased both when diagnosed with cancer in childhood (0-14 years of age); HR = 2.3 (95% CI: 1.2-4.6), and during adolescence/young adulthood (15-24 years); HR = 2.6 (95% CI: 1.5-4.2). Survivors of bone/soft tissue sarcomas, CNS tumors and testicular cancer were at particular risk. The risk of non-suicidal violent death was not increased in the cancer survivors (HR = 1.0; 95% CI: 0.6-1.7). Although based on small numbers and the absolute risk of suicide being low, these are novel findings with important implications for establishing adequate follow-up including suicide prevention strategies for young cancer survivors. © 2016 UICC.

Invasive Cancer Incidence, 2004-2013, and Deaths, 2006-2015, in Nonmetropolitan and Metropolitan Counties - United States.

PubMed

Henley, S Jane; Anderson, Robert N; Thomas, Cheryll C; Massetti, Greta M; Peaker, Brandy; Richardson, Lisa C

2017-07-07

Previous reports have shown that persons living in nonmetropolitan (rural or urban) areas in the United States have higher death rates from all cancers combined than persons living in metropolitan areas. Disparities might vary by cancer type and between occurrence and death from the disease. This report provides a comprehensive assessment of cancer incidence and deaths by cancer type in nonmetropolitan and metropolitan counties. 2004-2015. Cancer incidence data from CDC's National Program of Cancer Registries and the National Cancer Institute's Surveillance, Epidemiology, and End Results program were used to calculate average annual age-adjusted incidence rates for 2009-2013 and trends in annual age-adjusted incidence rates for 2004-2013. Cancer mortality data from the National Vital Statistics System were used to calculate average annual age-adjusted death rates for 2011-2015 and trends in annual age-adjusted death rates for 2006-2015. For 5-year average annual rates, counties were classified into four categories (nonmetropolitan rural, nonmetropolitan urban, metropolitan with population <1 million, and metropolitan with population ≥1 million). For the trend analysis, which used annual rates, these categories were combined into two categories (nonmetropolitan and metropolitan). Rates by county classification were examined by sex, age, race/ethnicity, U.S. census region, and cancer site. Trends in rates were examined by county classification and cancer site. During the most recent 5-year period for which data were available, nonmetropolitan rural areas had lower average annual age-adjusted cancer incidence rates for all anatomic cancer sites combined but higher death rates than metropolitan areas. During 2006-2015, the annual age-adjusted death rates for all cancer sites combined decreased at a slower pace in nonmetropolitan areas (-1.0% per year) than in metropolitan areas (-1.6% per year), increasing the differences in these rates. In contrast, annual age-adjusted incidence rates for all cancer sites combined decreased approximately 1% per year during 2004-2013 both in nonmetropolitan and metropolitan counties. This report provides the first comprehensive description of cancer incidence and mortality in nonmetropolitan and metropolitan counties in the United States. Nonmetropolitan rural counties had higher incidence of and deaths from several cancers related to tobacco use and cancers that can be prevented by screening. Differences between nonmetropolitan and metropolitan counties in cancer incidence might reflect differences in risk factors such as cigarette smoking, obesity, and physical inactivity, whereas differences in cancer death rates might reflect disparities in access to health care and timely diagnosis and treatment. Many cancer cases and deaths could be prevented, and public health programs can use evidence-based strategies from the U.S. Preventive Services Task Force and Advisory Committee for Immunization Practices (ACIP) to support cancer prevention and control. The U.S. Preventive Services Task Force recommends population-based screening for colorectal, female breast, and cervical cancers among adults at average risk for these cancers and for lung cancer among adults at high risk; screening adults for tobacco use and excessive alcohol use, offering counseling and interventions as needed; and using low-dose aspirin to prevent colorectal cancer among adults considered to be at high risk for cardiovascular disease based on specific criteria. ACIP recommends vaccination against cancer-related infectious diseases including human papillomavirus and hepatitis B virus. The Guide to Community Preventive Services describes program and policy interventions proven to increase cancer screening and vaccination rates and to prevent tobacco use, excessive alcohol use, obesity, and physical inactivity.

Effect of age and biological subtype on the risk and timing of brain metastasis in breast cancer patients.

PubMed

Hung, Man-Hsin; Liu, Chun-Yu; Shiau, Cheng-Ying; Hsu, Chin-Yi; Tsai, Yi-Fang; Wang, Yu-Ling; Tai, Ling-Chen; King, Kuang-Liang; Chao, Ta-Chung; Chiu, Jen-Hwey; Su, Cheng-Hsi; Lo, Su-Shun; Tzeng, Cheng-Hwai; Shyr, Yi-Ming; Tseng, Ling-Ming

2014-01-01

Brain metastasis is a major complication of breast cancer. This study aimed to analyze the effect of age and biological subtype on the risk and timing of brain metastasis in breast cancer patients. We identified subtypes of invasive ductal carcinoma of the breast by determining estrogen receptor, progesterone receptor and HER2 status. Time to brain metastasis according to age and cancer subtype was analyzed by Cox proportional hazard analysis. Of the 2248 eligible patients, 164 (7.3%) developed brain metastasis over a median follow-up of 54.2 months. Age 35 or younger, HER2-enriched subtype, and triple-negative breast cancer were significant risk factors of brain metastasis. Among patients aged 35 or younger, the risk of brain metastasis was independent of biological subtype (P = 0.507). Among patients aged 36-59 or >60 years, those with triple-negative or HER2-enriched subtypes had consistently increased risk of brain metastasis, as compared with those with luminal A tumors. Patients with luminal B tumors had higher risk of brain metastasis than luminal A only in patients >60 years. Breast cancer subtypes are associated with differing risks of brain metastasis among different age groups. Patients age 35 or younger are particularly at risk of brain metastasis independent of biological subtype.

Trend surface models in the representation and analysis of time factors in cancer mortality.

PubMed

Cislaghi, C; Negri, E; La Vecchia, C; Levi, F

1990-01-01

A method of graphic representation of time factors in cancer mortality is presented, based on different tonalities of grey applied to the surface of the matrix defined by various age-specific rates. It is illustrated using mortality data from cancers of the mouth or pharynx, oesophagus, larynx and lung in Italian and Swiss males. Progressively more complex regression surface equations are defined, on the basis of two independent variables (age and cohort) and a dependent one (each age-specific rate). General patterns of trends were thus identified, showing important similarities in cohort and period effects, but also noticeable differences in time-related factors in mortality from various neoplasms of the upper digestive and respiratory tract. For instance, there were declines in mortality from cancers of the mouth or pharynx in the oldest age groups, whereas rates were appreciably upwards at younger and middle age, particularly in Italy. Likewise, cancers of the oesophagus and, chiefly, of the larynx were substantially increasing, on a cohort basis, in oldest Italian males. Temporal pattern for laryngeal cancer in Italy was similar to that of lung cancer, thus suggesting that (cigarette) smoking has a greater impact on this cancer site as compared with alcohol. However, it is difficult to explain, on this basis alone, the totally diverging pattern for cancer of the larynx (downwards) and of the lung (upwards) observed among older Swiss males. These examples indicate that trend surface models are a useful summary guide to illustrate and understand the general patterns of age, period and cohort effects in cancer mortality.

Adoption consideration and concerns among young adult female cancer survivors.

PubMed

Gorman, Jessica R; Whitcomb, Brian W; Standridge, Daniel; Malcarne, Vanessa L; Romero, Sally A D; Roberts, Samantha A; Su, H Irene

2017-02-01

We compared adoption consideration between female young adult cancer survivors and women of the same age in the general US population, hypothesizing that cancer survivors who desired children would report greater interest in adoption than an age-adjusted general population sample who desired children. After age-standardizing the cancer survivor cohort to match the age distribution of the 2006-2010 National Survey for Family Growth (NSFG), we estimated adoption consideration among women age 18-35 years who wanted a (another) child in the two cohorts overall and within age groups. We assessed characteristics and concerns related to adoption consideration among cancer survivors. Among cancer survivors, 81.6 % (95 % CI 75.7-87.6) reported that they would consider adoption compared to 40.3 % (95 % CI 40.3-40.3) of women in the general population. While over 80 % of the cancer survivor sample reported that they would consider adoption, only 15 % of cancer survivors reported no concerns about adoption. The most common concerns were desire for a biological child (48 %), expense (45 %), adoption agency candidacy (41 %), and needing more information (39 %). We observed a twofold higher interest in adoption when comparing the cancer survivor with the general population, suggesting that adoption is a consideration for many young women who have survived cancer. Adoption is an important family-building option for those who want to have a child but are unable to or choose not to have a biological child. However, young adult survivors may need more support to understand and navigate this process.

Cost-effectiveness of screening women with familial risk for breast cancer with magnetic resonance imaging.

PubMed

Saadatmand, Sepideh; Tilanus-Linthorst, Madeleine M A; Rutgers, Emiel J T; Hoogerbrugge, Nicoline; Oosterwijk, Jan C; Tollenaar, Rob A E M; Hooning, Maartje; Loo, Claudette E; Obdeijn, Inge-Marie; Heijnsdijk, Eveline A M; de Koning, Harry J

2013-09-04

To reduce mortality, women with a family history of breast cancer are often screened with mammography before age 50 years. Additional magnetic resonance imaging (MRI) improves sensitivity and is cost-effective for BRCA1/2 mutation carriers. However, for women with a family history without a proven mutation, cost-effectiveness is unclear. We evaluated data of the largest prospective MRI screening study (MRISC). Between 1999 and 2007, 1597 women (8370 woman-years at risk) aged 25 to 70 years with an estimated cumulative lifetime risk of 15% to 50% for breast cancer were screened with clinical breast examination every 6 months and with annual mammography and MRI. We calculated the cost per detected and treated breast cancer. After incorporating MRISC data into a microsimulation screening analysis model (MISCAN), different schemes were evaluated, and cost per life-year gained (LYG) was estimated in comparison with the Dutch nationwide breast cancer screening program (biennial mammography from age 50 to 75 years). All statistical tests were two-sided. Forty-seven breast cancers (9 ductal carcinoma in situ) were detected. Screening with additional MRI costs $123 672 (€93 639) per detected breast cancer. In increasing age-cohorts, costs per detected and treated breast cancer decreased, but, unexpectedly, the percentage of MRI-only detected cancers increased. Screening under the MRISC-scheme from age 35 to 50 years was estimated to reduce breast cancer mortality by 25% at $134 932 (€102 164) per LYG (3.5% discounting) compared with 17% mortality reduction at $54 665 (€41 390) per LYG with mammography only. Screening with MRI may improve survival for women with familial risk for breast cancer but is expensive, especially in the youngest age categories.

Decreases in Smoking-Related Cancer Mortality Rates Are Associated with Birth Cohort Effects in Korean Men.

PubMed

Jee, Yon Ho; Shin, Aesun; Lee, Jong-Keun; Oh, Chang-Mo

2016-12-05

Background: This study aimed to examine trends in smoking-related cancer mortality rates and to investigate the effect birth cohort on smoking-related cancer mortality in Korean men. Methods: The number of smoking-related cancer deaths and corresponding population numbers were obtained from Statistics Korea for the period 1984-2013. Joinpoint regression analysis was used to detect changes in trends in age-standardized mortality rates. Birth-cohort specific mortality rates were illustrated by 5 year age groups. Results: The age-standardized mortality rates for oropharyngeal decreased from 2003 to 2013 (annual percent change (APC): -3.1 (95% CI, -4.6 to -1.6)) and lung cancers decreased from 2002 to 2013 (APC -2.4 (95% CI -2.7 to -2.2)). The mortality rates for esophageal declined from 1994 to 2002 (APC -2.5 (95% CI -4.1 to -0.8)) and from 2002 to 2013 (APC -5.2 (95% CI -5.7 to -4.7)) and laryngeal cancer declined from 1995 to 2013 (average annual percent change (AAPC): -3.3 (95% CI -4.7 to -1.8)). By the age group, the trends for the smoking-related cancer mortality except for oropharyngeal cancer have changed earlier to decrease in the younger age group. The birth-cohort specific mortality rates and age-period-cohort analysis consistently showed that all birth cohorts born after 1930 showed reduced mortality of smoking-related cancers. Conclusions: In Korean men, smoking-related cancer mortality rates have decreased. Our findings also indicate that current decreases in smoking-related cancer mortality rates have mainly been due to a decrease in the birth cohort effect, which suggest that decrease in smoking rates.

Decreases in Smoking-Related Cancer Mortality Rates Are Associated with Birth Cohort Effects in Korean Men

PubMed Central

Jee, Yon Ho; Shin, Aesun; Lee, Jong-Keun; Oh, Chang-Mo

2016-01-01

Background: This study aimed to examine trends in smoking-related cancer mortality rates and to investigate the effect birth cohort on smoking-related cancer mortality in Korean men. Methods: The number of smoking-related cancer deaths and corresponding population numbers were obtained from Statistics Korea for the period 1984–2013. Joinpoint regression analysis was used to detect changes in trends in age-standardized mortality rates. Birth-cohort specific mortality rates were illustrated by 5 year age groups. Results: The age-standardized mortality rates for oropharyngeal decreased from 2003 to 2013 (annual percent change (APC): −3.1 (95% CI, −4.6 to −1.6)) and lung cancers decreased from 2002 to 2013 (APC −2.4 (95% CI −2.7 to −2.2)). The mortality rates for esophageal declined from 1994 to 2002 (APC −2.5 (95% CI −4.1 to −0.8)) and from 2002 to 2013 (APC −5.2 (95% CI −5.7 to −4.7)) and laryngeal cancer declined from 1995 to 2013 (average annual percent change (AAPC): −3.3 (95% CI −4.7 to −1.8)). By the age group, the trends for the smoking-related cancer mortality except for oropharyngeal cancer have changed earlier to decrease in the younger age group. The birth-cohort specific mortality rates and age-period-cohort analysis consistently showed that all birth cohorts born after 1930 showed reduced mortality of smoking-related cancers. Conclusions: In Korean men, smoking-related cancer mortality rates have decreased. Our findings also indicate that current decreases in smoking-related cancer mortality rates have mainly been due to a decrease in the birth cohort effect, which suggest that decrease in smoking rates. PMID:27929405

Recent trends and patterns in breast cancer incidence among Eastern and Southeastern Asian women.

PubMed

Shin, Hai-Rim; Joubert, Clementine; Boniol, Mathieu; Hery, Clarisse; Ahn, Sei Hyun; Won, Young-Joo; Nishino, Yoshikazu; Sobue, Tomotaka; Chen, Chien-Jen; You, San-Lin; Mirasol-Lumague, Maria Rica; Law, Stephen Chun-Key; Mang, Oscar; Xiang, Yong-Bing; Chia, Kee-Seng; Rattanamongkolgul, Suthee; Chen, Jian-Guo; Curado, Maria Paula; Autier, Philippe

2010-11-01

Incidence of breast cancer is rising in Asian countries, and breast cancer is the most common cancer among Asian women. However, there are few recent descriptive reports on the epidemiology of breast cancer among Eastern and Southeastern Asian populations. We examined incidence trends for invasive breast cancer in women aged ≥20 years from 15 registries in Eastern (China, Japan, the Republic of Korea, Taiwan) and Southeastern Asia (the Philippines, Singapore, Thailand) for the period 1993-2002 mainly using data from Cancer Incidence in Five Continents, Volumes VIII and IX. We compared trends in annual incidence rates and age-specific incidence curves over a 10-year period. We also compared the incidence rates of Asian-Americans with the rates of their Asian counterparts. Breast cancer incidence rates increased gradually over time in all study populations. Rates were relatively high in Southeastern Asia and became progressively lower along a south-to-north gradient, with a fourfold geographic variation within the study populations. Age-specific incidence curves showed patterns that gradually changed according to incidence rates. Breast cancer incidence among Asian women living in the United States was 1.5-4 times higher than the corresponding incidence rate in the women's respective countries of origin. Breast cancer incidence is expected to continue to increase for the next 10 years in Asia and may approach rates reported among Asian-Americans. The number and mean age of breast cancer cases is expected to increase as the female Asian population ages, the prevalence of certain risk factors changes (early menarche, late menopause, low parity, late age at first live birth, and low prevalence of breastfeeding), and as Asian countries introduce mass screening programs.

Cell Senescence: Aging and Cancer

ScienceCinema

Campisi, Judith

2017-12-27

Scientists have identified a molecular cause behind the ravages of old age and in doing so have also shown how a natural process for fighting cancer in younger persons can actually promote cancer in older individuals.

Description of cervical cancer mortality in Belgium using Bayesian age-period-cohort models

PubMed Central

2009-01-01

Objective To correct cervical cancer mortality rates for death cause certification problems in Belgium and to describe the corrected trends (1954-1997) using Bayesian models. Method Cervical cancer (cervix uteri (CVX), corpus uteri (CRP), not otherwise specified (NOS) uterus cancer and other very rare uterus cancer (OTH) mortality data were extracted from the WHO mortality database together with population data for Belgium and the Netherlands. Different ICD (International Classification of Diseases) were used over time for death cause certification. In the Netherlands, the proportion of not-otherwise specified uterine cancer deaths was small over large periods and therefore internal reallocation could be used to estimate the corrected rates cervical cancer mortality. In Belgium, the proportion of improperly defined uterus deaths was high. Therefore, the age-specific proportions of uterus cancer deaths that are probably of cervical origin for the Netherlands was applied to Belgian uterus cancer deaths to estimate the corrected number of cervix cancer deaths (corCVX). A Bayesian loglinear Poisson-regression model was performed to disentangle the separate effects of age, period and cohort. Results The corrected age standardized mortality rate (ASMR) decreased regularly from 9.2/100 000 in the mid 1950s to 2.5/100,000 in the late 1990s. Inclusion of age, period and cohort into the models were required to obtain an adequate fit. Cervical cancer mortality increases with age, declines over calendar period and varied irregularly by cohort. Conclusion Mortality increased with ageing and declined over time in most age-groups, but varied irregularly by birth cohort. In global, with some discrete exceptions, mortality decreased for successive generations up to the cohorts born in the 1930s. This decline stopped for cohorts born in the 1940s and thereafter. For the youngest cohorts, even a tendency of increasing risk of dying from cervical cancer could be observed, reflecting increased exposure to risk factors. The fact that this increase was limited for the youngest cohorts could be explained as an effect of screening. Bayesian modeling provided similar results compared to previously used classical Poisson models. However, Bayesian models are more robust for estimating rates when data are sparse (youngest age groups, most recent cohorts) and can be used to for predicting future trends.

Residence in Proximity of a Coal-Oil-Fired Thermal Power Plant and Risk of Lung and Bladder Cancer in North-Eastern Italy. A Population-Based Study: 1995-2009.

PubMed

Collarile, Paolo; Bidoli, Ettore; Barbone, Fabio; Zanier, Loris; Del Zotto, Stefania; Fuser, Simonetta; Stel, Fulvio; Panato, Chiara; Gallai, Irene; Serraino, Diego

2017-07-31

This study investigated the risk of lung and bladder cancers in people residing in proximity of a coal-oil-fired thermal power plant in an area of north-eastern Italy, covered by a population-based cancer registry. Incidence rate ratios (IRR) by sex, age, and histology were computed according to tertiles of residential exposure to benzene, nitrogen dioxide (NO2), particular matter, and sulfur dioxide (SO2) among 1076 incident cases of lung and 650 cases of bladder cancers. In men of all ages and in women under 75 years of age, no significant associations were observed. Conversely, in women aged ≥75 years significantly increased risks of lung and bladder cancers were related to high exposure to benzene (IRR for highest vs. lowest tertile: 2.00 for lung cancer and 1.94 for bladder cancer) and NO2 (IRR: 1.72 for lung cancer; and 1.94 for bladder cancer). In these women, a 1.71-fold higher risk of lung cancer was also related to a high exposure to SO2. Acknowledging the limitations of our study, in particular that we did not have information regarding cigarette smoking habits, the findings of this study indicate that air pollution exposure may have had a role with regard to the risk of lung and bladder cancers limited to women aged ≥75 years. Such increased risk warrants further analytical investigations.

Burden of cancer associated with type 2 diabetes mellitus in Japan, 2010-2030.

PubMed

Saito, Eiko; Charvat, Hadrien; Goto, Atsushi; Matsuda, Tomohiro; Noda, Mitsuhiko; Sasazuki, Shizuka; Inoue, Manami

2016-04-01

Diabetes mellitus constitutes a major disease burden globally, and the prevalence of diabetes continues to increase worldwide. We aimed to estimate the burden of cancer associated with type 2 diabetes mellitus in Japan between 2010 and 2030. In this study, we estimated the population attributable fraction of cancer risk associated with type 2 diabetes in 2010 and 2030 using the prevalence estimates of type 2 diabetes in Japan from 1990 to 2030, summary hazard ratios of diabetes and cancer risk from a pooled analysis of eight large-scale Japanese cohort studies, observed incidence/mortality of cancer in 2010 and predicted incidence/mortality for 2030 derived from the age-period-cohort model. Our results showed that between 2010 and 2030, the total numbers of cancer incidence and mortality were predicted to increase by 38.9% and 10.5% in adults aged above 20 years, respectively. In the number of excess incident cancer cases associated with type 2 diabetes, an increase of 26.5% in men and 53.2% in women is expected between 2010 and 2030. The age-specific analysis showed that the population attributable fraction of cancer will increase in adults aged >60 years over time, but will not change in adults aged 20-59 years. In conclusion, this study suggests a modest but steady increase in cancers associated with type 2 diabetes. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Anxiety and depression in working-age cancer survivors: a register-based study.

PubMed

Inhestern, Laura; Beierlein, Volker; Bultmann, Johanna Christine; Möller, Birgit; Romer, Georg; Koch, Uwe; Bergelt, Corinna

2017-05-19

Anxiety and depression can be a long-term strain in cancer survivors. Little is known about the emotional situation of cancer survivors who have to deal with work- and family-related issues. The purpose of this study was to investigate anxiety and depression in working-age cancer survivors and associated factors. A register-based sample of 3370 cancer survivors (25 to 55 years at time of diagnosis) diagnosed up to six years prior to the survey was recruited from two German cancer registries. Demographic and medical characteristics as well as self-reported measures were used. Overall, approximately 40% of the survivors reported moderate to high anxiety scores and approximately 20% reported moderate to high depression scores. Compared to the general population, working-age cancer survivors were more anxious but less depressed (p < .001). Subgroups with regard to time since diagnosis did not differ in anxiety or depression. Anxiety and depression in cancer survivors were associated with various variables. Better social support, family functioning and physical health were associated with lower anxiety and depression. Overall, we found higher anxiety levels in cancer survivors of working-age than in the general population. A considerable portion of cancer survivors reported moderate to high levels of anxiety and depression. The results indicate the need for psychosocial screening and psycho-oncological support e.g. in survivorship programs for working-age cancer survivors. Assessing the physical health, social support and family background might help to identify survivors at risk for higher emotional distress.

Estimates of over-diagnosis of breast cancer due to population-based mammography screening in South Australia after adjustment for lead time effects.

PubMed

Beckmann, Kerri; Duffy, Stephen W; Lynch, John; Hiller, Janet; Farshid, Gelareh; Roder, David

2015-09-01

To estimate over-diagnosis due to population-based mammography screening using a lead time adjustment approach, with lead time measures based on symptomatic cancers only. Women aged 40-84 in 1989-2009 in South Australia eligible for mammography screening. Numbers of observed and expected breast cancer cases were compared, after adjustment for lead time. Lead time effects were modelled using age-specific estimates of lead time (derived from interval cancer rates and predicted background incidence, using maximum likelihood methods) and screening sensitivity, projected background breast cancer incidence rates (in the absence of screening), and proportions screened, by age and calendar year. Lead time estimates were 12, 26, 43 and 53 months, for women aged 40-49, 50-59, 60-69 and 70-79 respectively. Background incidence rates were estimated to have increased by 0.9% and 1.2% per year for invasive and all breast cancer. Over-diagnosis among women aged 40-84 was estimated at 7.9% (0.1-12.0%) for invasive cases and 12.0% (5.7-15.4%) when including ductal carcinoma in-situ (DCIS). We estimated 8% over-diagnosis for invasive breast cancer and 12% inclusive of DCIS cancers due to mammography screening among women aged 40-84. These estimates may overstate the extent of over-diagnosis if the increasing prevalence of breast cancer risk factors has led to higher background incidence than projected. © The Author(s) 2015.

Intratumoral heterogeneity and clonal evolution in blood malignancies and solid tumors.

PubMed

Varela, Ignacio; Menendez, Pablo; Sanjuan-Pla, Alejandra

2017-09-12

This meeting held at the University of Barcelona in March 2017, brought together scientists and clinicians worldwide to discuss current and future clinico-biological implications of intratumoral heterogeneity (ITH) and subclonal evolution in cancer diagnosis, patient stratification, and treatment resistance in diagnosis, treatment and follow-up. There was consensus that both longitudinal and tumor multi-region studies in matched samples are needed to better understand the dynamics of ITH. The contribution of the epigenome and microenvironment to ITH and subclone evolution remains understudied. It was recommended to combine computational, pathology and imaging tools to study the role of the microenvironment in subclone selection/evolution.

Mass media and risk factors for cancer: the under-representation of age.

PubMed

Macdonald, Sara; Cunningham, Yvonne; Patterson, Chris; Robb, Katie; Macleod, Una; Anker, Thomas; Hilton, Shona

2018-04-26

Increasing age is a risk factor for developing cancer. Yet, older people commonly underestimate this risk, are less likely to be aware of the early symptoms, and are more likely to be diagnosed with advanced stage cancer. Mass media are a key influence on the public's understanding health issues, including cancer risk. This study investigates how news media have represented age and other risk factors in the most common cancers over time. Eight hundred articles about the four most common cancers (breast, prostate, lung and colorectal) published within eight UK national newspapers in 2003, 2004, 2013 and 2014 were identified using the Nexis database. Relevant manifest content of articles was coded quantitatively and subjected to descriptive statistical analysis in SPSS to identify patterns across the data. Risk was presented in half of the articles but this was rarely discussed in any depth and around a quarter of all articles introduced more than one risk factor, irrespective of cancer site. Age was mentioned as a risk factor in approximately 12% of all articles and this varied by cancer site. Age was most frequently reported in relation to prostate cancer and least often in articles about lung cancer. Articles featuring personal narratives more frequently focused on younger people and this was more pronounced in non-celebrity stories; only 15% of non-celebrity narratives were about people over 60. Other common risks discussed were family history and genetics, smoking, diet, alcohol, and environmental factors. Family history and genetics together featured as the most common risk factors. Risk factor reporting varied by site and family history was most commonly associated with breast cancer, diet with bowel cancer and smoking with lung cancer. Age and older adults were largely obscured in media representation of cancer and cancer experience. Indeed common risk factors in general were rarely discussed in any depth. Our findings will usefully inform the development of future cancer awareness campaigns and media guidelines. It is important that older adults appreciate their heightened risk, particularly in the context of help-seeking decisions.

A Molecular Framework for Understanding DCIS

DTIC Science & Technology

2017-10-01

common form of breast cancer. IDC accounts for 80% of all breast cancers, predominantly affecting women aged 55 and older; however, at least a third of...Carcinoma (IDC), the most common form of breast cancer. IDC accounts for 80% of all breast cancers, predominantly affecting women aged 55 and older

Cell plasticity and heterogeneity in cancer.

PubMed

Marjanovic, Nemanja D; Weinberg, Robert A; Chaffer, Christine L

2013-01-01

Heterogeneity within a given cancer arises from diverse cell types recruited to the tumor and from genetic and/or epigenetic differences amongst the cancer cells themselves. These factors conspire to create a disease with various phenotypes. There are 2 established models of cancer development and progression to metastatic disease. These are the clonal evolution and cancer stem cell models. The clonal evolution theory suggests that successive mutations accumulating in a given cell generate clonal outgrowths that thrive in response to microenvironmental selection pressures, dictating the phenotype of the tumor. The alternative cancer stem cell (CSC) model suggests that cancer cells with similar genetic backgrounds can be hierarchically organized according to their tumorigenic potential. Accordingly, CSCs reside at the apex of the hierarchy and are thought to possess the majority of a cancer's tumor-initiating and metastatic ability. A defining feature of this model is its apparent unidirectional nature, whereby CSCs undergo symmetric division to replenish the CSC pool and irreversible asymmetric division to generate daughter cells (non-CSCs) with low tumorigenic potential. However, evolving evidence supports a new model of tumorigenicity, in which considerable plasticity exists between the non-CSC and CSC compartments, such that non-CSCs can reacquire a CSC phenotype. These findings suggest that some tumors may adhere to a plastic CSC model, in which bidirectional conversions are common and essential components of tumorigenicity. Accumulating evidence surrounding the plasticity of cancer cells, in particular, suggests that aggressive CSCs can be created de novo within a tumor. Given the current focus on therapeutic targeting of CSCs, we discuss the implications of non-CSC-to-CSC conversions on the development of future therapies. © 2012 American Association for Clinical Chemistry

Pharmacokinetics and Drug Interactions Determine Optimum Combination Strategies in Computational Models of Cancer Evolution.

PubMed

Chakrabarti, Shaon; Michor, Franziska

2017-07-15

The identification of optimal drug administration schedules to battle the emergence of resistance is a major challenge in cancer research. The existence of a multitude of resistance mechanisms necessitates administering drugs in combination, significantly complicating the endeavor of predicting the evolutionary dynamics of cancers and optimal intervention strategies. A thorough understanding of the important determinants of cancer evolution under combination therapies is therefore crucial for correctly predicting treatment outcomes. Here we developed the first computational strategy to explore pharmacokinetic and drug interaction effects in evolutionary models of cancer progression, a crucial step towards making clinically relevant predictions. We found that incorporating these phenomena into our multiscale stochastic modeling framework significantly changes the optimum drug administration schedules identified, often predicting nonintuitive strategies for combination therapies. We applied our approach to an ongoing phase Ib clinical trial (TATTON) administering AZD9291 and selumetinib to EGFR-mutant lung cancer patients. Our results suggest that the schedules used in the three trial arms have almost identical efficacies, but slight modifications in the dosing frequencies of the two drugs can significantly increase tumor cell eradication. Interestingly, we also predict that drug concentrations lower than the MTD are as efficacious, suggesting that lowering the total amount of drug administered could lower toxicities while not compromising on the effectiveness of the drugs. Our approach highlights the fact that quantitative knowledge of pharmacokinetic, drug interaction, and evolutionary processes is essential for identifying best intervention strategies. Our method is applicable to diverse cancer and treatment types and allows for a rational design of clinical trials. Cancer Res; 77(14); 3908-21. ©2017 AACR . ©2017 American Association for Cancer Research.

A Study of Black and White Men With a Family History of Prostate Cancer

DTIC Science & Technology

2002-03-01

l4lbTyp)___ (QO l4lbAge)___ TIPO DE CANCER: 1 COLON 3 SENO 4 CERVIZ 5 PULMONES 6 OVARIOS 7 ENDOMIETPJO V OTRO W DK X RF Q014_lc Su hermana es... 1 su...diagnosticada? (QOl4 -2aAge) - (QOl4-2bAge)____ TIPO DE CANCER: 1 COLON 3 SENO 4 CERVJZ 5 PULMONES 6 OVARIOS 7 ENDOMIETRIO V OTRO W DK X RF QO142c Su...6_aTyp)___ (QO l6laAge)____ (QOl6_lbTyp)___ (QO l6lbAge)___ TWPO DE CANCER: 1 COLON 3 SENO 4 CERVIZ 5 PULMONES 6 OVARIOS 7 ENDOM[ETPJO V OTRO W DK X RF

Quantitative Imaging in Cancer Evolution and Ecology

PubMed Central

Grove, Olya; Gillies, Robert J.

2013-01-01

Cancer therapy, even when highly targeted, typically fails because of the remarkable capacity of malignant cells to evolve effective adaptations. These evolutionary dynamics are both a cause and a consequence of cancer system heterogeneity at many scales, ranging from genetic properties of individual cells to large-scale imaging features. Tumors of the same organ and cell type can have remarkably diverse appearances in different patients. Furthermore, even within a single tumor, marked variations in imaging features, such as necrosis or contrast enhancement, are common. Similar spatial variations recently have been reported in genetic profiles. Radiologic heterogeneity within tumors is usually governed by variations in blood flow, whereas genetic heterogeneity is typically ascribed to random mutations. However, evolution within tumors, as in all living systems, is subject to Darwinian principles; thus, it is governed by predictable and reproducible interactions between environmental selection forces and cell phenotype (not genotype). This link between regional variations in environmental properties and cellular adaptive strategies may permit clinical imaging to be used to assess and monitor intratumoral evolution in individual patients. This approach is enabled by new methods that extract, report, and analyze quantitative, reproducible, and mineable clinical imaging data. However, most current quantitative metrics lack spatialness, expressing quantitative radiologic features as a single value for a region of interest encompassing the whole tumor. In contrast, spatially explicit image analysis recognizes that tumors are heterogeneous but not well mixed and defines regionally distinct habitats, some of which appear to harbor tumor populations that are more aggressive and less treatable than others. By identifying regional variations in key environmental selection forces and evidence of cellular adaptation, clinical imaging can enable us to define intratumoral Darwinian dynamics before and during therapy. Advances in image analysis will place clinical imaging in an increasingly central role in the development of evolution-based patient-specific cancer therapy. © RSNA, 2013 PMID:24062559

Older cancer patients in cancer clinical trials are underrepresented. Systematic literature review of almost 5000 meta- and pooled analyses of phase III randomized trials of survival from breast, prostate and lung cancer.

PubMed

Dunn, Cita; Wilson, Andrew; Sitas, Freddy

2017-12-01

Older people represent increasing proportions of the population with cancer. To understand the representivity of cancer treatments in older people, we performed a systematic literature review using PRISMA guidelines of the age distribution of clinical trial participants for three leading cancer types, namely breast, prostate, and lung. We used PubMed to identify articles detailing meta or pooled-analyses of phase III, randomised controlled trials (RCTs) of survival for breast, prostate and lung cancer, published ≤5 years from 2016. We compared the age distribution of participants to that of these cancers for "More developed regions". 4993 potential papers were identified, but only three papers on breast cancer, three on lung cancer, and none on prostate cancer presented the age distribution of their participants. Except for one paper of breast cancer, participants ≥70 years in all other papers were underrepresented. We recommend the age distribution of patients be clearly reported in all clinical trials, as per guidelines. Clinical trials ought to be more representative of the populations most affected by the disease for which treatments are being tested. This should lead to better knowledge of effectiveness of treatments and better translation of trial results to optimal care of older cancer patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

Influence of genetic factors on the development of breast cancer in the older woman.

PubMed

Bouwens, Christianne S H; van Rensburg, Susan J; de Kock, Lizanne; Apffelstaedt, Justus P A; Kotze, Maritha J

2012-07-01

Although the major part of the burden of disease for female breast cancer occurs at older age, less is known about the development and progression in this age group than in women under 60 years of age. As the world population continues to age, the percentage of elderly is increasing in all communities and the incidence of breast cancer will rise accordingly. Improving detection and diagnosis, and a better understanding of the mechanisms that play a role in this age group, will not only improve quality of life in older sufferers but could also contribute to the management of this disease in the adult population as well. Development of breast cancer in the older woman is influenced by many variables that may differ from the risk factors that are involved in younger women. In addition to well-described variables at younger ages such as family history, hormonal exposure, lifestyle factors and pre-existing benign breast disease, in older women age-related changes in breast tissue, biochemistry, inflammatory responses and the immune system, as well as accumulation of DNA damage and spontaneous mutations are suspected to contribute to the complex relationship between ageing and breast cancer. We review the available data on the role of age-related changes and genetic mutations in the development of breast cancer in older women as well as their effects on estrogen metabolism and free oxygen radical inactivation.

Optimizing colorectal cancer screening by race and sex: Microsimulation analysis II to inform the American Cancer Society colorectal cancer screening guideline.

PubMed

Meester, Reinier G S; Peterse, Elisabeth F P; Knudsen, Amy B; de Weerdt, Anne C; Chen, Jennifer C; Lietz, Anna P; Dwyer, Andrea; Ahnen, Dennis J; Siegel, Rebecca L; Smith, Robert A; Zauber, Ann G; Lansdorp-Vogelaar, Iris

2018-05-30

Colorectal cancer (CRC) risk varies by race and sex. This study, 1 of 2 microsimulation analyses to inform the 2018 American Cancer Society CRC screening guideline, explored the influence of race and sex on optimal CRC screening strategies. Two Cancer Intervention and Surveillance Modeling Network microsimulation models, informed by US incidence data, were used to evaluate a variety of screening methods, ages to start and stop, and intervals for 4 demographic subgroups (black and white males and females) under 2 scenarios for the projected lifetime CRC risk for 40-year-olds: 1) assuming that risk had remained stable since the early screening era and 2) assuming that risk had increased proportionally to observed incidence trends under the age of 40 years. Model-based screening recommendations were based on the predicted level of benefit (life-years gained) and burden (required number of colonoscopies), the incremental burden-to-benefit ratio, and the relative efficiency in comparison with strategies with similar burdens. When lifetime CRC risk was assumed to be stable over time, the models differed in the recommended age to start screening for whites (45 vs 50 years) but consistently recommended screening from the age of 45 years for blacks. When CRC risk was assumed to be increased, the models recommended starting at the age of 45 years, regardless of race and sex. Strategies recommended under both scenarios included colonoscopy every 10 or 15 years, annual fecal immunochemical testing, and computed tomographic colonography every 5 years through the age of 75 years. Microsimulation modeling suggests that CRC screening should be considered from the age of 45 years for blacks and for whites if the lifetime risk has increased proportionally to the incidence for younger adults. Cancer 2018. © 2018 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. © 2018 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

Breast Cancer Trend in Iran from 2000 to 2009 and Prediction till 2020 using a Trend Analysis Method.

PubMed

Zahmatkesh, Bibihajar; Keramat, Afsaneh; Alavi, Nasrinossadat; Khosravi, Ahmad; Kousha, Ahmad; Motlagh, Ali Ghanbari; Darman, Mahboobeh; Partovipour, Elham; Chaman, Reza

2016-01-01

Breast cancer is the most common cancer in women worldwide with a rising incidence rate in most countries. Considering the increase in life expectancy and change in lifestyle of Iranian women, this study investigated the age-adjusted trend of breast cancer incidence during 2000-2009 and predicted its incidence to 2020. The 1997 and 2006 census results were used for the projection of female population by age through the cohort-component method over the studied years. Data from the Iranian cancer registration system were used to calculate the annual incidence rate of breast cancer. The age-adjusted incidence rate was then calculated using the WHO standard population distribution. The five-year-age-specific incidence rates were also obtained for each year and future incidence was determined using the trend analysis method. Annual percentage change (APC) was calculated through the joinpoint regression method. The bias adjusted incidence rate of breast cancer increased from 16.7 per 100,000 women in 2000 to 33.6 per 100,000 women in 2009. The incidence of breast cancer had a growing trend in almost all age groups above 30 years over the studied years. In this period, the age groups of 45-65 years had the highest incidence. Investigation into the joinpoint curve showed that the curve had a steep slope with an APC of 23.4% before the first joinpoint, but became milder after this. From 2005 to 2009, the APC was calculated as 2.7%, through which the incidence of breast cancer in 2020 was predicted as 63.0 per 100,000 women. The age-adjusted incidence rate of breast cancer continues to increas in Iranian women. It is predicted that this trend will continue until 2020. Therefore, it seems necessary to prioritize the prevention, control and care for breast cancer in Iran.

Mutational profiles of breast cancer metastases from a rapid autopsy series reveal multiple evolutionary trajectories.

PubMed

Avigdor, Bracha Erlanger; Cimino-Mathews, Ashley; DeMarzo, Angelo M; Hicks, Jessica L; Shin, James; Sukumar, Saraswati; Fetting, John; Argani, Pedram; Park, Ben H; Wheelan, Sarah J

2017-12-21

Heterogeneity within and among tumors in a metastatic cancer patient is a well-established phenomenon that may confound treatment and accurate prognosis. Here, we used whole-exome sequencing to survey metastatic breast cancer tumors from 5 patients in a rapid autopsy program to construct the origin and genetic development of metastases. Metastases were obtained from 5 breast cancer patients using a rapid autopsy protocol and subjected to whole-exome sequencing. Metastases were evaluated for sharing of somatic mutations, correlation of copy number variation and loss of heterozygosity, and genetic similarity scores. Pathological features of the patients' disease were assessed by immunohistochemical analyses. Our data support a monoclonal origin of metastasis in 3 cases, but in 2 cases, metastases arose from at least 2 distinct subclones in the primary tumor. In the latter 2 cases, the primary tumor presented with mixed histologic and pathologic features, suggesting early divergent evolution within the primary tumor with maintenance of metastatic capability in multiple lineages. We used genetic and histopathological evidence to demonstrate that metastases can be derived from a single or multiple independent clones within a primary tumor. This underscores the complexity of breast cancer clonal evolution and has implications for how best to determine and implement therapies for early- and late-stage disease.

Mutational profiles of breast cancer metastases from a rapid autopsy series reveal multiple evolutionary trajectories

PubMed Central

Avigdor, Bracha Erlanger; Cimino-Mathews, Ashley; DeMarzo, Angelo M.; Hicks, Jessica L.; Shin, James; Sukumar, Saraswati; Fetting, John; Argani, Pedram; Park, Ben H.; Wheelan, Sarah J.

2017-01-01

Heterogeneity within and among tumors in a metastatic cancer patient is a well-established phenomenon that may confound treatment and accurate prognosis. Here, we used whole-exome sequencing to survey metastatic breast cancer tumors from 5 patients in a rapid autopsy program to construct the origin and genetic development of metastases. Metastases were obtained from 5 breast cancer patients using a rapid autopsy protocol and subjected to whole-exome sequencing. Metastases were evaluated for sharing of somatic mutations, correlation of copy number variation and loss of heterozygosity, and genetic similarity scores. Pathological features of the patients’ disease were assessed by immunohistochemical analyses. Our data support a monoclonal origin of metastasis in 3 cases, but in 2 cases, metastases arose from at least 2 distinct subclones in the primary tumor. In the latter 2 cases, the primary tumor presented with mixed histologic and pathologic features, suggesting early divergent evolution within the primary tumor with maintenance of metastatic capability in multiple lineages. We used genetic and histopathological evidence to demonstrate that metastases can be derived from a single or multiple independent clones within a primary tumor. This underscores the complexity of breast cancer clonal evolution and has implications for how best to determine and implement therapies for early- and late-stage disease. PMID:29263308

Lessons from applied ecology: cancer control using an evolutionary double bind.

PubMed

Gatenby, Robert A; Brown, Joel; Vincent, Thomas

2009-10-01

Because the metastatic cascade is largely governed by the ability of malignant cells to adapt and proliferate at the distant tissue site, we propose that disseminated cancers are analogous in many important ways to the evolutionary and ecological dynamics of exotic species. Although pests can be decimated through the application of chemical toxins, this strategy virtually never achieves robust control as evolution of resistant phenotypes typically permits population recovery to pretreatment levels. In general, biological strategies that introduce predators, parasitoids, or pathogens have achieved more durable control of pest populations even after emergence of resistant phenotypes. From this we propose that long term outcome from any treatment strategy for invasive pests, including cancer, is not limited by evolution of resistance, but rather by the phenotypic cost of that resistance. If a cancerous cell's adaptation to therapy is achieved by upregulating xenobiotic metabolism or a redundant signaling pathway, the required investment in resources is small, and the original malignant phenotype remains essentially intact. As a result, the cancer cells' initial high level of fitness is little changed and unconstrained proliferation will resume once resistance evolves. Robust population control is possible if resistance to therapy requires a substantial and costly phenotypic adaptation that also significantly reduces the organism's fitness in its original niche: an evolutionary double bind.

Economic independence in survivors of cancer diagnosed at a young age: A Norwegian national cohort study.

PubMed

Gunnes, Maria W; Lie, Rolv Terje; Bjørge, Tone; Syse, Astri; Ruud, Ellen; Wesenberg, Finn; Moster, Dag

2016-12-15

The impact of cancer on socioeconomic outcomes is attracting attention as the number of survivors of cancer in young age continues to rise. This study examines economic independence in a national cohort of survivors of cancer at a young age in Norway. Through the linkage of several national registries, the study cohort comprised 1,212,013 individuals born in Norway during 1965 through 1985, of which 5440 had received a cancer diagnosis before age 25 years. Follow-up was through 2007, and the main outcomes were receipt of governmental financial assistance, employment, income, and occupation. Analytic methods included Cox proportional hazard regression, log-binomial regression, and quantile regression models. Individuals in the cancer survivor group had an increased probability of receiving governmental financial assistance (men: hazard ratio [HR], 1.4; 95% confidence interval [CI], 1.3-1.5; women: HR, 1.5; 95% CI, 1.3-1.6) and of not being employed (men: HR, 1.4; 95% CI, 1.2-1.7; women: HR, 1.4; 95% CI, 1.2-1.6) compared with those in the noncancer group. Income discrepancies were particularly pronounced for survivors of central nervous system tumors. There was no difference in representation in higher skilled occupations. Survivors of cancer at a young age in Norway had an increased risk of being economically dependent and unemployed. This was evident in several tumor groups and was most pronounced in female survivors. There were only small differences in income or representation in higher skilled occupations for most employed survivors compared with the noncancer group. The current results are important for understanding the impact of a cancer diagnosis at a young age on subsequent job market outcomes. Cancer 2016;122:3873-3882. © 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. © 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

Differences between right- and left-sided colon cancer in patient characteristics, cancer morphology and histology.

PubMed

Nawa, Toru; Kato, Jun; Kawamoto, Hirofumi; Okada, Hiroyuki; Yamamoto, Hiroshi; Kohno, Hiroyuki; Endo, Hisayuki; Shiratori, Yasushi

2008-03-01

Recently, the clinical and biological differences between right- and left-sided colon cancers have been widely debated. However, close analyses of these clinical differences, based on large-scale studies, have been scarcely reported. A total of 3552 consecutive Japanese colorectal cancer cases were examined and the clinical differences between right- and left-sided colon cancer cases were investigated. The proportion of right-sided colon cancer was relatively high in patients aged less than 40 years (33%) and more than 80 years (43%). The proportion of right-sided colon cancer in patients aged 40-59 years was relatively low (male 22% and female 29%). In male patients the proportion increased in the 70-79 years age group (30%), while in female patients the proportion increased in the 60-69 years age group (39%). Right-sided colon cancer was more likely to be detected at an advanced stage (T1 stage; left 22%, right 15%) (P < 0.01) with severe symptoms. Polypoid-type early cancer was dominant in the left colon (left 59%; right 40%) (P < 0.01), while the proportion of flat-type early cancer in the right colon was significantly higher than that in the left colon (left 25%; right 44%) (P < 0.01). Specific age distribution of right-sided colon cancer was observed and the difference between male and female patients was highlighted. Other clinical features also differed between right- and left-sided colon cancer, suggesting that different mechanisms may be at work during right and left colon carcinogenesis.

Methodological choices affect cancer incidence rates: a cohort study.

PubMed

Brooke, Hannah L; Talbäck, Mats; Feychting, Maria; Ljung, Rickard

2017-01-19

Incidence rates are fundamental to epidemiology, but their magnitude and interpretation depend on methodological choices. We aimed to examine the extent to which the definition of the study population affects cancer incidence rates. All primary cancer diagnoses in Sweden between 1958 and 2010 were identified from the national Cancer Register. Age-standardized and age-specific incidence rates of 29 cancer subtypes between 2000 and 2010 were calculated using four definitions of the study population: persons resident in Sweden 1) based on general population statistics; 2) with no previous subtype-specific cancer diagnosis; 3) with no previous cancer diagnosis except non-melanoma skin cancer; and 4) with no previous cancer diagnosis of any type. We calculated absolute and relative differences between methods. Age-standardized incidence rates calculated using general population statistics ranged from 6% lower (prostate cancer, incidence rate difference: -13.5/100,000 person-years) to 8% higher (breast cancer in women, incidence rate difference: 10.5/100,000 person-years) than incidence rates based on individuals with no previous subtype-specific cancer diagnosis. Age-standardized incidence rates in persons with no previous cancer of any type were up to 10% lower (bladder cancer in women) than rates in those with no previous subtype-specific cancer diagnosis; however, absolute differences were <5/100,000 person-years for all cancer subtypes. For some cancer subtypes incidence rates vary depending on the definition of the study population. For these subtypes, standardized incidence ratios calculated using general population statistics could be misleading. Moreover, etiological arguments should be used to inform methodological choices during study design.

Divergent evolution of life span associated with mitochondrial DNA evolution.

PubMed

Stojković, Biljana; Sayadi, Ahmed; Đorđević, Mirko; Jović, Jelena; Savković, Uroš; Arnqvist, Göran

2017-01-01

Mitochondria play a key role in ageing. The pursuit of genes that regulate variation in life span and ageing have shown that several nuclear-encoded mitochondrial genes are important. However, the role of mitochondrial encoded genes (mtDNA) is more controversial and our appreciation of the role of mtDNA for the evolution of life span is limited. We use replicated lines of seed beetles that have been artificially selected for long or short life for >190 generations, now showing dramatic phenotypic differences, to test for a possible role of mtDNA in the divergent evolution of ageing and life span. We show that these divergent selection regimes led to the evolution of significantly different mtDNA haplotype frequencies. Selection for a long life and late reproduction generated positive selection for one specific haplotype, which was fixed in most such lines. In contrast, selection for reproduction early in life led to both positive selection as well as negative frequency-dependent selection on two different haplotypes, which were both present in all such lines. Our findings suggest that the evolution of life span was in part mediated by mtDNA, providing support for the emerging general tenet that adaptive evolution of life-history syndromes may involve mtDNA. © 2016 The Author(s). Evolution © 2016 The Society for the Study of Evolution.

Tumor progression: chance and necessity in Darwinian and Lamarckian somatic (mutationless) evolution.

PubMed

Huang, Sui

2012-09-01

Current investigation of cancer progression towards increasing malignancy focuses on the molecular pathways that produce the various cancerous traits of cells. Their acquisition is explained by the somatic mutation theory: tumor progression is the result of a neo-Darwinian evolution in the tissue. Herein cells are the units of selection. Random genetic mutations permanently affecting these pathways create malignant cell phenotypes that are selected for in the disturbed tissue. However, could it be that the capacity of the genome and its gene regulatory network to generate the vast diversity of cell types during development, i.e., to produce inheritable phenotypic changes without mutations, is harnessed by tumorigenesis to propel a directional change towards malignancy? Here we take an encompassing perspective, transcending the orthodoxy of molecular carcinogenesis and review mechanisms of somatic evolution beyond the Neo-Darwinian scheme. We discuss the central concept of "cancer attractors" - the hidden stable states of gene regulatory networks normally not occupied by cells. Noise-induced transitions into such attractors provide a source for randomness (chance) and regulatory constraints (necessity) in the acquisition of novel expression profiles that can be inherited across cell divisions, and hence, can be selected for. But attractors can also be reached in response to environmental signals - thus offering the possibility for inheriting acquired traits that can also be selected for. Therefore, we face the possibility of non-genetic (mutation-independent) equivalents to both Darwinian and Lamarckian evolution which may jointly explain the arrow of change pointing toward increasing malignancy. Copyright © 2012 Elsevier Ltd. All rights reserved.

SciClone: inferring clonal architecture and tracking the spatial and temporal patterns of tumor evolution.

PubMed

Miller, Christopher A; White, Brian S; Dees, Nathan D; Griffith, Malachi; Welch, John S; Griffith, Obi L; Vij, Ravi; Tomasson, Michael H; Graubert, Timothy A; Walter, Matthew J; Ellis, Matthew J; Schierding, William; DiPersio, John F; Ley, Timothy J; Mardis, Elaine R; Wilson, Richard K; Ding, Li

2014-08-01

The sensitivity of massively-parallel sequencing has confirmed that most cancers are oligoclonal, with subpopulations of neoplastic cells harboring distinct mutations. A fine resolution view of this clonal architecture provides insight into tumor heterogeneity, evolution, and treatment response, all of which may have clinical implications. Single tumor analysis already contributes to understanding these phenomena. However, cryptic subclones are frequently revealed by additional patient samples (e.g., collected at relapse or following treatment), indicating that accurately characterizing a tumor requires analyzing multiple samples from the same patient. To address this need, we present SciClone, a computational method that identifies the number and genetic composition of subclones by analyzing the variant allele frequencies of somatic mutations. We use it to detect subclones in acute myeloid leukemia and breast cancer samples that, though present at disease onset, are not evident from a single primary tumor sample. By doing so, we can track tumor evolution and identify the spatial origins of cells resisting therapy.

SciClone: Inferring Clonal Architecture and Tracking the Spatial and Temporal Patterns of Tumor Evolution

PubMed Central

Dees, Nathan D.; Griffith, Malachi; Welch, John S.; Griffith, Obi L.; Vij, Ravi; Tomasson, Michael H.; Graubert, Timothy A.; Walter, Matthew J.; Ellis, Matthew J.; Schierding, William; DiPersio, John F.; Ley, Timothy J.; Mardis, Elaine R.; Wilson, Richard K.; Ding, Li

2014-01-01

The sensitivity of massively-parallel sequencing has confirmed that most cancers are oligoclonal, with subpopulations of neoplastic cells harboring distinct mutations. A fine resolution view of this clonal architecture provides insight into tumor heterogeneity, evolution, and treatment response, all of which may have clinical implications. Single tumor analysis already contributes to understanding these phenomena. However, cryptic subclones are frequently revealed by additional patient samples (e.g., collected at relapse or following treatment), indicating that accurately characterizing a tumor requires analyzing multiple samples from the same patient. To address this need, we present SciClone, a computational method that identifies the number and genetic composition of subclones by analyzing the variant allele frequencies of somatic mutations. We use it to detect subclones in acute myeloid leukemia and breast cancer samples that, though present at disease onset, are not evident from a single primary tumor sample. By doing so, we can track tumor evolution and identify the spatial origins of cells resisting therapy. PMID:25102416

Trends in Female Breast Cancer by Age Group in the Chiang Mai Population

PubMed Central

Sripan, Patumrat; Sriplung, Hutcha; Pongnikorn, Donsuk; Virani, Shama; Bilheem, Surichai; Chaisaengkhaum, Udomlak; Maneesai, Puttachart; Waisri, Narate; Hanpragopsuk, Chirapong; Tansiri, Panrada; Khamsan, Varunee; Poungsombat, Malisa; Mawoot, Aumnart; Chitapanarux, Imjai

2017-01-01

Objectives: This study was conducted to determine incidence trends of female breast cancer according to age groups and to predict future change in Chiang Mai women through 2028. Method: Data were collected from all hospitals in Chiang Mai in northern Thailand, from 1989 through 2013, and used to investigate effects of age, year of diagnosis (period) and year of birth (cohort) on female breast cancer incidences using an age-period-cohort model. This model features geometric cut trends to predict change by young (<40 years), middle-aged (40-59) and elderly (≥60) age groups. Result: Of 5, 417 female breast cancer patients with a median age of 50 years (interquartile range: 43 to 59 years), 15%, 61% and 24% were young, middle-aged and elderly, respectively. Seventy nine percent of cancer cases in this study were detected at advanced stage. The trend in stage classification showed an increase in percentage of early stage and a decrease in metastatic cancers. Linear trends for cohort and period were not found in young females but were observed in middle-aged and elderly groups. Age-standardized rates (ASR) can be expected to remain stable around 6.8 per 100,000 women-years in young females. In the other age groups, the ASR trends were calculated to increase and reach peaks in 2024 of 120.2 and 138.2 per 100,000 women-years, respectively. Conclusion: Cohort effects or generation-specific effects, such as life style factors and the year of diagnosis (period) might have impacted on increased incidence in women aged over 40 years but not those under 40 years. A budget should be provided for treatment facilities and strategies to detect early stage cancers. The cost effectiveness of screening measures i.e. mammographic screening may need to be reconsidered for women age over 40 years. PMID:28612595

Identity reconstruction among older cancer survivors: Age and meaning in the context of a life-altering illness.

PubMed

Hannum, Susan M; Clegg Smith, Katherine; Coa, Kisha; Klassen, Ann C

2016-01-01

This article evaluates how older cancer patients describe cancer survivorship and incorporate the cancer experience into long-term evaluations of health. From a series of 53 qualitative interviews with adults with histories of breast and prostate cancers and non-Hodgkin's lymphoma, we analyzed age-related discussions among those 65 and older (n = 21). Emergent themes revealed the: (1) historical conceptualization of cancer, (2) changed perspective following diagnosis, (3) cancer in the context of a long biography, (4) cancer in the context of the aging body and decline, and (5) meaning of time remaining and quality of life. One important suggestion from our work, relevant to all clinicians regardless of specialty or role, is to incorporate goals for the future into individualized survivor care plans for older survivors.

Trends in mouth cancer incidence in Mumbai, India (1995-2009): An age-period-cohort analysis.

PubMed

Shridhar, Krithiga; Rajaraman, Preetha; Koyande, Shravani; Parikh, Purvish M; Chaturvedi, Pankaj; Dhillon, Preet K; Dikshit, Rajesh P

2016-06-01

Despite tobacco control and health promotion efforts, the incidence rates of mouth cancer are increasing across most regions in India. Analysing the influence of age, time period and birth cohort on these secular trends can point towards underlying factors and help identify high-risk populations for improved cancer control programmes. We evaluated secular changes in mouth cancer incidence among men and women aged 25-74 years in Mumbai between 1995 and 2009 by calculating age-specific and age-standardized incidence rates (ASR). We estimated the age-adjusted linear trend for annual percent change (EAPC) using the drift parameter, and conducted an age-period-cohort (APC) analysis to quantify recent time trends and to evaluate the significance of birth cohort and calendar period effects. Over the 15-year period, age-standardized incidence rates of mouth cancer in men in Mumbai increased by 2.7% annually (95% CI:1.9 to 3.4), p<0.0001) while rates among women decreased (EAPC=-0.01% (95% CI:-0.02 to -0.002), p=0.03). APC analysis revealed significant non-linear positive period and cohort effects in men, with higher effects among younger men (25-49 years). Non-significant increasing trends were observed in younger women (25-49 years). APC analyses from the Mumbai cancer registry indicate a significant linear increase of mouth cancer incidence from 1995 to 2009 in men, which was driven by younger men aged 25-49 years, and a non-significant upward trend in similarly aged younger women. Health promotion efforts should more effectively target younger cohorts. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Breast Cancer in Young Women

PubMed Central

Trogdon, Justin G.; Ekwueme, Donatus U.; Chamiec-Case, Linda; Guy, Gery P.

2018-01-01

Introduction Little is known about the effect of breast cancers on health-related quality of life among women diagnosed between age 18 and 44 years. The goal of this study is to estimate the effect of breast cancer on health state utility by age at diagnosis (18–44 years versus ≥45 years) and by race/ethnicity. Methods The analytic sample, drawn from the 2009 and 2010 Behavioral Risk Factor Surveillance System and analyzed in 2013, included women diagnosed with breast cancer between age 18 and 44 years (n=1,389) and age ≥45 years (n=6,037). Health state utility values were estimated using Healthy Days variables and a published algorithm. Regression analysis was conducted separately by age at diagnosis and race/ethnicity. Results The breast cancer health state utility decrement within 1 year from date of diagnosis was larger for women diagnosed at age 18–44 years than for women diagnosed at age ≥45 years (−0.116 vs −0.070, p<0.05). Within the younger age-at-diagnosis group, Hispanic women 2–4 years after diagnosis had the largest health state utility decrement (−0.221, p<0.01), followed by non-Hispanic white women within 1 year of diagnosis (−0.126, p<0.01). Conclusions This study is the first to report estimates of health state utility values for breast cancer by age at diagnosis and race/ethnicity from a nationwide sample. The results highlight the need for separate quality of life adjustments for women by age at diagnosis and race/ethnicity when conducting cost-effectiveness analysis of breast cancer prevention, detection, and treatment. PMID:26775905

[Trends in the mortality of liver cancer in Qidong, China: an analysis of fifty years].

PubMed

Chen, Jian-guo; Zhu, Jian; Zhang, Yong-hui; Chen, Yong-sheng; Ding, Lu-lu; Lu, Jian-hua; Zhu, Yuan-rong

2012-07-01

To describe and analyze the charecteristics and trends of liver cancer mortality during the past fifty years in Qidong, China. Retrospective mortality survey was conducted to get the data on liver cancer death in the period of 1958-1971, and the data from 1972 to 2007 were obtained from the records of cancer registration in Qidong. The crude mortality rate (CR) of liver cancer, and age-standardized rate by Chinese population (CASR) and by world population (WASR) were calculated and analyzed. The total percent changes (PC) and annual percent changes (APC) were used for evaluating the increasing trends of the mortality. The sex-specific rate, age-specific rate, truncated rate of the age group 35 - 64, cumulative rate of the age group 0-74, cumulative risk, period-rate, and the rate for age-birth cohort were compared. The natural death rate in Qidong residents for the past five-decade period experienced a wave interval of 8.62‰ in 1958 down to 5.37‰ in 1979, and up to 7.75‰ in 2007. The mortality rate for all-site cancers was increased from 56.69 per 100, 000 to 234.97 per 100, 000. The mortality rate of liver cancer, being 20.45 per 100, 100 in 1958 was increased to 49.04 per 100, 000 in 1972, and up to 69.29 per 100, 000 in 2007. According to the registration data of 1972 - 2007, the death from liver cancer was accounted for 34.88% of all deaths due to cancers, with a CR of 58.86 per 100, 000, CASR of 38.36 per 100, 000, and WASR, 49.37 Per 100, 000 in Qidong. The truncated rate for the age group 35 - 64 was 117.08 per 100, 000, and the cumulative rate for the age group 0-74 and the cumulative risk were 5.15% and 5.02%, respectively. The CRs for males was 90.52 per 100, 000 and for females was 27.93 per 100, 000, with a sex ratio of 3.24:1. For the period of 1972 - 2007, the PC for CR was 49.71%, and APC was +1.41%, showing an increasing variation tendency. The APCs for CASR and WASR, however, were decreasing, with a percentage of -1.11%, and -0.84%, respectively. The age-specific mortality rates by period showed a decreasing trend for those under age of 44. Moreover, age-birth cohort analysis showed a more rapid lowering mortality in the age groups 35-, 30-, 25-, and 15-, that is, those born after 1950's. Liver cancer remains the leading death cause due to cancers in Qidong, with a continuing higher crude mortality rate. Yet the age-standardized mortality rate has presented a declining posture. The liver cancer mortality in young people in Qidong demonstrates a continuously falling trend. The campaign for the control of liver cancer in Qidong has achieved initial success.

Demography, life history, and the evolution of age-dependent social behaviour.

PubMed

Rodrigues, António M M

2018-06-14

Since the inception of modern social evolution theory, a vast majority of studies have sought to explain cooperation using relatedness-driven hypotheses. Natural populations, however, show a substantial amount of variation in social behaviour that is uncorrelated with relatedness. Age offers a major alternative explanation for variation in behaviour that remains unaccounted for. Most natural populations are structured into age-classes, with ageing being a nearly universal feature of most major taxa, including eukaryotic and prokaryotic organisms. Despite this, the theoretical underpinnings of age-dependent social behaviour remain limited. Here, we investigate how group age-composition, demography, and life history shape trajectories of age-dependent behaviours that are expressed conditionally on an actor and recipient's age. We show that demography introduces novel age-dependent selective pressures acting on social phenotypes. Furthermore, we find that life history traits influence the costs and benefits of cooperation directly, but also indirectly. Life history has a strong impact not only on the genetic structure of the population but also on the distribution of group age-compositions, with both of these processes influencing the expression of age-dependent cooperation. Age of peak reproductive performance, in particular, is of chief importance for the evolution of cooperation, as this will largely determine the age and relatedness of social partners. Moreover, our results suggest that later-life reproductive senescence may occur because of demographic effects alone, which opens new vistas on the evolution of menopause and related phenomena. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Has cancer survival improved for older people as for younger people? New South Wales, 1980-2012.

PubMed

Li, Ming; Morrell, Stephen; Creighton, Nicola; Tervonen, Hanna; You, Hui; Roder, David; Currow, David

2018-05-11

Cancer survival has improved markedly in Australia for all ages but it is still lower in older patients. We hypothesize that the survival gap by age has increased. Our rationale is that treatment constraints in older people and potentially their limited participation in trials may have limited opportunities for survival gain. Post-diagnostic five-year cancer-specific mortality rates were analysed by age group for cancers recorded on the NSW Cancer Registry. Live cases were censored on December 31st, 2012. Hazards ratios (HRs) were obtained from proportional hazards regression for 1990-99 and 2000-12 diagnostic periods, using 1980-89 as the reference, adjusting for socio-demographic factors, degree of cancer spread, and for all cancers combined, for cancer sites. Five-year mortality reduced by diagnostic period for all cancers collectively from 53% in 1980-89 to 33% in 2000-12, with decreases for separate cancer sites. Adjusted HRs (95% confidence intervals) were 0.78 (0.77, 0.80) for 1990-99 and 0.61 (0.58, 0.63) for 2000-12 for all cancers combined. The downward trend in HRs was smaller for the 80+ year age group, leading to significantly higher HRs of 0.83 (0.81, 0.87) and 0.73 (0.70, 0.76) for 1990-99 and 2000-12 respectively. Results were similar using competing risk regression and 5-year rather than 10-year age strata. The reduction in cancer mortality was smaller in older people, as seen in the USA. Research is needed to achieve the best trade-offs between cancer control and harm avoidance in older people. Multidisciplinary teams have an important contribution to make. Copyright © 2018 Elsevier Ltd. All rights reserved.

Childhood growth and breast cancer.

PubMed

De Stavola, B L; dos Santos Silva, I; McCormack, V; Hardy, R J; Kuh, D J; Wadsworth, M E J

2004-04-01

Adult height is known to be positively associated with breast cancer risk. The mechanism underlying this association is complex, since adult height is positively correlated with age at menarche, which in turn is negatively associated with breast cancer risk. The authors used prospective data from a British cohort of 2,547 girls followed from birth in 1946 to the end of 1999 to examine breast cancer risk in relation to childhood growth. As expected, adult height was positively associated with age at menarche and breast cancer. In childhood, cases were taller and leaner, on average, than noncases. Significant predictors of breast cancer risk in models containing all components of growth were height velocity at age 4-7 years (for a one-standard-deviation increase, odds ratio (OR) = 1.54, 95% confidence interval (CI): 1.13, 2.09) and age 11-15 years (OR = 1.29, 95% CI: 0.97, 1.71) and body mass index velocity (weight (kg)/height (m)(2)/year) at age 2-4 years (OR = 0.63, 95% CI: 0.48, 0.83). The effects of these variables were particularly marked in women with early menarche (age <12.5 years). These findings suggest that women who grow faster in childhood and reach an adult height above the average for their menarche category are at particularly increased risk of breast cancer.

Cancer treatment decision-making among young adults with lung and colorectal cancer: a comparison with adults in middle age.

PubMed

Mack, Jennifer W; Cronin, Angel; Fasciano, Karen; Block, Susan D; Keating, Nancy L

2016-09-01

Our aim is to understand experiences with treatment decision-making among young adults with cancer. We studied patients with lung cancer or colorectal cancer in the Cancer Care Outcomes Research and Surveillance Consortium, a prospective cohort study. We identified 148 young adult patients aged 21-40 years who completed baseline interview questions about cancer treatment decision-making; each was propensity score matched to three middle adult patients aged 41-60 years, for a cohort of 592 patients. Patients were asked about decision-making preferences, family involvement in decision-making, and worries about treatment. An ordinal logistic regression model evaluated factors associated with more treatment worries. Young and middle-aged adults reported similar decision-making preferences (p = 0.80) and roles relative to physicians (p = 0.36). Although family involvement was similar in the age groups (p = 0.21), young adults were more likely to have dependent children in the home (60% younger versus 28% middle-aged adults, p < 0.001). Young adults reported more worries about time away from family (p = 0.002), and, in unadjusted analyses, more cancer treatment-related worries (mean number of responses of 'somewhat' or 'very' worried 2.5 for younger versus 2.2 for middle-aged adults, p = 0.02.) However, in adjusted analyses, worries were associated with the presence of dependent children in the home (odds ratio [OR] 1.55, 95% CI = 1.07-2.24, p = 0.02), rather than age. Young adults involve doctors and family members in decisions at rates similar to middle-aged adults but experience more worries about time away from family. Patients with dependent children are especially likely to experience worries. Treatment decision-making strategies should be based on individual preferences and needs rather than age alone. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Removing the Taboo on the Surgical Violation (Cut-Through) of Cancer.

PubMed

Robbins, K Thomas; Bradford, Carol R; Rodrigo, Juan P; Suárez, Carlos; de Bree, Remco; Kowalski, Luiz P; Rinaldo, Alessandra; Silver, Carl E; Lund, Valerie J; Nibu, Ken-Ichi; Ferlito, Alfio

2016-10-01

The surgical dictum of en bloc resection without violating cancer tissue has been challenged by novel treatments in head and neck cancer. An analysis of treatment outcomes involving piecemeal removal of sinonasal, laryngeal, oropharyngeal, and hypopharyngeal cancer shows that it did not compromise tumor control. The rationale for the evolution toward use of this technique is outlined. While complete resection with clear margins remains a key end point in surgical oncology, we believe it is time to acknowledge that this time-honored dictum of avoiding tumor violation is no longer valid in selected situations.

[To understand the words of cancer: Lexonco, dictionary of oncology SOR SAVOIR PATIENT for patients and relatives. Methodological aspects].

PubMed

Delavigne, V; Carretier, J; Brusco, Sylvie; Leichtnam-Dugarin, L; Déchelette, M; Philip, Thierry

2007-04-01

In response to the evolution of the information-seeking behaviour of patients and concerns from health professionals regarding cancer patient information, the French National Federation of Comprehensive Cancer Centres (FNCLCC) introduced, in 1998, an information and education program dedicated to patients and relatives, the SOR SAVOIR PATIENT program. Lexonco project is a dictionary on oncology adapted for patients and relatives and validated by medical experts and cancer patients. This paper describes the methodological aspects which take into account patients and experts' perspectives to produce the defi nitions.

A Study to Determine the Evolution of Advances in Medical Technology Expected in the Next 25 Years and Possible Impacts on Coast Guard Operations and Support Programs. Appendix A. Medicine: The 20-Year Outlook.

DTIC Science & Technology

1980-05-01

increased risk of breast cancer . Diuretics usually are preferred because of fewer side effects and better patient compliance. Availability of sustained...exposing cancer cells to glutaraldehyde. Diagnosis Availa’e tests to detect earl7 cancer range from self-administered ( breast self-examination...gastrointestinal tuors, lung and breast cancer , and kidney 5"OncoloqT: 3lood Test for Ear17 Ca," Medical Wiorld News, Vol. 17, No. 4 (February 23, 1976), pp. 6

Evolution of cancer risk assessment and counseling related to psychological, financial and legal implications.

PubMed

Snyder, Carrie

2016-07-01

Cancer risk assessment, genetic counseling and genetic testing have experienced advances and changes over the past two decades due to improved technology, legal movements to protect those at an increased risk for cancer due to genetics, as well as advances in detection, prevention and treatment. This brief article will provide a summary of these advances over three eras of cancer genetics: pre-discovery of the more common high impact genes, namely BRCA1/BRCA2 and the mismatch repair genes associated with Lynch syndrome; the time during which the genes were being discovered; and current day.

Elderly postmenopausal patients with breast cancer are at increased risk for distant recurrence: a tamoxifen exemestane adjuvant multinational study analysis.

PubMed

van de Water, Willemien; Seynaeve, Caroline; Bastiaannet, Esther; Markopoulos, Christos; Jones, Steve E; Rea, Daniel; Hasenburg, Annette; Putter, Hein; Hille, Elysée T M; Paridaens, Robert; de Craen, Anton J M; Westendorp, Rudi G J; van de Velde, Cornelis J H; Liefers, Gerrit-Jan

2013-01-01

For postmenopausal patients with hormone-sensitive breast cancer, outcome is worse with increasing age at diagnosis. The aim of this study was to assess the incidence of breast cancer recurrence (locoregional and distant), and contralateral breast cancer by age at diagnosis. Patients enrolled in the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial were included. Primary endpoints were locoregional recurrence, distant recurrence, and contralateral breast cancer. Age at diagnosis was categorized as younger than 65 years, 65-74 years, and 75 years or older. Overall, 9,766 patients were included, of which 5,349 were younger than 65 years (reference group), 3,060 were 65-74 years, and 1,357 were 75 years or older. With increasing age, a decreased administration of radiotherapy after breast conserving surgery (94%, 92%, and 88%, respectively) and adjuvant chemotherapy (51%, 23%, and 5%, respectively) was observed. Risk of distant recurrence increased with age at diagnosis; multivariable hazard ratio for patients aged 65-74 years was 1.20 (95% confidence interval [CI]: 1.00-1.44), hazard ratio for patients aged 75 years or older was 1.39 (95% CI: 1.08-1.79). Risks of locoregional recurrence and contralateral breast cancer were not significantly different across age groups. Elderly patients with breast cancer were at increased risk for distant recurrence. Other studies have shown that the risk of distant recurrence is mainly affected by adjuvant systemic therapy. All TEAM patients received adjuvant endocrine treatment; however, chemotherapy was administered less often in elderly patients. These findings are suggestive for consideration of chemotherapy in relatively fit elderly breast cancer patients with hormone-sensitive disease.

Elderly Postmenopausal Patients With Breast Cancer Are at Increased Risk for Distant Recurrence: A Tamoxifen Exemestane Adjuvant Multinational Study Analysis

PubMed Central

van de Water, Willemien; Seynaeve, Caroline; Bastiaannet, Esther; Markopoulos, Christos; Jones, Steve E.; Rea, Daniel; Hasenburg, Annette; Putter, Hein; Hille, Elysée T.M.; Paridaens, Robert; de Craen, Anton J.M.; Westendorp, Rudi G.J.; Liefers, Gerrit-Jan

2013-01-01

Introduction. For postmenopausal patients with hormone-sensitive breast cancer, outcome is worse with increasing age at diagnosis. The aim of this study was to assess the incidence of breast cancer recurrence (locoregional and distant), and contralateral breast cancer by age at diagnosis. Methods. Patients enrolled in the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial were included. Primary endpoints were locoregional recurrence, distant recurrence, and contralateral breast cancer. Age at diagnosis was categorized as younger than 65 years, 65–74 years, and 75 years or older. Results. Overall, 9,766 patients were included, of which 5,349 were younger than 65 years (reference group), 3,060 were 65–74 years, and 1,357 were 75 years or older. With increasing age, a decreased administration of radiotherapy after breast conserving surgery (94%, 92%, and 88%, respectively) and adjuvant chemotherapy (51%, 23%, and 5%, respectively) was observed. Risk of distant recurrence increased with age at diagnosis; multivariable hazard ratio for patients aged 65–74 years was 1.20 (95% confidence interval [CI]: 1.00–1.44), hazard ratio for patients aged 75 years or older was 1.39 (95% CI: 1.08–1.79). Risks of locoregional recurrence and contralateral breast cancer were not significantly different across age groups. Conclusion. Elderly patients with breast cancer were at increased risk for distant recurrence. Other studies have shown that the risk of distant recurrence is mainly affected by adjuvant systemic therapy. All TEAM patients received adjuvant endocrine treatment; however, chemotherapy was administered less often in elderly patients. These findings are suggestive for consideration of chemotherapy in relatively fit elderly breast cancer patients with hormone-sensitive disease. PMID:23263290

ENZYME-CATALYZED MUTATION IN BREAST CANCER

DTIC Science & Technology

2015-10-01

ATCC)  and  hTERT-­‐HMEC  (a  gift   from  the  lab  of  Dr.   Vitaly  Polunovsky)  to  over-­‐express  A3B   by...PMC3978439 Swanton, C., N . McGranahan, G.J. Starrett & R.S. Harris (2015) APOBEC enzymes: mutagenic fuel for cancer evolution and heterogeneity. Cancer... N , Brady JJ, Damian M, Sacco A, Corbel SY, Blau HM. Reprogramming towards pluripotency requires AID-dependent DNA demethylation. Nature. 2010;463