Science.gov

Sample records for east cancer consortium

  1. Strategic planning by the palliative care steering committee of the Middle East Cancer Consortium.

    PubMed

    Moore, Shannon Y; Pirrello, Rosene D; Christianson, Sonya K; Ferris, Frank D

    2011-04-01

    High quality comprehensive palliative care is a critical need for millions of patients and families, but remains only a dream in many parts of the world. The failure to do a strategic planning process is one obstacle to advancing education and pain prevention and relief. The Middle Eastern Cancer Consortium Steering Committee attendees completed an initial strategic planning process and identified "developmental steps" to advance palliative care. Underscoring the multi-disciplinary nature of comprehensive palliative care, discipline-specific planning was done (adult and pediatric cancer and medicine, pharmacy, nursing) in a separate process from country-specific planning. Delineating the layers of intersection and differences between disciplines and countries was very powerful. Finding the common strengths and weaknesses in the status quo creates the potential for a more powerful regional response to the palliative care needs. Implementing and refining these preliminary strategic plans will augment and align the efforts to advance palliative care education and pain management in the Middle East. The dream to prevent and relieve suffering for millions of patients with advanced disease will become reality with a powerful strategic planning process well implemented.

  2. East bay fire chiefs' consortium

    Treesearch

    Michael Bradley

    1995-01-01

    The traditional approach to planning for public fire protection has been based on independent actions by each fire department or district. The county fire chiefs’ associations, while providing interagency communication, were not adequate to deal with the regional nature of the wildland urban interface problem. The formation of the East Bay Fire Chiefs’ Consortium grew...

  3. PanScan, the Pancreatic Cancer Cohort Consortium, and the Pancreatic Cancer Case-Control Consortium

    Cancer.gov

    The Pancreatic Cancer Cohort Consortium consists of more than a dozen prospective epidemiologic cohort studies within the NCI Cohort Consortium, whose leaders work together to investigate the etiology and natural history of pancreatic cancer.

  4. International Cancer Proteogenome Consortium | Office of Cancer Clinical Proteomics Research

    Cancer.gov

    The International Cancer Proteogenome Consortium (ICPC), is a voluntary scientific organization that provides a forum for collaboration among some of the world's leading cancer and proteogenomic research centers.

  5. Pancreatic Cancer Detection Consortium (PCDC) | Division of Cancer Prevention

    Cancer.gov

    The Pancreatic Cancer Detection Consortium (PCDC) develops and tests new molecular and imagi | Develops and tests new molecular and imaging biomarkers to detect early stage PDAC and its precursor lesions.

  6. International Childhood Cancer Cohort Consortium

    Cancer.gov

    An alliance of several large-scale prospective cohort studies of children to pool data and biospecimens from individual cohorts to study various modifiable and genetic factors in relation to cancer risk

  7. The Pittsburgh Breast Cancer Consortium

    DTIC Science & Technology

    2005-08-01

    Randomized. Open-Label. Dose Comparison Study of Recombinant Human Chorionic Gonadotropin for Third Line Treatment of Metastatic Breast Cancer in...by the sponsor. Phase I Dose-Escalation Study of Thrice Weekly Recombinant Human Interleukin-2 in Combination with Trastuzumab in Subjects with

  8. Breast and Prostate Cancer Cohort Consortium (BPC3)

    Cancer.gov

    Breast and Prostate Cancer Cohort Consortium collaborates with three genomic facilities, epidemiologists, population geneticists, and biostatisticians from multiple institutions to study hormone-related gene variants and environmental factors in breast and prostate cancers.

  9. Epidemiology of Endometrial Cancer Consortium (E2C2)

    Cancer.gov

    The Epidemiology of Endometrial Cancer Consortium studies the etiology of this common cancer and build on resources from existing studies by combining data across studies in order to advance the understanding of the etiology of this disease.

  10. The Global Cancer Genomics Consortium: interfacing genomics and cancer medicine.

    PubMed

    2012-08-01

    The Global Cancer Genomics Consortium (GCGC) is an international collaborative platform that amalgamates cancer biologists, cutting-edge genomics, and high-throughput expertise with medical oncologists and surgical oncologists; they address the most important translational questions that are central to cancer research and treatment. The annual GCGC symposium was held at the Advanced Centre for Treatment Research and Education in Cancer, Mumbai, India, from November 9 to 11, 2011. The symposium showcased international next-generation sequencing efforts that explore cancer-specific transcriptomic changes, single-nucleotide polymorphism, and copy number variations in various types of cancers, as well as the structural genomics approach to develop new therapeutic targets and chemical probes. From the spectrum of studies presented at the symposium, it is evident that the translation of emerging cancer genomics knowledge into clinical applications can only be achieved through the integration of multidisciplinary expertise. In summary, the GCGC symposium provided practical knowledge on structural and cancer genomics approaches, as well as an exclusive platform for focused cancer genomics endeavors. ©2012 AACR.

  11. The East Bay Vegetation Management Consortium:\\ta subregional approach to resource management and planning

    Treesearch

    Tony Acosta

    1995-01-01

    Formed in response to the October 20, 1991, Oakland/Berkeley hills firestorm, the East Bay Vegetation Management Consortium (EBVMC) is a voluntary association of public agencies concerned with vegetation management and planning related to fire hazard reduction in the Oakland/ Berkeley hills. To date, a total of nine agencies are participating in the EBVMC, including...

  12. Prostate Cancer Clinical Consortium Clinical Research Site:Targeted Therapies

    DTIC Science & Technology

    2015-10-01

    Cornell Medical College Prostate Cancer Research Program (WCMC-PCRP) is a Clinical Research Site of the Prostate Cancer Clinical Trials Consortium...effectively bring novel agents and new biomarker driven trials directly to patients 17 Table of Contents Page 1. Introduction...purpose and scope of the research. The Weill Cornell Medical College Prostate Cancer Research Program (WCMC-PCRP) is a Clinical Research Site of the

  13. INTERNATIONAL CHILDHOOD CANCER COHORT CONSORTIUM (Journal Article)

    EPA Science Inventory

    Childhood cancers are rare conditions whose etiology is poorly understood. There is evidence that for some, the causal pathway may commence in utero or during peri-conception. One traditional epidemiologic approach to the study of rare diseases is the use of a retrospective cas...

  14. NCI International EBV-Gastric Cancer Consortium

    Cancer.gov

    A collaboration among NCI and extramural investigators, established by DCEG in 2006, that utilizes data and biospecimens from completed and ongoing case series and observational studies of gastric cancer to replicate and extend findings from previous studies hindered by small numbers of EBV-positive cases, and to stimulate multidisciplinary research in this area.

  15. INTERNATIONAL CHILDHOOD CANCER COHORT CONSORTIUM (Journal Article)

    EPA Science Inventory

    Childhood cancers are rare conditions whose etiology is poorly understood. There is evidence that for some, the causal pathway may commence in utero or during peri-conception. One traditional epidemiologic approach to the study of rare diseases is the use of a retrospective cas...

  16. Global cancer consortiums: moving from consensus to practice.

    PubMed

    Ilbawi, André M; Anderson, Benjamin O

    2015-03-01

    The failure to translate cancer knowledge into action contributes to regional, national, and international health inequities. Disparities in cancer care are the most severe in low-resource settings, where delivery obstacles are compounded by health infrastructure deficits and inadequate basic services. Global cancer consortiums (GCCs) have developed to strengthen cancer care expertise, advance knowledge on best practices, and bridge the cancer gap worldwide. Within the complex matrix of public health priorities, consensus is emerging on cost-effective cancer care interventions in low- and medium-resource countries, which include the critical role of surgical services. Distinct from traditional health partnerships that collaborate to provide care at the local level, GCCs collaborate more broadly to establish consensus on best practice models for service delivery. To realize the benefit of programmatic interventions and achieve tangible improvements in patient outcomes, GCCs must construct and share evidence-based implementation strategies to be tested in real world settings. Implementation research should inform consensus formation, program delivery, and outcome monitoring to achieve the goals articulated by GCCs. Fundamental steps to successful implementation are: (1) to adopt an integrated, multisectoral plan with local involvement; (2) to define shared implementation priorities by establishing care pathways that avoid prescriptive but suboptimal health care delivery; (3) to build capacity through education, technology transfer, and surveillance of outcomes; and (4) to promote equity and balanced collaboration. GCCs can bridge the gap between what is known and what is done, translating normative sharing of clinical expertise into tangible improvements in patient care.

  17. Department of Defense prostate cancer clinical trials consortium: a new instrument for prostate cancer clinical research.

    PubMed

    Morris, Michael J; Basch, Ethan M; Wilding, George; Hussain, Maha; Carducci, Michael A; Higano, Celestia; Kantoff, Philip; Oh, William K; Small, Eric J; George, Daniel; Mathew, Paul; Beer, Tomasz M; Slovin, Susan F; Ryan, Charles; Logothetis, Christopher; Scher, Howard I

    2009-01-01

    In 2005, the US Department of Defense, through the US Army Medical Research and Materiel Command, Office of the Congressionally Directed Medical Research Programs, created a funding mechanism to form a clinical trials consortium to conduct phase I and II studies in prostate cancer. This is the first report of the Prostate Cancer Clinical Trials Consortium (PCCTC). The Department of Defense award supports a consortium of 10 prostate cancer research centers. Memorial Sloan-Kettering Cancer Center was awarded the Coordinating Center grant for the consortium and charged with creating an infrastructure to conduct early-phase multicenter clinical trials. Each participating center was required to introduce >or=1 clinical trial per year and maintain accrual of a minimum of 35 patients per year. The PCCTC was launched in 2006 and now encompasses 10 leading prostate cancer research centers. Fifty-one trials have been opened, and 1386 patients have been accrued at member sites. Members share an online clinical trial management system for protocol tracking, electronic data capture, and data storage. A legal framework has been instituted, and standard operating procedures, an administrative structure, editorial support, centralized budgeting, and mechanisms for scientific review are established. The PCCTC fulfills a congressional directive to create a clinical trials instrument dedicated to early-phase prostate cancer studies. The member institutions have built an administrative, informatics, legal, financial, statistical, and scientific infrastructure to support this endeavor. Clinical trials are open and accruing in excess of federally mandated goals.

  18. Southeast Clinical Oncology Research Consortium, Inc. (SCOR) | Division of Cancer Prevention

    Cancer.gov

    DESCRIPTION (provided by applicant): The SCCC-Upstate is a merger of two successful legacy CCOPs known as Southeast Cancer Control Consortium, Inc. (SCCC) and Upstate Carolina (hereafter the Consortium) comprised of 23 components and 63 sub-components, located in a five-state area of the Southeast US (GA, NC, SC, TN, and VA) with a nonclinical Administrative Office (AO) in Winston-Salem, NC. The Consortium eliminates a critical barrier by supplying service to the rural southeastern area. |

  19. Cancer Core Europe: a consortium to address the cancer care-cancer research continuum challenge.

    PubMed

    Eggermont, Alexander M M; Caldas, Carlos; Ringborg, Ulrik; Medema, René; Tabernero, Josep; Wiestler, Otmar

    2014-11-01

    European cancer research for a transformative initiative by creating a consortium of six leading excellent comprehensive cancer centres that will work together to address the cancer care-cancer research continuum. Prerequisites for joint translational and clinical research programs are very demanding. These require the creation of a virtual single 'e-hospital' and a powerful translational platform, inter-compatible clinical molecular profiling laboratories with a robust underlying computational biology pipeline, standardised functional and molecular imaging, commonly agreed Standard Operating Procedures (SOPs) for liquid and tissue biopsy procurement, storage and processing, for molecular diagnostics, 'omics', functional genetics, immune-monitoring and other assessments. Importantly also it requires a culture of data collection and data storage that provides complete longitudinal data sets to allow for: effective data sharing and common database building, and to achieve a level of completeness of data that is required for conducting outcome research, taking into account our current understanding of cancers as communities of evolving clones. Cutting edge basic research and technology development serve as an important driving force for innovative translational and clinical studies. Given the excellent track records of the six participants in these areas, Cancer Core Europe will be able to support the full spectrum of research required to address the cancer research- cancer care continuum. Cancer Core Europe also constitutes a unique environment to train the next generation of talents in innovative translational and clinical oncology.

  20. Consortium for Imaging and Biomarkers (CIB) Created: Eight Grants Awarded | Division of Cancer Prevention

    Cancer.gov

    The NCI Division of Cancer Prevention awarded eight grants to create the Consortium for Imaging and Biomarkers (CIB) on August 3, 2015. | 8 lead investigators combining imaging methods for the visualization of lesions with biomarkers to improve the accuracy of screening, early cancer detection, and the diagnosis of early stage cancers.

  1. History of Comorbidities and Survival of Ovarian Cancer Patients, Results from the Ovarian Cancer Association Consortium.

    PubMed

    Minlikeeva, Albina N; Freudenheim, Jo L; Eng, Kevin H; Cannioto, Rikki A; Friel, Grace; Szender, J Brian; Segal, Brahm; Odunsi, Kunle; Mayor, Paul; Diergaarde, Brenda; Zsiros, Emese; Kelemen, Linda E; Köbel, Martin; Steed, Helen; deFazio, Anna; Jordan, Susan J; Fasching, Peter A; Beckmann, Matthias W; Risch, Harvey A; Rossing, Mary Anne; Doherty, Jennifer A; Chang-Claude, Jenny; Goodman, Marc T; Dörk, Thilo; Edwards, Robert; Modugno, Francesmary; Ness, Roberta B; Matsuo, Keitaro; Mizuno, Mika; Karlan, Beth Y; Goode, Ellen L; Kjær, Susanne K; Høgdall, Estrid; Schildkraut, Joellen M; Terry, Kathryn L; Cramer, Daniel W; Bandera, Elisa V; Paddock, Lisa E; Kiemeney, Lambertus A; Massuger, Leon F A G; Sutphen, Rebecca; Anton-Culver, Hoda; Ziogas, Argyrios; Menon, Usha; Gayther, Simon A; Ramus, Susan J; Gentry-Maharaj, Aleksandra; Pearce, Celeste L; Wu, Anna H; Kupryjanczyk, Jolanta; Jensen, Allan; Webb, Penelope M; Moysich, Kirsten B

    2017-09-01

    Background: Comorbidities can affect survival of ovarian cancer patients by influencing treatment efficacy. However, little evidence exists on the association between individual concurrent comorbidities and prognosis in ovarian cancer patients.Methods: Among patients diagnosed with invasive ovarian carcinoma who participated in 23 studies included in the Ovarian Cancer Association Consortium, we explored associations between histories of endometriosis; asthma; depression; osteoporosis; and autoimmune, gallbladder, kidney, liver, and neurological diseases and overall and progression-free survival. Using Cox proportional hazards regression models adjusted for age at diagnosis, stage of disease, histology, and study site, we estimated pooled HRs and 95% confidence intervals to assess associations between each comorbidity and ovarian cancer outcomes.Results: None of the comorbidities were associated with ovarian cancer outcome in the overall sample nor in strata defined by histologic subtype, weight status, age at diagnosis, or stage of disease (local/regional vs. advanced).Conclusions: Histories of endometriosis; asthma; depression; osteoporosis; and autoimmune, gallbladder, kidney, liver, or neurologic diseases were not associated with ovarian cancer overall or progression-free survival.Impact: These previously diagnosed chronic diseases do not appear to affect ovarian cancer prognosis. Cancer Epidemiol Biomarkers Prev; 26(9); 1470-3. ©2017 AACR. ©2017 American Association for Cancer Research.

  2. Delaware Consortium for Undergraduate Minority Training in Prostate Cancer

    DTIC Science & Technology

    2007-02-01

    in fertilization, and it is best known for its neutral hyaluronidase activity. The human SPAM 1 gene, which is located on chromosome 7q31 , is...AD_________________ Award Number: W81XWH-06- 1 -0244 TITLE: Delaware Consortium for Undergraduate...DOCUMENTATION PAGE Form Approved OMB No. 0704-0188 Public reporting burden for this collection of information is estimated to average 1 hour per

  3. Consortium for Molecular Characterization of Screen-Detected Lesions Created: Eight Grants Awarded | Division of Cancer Prevention

    Cancer.gov

    The NCI has awarded eight grants to create the Consortium for Molecular Characterization of Screen-Detected Lesions. The consortium has seven molecular characterization laboratories (MCLs) and a coordinating center, and is supported by the Division of Cancer Prevention and the Division of Cancer Biology. | 7 laboratories and a coordinating center focused on identifying screening-detected pre-cancers and early cancers, including within the tumor microenvironment.

  4. FGF receptor genes and breast cancer susceptibility: results from the Breast Cancer Association Consortium

    PubMed Central

    Agarwal, D; Pineda, S; Michailidou, K; Herranz, J; Pita, G; Moreno, L T; Alonso, M R; Dennis, J; Wang, Q; Bolla, M K; Meyer, K B; Menéndez-Rodríguez, P; Hardisson, D; Mendiola, M; González-Neira, A; Lindblom, A; Margolin, S; Swerdlow, A; Ashworth, A; Orr, N; Jones, M; Matsuo, K; Ito, H; Iwata, H; Kondo, N; Hartman, M; Hui, M; Lim, W Y; T-C Iau, P; Sawyer, E; Tomlinson, I; Kerin, M; Miller, N; Kang, D; Choi, J-Y; Park, S K; Noh, D-Y; Hopper, J L; Schmidt, D F; Makalic, E; Southey, M C; Teo, S H; Yip, C H; Sivanandan, K; Tay, W-T; Brauch, H; Brüning, T; Hamann, U; Dunning, A M; Shah, M; Andrulis, I L; Knight, J A; Glendon, G; Tchatchou, S; Schmidt, M K; Broeks, A; Rosenberg, E H; van't Veer, L J; Fasching, P A; Renner, S P; Ekici, A B; Beckmann, M W; Shen, C-Y; Hsiung, C-N; Yu, J-C; Hou, M-F; Blot, W; Cai, Q; Wu, A H; Tseng, C-C; Van Den Berg, D; Stram, D O; Cox, A; Brock, I W; Reed, M W R; Muir, K; Lophatananon, A; Stewart-Brown, S; Siriwanarangsan, P; Zheng, W; Deming-Halverson, S; Shrubsole, M J; Long, J; Shu, X-O; Lu, W; Gao, Y-T; Zhang, B; Radice, P; Peterlongo, P; Manoukian, S; Mariette, F; Sangrajrang, S; McKay, J; Couch, F J; Toland, A E; Yannoukakos, D; Fletcher, O; Johnson, N; Silva, I dos Santos; Peto, J; Marme, F; Burwinkel, B; Guénel, P; Truong, T; Sanchez, M; Mulot, C; Bojesen, S E; Nordestgaard, B G; Flyer, H; Brenner, H; Dieffenbach, A K; Arndt, V; Stegmaier, C; Mannermaa, A; Kataja, V; Kosma, V-M; Hartikainen, J M; Lambrechts, D; Yesilyurt, B T; Floris, G; Leunen, K; Chang-Claude, J; Rudolph, A; Seibold, P; Flesch-Janys, D; Wang, X; Olson, J E; Vachon, C; Purrington, K; Giles, G G; Severi, G; Baglietto, L; Haiman, C A; Henderson, B E; Schumacher, F; Le Marchand, L; Simard, J; Dumont, M; Goldberg, M S; Labrèche, F; Winqvist, R; Pylkäs, K; Jukkola-Vuorinen, A; Grip, M; Devilee, P; Tollenaar, R A E M; Seynaeve, C; García-Closas, M; Chanock, S J; Lissowska, J; Figueroa, J D; Czene, K; Eriksson, M; Humphreys, K; Darabi, H; Hooning, M J; Kriege, M; Collée, J M; Tilanus-Linthorst, M; Li, J; Jakubowska, A; Lubinski, J; Jaworska-Bieniek, K; Durda, K; Nevanlinna, H; Muranen, T A; Aittomäki, K; Blomqvist, C; Bogdanova, N; Dörk, T; Hall, P; Chenevix-Trench, G; Easton, D F; Pharoah, P D P; Arias-Perez, J I; Zamora, P; Benítez, J; Milne, R L

    2014-01-01

    Background: Breast cancer is one of the most common malignancies in women. Genome-wide association studies have identified FGFR2 as a breast cancer susceptibility gene. Common variation in other fibroblast growth factor (FGF) receptors might also modify risk. We tested this hypothesis by studying genotyped single-nucleotide polymorphisms (SNPs) and imputed SNPs in FGFR1, FGFR3, FGFR4 and FGFRL1 in the Breast Cancer Association Consortium. Methods: Data were combined from 49 studies, including 53 835 cases and 50 156 controls, of which 89 050 (46 450 cases and 42 600 controls) were of European ancestry, 12 893 (6269 cases and 6624 controls) of Asian and 2048 (1116 cases and 932 controls) of African ancestry. Associations with risk of breast cancer, overall and by disease sub-type, were assessed using unconditional logistic regression. Results: Little evidence of association with breast cancer risk was observed for SNPs in the FGF receptor genes. The strongest evidence in European women was for rs743682 in FGFR3; the estimated per-allele odds ratio was 1.05 (95% confidence interval=1.02–1.09, P=0.0020), which is substantially lower than that observed for SNPs in FGFR2. Conclusion: Our results suggest that common variants in the other FGF receptors are not associated with risk of breast cancer to the degree observed for FGFR2. PMID:24548884

  5. Diabetes and risk of pancreatic cancer: a pooled analysis from the pancreatic cancer cohort consortium.

    PubMed

    Elena, Joanne W; Steplowski, Emily; Yu, Kai; Hartge, Patricia; Tobias, Geoffrey S; Brotzman, Michelle J; Chanock, Stephen J; Stolzenberg-Solomon, Rachael Z; Arslan, Alan A; Bueno-de-Mesquita, H Bas; Helzlsouer, Kathy; Jacobs, Eric J; LaCroix, Andrea; Petersen, Gloria; Zheng, Wei; Albanes, Demetrius; Allen, Naomi E; Amundadottir, Laufey; Bao, Ying; Boeing, Heiner; Boutron-Ruault, Marie-Christine; Buring, Julie E; Gaziano, J Michael; Giovannucci, Edward L; Duell, Eric J; Hallmans, Göran; Howard, Barbara V; Hunter, David J; Hutchinson, Amy; Jacobs, Kevin B; Kooperberg, Charles; Kraft, Peter; Mendelsohn, Julie B; Michaud, Dominique S; Palli, Domenico; Phillips, Lawrence S; Overvad, Kim; Patel, Alpa V; Sansbury, Leah; Shu, Xiao-Ou; Simon, Michael S; Slimani, Nadia; Trichopoulos, Dimitrios; Visvanathan, Kala; Virtamo, Jarmo; Wolpin, Brian M; Zeleniuch-Jacquotte, Anne; Fuchs, Charles S; Hoover, Robert N; Gross, Myron

    2013-01-01

    Diabetes is a suspected risk factor for pancreatic cancer, but questions remain about whether it is a risk factor or a result of the disease. This study prospectively examined the association between diabetes and the risk of pancreatic adenocarcinoma in pooled data from the NCI pancreatic cancer cohort consortium (PanScan). The pooled data included 1,621 pancreatic adenocarcinoma cases and 1,719 matched controls from twelve cohorts using a nested case-control study design. Subjects who were diagnosed with diabetes near the time (<2 years) of pancreatic cancer diagnosis were excluded from all analyses. All analyses were adjusted for age, race, gender, study, alcohol use, smoking, BMI, and family history of pancreatic cancer. Self-reported diabetes was associated with a forty percent increased risk of pancreatic cancer (OR = 1.40, 95 % CI: 1.07, 1.84). The association differed by duration of diabetes; risk was highest for those with a duration of 2-8 years (OR = 1.79, 95 % CI: 1.25, 2.55); there was no association for those with 9+ years of diabetes (OR = 1.02, 95 % CI: 0.68, 1.52). These findings provide support for a relationship between diabetes and pancreatic cancer risk. The absence of association in those with the longest duration of diabetes may reflect hypoinsulinemia and warrants further investigation.

  6. Validating genetic risk associations for ovarian cancer through the international Ovarian Cancer Association Consortium

    PubMed Central

    Pearce, C L; Near, A M; Van Den Berg, D J; Ramus, S J; Gentry-Maharaj, A; Menon, U; Gayther, S A; Anderson, A R; Edlund, C K; Wu, A H; Chen, X; Beesley, J; Webb, P M; Holt, S K; Chen, C; Doherty, J A; Rossing, M A; Whittemore, A S; McGuire, V; DiCioccio, R A; Goodman, M T; Lurie, G; Carney, M E; Wilkens, L R; Ness, R B; Moysich, K B; Edwards, R; Jennison, E; Kjaer, S K; Hogdall, E; Hogdall, C K; Goode, E L; Sellers, T A; Vierkant, R A; Cunningham, J C; Schildkraut, J M; Berchuck, A; Moorman, P G; Iversen, E S; Cramer, D W; Terry, K L; Vitonis, A F; Titus-Ernstoff, L; Song, H; Pharoah, P D P; Spurdle, A B; Anton-Culver, H; Ziogas, A; Brewster, W; Galitovskiy, V; Chenevix-Trench, G

    2009-01-01

    The search for genetic variants associated with ovarian cancer risk has focused on pathways including sex steroid hormones, DNA repair, and cell cycle control. The Ovarian Cancer Association Consortium (OCAC) identified 10 single-nucleotide polymorphisms (SNPs) in genes in these pathways, which had been genotyped by Consortium members and a pooled analysis of these data was conducted. Three of the 10 SNPs showed evidence of an association with ovarian cancer at P⩽0.10 in a log-additive model: rs2740574 in CYP3A4 (P=0.011), rs1805386 in LIG4 (P=0.007), and rs3218536 in XRCC2 (P=0.095). Additional genotyping in other OCAC studies was undertaken and only the variant in CYP3A4, rs2740574, continued to show an association in the replication data among homozygous carriers: ORhomozygous(hom)=2.50 (95% CI 0.54-11.57, P=0.24) with 1406 cases and 2827 controls. Overall, in the combined data the odds ratio was 2.81 among carriers of two copies of the minor allele (95% CI 1.20–6.56, P=0.017, phet across studies=0.42) with 1969 cases and 3491 controls. There was no association among heterozygous carriers. CYP3A4 encodes a key enzyme in oestrogen metabolism and our finding between rs2740574 and risk of ovarian cancer suggests that this pathway may be involved in ovarian carcinogenesis. Additional follow-up is warranted. PMID:19127255

  7. Validating genetic risk associations for ovarian cancer through the international Ovarian Cancer Association Consortium.

    PubMed

    Pearce, C L; Near, A M; Van Den Berg, D J; Ramus, S J; Gentry-Maharaj, A; Menon, U; Gayther, S A; Anderson, A R; Edlund, C K; Wu, A H; Chen, X; Beesley, J; Webb, P M; Holt, S K; Chen, C; Doherty, J A; Rossing, M A; Whittemore, A S; McGuire, V; DiCioccio, R A; Goodman, M T; Lurie, G; Carney, M E; Wilkens, L R; Ness, R B; Moysich, K B; Edwards, R; Jennison, E; Kjaer, S K; Hogdall, E; Hogdall, C K; Goode, E L; Sellers, T A; Vierkant, R A; Cunningham, J M; Cunningham, J C; Schildkraut, J M; Berchuck, A; Moorman, P G; Iversen, E S; Cramer, D W; Terry, K L; Vitonis, A F; Titus-Ernstoff, L; Song, H; Pharoah, P D P; Spurdle, A B; Anton-Culver, H; Ziogas, A; Brewster, W; Galitovskiy, V; Chenevix-Trench, G

    2009-01-27

    The search for genetic variants associated with ovarian cancer risk has focused on pathways including sex steroid hormones, DNA repair, and cell cycle control. The Ovarian Cancer Association Consortium (OCAC) identified 10 single-nucleotide polymorphisms (SNPs) in genes in these pathways, which had been genotyped by Consortium members and a pooled analysis of these data was conducted. Three of the 10 SNPs showed evidence of an association with ovarian cancer at P< or =0.10 in a log-additive model: rs2740574 in CYP3A4 (P=0.011), rs1805386 in LIG4 (P=0.007), and rs3218536 in XRCC2 (P=0.095). Additional genotyping in other OCAC studies was undertaken and only the variant in CYP3A4, rs2740574, continued to show an association in the replication data among homozygous carriers: OR(homozygous(hom))=2.50 (95% CI 0.54-11.57, P=0.24) with 1406 cases and 2827 controls. Overall, in the combined data the odds ratio was 2.81 among carriers of two copies of the minor allele (95% CI 1.20-6.56, P=0.017, p(het) across studies=0.42) with 1969 cases and 3491 controls. There was no association among heterozygous carriers. CYP3A4 encodes a key enzyme in oestrogen metabolism and our finding between rs2740574 and risk of ovarian cancer suggests that this pathway may be involved in ovarian carcinogenesis. Additional follow-up is warranted.

  8. University of Washington Prostate Cancer Clinical Trials Consortium Application

    DTIC Science & Technology

    2011-04-01

    in the radium 223 working group and Dr. Yu is a member of the Imaging Group. Dr. Celestia Higano is the co-chair of the Consortium Publications...09-030 (OGX-011 doc pain), 09-039 (KX2-391), and 09-056 ( radium 223) studies led by other sites. As scientific advisors and/or investigators in...investigators to review toxicity of KX2-391 (09-047) study. Dr. Higano reviewed toxicity data for the Phase I radium 223 trial with the PI (Morris) and joined

  9. Association of body mass index and risk of death from pancreas cancer in Asians: findings from the Asia Cohort Consortium.

    PubMed

    Lin, Yingsong; Fu, Rong; Grant, Eric; Chen, Yu; Lee, Jung Eun; Gupta, Prakash C; Ramadas, Kunnambath; Inoue, Manami; Tsugane, Shoichiro; Gao, Yu-Tang; Tamakoshi, Akiko; Shu, Xiao-Ou; Ozasa, Kotaro; Tsuji, Ichiro; Kakizaki, Masako; Tanaka, Hideo; Chen, Chien-Jen; Yoo, Keun-Young; Ahn, Yoon-Ok; Ahsan, Habibul; Pednekar, Mangesh S; Sauvaget, Catherine; Sasazuki, Shizuka; Yang, Gong; Xiang, Yong-Bing; Ohishi, Waka; Watanabe, Takashi; Nishino, Yoshikazu; Matsuo, Keitaro; You, San-Lin; Park, Sue K; Kim, Dong-Hyun; Parvez, Faruque; Rolland, Betsy; McLerran, Dale; Sinha, Rashmi; Boffetta, Paolo; Zheng, Wei; Thornquist, Mark; Feng, Ziding; Kang, Daehee; Potter, John D

    2013-05-01

    We aimed to examine the association between BMI and the risk of death from pancreas cancer in a pooled analysis of data from the Asia Cohort Consortium. The data for this pooled analysis included 883 529 men and women from 16 cohort studies in Asian countries. Cox proportional-hazards models were used to estimate the hazard ratios and 95% confidence intervals for pancreas cancer mortality in relation to BMI. Seven predefined BMI categories (<18.5, 18.5-19.9, 20.0-22.4, 22.5-24.9, 25.0-27.4, 27.5-29.9, ≥ 30) were used in the analysis, with BMI of 22.5-24.9 serving as the reference group. The multivariable analyses were adjusted for known risk factors, including age, smoking, and a history of diabetes. We found no statistically significant overall association between each BMI category and the risk of death from pancreas cancer in all Asians, and obesity was unrelated to the risk of mortality in both East Asians and South Asians. Age, smoking, and a history of diabetes did not modify the association between BMI and the risk of death from pancreas cancer. In planned subgroup analyses among East Asians, an increased risk of death from pancreas cancer among those with a BMI less than 18.5 was observed for individuals with a history of diabetes; hazard ratio=2.01 (95% confidence interval: 1.01-4.00) (P for interaction=0.07). The data do not support an association between BMI and the risk of death from pancreas cancer in these Asian populations.

  10. Vitamin D and pancreatic cancer: a pooled analysis from the Pancreatic Cancer Case-Control Consortium.

    PubMed

    Waterhouse, M; Risch, H A; Bosetti, C; Anderson, K E; Petersen, G M; Bamlet, W R; Cotterchio, M; Cleary, S P; Ibiebele, T I; La Vecchia, C; Skinner, H G; Strayer, L; Bracci, P M; Maisonneuve, P; Bueno-de-Mesquita, H B; Zaton Ski, W; Lu, L; Yu, H; Janik-Koncewicz, K; Polesel, J; Serraino, D; Neale, R E

    2015-08-01

    The potential role of vitamin D in the aetiology of pancreatic cancer is unclear, with recent studies suggesting both positive and negative associations. We used data from nine case-control studies from the International Pancreatic Cancer Case-Control Consortium (PanC4) to examine associations between pancreatic cancer risk and dietary vitamin D intake. Study-specific odds ratios (ORs) were estimated using multivariable logistic regression, and ORs were then pooled using a random-effects model. From a subset of four studies, we also calculated pooled estimates of association for supplementary and total vitamin D intake. Risk of pancreatic cancer increased with dietary intake of vitamin D [per 100 international units (IU)/day: OR = 1.13, 95% confidence interval (CI) 1.07-1.19, P = 7.4 × 10(-6), P-heterogeneity = 0.52; ≥230 versus <110 IU/day: OR = 1.31, 95% CI 1.10-1.55, P = 2.4 × 10(-3), P-heterogeneity = 0.81], with the association possibly stronger in people with low retinol/vitamin A intake. Increased risk of pancreatic cancer was observed with higher levels of dietary vitamin D intake. Additional studies are required to determine whether or not our finding has a causal basis. © 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.

  11. Vitamin D and pancreatic cancer: a pooled analysis from the Pancreatic Cancer Case–Control Consortium

    PubMed Central

    Waterhouse, M.; Risch, H. A.; Bosetti, C.; Anderson, K. E.; Petersen, G. M.; Bamlet, W. R.; Cotterchio, M.; Cleary, S. P.; Ibiebele, T. I.; La Vecchia, C.; Skinner, H. G.; Strayer, L.; Bracci, P. M.; Maisonneuve, P.; Bueno-de-Mesquita, H. B.; Zaton´ski, W.; Lu, L.; Yu, H.; Janik-Koncewicz, K.; Neale, R. E.

    2015-01-01

    Background The potential role of vitamin D in the aetiology of pancreatic cancer is unclear, with recent studies suggesting both positive and negative associations. Patients and methods We used data from nine case–control studies from the International Pancreatic Cancer Case–Control Consortium (PanC4) to examine associations between pancreatic cancer risk and dietary vitamin D intake. Study-specific odds ratios (ORs) were estimated using multivariable logistic regression, and ORs were then pooled using a random-effects model. From a subset of four studies, we also calculated pooled estimates of association for supplementary and total vitamin D intake. Results Risk of pancreatic cancer increased with dietary intake of vitamin D [per 100 international units (IU)/day: OR = 1.13, 95% confidence interval (CI) 1.07–1.19, P = 7.4 × 10−6, P-heterogeneity = 0.52; ≥230 versus <110 IU/day: OR = 1.31, 95% CI 1.10–1.55, P = 2.4 × 10−3, P-heterogeneity = 0.81], with the association possibly stronger in people with low retinol/vitamin A intake. Conclusion Increased risk of pancreatic cancer was observed with higher levels of dietary vitamin D intake. Additional studies are required to determine whether or not our finding has a causal basis. PMID:25977560

  12. Consortium for Imaging and Biomarkers (CIB) | Division of Cancer Prevention

    Cancer.gov

    Overdiagnosis and false positives present | 8 lead investigators combining imaging methods for the visualization of lesions with biomarkers to improve the accuracy of screening, early cancer detection, and the diagnosis of early stage cancers.

  13. History of Recreational Physical Activity and Survival After Breast Cancer: The California Breast Cancer Survivorship Consortium.

    PubMed

    Lu, Yani; John, Esther M; Sullivan-Halley, Jane; Vigen, Cheryl; Gomez, Scarlett Lin; Kwan, Marilyn L; Caan, Bette J; Lee, Valerie S; Roh, Janise M; Shariff-Marco, Salma; Keegan, Theresa H M; Kurian, Allison W; Monroe, Kristine R; Cheng, Iona; Sposto, Richard; Wu, Anna H; Bernstein, Leslie

    2015-06-15

    Recent epidemiologic evidence suggests that prediagnosis physical activity is associated with survival in women diagnosed with breast cancer. However, few data exist for racial/ethnic groups other than non-Latina whites. To examine the association between prediagnosis recreational physical activity and mortality by race/ethnicity, we pooled data from the California Breast Cancer Survivorship Consortium for 3 population-based case-control studies of breast cancer patients (n=4,608) diagnosed from 1994 to 2002 and followed up through 2010. Cox proportional hazards models provided estimates of the relative hazard ratio for mortality from all causes, breast cancer, and causes other than breast cancer associated with recent recreational physical activity (i.e., in the 10 years before diagnosis). Among 1,347 ascertained deaths, 826 (61%) were from breast cancer. Compared with women with the lowest level of recent recreational physical activity, those with the highest level had a marginally decreased risk of all-cause mortality (hazard ratio=0.88, 95% confidence interval: 0.76, 1.01) and a statistically significant decreased risk of mortality from causes other than breast cancer (hazard ratio=0.63, 95% confidence interval: 0.49, 0.80), and particularly from cardiovascular disease. No association was observed for breast cancer-specific mortality. These risk patterns did not differ by race/ethnicity (non-Latina white, African American, Latina, and Asian American). Our findings suggest that physical activity is beneficial for overall survival regardless of race/ethnicity. © The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  14. Ovarian Cancer Risk Factors by Histologic Subtype: An Analysis From the Ovarian Cancer Cohort Consortium.

    PubMed

    Wentzensen, Nicolas; Poole, Elizabeth M; Trabert, Britton; White, Emily; Arslan, Alan A; Patel, Alpa V; Setiawan, V Wendy; Visvanathan, Kala; Weiderpass, Elisabete; Adami, Hans-Olov; Black, Amanda; Bernstein, Leslie; Brinton, Louise A; Buring, Julie; Butler, Lesley M; Chamosa, Saioa; Clendenen, Tess V; Dossus, Laure; Fortner, Renee; Gapstur, Susan M; Gaudet, Mia M; Gram, Inger T; Hartge, Patricia; Hoffman-Bolton, Judith; Idahl, Annika; Jones, Michael; Kaaks, Rudolf; Kirsh, Victoria; Koh, Woon-Puay; Lacey, James V; Lee, I-Min; Lundin, Eva; Merritt, Melissa A; Onland-Moret, N Charlotte; Peters, Ulrike; Poynter, Jenny N; Rinaldi, Sabina; Robien, Kim; Rohan, Thomas; Sandler, Dale P; Schairer, Catherine; Schouten, Leo J; Sjöholm, Louise K; Sieri, Sabina; Swerdlow, Anthony; Tjonneland, Anna; Travis, Ruth; Trichopoulou, Antonia; van den Brandt, Piet A; Wilkens, Lynne; Wolk, Alicja; Yang, Hannah P; Zeleniuch-Jacquotte, Anne; Tworoger, Shelley S

    2016-08-20

    An understanding of the etiologic heterogeneity of ovarian cancer is important for improving prevention, early detection, and therapeutic approaches. We evaluated 14 hormonal, reproductive, and lifestyle factors by histologic subtype in the Ovarian Cancer Cohort Consortium (OC3). Among 1.3 million women from 21 studies, 5,584 invasive epithelial ovarian cancers were identified (3,378 serous, 606 endometrioid, 331 mucinous, 269 clear cell, 1,000 other). By using competing-risks Cox proportional hazards regression stratified by study and birth year and adjusted for age, parity, and oral contraceptive use, we assessed associations for all invasive cancers by histology. Heterogeneity was evaluated by likelihood ratio test. Most risk factors exhibited significant heterogeneity by histology. Higher parity was most strongly associated with endometrioid (relative risk [RR] per birth, 0.78; 95% CI, 0.74 to 0.83) and clear cell (RR, 0.68; 95% CI, 0.61 to 0.76) carcinomas (P value for heterogeneity [P-het] < .001). Similarly, age at menopause, endometriosis, and tubal ligation were only associated with endometrioid and clear cell tumors (P-het ≤ .01). Family history of breast cancer (P-het = .008) had modest heterogeneity. Smoking was associated with an increased risk of mucinous (RR per 20 pack-years, 1.26; 95% CI, 1.08 to 1.46) but a decreased risk of clear cell (RR, 0.72; 95% CI, 0.55 to 0.94) tumors (P-het = .004). Unsupervised clustering by risk factors separated endometrioid, clear cell, and low-grade serous carcinomas from high-grade serous and mucinous carcinomas. The heterogeneous associations of risk factors with ovarian cancer subtypes emphasize the importance of conducting etiologic studies by ovarian cancer subtypes. Most established risk factors were more strongly associated with nonserous carcinomas, which demonstrate challenges for risk prediction of serous cancers, the most fatal subtype. © 2016 by American Society of Clinical Oncology.

  15. Ovarian Cancer Risk Factors by Histologic Subtype: An Analysis From the Ovarian Cancer Cohort Consortium

    PubMed Central

    Poole, Elizabeth M.; Trabert, Britton; White, Emily; Arslan, Alan A.; Patel, Alpa V.; Setiawan, V. Wendy; Visvanathan, Kala; Weiderpass, Elisabete; Adami, Hans-Olov; Black, Amanda; Bernstein, Leslie; Brinton, Louise A.; Buring, Julie; Butler, Lesley M.; Chamosa, Saioa; Clendenen, Tess V.; Dossus, Laure; Fortner, Renee; Gapstur, Susan M.; Gaudet, Mia M.; Gram, Inger T.; Hartge, Patricia; Hoffman-Bolton, Judith; Idahl, Annika; Jones, Michael; Kaaks, Rudolf; Kirsh, Victoria; Koh, Woon-Puay; Lacey, James V.; Lee, I-Min; Lundin, Eva; Merritt, Melissa A.; Onland-Moret, N. Charlotte; Peters, Ulrike; Poynter, Jenny N.; Rinaldi, Sabina; Robien, Kim; Rohan, Thomas; Sandler, Dale P.; Schairer, Catherine; Schouten, Leo J.; Sjöholm, Louise K.; Sieri, Sabina; Swerdlow, Anthony; Tjonneland, Anna; Travis, Ruth; Trichopoulou, Antonia; van den Brandt, Piet A.; Wilkens, Lynne; Wolk, Alicja; Yang, Hannah P.; Zeleniuch-Jacquotte, Anne; Tworoger, Shelley S.

    2016-01-01

    Purpose An understanding of the etiologic heterogeneity of ovarian cancer is important for improving prevention, early detection, and therapeutic approaches. We evaluated 14 hormonal, reproductive, and lifestyle factors by histologic subtype in the Ovarian Cancer Cohort Consortium (OC3). Patients and Methods Among 1.3 million women from 21 studies, 5,584 invasive epithelial ovarian cancers were identified (3,378 serous, 606 endometrioid, 331 mucinous, 269 clear cell, 1,000 other). By using competing-risks Cox proportional hazards regression stratified by study and birth year and adjusted for age, parity, and oral contraceptive use, we assessed associations for all invasive cancers by histology. Heterogeneity was evaluated by likelihood ratio test. Results Most risk factors exhibited significant heterogeneity by histology. Higher parity was most strongly associated with endometrioid (relative risk [RR] per birth, 0.78; 95% CI, 0.74 to 0.83) and clear cell (RR, 0.68; 95% CI, 0.61 to 0.76) carcinomas (P value for heterogeneity [P-het] < .001). Similarly, age at menopause, endometriosis, and tubal ligation were only associated with endometrioid and clear cell tumors (P-het ≤ .01). Family history of breast cancer (P-het = .008) had modest heterogeneity. Smoking was associated with an increased risk of mucinous (RR per 20 pack-years, 1.26; 95% CI, 1.08 to 1.46) but a decreased risk of clear cell (RR, 0.72; 95% CI, 0.55 to 0.94) tumors (P-het = .004). Unsupervised clustering by risk factors separated endometrioid, clear cell, and low-grade serous carcinomas from high-grade serous and mucinous carcinomas. Conclusion The heterogeneous associations of risk factors with ovarian cancer subtypes emphasize the importance of conducting etiologic studies by ovarian cancer subtypes. Most established risk factors were more strongly associated with nonserous carcinomas, which demonstrate challenges for risk prediction of serous cancers, the most fatal subtype. PMID:27325851

  16. Breast cancer risk and 6q22.33: combined results from Breast Cancer Association Consortium and Consortium of Investigators on Modifiers of BRCA1/2.

    PubMed

    Kirchhoff, Tomas; Gaudet, Mia M; Antoniou, Antonis C; McGuffog, Lesley; Humphreys, Manjeet K; Dunning, Alison M; Bojesen, Stig E; Nordestgaard, Børge G; Flyger, Henrik; Kang, Daehee; Yoo, Keun-Young; Noh, Dong-Young; Ahn, Sei-Hyun; Dork, Thilo; Schürmann, Peter; Karstens, Johann H; Hillemanns, Peter; Couch, Fergus J; Olson, Janet; Vachon, Celine; Wang, Xianshu; Cox, Angela; Brock, Ian; Elliott, Graeme; Reed, Malcolm W R; Burwinkel, Barbara; Meindl, Alfons; Brauch, Hiltrud; Hamann, Ute; Ko, Yon-Dschun; Broeks, Annegien; Schmidt, Marjanka K; Van 't Veer, Laura J; Braaf, Linde M; Johnson, Nichola; Fletcher, Olivia; Gibson, Lorna; Peto, Julian; Turnbull, Clare; Seal, Sheila; Renwick, Anthony; Rahman, Nazneen; Wu, Pei-Ei; Yu, Jyh-Cherng; Hsiung, Chia-Ni; Shen, Chen-Yang; Southey, Melissa C; Hopper, John L; Hammet, Fleur; Van Dorpe, Thijs; Dieudonne, Anne-Sophie; Hatse, Sigrid; Lambrechts, Diether; Andrulis, Irene L; Bogdanova, Natalia; Antonenkova, Natalia; Rogov, Juri I; Prokofieva, Daria; Bermisheva, Marina; Khusnutdinova, Elza; van Asperen, Christi J; Tollenaar, Robert A E M; Hooning, Maartje J; Devilee, Peter; Margolin, Sara; Lindblom, Annika; Milne, Roger L; Arias, José Ignacio; Zamora, M Pilar; Benítez, Javier; Severi, Gianluca; Baglietto, Laura; Giles, Graham G; Spurdle, Amanda B; Beesley, Jonathan; Chen, Xiaoqing; Holland, Helene; Healey, Sue; Wang-Gohrke, Shan; Chang-Claude, Jenny; Mannermaa, Arto; Kosma, Veli-Matti; Kauppinen, Jaana; Kataja, Vesa; Agnarsson, Bjarni A; Caligo, Maria A; Godwin, Andrew K; Nevanlinna, Heli; Heikkinen, Tuomas; Fredericksen, Zachary; Lindor, Noralane; Nathanson, Katherine L; Domchek, Susan M; Loman, Niklas; Karlsson, Per; Stenmark Askmalm, Marie; Melin, Beatrice; von Wachenfeldt, Anna; Hogervorst, Frans B L; Verheus, Martijn; Rookus, Matti A; Seynaeve, Caroline; Oldenburg, Rogier A; Ligtenberg, Marjolijn J; Ausems, Margreet G E M; Aalfs, Cora M; Gille, Hans J P; Wijnen, Juul T; Gómez García, Encarna B; Peock, Susan; Cook, Margaret; Oliver, Clare T; Frost, Debra; Luccarini, Craig; Pichert, Gabriella; Davidson, Rosemarie; Chu, Carol; Eccles, Diana; Ong, Kai-Ren; Cook, Jackie; Douglas, Fiona; Hodgson, Shirley; Evans, D Gareth; Eeles, Rosalind; Gold, Bert; Pharoah, Paul D P; Offit, Kenneth; Chenevix-Trench, Georgia; Easton, Douglas F

    2012-01-01

    Recently, a locus on chromosome 6q22.33 (rs2180341) was reported to be associated with increased breast cancer risk in the Ashkenazi Jewish (AJ) population, and this association was also observed in populations of non-AJ European ancestry. In the present study, we performed a large replication analysis of rs2180341 using data from 31,428 invasive breast cancer cases and 34,700 controls collected from 25 studies in the Breast Cancer Association Consortium (BCAC). In addition, we evaluated whether rs2180341 modifies breast cancer risk in 3,361 BRCA1 and 2,020 BRCA2 carriers from 11 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Based on the BCAC data from women of European ancestry, we found evidence for a weak association with breast cancer risk for rs2180341 (per-allele odds ratio (OR) = 1.03, 95% CI 1.00-1.06, p = 0.023). There was evidence for heterogeneity in the ORs among studies (I(2) = 49.3%; p = <0.004). In CIMBA, we observed an inverse association with the minor allele of rs2180341 and breast cancer risk in BRCA1 mutation carriers (per-allele OR = 0.89, 95%CI 0.80-1.00, p = 0.048), indicating a potential protective effect of this allele. These data suggest that that 6q22.33 confers a weak effect on breast cancer risk.

  17. Breast Cancer Risk and 6q22.33: Combined Results from Breast Cancer Association Consortium and Consortium of Investigators on Modifiers of BRCA1/2

    PubMed Central

    Antoniou, Antonis C.; McGuffog, Lesley; Humphreys, Manjeet K.; Dunning, Alison M.; Bojesen, Stig E.; Nordestgaard, Børge G.; Flyger, Henrik; Kang, Daehee; Yoo, Keun-Young; Noh, Dong-Young; Ahn, Sei-Hyun; Dork, Thilo; Schürmann, Peter; Karstens, Johann H.; Hillemanns, Peter; Couch, Fergus J.; Olson, Janet; Vachon, Celine; Wang, Xianshu; Cox, Angela; Brock, Ian; Elliott, Graeme; Reed, Malcolm W.R.; Burwinkel, Barbara; Meindl, Alfons; Brauch, Hiltrud; Hamann, Ute; Ko, Yon-Dschun; Broeks, Annegien; Schmidt, Marjanka K.; Van ‘t Veer, Laura J.; Braaf, Linde M.; Johnson, Nichola; Fletcher, Olivia; Gibson, Lorna; Peto, Julian; Turnbull, Clare; Seal, Sheila; Renwick, Anthony; Rahman, Nazneen; Wu, Pei-Ei; Yu, Jyh-Cherng; Hsiung, Chia-Ni; Shen, Chen-Yang; Southey, Melissa C.; Hopper, John L.; Hammet, Fleur; Van Dorpe, Thijs; Dieudonne, Anne-Sophie; Hatse, Sigrid; Lambrechts, Diether; Andrulis, Irene L.; Bogdanova, Natalia; Antonenkova, Natalia; Rogov, Juri I.; Prokofieva, Daria; Bermisheva, Marina; Khusnutdinova, Elza; van Asperen, Christi J.; Tollenaar, Robert A.E.M.; Hooning, Maartje J.; Devilee, Peter; Margolin, Sara; Lindblom, Annika; Milne, Roger L.; Arias, José Ignacio; Zamora, M. Pilar; Benítez, Javier; Severi, Gianluca; Baglietto, Laura; Giles, Graham G.; kConFab; Group, AOCS Study; Spurdle, Amanda B.; Beesley, Jonathan; Chen, Xiaoqing; Holland, Helene; Healey, Sue; Wang-Gohrke, Shan; Chang-Claude, Jenny; Mannermaa, Arto; Kosma, Veli-Matti; Kauppinen, Jaana; Kataja, Vesa; Agnarsson, Bjarni A.; Caligo, Maria A.; Godwin, Andrew K.; Nevanlinna, Heli; Heikkinen, Tuomas; Fredericksen, Zachary; Lindor, Noralane; Nathanson, Katherine L.; Domchek, Susan M.; SWE-BRCA; Loman, Niklas; Karlsson, Per; Askmalm, Marie Stenmark; Melin, Beatrice; von Wachenfeldt, Anna; HEBON; Hogervorst, Frans B. L.; Verheus, Martijn; Rookus, Matti A.; Seynaeve, Caroline; Oldenburg, Rogier A.; Ligtenberg, Marjolijn J.; Ausems, Margreet G.E.M.; Aalfs, Cora M.; Gille, Hans J.P.; Wijnen, Juul T.; Gómez García, Encarna B.; EMBRACE; Peock, Susan; Cook, Margaret; Oliver, Clare T.; Frost, Debra; Luccarini, Craig; Pichert, Gabriella; Davidson, Rosemarie; Chu, Carol; Eccles, Diana; Ong, Kai-Ren; Cook, Jackie; Douglas, Fiona; Hodgson, Shirley; Evans, D. Gareth; Eeles, Rosalind; Gold, Bert; Pharoah, Paul D.P.; Offit, Kenneth; Chenevix-Trench, Georgia; Easton, Douglas F.

    2012-01-01

    Recently, a locus on chromosome 6q22.33 (rs2180341) was reported to be associated with increased breast cancer risk in the Ashkenazi Jewish (AJ) population, and this association was also observed in populations of non-AJ European ancestry. In the present study, we performed a large replication analysis of rs2180341 using data from 31,428 invasive breast cancer cases and 34,700 controls collected from 25 studies in the Breast Cancer Association Consortium (BCAC). In addition, we evaluated whether rs2180341 modifies breast cancer risk in 3,361 BRCA1 and 2,020 BRCA2 carriers from 11 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Based on the BCAC data from women of European ancestry, we found evidence for a weak association with breast cancer risk for rs2180341 (per-allele odds ratio (OR) = 1.03, 95% CI 1.00–1.06, p = 0.023). There was evidence for heterogeneity in the ORs among studies (I2 = 49.3%; p = <0.004). In CIMBA, we observed an inverse association with the minor allele of rs2180341 and breast cancer risk in BRCA1 mutation carriers (per-allele OR = 0.89, 95%CI 0.80–1.00, p = 0.048), indicating a potential protective effect of this allele. These data suggest that that 6q22.33 confers a weak effect on breast cancer risk. PMID:22768030

  18. Factors associated with oxidative stress and cancer risk in the Breast and Prostate Cancer Cohort Consortium.

    PubMed

    Blein, S; Berndt, S; Joshi, A D; Campa, D; Ziegler, R G; Riboli, E; Cox, D G

    2014-03-01

    Both endogenous factors (genomic variations) and exogenous factors (environmental exposures, lifestyle) impact the balance of reactive oxygen species (ROS). Variants of the ND3 (rs2853826; G10398A) gene of the mitochondrial genome, manganese superoxide dismutase (MnSOD; rs4880 Val16Ala) and glutathione peroxidase (GPX-1; rs1050450 Pro198Leu), are purported to have functional effects on regulation of ROS balance. In this study, we examined associations of breast and prostate cancer risks and survival with these variants, and interactions between rs4880-rs1050450, and alcohol consumption-rs2853826. Nested case-control studies were conducted in the Breast and Prostate Cancer Cohort Consortium (BPC3), consisting of nine cohorts. The analyses included over 10726 post-menopausal breast and 7532 prostate cancer cases with matched controls. Logistic regression models were used to evaluate associations with risk, and proportional hazard models were used for survival outcomes. We did not observe significant interactions between polymorphisms in MnSOD and GPX-1, or between mitochondrial polymorphisms and alcohol intake and risk of either breast (p-interaction of 0.34 and 0.98, respectively) or prostate cancer (p-interaction of 0.49 and 0.50, respectively). We observed a weak inverse association between prostate cancer risk and GPX-1 Leu198Leu carriers (OR 0.87, 95% CI 0.79-0.97, p = 0.01). Overall survival among women with breast cancer was inversely associated with G10398 carriers who consumed alcohol (HR 0.66 95% CI 0.49-0.88). Given the high power in our study, it is unlikely that interactions tested have more than moderate effects on breast or prostate cancer risk. Observed associations need both further epidemiological and biological confirmation.

  19. Obesity and risk of ovarian cancer subtypes: evidence from the Ovarian Cancer Association Consortium.

    PubMed

    Olsen, Catherine M; Nagle, Christina M; Whiteman, David C; Ness, Roberta; Pearce, Celeste Leigh; Pike, Malcolm C; Rossing, Mary Anne; Terry, Kathryn L; Wu, Anna H; Risch, Harvey A; Yu, Herbert; Doherty, Jennifer A; Chang-Claude, Jenny; Hein, Rebecca; Nickels, Stefan; Wang-Gohrke, Shan; Goodman, Marc T; Carney, Michael E; Matsuno, Rayna K; Lurie, Galina; Moysich, Kirsten; Kjaer, Susanne K; Jensen, Allan; Hogdall, Estrid; Goode, Ellen L; Fridley, Brooke L; Vierkant, Robert A; Larson, Melissa C; Schildkraut, Joellen; Hoyo, Cathrine; Moorman, Patricia; Weber, Rachel P; Cramer, Daniel W; Vitonis, Allison F; Bandera, Elisa V; Olson, Sara H; Rodriguez-Rodriguez, Lorna; King, Melony; Brinton, Louise A; Yang, Hannah; Garcia-Closas, Montserrat; Lissowska, Jolanta; Anton-Culver, Hoda; Ziogas, Argyrios; Gayther, Simon A; Ramus, Susan J; Menon, Usha; Gentry-Maharaj, Aleksandra; Webb, Penelope M

    2013-04-01

    Whilst previous studies have reported that higher BMI increases a woman's risk of developing ovarian cancer, associations for the different histological subtypes have not been well defined. As the prevalence of obesity has increased dramatically, and classification of ovarian histology has improved in the last decade, we sought to examine the association in a pooled analysis of recent studies participating in the Ovarian Cancer Association Consortium. We evaluated the association between BMI (recent, maximum and in young adulthood) and ovarian cancer risk using original data from 15 case-control studies (13 548 cases and 17 913 controls). We combined study-specific adjusted odds ratios (ORs) using a random-effects model. We further examined the associations by histological subtype, menopausal status and post-menopausal hormone use. High BMI (all time-points) was associated with increased risk. This was most pronounced for borderline serous (recent BMI: pooled OR=1.24 per 5 kg/m(2); 95% CI 1.18-1.30), invasive endometrioid (1.17; 1.11-1.23) and invasive mucinous (1.19; 1.06-1.32) tumours. There was no association with serous invasive cancer overall (0.98; 0.94-1.02), but increased risks for low-grade serous invasive tumours (1.13, 1.03-1.25) and in pre-menopausal women (1.11; 1.04-1.18). Among post-menopausal women, the associations did not differ between hormone replacement therapy users and non-users. Whilst obesity appears to increase risk of the less common histological subtypes of ovarian cancer, it does not increase risk of high-grade invasive serous cancers, and reducing BMI is therefore unlikely to prevent the majority of ovarian cancer deaths. Other modifiable factors must be identified to control this disease.

  20. Cannabis smoking and lung cancer risk: Pooled analysis in the International Lung Cancer Consortium.

    PubMed

    Zhang, Li Rita; Morgenstern, Hal; Greenland, Sander; Chang, Shen-Chih; Lazarus, Philip; Teare, M Dawn; Woll, Penella J; Orlow, Irene; Cox, Brian; Brhane, Yonathan; Liu, Geoffrey; Hung, Rayjean J

    2015-02-15

    To investigate the association between cannabis smoking and lung cancer risk, data on 2,159 lung cancer cases and 2,985 controls were pooled from 6 case-control studies in the US, Canada, UK, and New Zealand within the International Lung Cancer Consortium. Study-specific associations between cannabis smoking and lung cancer were estimated using unconditional logistic regression adjusting for sociodemographic factors, tobacco smoking status and pack-years; odds-ratio estimates were pooled using random effects models. Subgroup analyses were done for sex, histology and tobacco smoking status. The shapes of dose-response associations were examined using restricted cubic spline regression. The overall pooled OR for habitual versus nonhabitual or never users was 0.96 (95% CI: 0.66-1.38). Compared to nonhabitual or never users, the summary OR was 0.88 (95%CI: 0.63-1.24) for individuals who smoked 1 or more joint-equivalents of cannabis per day and 0.94 (95%CI: 0.67-1.32) for those consumed at least 10 joint-years. For adenocarcinoma cases the ORs were 1.73 (95%CI: 0.75-4.00) and 1.74 (95%CI: 0.85-3.55), respectively. However, no association was found for the squamous cell carcinoma based on small numbers. Weak associations between cannabis smoking and lung cancer were observed in never tobacco smokers. Spline modeling indicated a weak positive monotonic association between cumulative cannabis use and lung cancer, but precision was low at high exposure levels. Results from our pooled analyses provide little evidence for an increased risk of lung cancer among habitual or long-term cannabis smokers, although the possibility of potential adverse effect for heavy consumption cannot be excluded. © 2014 UICC.

  1. New Funding Opportunity Announcements (FOAs): Reissuance of Clinical Proteomic Tumor Analysis Consortium (CPTAC) | Office of Cancer Clinical Proteomics Research

    Cancer.gov

    The National Cancer Institute is soliciting applications for the reissuance of its Clinical Proteomic Tumor Analysis Consortium (CPTAC) program.   CPTAC will support broad efforts focused on several cancer types to explore further the complexities of cancer proteomes and their connections to abnormalities in cancer genomes.

  2. Connecting Genomic Alterations to Cancer Biology with Proteomics: The NCI Clinical Proteomic Tumor Analysis Consortium

    SciTech Connect

    Ellis, Matthew; Gillette, Michael; Carr, Steven A.; Paulovich, Amanda G.; Smith, Richard D.; Rodland, Karin D.; Townsend, Reid; Kinsinger, Christopher; Mesri, Mehdi; Rodriguez, Henry; Liebler, Daniel

    2013-10-03

    The National Cancer Institute (NCI) Clinical Proteomic Tumor Analysis Consortium is applying the latest generation of proteomic technologies to genomically annotated tumors from The Cancer Genome Atlas (TCGA) program, a joint initiative of the NCI and the National Human Genome Research Institute. By providing a fully integrated accounting of DNA, RNA, and protein abnormalities in individual tumors, these datasets will illuminate the complex relationship between genomic abnormalities and cancer phenotypes, thus producing biologic insights as well as a wave of novel candidate biomarkers and therapeutic targets amenable to verifi cation using targeted mass spectrometry methods.

  3. The African cancer advocacy consortium: shaping the path for advocacy in Africa

    PubMed Central

    2013-01-01

    Although there is significant evidence of a cancer epidemic in Africa, there is limited awareness about cancer in most African countries. By partnering with international organizations and institutions such as the University of Florida and the Prostate Net, the African Organisation for Research and Training in Cancer (AORTIC) is committed to improving cancer advocacy in Africa. This paper presents some of the recent efforts on cancer advocacy in Africa, including the results of a SWOT analysis conducted for the cancer advocacy workshop and the guidelines developed by cancer advocates on best practices for cancer advocacy in Africa. One of the outcomes of these efforts is the African Cancer Advocates Consortium (ACAC) founded by cancer advocates in Africa to, “Make Cancer a Top Priority in Africa”. While we have started the work to strengthen cancer advocacy in Africa, we still have a long way to go. Our goal of making cancer a priority in Africa can mainly be achieved by: (1) increasing the manpower for cancer advocacy through education and training; and (2) strengthening the network of cancer advocates across the continent. PMID:23902674

  4. Birthweight and Childhood Cancer: Preliminary Findings from the International Childhood Cancer Cohort Consortium (I4C)

    PubMed Central

    Paltiel, Ora; Tikellis, Gabriella; Linet, Martha; Golding, Jean; Lemeshow, Stanley; Phillips, Gary; Lamb, Karen; Stoltenberg, Camilla; Håberg, Siri E; Strøm, Marin; Granstrøm, Charlotta; Northstone, Kate; Klebanoff, Mark; Ponsonby, Anne-Louise; Milne, Elizabeth; Pedersen, Marie; Kogevinas, Manolis; Ha, Eunhee; Dwyer, Terence

    2015-01-01

    Background Evidence relating childhood cancer to high birthweight is derived primarily from registry and case–control studies. We aimed to investigate this association, exploring the potential modifying roles of age at diagnosis and maternal anthropometrics, using prospectively collected data from the International Childhood Cancer Cohort Consortium. Methods We pooled data on infant and parental characteristics and cancer incidence from six geographically and temporally diverse member cohorts [the Avon Longitudinal Study of Parents and Children (UK), the Collaborative Perinatal Project (USA), the Danish National Birth Cohort (Denmark), the Jerusalem Perinatal Study (Israel), the Norwegian Mother and Child Cohort Study (Norway), and the Tasmanian Infant Health Survey (Australia)]. Birthweight metrics included a continuous measure, deciles, and categories (≥4.0 vs. <4.0 kilogram). Childhood cancer (377 cases diagnosed prior to age 15 years) risk was analysed by type (all sites, leukaemia, acute lymphoblastic leukaemia, and non-leukaemia) and age at diagnosis. We estimated hazard ratios (HR) and 95% confidence intervals (CI) from Cox proportional hazards models stratified by cohort. Results A linear relationship was noted for each kilogram increment in birthweight adjusted for gender and gestational age for all cancers [HR = 1.26; 95% CI 1.02, 1.54]. Similar trends were observed for leukaemia. There were no significant interactions with maternal pre-pregnancy overweight or pregnancy weight gain. Birthweight ≥4.0 kg was associated with non-leukaemia cancer among children diagnosed at age ≥3 years [HR = 1.62; 95% CI 1.06, 2.46], but not at younger ages [HR = 0.7; 95% CI 0.45, 1.24, P for difference = 0.02]. Conclusion Childhood cancer incidence rises with increasing birthweight. In older children, cancers other than leukaemia are particularly related to high birthweight. Maternal adiposity, currently widespread, was not demonstrated to

  5. Birthweight and Childhood Cancer: Preliminary Findings from the International Childhood Cancer Cohort Consortium (I4C).

    PubMed

    Paltiel, Ora; Tikellis, Gabriella; Linet, Martha; Golding, Jean; Lemeshow, Stanley; Phillips, Gary; Lamb, Karen; Stoltenberg, Camilla; Håberg, Siri E; Strøm, Marin; Granstrøm, Charlotta; Northstone, Kate; Klebanoff, Mark; Ponsonby, Anne-Louise; Milne, Elizabeth; Pedersen, Marie; Kogevinas, Manolis; Ha, Eunhee; Dwyer, Terence

    2015-07-01

    Evidence relating childhood cancer to high birthweight is derived primarily from registry and case-control studies. We aimed to investigate this association, exploring the potential modifying roles of age at diagnosis and maternal anthropometrics, using prospectively collected data from the International Childhood Cancer Cohort Consortium. We pooled data on infant and parental characteristics and cancer incidence from six geographically and temporally diverse member cohorts [the Avon Longitudinal Study of Parents and Children (UK), the Collaborative Perinatal Project (USA), the Danish National Birth Cohort (Denmark), the Jerusalem Perinatal Study (Israel), the Norwegian Mother and Child Cohort Study (Norway), and the Tasmanian Infant Health Survey (Australia)]. Birthweight metrics included a continuous measure, deciles, and categories (≥ 4.0 vs. < 4.0 kilogram). Childhood cancer (377 cases diagnosed prior to age 15 years) risk was analysed by type (all sites, leukaemia, acute lymphoblastic leukaemia, and non-leukaemia) and age at diagnosis. We estimated hazard ratios (HR) and 95% confidence intervals (CI) from Cox proportional hazards models stratified by cohort. A linear relationship was noted for each kilogram increment in birthweight adjusted for gender and gestational age for all cancers [HR = 1.26; 95% CI 1.02, 1.54]. Similar trends were observed for leukaemia. There were no significant interactions with maternal pre-pregnancy overweight or pregnancy weight gain. Birthweight ≥ 4.0 kg was associated with non-leukaemia cancer among children diagnosed at age ≥ 3 years [HR = 1.62; 95% CI 1.06, 2.46], but not at younger ages [HR = 0.7; 95% CI 0.45, 1.24, P for difference = 0.02]. Childhood cancer incidence rises with increasing birthweight. In older children, cancers other than leukaemia are particularly related to high birthweight. Maternal adiposity, currently widespread, was not demonstrated to substantially modify these associations. Common factors

  6. International Lung Cancer Consortium: Coordinated association study of 10 potential lung cancer susceptibility variants

    PubMed Central

    Truong, Therese; Sauter, Wiebke; McKay, James D.; Hosgood, H.Dean; Gallagher, Carla; Amos, Christopher I.; Spitz, Margaret; Muscat, Joshua; Lazarus, Philip; Illig, Thomas; Wichmann, H.Erich; Bickeböller, Heike; Risch, Angela; Dienemann, Hendrik; Zhang, Zuo-Feng; Naeim, Behnaz Pezeshki; Yang, Ping; Zienolddiny, Shanbeh; Haugen, Aage; Le Marchand, Loïc; Hong, Yun-Chul; Kim, Jin Hee; Duell, Eric J.; Andrew, Angeline S.; Kiyohara, Chikako; Shen, Hongbing; Matsuo, Keitaro; Suzuki, Takeshi; Seow, Adeline; Ng, Daniel P.K.; Lan, Qing; Zaridze, David; Szeszenia-Dabrowska, Neonilia; Lissowska, Jolanta; Rudnai, Peter; Fabianova, Eleonora; Constantinescu, Vali; Bencko, Vladimir; Foretova, Lenka; Janout, Vladimir; Caporaso, Neil E.; Albanes, Demetrius; Thun, Michael; Landi, Maria Teresa; Trubicka, Joanna; Lener, Marcin; Lubiński, Jan; Wang, Ying; Chabrier, Amélie; Boffetta, Paolo; Brennan, Paul; Hung, Rayjean J.

    2010-01-01

    Background. Analysis of candidate genes in individual studies has had only limited success in identifying particular gene variants that are conclusively associated with lung cancer risk. In the International Lung Cancer Consortium (ILCCO), we conducted a coordinated genotyping study of 10 common variants selected because of their prior evidence of an association with lung cancer. These variants belonged to candidate genes from different cancer-related pathways including inflammation (IL1B), folate metabolism (MTHFR), regulatory function (AKAP9 and CAMKK1), cell adhesion (SEZL6) and apoptosis (FAS, FASL, TP53, TP53BP1 and BAT3). Methods. Genotype data from 15 ILCCO case–control studies were available for a total of 8431 lung cancer cases and 11 072 controls of European descent and Asian ethnic groups. Unconditional logistic regression was used to model the association between each variant and lung cancer risk. Results. Only the association between a non-synonymous variant of TP53BP1 (rs560191) and lung cancer risk was significant (OR = 0.91, P = 0.002). This association was more striking for squamous cell carcinoma (OR = 0.86, P = 6 × 10−4). No heterogeneity by center, ethnicity, smoking status, age group or sex was observed. In order to confirm this association, we included results for this variant from a set of independent studies (9966 cases/11 722 controls) and we reported similar results. When combining all these studies together, we reported an overall OR = 0.93 (0.89–0.97) (P = 0.001). This association was significant only for squamous cell carcinoma [OR = 0.89 (0.85–0.95), P = 1 × 10−4]. Conclusion. This study suggests that rs560191 is associated to lung cancer risk and further highlights the value of consortia in replicating or refuting published genetic associations. PMID:20106900

  7. Delaware Consortium for Undergraduate Minority Training in Prostate Cancer

    DTIC Science & Technology

    2008-02-01

    Sikes & Michael Bonder) ♦ The Roles of RhoG, Rac1, and Rac3 GTPases in PC-3 Human Prostate Cancer Tumor Cell Diapedesis . Mashariki Jenkins-Kabaila...GTPases in PC-3 Human Prostate Cancer Tumor Cell Diapedesis Mashariki Jenkins-Kabaila, Moumita Chatterjee, Kenneth Van Golen, Ph D. Lincoln University...cells. A tumor cell diapedesis assay will be done across a monolayer of bone marrow endothelial cells after siRNA treatment of Rac1, Rac3, and RhoG

  8. Chronic Recreational Physical Inactivity and Epithelial Ovarian Cancer Risk: Evidence from the Ovarian Cancer Association Consortium

    PubMed Central

    Cannioto, Rikki; LaMonte, Michael J.; Risch, Harvey A.; Hong, Chi-Chen; Sucheston-Campbell, Lara E.; Eng, Kevin H.; Szender, J. Brian; Chang-Claude, Jenny; Schmalfeldt, Barbara; Klapdor, Ruediger; Gower, Emily; Minlikeeva, Albina N.; Zirpoli, Gary; Bandera, Elisa V.; Berchuck, Andrew; Cramer, Daniel; Doherty, Jennifer A.; Edwards, Robert P.; Fridley, Brooke L.; Goode, Ellen L.; Goodman, Marc T.; Hogdall, Estrid; Hosono, Satoyo; Jensen, Allan; Jordan, Susan; Kjaer, Susanne K.; Matsuo, Keitaro; Ness, Roberta B.; Olsen, Catherine M.; Olson, Sara H.; Pearce, Celeste Leigh; Pike, Malcolm C.; Rossing, Mary Anne; Szamreta, Elizabeth A.; Thompson, Pamela J.; Tseng, Chiu-Chen; Vierkant, Robert A.; Webb, Penelope M.; Wentzensen, Nicolas; Wicklund, Kristine G.; Winham, Stacey J.; Wu, Anna H.; Modugno, Francesmary; Schildkraut, Joellen M.; Terry, Kathryn L.; Kelemen, Linda E.; Moysich, Kirsten B.

    2016-01-01

    Background Despite a large body of literature evaluating the association between recreational physical activity and epithelial ovarian cancer (EOC) risk, the extant evidence is inconclusive and little is known about the independent association between recreational physical inactivity and EOC risk. We conducted a pooled analysis of nine studies from the Ovarian Cancer Association Consortium (OCAC) to investigate the association between chronic recreational physical inactivity and EOC risk. Methods In accordance with the 2008 Physical Activity Guidelines for Americans, women reporting no regular, weekly recreational physical activity were classified as inactive. Multivariable logistic regression was utilized to estimate the odds ratios (OR) and 95% confidence intervals (CI) for the association between inactivity and EOC risk overall and by subgroups based upon histotype, menopausal status, race and body mass index (BMI). Results The current analysis included data from 8,309 EOC patients and 12,612 controls. We observed a significant positive association between inactivity and EOC risk (OR=1.34, 95% CI: 1.14-1.57) and similar associations were observed for each histotype. Conclusions In this large pooled analysis examining the association between recreational physical inactivity and EOC risk, we observed consistent evidence of an association between chronic inactivity and all EOC histotypes. Impact These data add to the growing body of evidence suggesting that inactivity is an independent risk factor for cancer. If the apparent association between inactivity and EOC risk is substantiated, additional work via targeted interventions should be pursued to characterize the dose of activity required to mitigate the risk of this highly fatal disease. PMID:27197285

  9. Cigarette Smoking and Pancreatic Cancer: A Pooled Analysis From the Pancreatic Cancer Cohort Consortium

    PubMed Central

    Vrieling, Alina; Lubin, Jay H.; Kraft, Peter; Mendelsohn, Julie B.; Hartge, Patricia; Canzian, Federico; Steplowski, Emily; Arslan, Alan A.; Gross, Myron; Helzlsouer, Kathy; Jacobs, Eric J.; LaCroix, Andrea; Petersen, Gloria; Zheng, Wei; Albanes, Demetrius; Amundadottir, Laufey; Bingham, Sheila A.; Boffetta, Paolo; Boutron-Ruault, Marie-Christine; Chanock, Stephen J.; Clipp, Sandra; Hoover, Robert N.; Jacobs, Kevin; Johnson, Karen C.; Kooperberg, Charles; Luo, Juhua; Messina, Catherine; Palli, Domenico; Patel, Alpa V.; Riboli, Elio; Shu, Xiao-Ou; Rodriguez Suarez, Laudina; Thomas, Gilles; Tjønneland, Anne; Tobias, Geoffrey S.; Tong, Elissa; Trichopoulos, Dimitrios; Virtamo, Jarmo; Ye, Weimin; Yu, Kai; Zeleniuch-Jacquette, Anne; Bueno-de-Mesquita, H. Bas; Stolzenberg-Solomon, Rachael Z.

    2009-01-01

    Smoking is an established risk factor for pancreatic cancer; however, detailed examination of the association of smoking intensity, smoking duration, and cumulative smoking dose with pancreatic cancer is limited. The authors analyzed pooled data from the international Pancreatic Cancer Cohort Consortium nested case-control study (1,481 cases, 1,539 controls). Odds ratios and 95% confidence intervals were calculated by using unconditional logistic regression. Smoking intensity effects were examined with an excess odds ratio model that was linear in pack-years and exponential in cigarettes smoked per day and its square. When compared with never smokers, current smokers had a significantly elevated risk (odds ratio (OR) = 1.77, 95% confidence interval (CI): 1.38, 2.26). Risk increased significantly with greater intensity (≥30 cigarettes/day: OR = 1.75, 95% CI: 1.27, 2.42), duration (≥50 years: OR = 2.13, 95% CI: 1.25, 3.62), and cumulative smoking dose (≥40 pack-years: OR = 1.78, 95% CI: 1.35, 2.34). Risk more than 15 years after smoking cessation was similar to that for never smokers. Estimates of excess odds ratio per pack-year declined with increasing intensity, suggesting greater risk for total exposure delivered at lower intensity for longer duration than for higher intensity for shorter duration. This finding and the decline in risk after smoking cessation suggest that smoking has a late-stage effect on pancreatic carcinogenesis. PMID:19561064

  10. Reducing the Burden of Cancer in East Africa

    Cancer.gov

    The mission of CGH is to advance global cancer research, build expertise, and leverage resources across nations to reduce cancer deaths worldwide. To carry out that mission, we facilitate the sharing of knowledge and expertise. CGH's latest effort, the East Africa Cancer Control Leadership Forum, carried out this mission by helping African partners develop their own individual cancer control programs.

  11. Bariatric Surgery and Liver Cancer in a Consortium of Academic Medical Centers.

    PubMed

    Yang, Baiyu; Yang, Hannah P; Ward, Kristy K; Sahasrabuddhe, Vikrant V; McGlynn, Katherine A

    2016-03-01

    Obesity is implicated as an important factor in the rising incidence of liver cancer in the USA. Bariatric surgery is increasingly used for treating morbid obesity and comorbidities. Using administrative data from UHC, a consortium of academic medical centers in the USA, we compared the prevalence of liver cancer among admissions with and without a history of bariatric surgery within a 3-year period. Admissions with a history of bariatric surgery had a 61 % lower prevalence of liver cancer compared to those without a history of bariatric surgery (prevalence ratio 0.39, 95 % confidence interval 0.35-0.44), and these inverse associations persisted within strata of sex, race, and ethnicity. This hospital administrative record-based analysis suggests that bariatric surgery could play a role in liver cancer prevention.

  12. Adult height and head and neck cancer: a pooled analysis within the INHANCE Consortium.

    PubMed

    Leoncini, Emanuele; Ricciardi, Walter; Cadoni, Gabriella; Arzani, Dario; Petrelli, Livia; Paludetti, Gaetano; Brennan, Paul; Luce, Daniele; Stucker, Isabelle; Matsuo, Keitaro; Talamini, Renato; La Vecchia, Carlo; Olshan, Andrew F; Winn, Deborah M; Herrero, Rolando; Franceschi, Silvia; Castellsague, Xavier; Muscat, Joshua; Morgenstern, Hal; Zhang, Zuo-Feng; Levi, Fabio; Dal Maso, Luigino; Kelsey, Karl; McClean, Michael; Vaughan, Thomas L; Lazarus, Philip; Purdue, Mark P; Hayes, Richard B; Chen, Chu; Schwartz, Stephen M; Shangina, Oxana; Koifman, Sergio; Ahrens, Wolfgang; Matos, Elena; Lagiou, Pagona; Lissowska, Jolanta; Szeszenia-Dabrowska, Neonila; Fernandez, Leticia; Menezes, Ana; Agudo, Antonio; Daudt, Alexander W; Richiardi, Lorenzo; Kjaerheim, Kristina; Mates, Dana; Betka, Jaroslav; Yu, Guo-Pei; Schantz, Stimson; Simonato, Lorenzo; Brenner, Hermann; Conway, David I; Macfarlane, Tatiana V; Thomson, Peter; Fabianova, Eleonora; Znaor, Ariana; Rudnai, Peter; Healy, Claire; Boffetta, Paolo; Chuang, Shu-Chun; Lee, Yuan-Chin Amy; Hashibe, Mia; Boccia, Stefania

    2014-01-01

    Several epidemiological studies have shown a positive association between adult height and cancer incidence. The only study conducted among women on mouth and pharynx cancer risk, however, reported an inverse association. This study aims to investigate the association between height and the risk of head and neck cancer (HNC) within a large international consortium of HNC. We analyzed pooled individual-level data from 24 case-control studies participating in the International Head and Neck Cancer Epidemiology Consortium. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated separately for men and women for associations between height and HNC risk. Educational level, tobacco smoking, and alcohol consumption were included in all regression models. Stratified analyses by HNC subsites were performed. This project included 17,666 cases and 28,198 controls. We found an inverse association between height and HNC (adjusted OR per 10 cm height = 0.91, 95% CI 0.86-0.95 for men; adjusted OR = 0.86, 95% CI 0.79-0.93 for women). In men, the estimated OR did vary by educational level, smoking status, geographic area, and control source. No differences by subsites were detected. Adult height is inversely associated with HNC risk. As height can be considered a marker of childhood illness and low energy intake, the inverse association is consistent with prior studies showing that HNC occur more frequently among deprived individuals. Further studies designed to elucidate the mechanism of such association would be warranted.

  13. Intrauterine devices and endometrial cancer risk: a pooled analysis of the Epidemiology of Endometrial Cancer Consortium.

    PubMed

    Felix, Ashley S; Gaudet, Mia M; La Vecchia, Carlo; Nagle, Christina M; Shu, Xiao Ou; Weiderpass, Elisabete; Adami, Hans Olov; Beresford, Shirley; Bernstein, Leslie; Chen, Chu; Cook, Linda S; De Vivo, Immaculata; Doherty, Jennifer A; Friedenreich, Christine M; Gapstur, Susan M; Hill, Dierdre; Horn-Ross, Pamela L; Lacey, James V; Levi, Fabio; Liang, Xiaolin; Lu, Lingeng; Magliocco, Anthony; McCann, Susan E; Negri, Eva; Olson, Sara H; Palmer, Julie R; Patel, Alpa V; Petruzella, Stacey; Prescott, Jennifer; Risch, Harvey A; Rosenberg, Lynn; Sherman, Mark E; Spurdle, Amanda B; Webb, Penelope M; Wise, Lauren A; Xiang, Yong-Bing; Xu, Wanghong; Yang, Hannah P; Yu, Herbert; Zeleniuch-Jacquotte, Anne; Brinton, Louise A

    2015-03-01

    Intrauterine devices (IUDs), long-acting and reversible contraceptives, induce a number of immunological and biochemical changes in the uterine environment that could affect endometrial cancer (EC) risk. We addressed this relationship through a pooled analysis of data collected in the Epidemiology of Endometrial Cancer Consortium. We combined individual-level data from 4 cohort and 14 case-control studies, in total 8,801 EC cases and 15,357 controls. Using multivariable logistic regression, we estimated pooled odds ratios (pooled-ORs) and 95% confidence intervals (CIs) for EC risk associated with ever use, type of device, ages at first and last use, duration of use and time since last use, stratified by study and adjusted for confounders. Ever use of IUDs was inversely related to EC risk (pooled-OR = 0.81, 95% CI = 0.74-0.90). Compared with never use, reduced risk of EC was observed for inert IUDs (pooled-OR = 0.69, 95% CI = 0.58-0.82), older age at first use (≥ 35 years pooled-OR = 0.53, 95% CI = 0.43-0.67), older age at last use (≥ 45 years pooled-OR = 0.60, 95% CI = 0.50-0.72), longer duration of use (≥ 10 years pooled-OR = 0.61, 95% CI = 0.52-0.71) and recent use (within 1 year of study entry pooled-OR = 0.39, 95% CI = 0.30-0.49). Future studies are needed to assess the respective roles of detection biases and biologic effects related to foreign body responses in the endometrium, heavier bleeding (and increased clearance of carcinogenic cells) and localized hormonal changes. © 2014 UICC.

  14. Androgens are differentially associated with ovarian cancer subtypes in the Ovarian Cancer Cohort Consortium.

    PubMed

    Ose, Jennifer; Poole, Elizabeth M; Schock, Helena; Lehtinen, Matti; Arslan, Alan A; Zeleniuch-Jacquotte, Anne; Visvanathan, Kala; Helzlsouer, Kathy J; Buring, Julie E; Lee, I-Min; Tjønneland, Anne; Dossus, Laure; Trichopoulou, Antonia; Masala, Giovanna; Onland-Moret, N Charlotte; Weiderpass, Elisabete; Duell, Eric J; Idahl, Annika; Travis, Ruth C; Rinaldi, Sabina; Merritt, Melissa A; Trabert, Britton; Wentzensen, Nicolas; Tworoger, Shelley S; Kaaks, Rudolf; Fortner, Renée T

    2017-04-05

    Invasive epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy. The etiology of EOC remains elusive; however, experimental and epidemiologic data suggest a role for hormone-related exposures in ovarian carcinogenesis and risk factor differences by histologic phenotypes and developmental pathways. Research on pre-diagnosis androgen concentrations and EOC risk has yielded inconclusive results, and analyses incorporating EOC subtypes are sparse. We conducted a pooled analysis of 7 nested case-control studies in the Ovarian Cancer Cohort Consortium to investigate the association between pre-diagnosis circulating androgens (testosterone, free testosterone, androstenedione, dehydroepiandrosterone sulfate (DHEAS)), sex hormone binding globulin (SHBG), and EOC risk by tumor characteristics (i.e. histology, grade, and stage). The final study population included 1,331 EOC cases and 3,017 matched controls. Multivariable conditional logistic regression was used to assess risk associations in pooled individual data. Testosterone was positively associated with EOC risk (all subtypes combined, Odds Ratio (OR)log2=1.12 [95% Confidence Interval (CI) 1.02-1.24]); other endogenous androgens and SHBG were not associated with overall risk. Higher concentrations of testosterone and androstenedione associated with an increased risk in endometrioid and mucinous tumors (e.g., testosterone, endometrioid tumors, ORlog2=1.40 [1.03-1.91]), but not serous or clear cell. An inverse association was observed between androstenedione and high grade serous tumors (ORlog2=0.76 [0.60-0.96]). Our analyses provide further evidence for a role of hormone-related pathways in EOC risk, with differences in associations between androgens and histologic subtypes of EOC.

  15. Intrauterine devices and endometrial cancer risk: a pooled analysis of the Epidemiology of Endometrial Cancer Consortium

    PubMed Central

    Felix, Ashley S.; Gaudet, Mia M.; La Vecchia, Carlo; Nagle, Christina M.; Ou Shu, Xiao; Weiderpass, Elisabete; Olov Adami, Hans; Beresford, Shirley; Bernstein, Leslie; Chen, Chu; Cook, Linda S.; De Vivo, Immaculata; Doherty, Jennifer A.; Friedenreich, Christine M.; Gapstur, Susan M.; Hill, Dierdre; Horn-Ross, Pamela L.; Lacey, James V.; Levi, Fabio; Liang, Xiaolin; Lu, Lingeng; Magliocco, Anthony; McCann, Susan E.; Negri, Eva; Olson, Sara H.; Palmer, Julie R.; Patel, Alpa V.; Petruzella, Stacey; Prescott, Jennifer; Risch, Harvey A.; Rosenberg, Lynn; Sherman, Mark E.; Spurdle, Amanda B.; Webb, Penelope M.; Wise, Lauren A.; Xiang, Yong-Bing; Xu, Wanghong; Yang, Hannah P.; Yu, Herbert; Zeleniuch-Jacquotte, Anne; Brinton, Louise A.

    2014-01-01

    Intrauterine devices (IUDs), long-acting and reversible contraceptives, induce a number of immunological and biochemical changes in the uterine environment that could affect endometrial cancer (EC) risk. We addressed this relationship through a pooled analysis of data collected in the Epidemiology of Endometrial Cancer Consortium. We combined individual-level data from 4 cohort and 14 case-control studies, in total 8,801 EC cases and 15,357 controls. Using multivariable logistic regression, we estimated pooled odds ratios (pooled-ORs) and 95% confidence intervals (CIs) for EC risk associated with ever use, type of device, ages at first and last use, duration of use, and time since last use, stratified by study and adjusted for confounders. Ever use of IUDs was inversely related to EC risk (pooled-OR=0.81, 95% CI=0.74–0.90). Compared with never use, reduced risk of EC was observed for inert IUDs (pooled-OR=0.69, 95% CI=0.58–0.82), older age at first use (≥35 years pooled-OR=0.53, 95% CI=0.43–0.67), older age at last use (≥45 years pooled-OR=0.60, 95% CI=0.50–0.72), longer duration of use (≥10 years pooled-OR=0.61, 95% CI=0.52–0.71), and recent use (within 1 year of study entry pooled-OR=0.39, 95% CI=0.30–0.49). Future studies are needed to assess the respective roles of detection biases and biologic effects related to foreign body responses in the endometrium, heavier bleeding (and increased clearance of carcinogenic cells), and localized hormonal changes. PMID:25242594

  16. Height, selected genetic markers and prostate cancer risk: results from the PRACTICAL consortium.

    PubMed

    Lophatananon, Artitaya; Stewart-Brown, Sarah; Kote-Jarai, Zsofia; Olama, Ali Amin Al; Garcia, Sara Benlloch; Neal, David E; Hamdy, Freddie C; Donovan, Jenny L; Giles, Graham G; Fitzgerald, Liesel M; Southey, Melissa C; Pharoah, Paul; Pashayan, Nora; Gronberg, Henrik; Wiklund, Fredrik; Aly, Markus; Stanford, Janet L; Brenner, Hermann; Dieffenbach, Aida K; Arndt, Volker; Park, Jong Y; Lin, Hui-Yi; Sellers, Thomas; Slavov, Chavdar; Kaneva, Radka; Mitev, Vanio; Batra, Jyotsna; Spurdle, Amanda; Clements, Judith A; Easton, Douglas; Eeles, Rosalind A; Muir, Kenneth

    2017-08-22

    Evidence on height and prostate cancer risk is mixed, however, recent studies with large data sets support a possible role for its association with the risk of aggressive prostate cancer. We analysed data from the PRACTICAL consortium consisting of 6207 prostate cancer cases and 6016 controls and a subset of high grade cases (2480 cases). We explored height, polymorphisms in genes related to growth processes as main effects and their possible interactions. The results suggest that height is associated with high-grade prostate cancer risk. Men with height >180 cm are at a 22% increased risk as compared to men with height <173 cm (OR 1.22, 95% CI 1.01-1.48). Genetic variants in the growth pathway gene showed an association with prostate cancer risk. The aggregate scores of the selected variants identified a significantly increased risk of overall prostate cancer and high-grade prostate cancer by 13% and 15%, respectively, in the highest score group as compared to lowest score group. There was no evidence of gene-environment interaction between height and the selected candidate SNPs.Our findings suggest a role of height in high-grade prostate cancer. The effect of genetic variants in the genes related to growth is seen in all cases and high-grade prostate cancer. There is no interaction between these two exposures.

  17. Height, selected genetic markers and prostate cancer risk: results from the PRACTICAL consortium

    PubMed Central

    Lophatananon, Artitaya; Stewart-Brown, Sarah; Kote-Jarai, Zsofia; Olama, Ali Amin Al; Garcia, Sara Benlloch; Neal, David E; Hamdy, Freddie C; Donovan, Jenny L; Giles, Graham G; Fitzgerald, Liesel M; Southey, Melissa C; Pharoah, Paul; Pashayan, Nora; Gronberg, Henrik; Wiklund, Fredrik; Aly, Markus; Stanford, Janet L; Brenner, Hermann; Dieffenbach, Aida K; Arndt, Volker; Park, Jong Y; Lin, Hui-Yi; Sellers, Thomas; Slavov, Chavdar; Kaneva, Radka; Mitev, Vanio; Batra, Jyotsna; Spurdle, Amanda; Clements, Judith A; Schleutker, Johanna; Nordestgaard, BØrge G; Wiklund, Fredrik; Travis, Ruth C; Haiman, Christopher A; Thibodeau, Stephen N; Maier, Christiane; Walther, Vogel; Blot, William J; Kibel, Adam S; Cybulski, Cezary; Cannon-Albright, Lisa; Pandha, Hardev; Teixeira, Manuel R; Cook, Margaret; Govindasami, Koveela; Guy, Michelle; Leongamornlert, Daniel; Sawyer, Emma J; Wilkinson, Rosemary; Morgan, Angela; Fisher, Cyril; Saunders, Edward J; Tymrakiewicz, Malgorzata; Livni, Naomi; Hazel, Steve; Dadaev, Tokhir; Cox, Angela; George, Anne; Lane, Athene; Marsden, Gemma; Davis, Michael; Brown, Paul; Pedersen, John; Hopper, John L; Karlsson, Ami; Cavalli-Bjoerkman, Carin; Adolfson, Jan; Johansson, Jan-Erik; Broms, Michael; Stattin, Paer; Kolb, Suzanne; Stegmaier, Christa; Zachariah, Babu; Park, Hyun; Haley, James; Pow-Sang, Julio; Rincon, Maria; Radlein, Selina; Vlahova, Aleksandrina; Mitkova, Atanaska; Kachakova, Darina; Popov, Elenko; Christova, Svetlana; Dikov, Tihomir; Eckert, Allison; Collins, Angus; Wood, Glenn; Malone, Greg; Alexander, Kimberly; Kerr, Kris; Kedda, Mary-Anne; Turner, Megan; Saunders, Pamela; Heathcote, Peter; Srinivasan, Srilakshmi; Omara, Tracy; Yeadon, Trina; Lose, Felicity; Easton, Douglas; Eeles, Rosalind A; Muir, Kenneth

    2017-01-01

    Background: Evidence on height and prostate cancer risk is mixed, however, recent studies with large data sets support a possible role for its association with the risk of aggressive prostate cancer. Methods: We analysed data from the PRACTICAL consortium consisting of 6207 prostate cancer cases and 6016 controls and a subset of high grade cases (2480 cases). We explored height, polymorphisms in genes related to growth processes as main effects and their possible interactions. Results: The results suggest that height is associated with high-grade prostate cancer risk. Men with height >180 cm are at a 22% increased risk as compared to men with height <173 cm (OR 1.22, 95% CI 1.01–1.48). Genetic variants in the growth pathway gene showed an association with prostate cancer risk. The aggregate scores of the selected variants identified a significantly increased risk of overall prostate cancer and high-grade prostate cancer by 13% and 15%, respectively, in the highest score group as compared to lowest score group. Conclusions: There was no evidence of gene-environment interaction between height and the selected candidate SNPs. Our findings suggest a role of height in high-grade prostate cancer. The effect of genetic variants in the genes related to growth is seen in all cases and high-grade prostate cancer. There is no interaction between these two exposures. PMID:28765617

  18. Radiogenomics Consortium (RGC)

    Cancer.gov

    The Radiogenomics Consortium's hypothesis is that a cancer patient's likelihood of developing toxicity to radiation therapy is influenced by common genetic variations, such as single nucleotide polymorphisms (SNPs).

  19. Seeking genetic susceptibility variants for colorectal cancer: the EPICOLON consortium experience.

    PubMed

    Castellví-Bel, Sergi; Ruiz-Ponte, Clara; Fernández-Rozadilla, Ceres; Abulí, Anna; Muñoz, Jenifer; Bessa, Xavier; Brea-Fernández, Alejandro; Ferro, Marta; Giráldez, María Dolores; Xicola, Rosa M; Llor, Xavier; Jover, Rodrigo; Piqué, Josep M; Andreu, Montserrat; Castells, Antoni; Carracedo, Angel

    2012-03-01

    The EPICOLON consortium was initiated in 1999 by the Gastrointestinal Oncology Group of the Spanish Gastroenterology Association. It recruited consecutive, unselected, population-based colorectal cancer (CRC) cases and control subjects matched by age and gender without personal or familial history of cancer all over Spain with the main goal of gaining knowledge in Lynch syndrome and familial CRC. This epidemiological, prospective and multicentre study collected extensive clinical data and biological samples from ∼2000 CRC cases and 2000 controls in Phases 1 and 2 involving 25 and 14 participating hospitals, respectively. Genetic susceptibility projects in EPICOLON have included candidate-gene approaches evaluating single-nucleotide polymorphisms/genes from the historical category (linked to CRC risk by previous studies), from human syntenic CRC susceptibility regions identified in mouse, from the CRC carcinogenesis-related pathways Wnt and BMP, from regions 9q22 and 3q22 with positive linkage in CRC families, and from the mucin gene family. This consortium has also participated actively in the identification 5 of the 16 common, low-penetrance CRC genetic variants identified so far by genome-wide association studies. Finishing their own pangenomic study and performing whole-exome sequencing in selected CRC samples are among EPICOLON future research prospects.

  20. Lack of Association for Reported Endocrine Pancreatic Cancer Risk Loci in the PANDoRA Consortium.

    PubMed

    Campa, Daniele; Obazee, Ofure; Pastore, Manuela; Panzuto, Francesco; Liço, Valbona; Greenhalf, William; Katzke, Verena; Tavano, Francesca; Costello, Eithne; Corbo, Vincenzo; Talar-Wojnarowska, Renata; Strobel, Oliver; Zambon, Carlo Federico; Neoptolemos, John P; Zerboni, Giulia; Kaaks, Rudolf; Key, Timothy J; Lombardo, Carlo; Jamroziak, Krzysztof; Gioffreda, Domenica; Hackert, Thilo; Khaw, Kay-Tee; Landi, Stefano; Milanetto, Anna Caterina; Landoni, Luca; Lawlor, Rita T; Bambi, Franco; Pirozzi, Felice; Basso, Daniela; Pasquali, Claudio; Capurso, Gabriele; Canzian, Federico

    2017-08-01

    Background: Pancreatic neuroendocrine tumors (PNETs) are rare neoplasms for which very little is known about either environmental or genetic risk factors. Only a handful of association studies have been performed so far, suggesting a small number of risk loci.Methods: To replicate the best findings, we have selected 16 SNPs suggested in previous studies to be relevant in PNET etiogenesis. We genotyped the selected SNPs (rs16944, rs1052536, rs1059293, rs1136410, rs1143634, rs2069762, rs2236302, rs2387632, rs3212961, rs3734299, rs3803258, rs4962081, rs7234941, rs7243091, rs12957119, and rs1800629) in 344 PNET sporadic cases and 2,721 controls in the context of the PANcreatic Disease ReseArch (PANDoRA) consortium.Results: After correction for multiple testing, we did not observe any statistically significant association between the SNPs and PNET risk. We also used three online bioinformatic tools (HaploReg, RegulomeDB, and GTEx) to predict a possible functional role of the SNPs, but we did not observe any clear indication.Conclusions: None of the selected SNPs were convincingly associated with PNET risk in the PANDoRA consortium.Impact: We can exclude a major role of the selected polymorphisms in PNET etiology, and this highlights the need for replication of epidemiologic findings in independent populations, especially in rare diseases such as PNETs. Cancer Epidemiol Biomarkers Prev; 26(8); 1349-51. ©2017 AACR. ©2017 American Association for Cancer Research.

  1. The Premenopausal Breast Cancer Collaboration: A Pooling Project of Studies Participating in the National Cancer Institute Cohort Consortium.

    PubMed

    Nichols, Hazel B; Schoemaker, Minouk J; Wright, Lauren B; McGowan, Craig; Brook, Mark N; McClain, Kathleen M; Jones, Michael E; Adami, Hans-Olov; Agnoli, Claudia; Baglietto, Laura; Bernstein, Leslie; Bertrand, Kimberly A; Blot, William J; Boutron-Ruault, Marie-Christine; Butler, Lesley; Chen, Yu; Doody, Michele M; Dossus, Laure; Eliassen, A Heather; Giles, Graham G; Gram, Inger T; Hankinson, Susan E; Hoffman-Bolton, Judy; Kaaks, Rudolf; Key, Timothy J; Kirsh, Victoria A; Kitahara, Cari M; Koh, Woon-Puay; Larsson, Susanna C; Lund, Eiliv; Ma, Huiyan; Merritt, Melissa A; Milne, Roger L; Navarro, Carmen; Overvad, Kim; Ozasa, Kotaro; Palmer, Julie R; Peeters, Petra H; Riboli, Elio; Rohan, Thomas E; Sadakane, Atsuko; Sund, Malin; Tamimi, Rulla M; Trichopoulou, Antonia; Vatten, Lars; Visvanathan, Kala; Weiderpass, Elisabete; Willett, Walter C; Wolk, Alicja; Zeleniuch-Jacquotte, Anne; Zheng, Wei; Sandler, Dale P; Swerdlow, Anthony J

    2017-09-01

    Breast cancer is a leading cancer diagnosis among premenopausal women around the world. Unlike rates in postmenopausal women, incidence rates of advanced breast cancer have increased in recent decades for premenopausal women. Progress in identifying contributors to breast cancer risk among premenopausal women has been constrained by the limited numbers of premenopausal breast cancer cases in individual studies and resulting low statistical power to subcategorize exposures or to study specific subtypes. The Premenopausal Breast Cancer Collaborative Group was established to facilitate cohort-based analyses of risk factors for premenopausal breast cancer by pooling individual-level data from studies participating in the United States National Cancer Institute Cohort Consortium. This article describes the Group, including the rationale for its initial aims related to pregnancy, obesity, and physical activity. We also describe the 20 cohort studies with data submitted to the Group by June 2016. The infrastructure developed for this work can be leveraged to support additional investigations. Cancer Epidemiol Biomarkers Prev; 26(9); 1360-9. ©2017 AACR. ©2017 American Association for Cancer Research.

  2. Adult height and head and neck cancer: a pooled analysis within the INHANCE Consortium

    PubMed Central

    Leoncini, Emanuele; Ricciardi, Walter; Cadoni, Gabriella; Arzani, Dario; Petrelli, Livia; Paludetti, Gaetano; Brennan, Paul; Luce, Daniele; Stucker, Isabelle; Matsuo, Keitaro; Talamini, Renato; La Vecchia, Carlo; Olshan, Andrew F.; Winn, Deborah M.; Herrero, Rolando; Franceschi, Silvia; Castellsague, Xavier; Muscat, Joshua; Morgenstern, Hal; Zhang, Zuo-Feng; Levi, Fabio; Maso, Luigino Dal; Kelsey, Karl; McClean, Michael; Vaughan, Thomas L; Lazarus, Philip; Purdue, Mark P.; Hayes, Richard B.; Chen, Chu; Schwartz, Stephen M.; Shangina, Oxana; Koifman, Sergio; Ahrens, Wolfgang; Matos, Elena; Lagiou, Pagona; Lissowska, Jolanta; Szeszenia-Dabrowska, Neonila; Fernandez, Leticia; Menezes, Ana; Agudo, Antonio; Daudt, Alexander W.; Richiardi, Lorenzo; Kjaerheim, Kristina; Mates, Dana; Betka, Jaroslav; Yu, Guo-Pei; Schantz, Stimson; Simonato, Lorenzo; Brenner, Hermann; Conway, David I; Macfarlane, Tatiana V.; Thomson, Peter; Fabianova, Eleonora; Znaor, Ariana; Rudnai, Peter; Healy, Claire; Boffetta, Paolo; Chuang, Shu-Chun; Lee, Yuan-Chin Amy; Hashibe, Mia; Boccia, Stefania

    2014-01-01

    Background Several epidemiological studies have shown a positive association between adult height and cancer incidence. The only study conducted among women on mouth and pharynx cancer risk, however, reported an inverse association. This study aims to investigate the association between height and the risk of head and neck cancer (HNC) within a large international consortium of HNC. Methods We analyzed pooled individual-level data from 24 case-control studies participating in the International Head and Neck Cancer Epidemiology Consortium. Odds Ratios (ORs) and 95% Confidence Intervals (CIs) were estimated separately for men and women for associations between height and HNC risk. Educational level, tobacco smoking, and alcohol consumption were included in all regression models. Stratified analyses by HNC subsites were performed. Results This project included 17,666 cases and 28,198 controls. We found an inverse association between height and HNC (adjusted OR per 10 cm height =0.91, 95% CI 0.86–0.95 for men; adjusted OR=0.86, 95% CI 0.79–0.93 for women). In men, the estimated OR did vary by educational level, smoking status, geographic area, and control source. No differences by subsites were detected. Conclusions Adult height is inversely associated with HNC risk. As height can be considered a marker of childhood illness and low energy intake, the inverse association is consistent with prior studies showing that HNC occur more frequently among deprived individuals. Further studies designed to elucidate the mechanism of such association would be warranted. PMID:24271556

  3. Circulating 25-hydroxyvitamin D and risk of esophageal and gastric cancer: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers.

    PubMed

    Abnet, Christian C; Chen, Yu; Chow, Wong-Ho; Gao, Yu-Tang; Helzlsouer, Kathy J; Le Marchand, Loïc; McCullough, Marjorie L; Shikany, James M; Virtamo, Jarmo; Weinstein, Stephanie J; Xiang, Yong-Bing; Yu, Kai; Zheng, Wei; Albanes, Demetrius; Arslan, Alan A; Campbell, David S; Campbell, Peter T; Hayes, Richard B; Horst, Ronald L; Kolonel, Laurence N; Nomura, Abraham M Y; Purdue, Mark P; Snyder, Kirk; Shu, Xiao-Ou

    2010-07-01

    Upper gastrointestinal (GI) cancers of the stomach and esophagus have high incidence and mortality worldwide, but they are uncommon in Western countries. Little information exists on the association between vitamin D and risk of upper GI cancers. This study examined the association between circulating 25-hydroxyvitamin D (25(OH)D) and upper GI cancer risk in the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers. Concentrations of 25(OH)D were measured from 1,065 upper GI cancer cases and 1,066 age-, sex-, race-, and season-of blood draw-matched controls from 8 prospective cohort studies. In multivariate-adjusted models, circulating 25(OH)D concentration was not significantly associated with upper GI cancer risk. Subgroup analysis by race showed that among Asians, but not Caucasians, lower concentrations of 25(OH)D (<25 nmol/L) were associated with a statistically significant decreased risk of upper GI cancer (reference: 50-<75 nmol/L) (odds ratio = 0.53, 95% confidence interval: 0.31, 0.91; P trend = 0.003). Never smokers with concentrations of <25 nmol/L showed a lower risk of upper GI cancers (odds ratio = 0.55, 95% confidence interval: 0.31, 0.96). Subgroup analyses by alcohol consumption produced opposing trends. Results do not support the hypothesis that interventions aimed at increasing vitamin D status would lead to a lower risk of these highly fatal cancers.

  4. Association between type 2 diabetes and risk of cancer mortality: a pooled analysis of over 771,000 individuals in the Asia Cohort Consortium.

    PubMed

    Chen, Yu; Wu, Fen; Saito, Eiko; Lin, Yingsong; Song, Minkyo; Luu, Hung N; Gupta, Prakash C; Sawada, Norie; Tamakoshi, Akiko; Shu, Xiao-Ou; Koh, Woon-Puay; Xiang, Yong-Bing; Tomata, Yasutake; Sugiyama, Kemmyo; Park, Sue K; Matsuo, Keitaro; Nagata, Chisato; Sugawara, Yumi; Qiao, You-Lin; You, San-Lin; Wang, Renwei; Shin, Myung-Hee; Pan, Wen-Harn; Pednekar, Mangesh S; Tsugane, Shoichiro; Cai, Hui; Yuan, Jian-Min; Gao, Yu-Tang; Tsuji, Ichiro; Kanemura, Seiki; Ito, Hidemi; Wada, Keiko; Ahn, Yoon-Ok; Yoo, Keun-Young; Ahsan, Habibul; Chia, Kee Seng; Boffetta, Paolo; Zheng, Wei; Inoue, Manami; Kang, Daehee; Potter, John D

    2017-06-01

    The aims of the study were to evaluate the association between type 2 diabetes and the risk of death from any cancer and specific cancers in East and South Asians. Pooled analyses were conducted of 19 prospective population-based cohorts included in the Asia Cohort Consortium, comprising data from 658,611 East Asians and 112,686 South Asians. HRs were used to compare individuals with diabetes at baseline with those without diabetes for the risk of death from any cancer and from site-specific cancers, including cancers of the oesophagus, stomach, colorectum, colon, rectum, liver, bile duct, pancreas, lung, breast, endometrium, cervix, ovary, prostate, bladder, kidney and thyroid, as well as lymphoma and leukaemia. During a mean follow-up of 12.7 years, 37,343 cancer deaths (36,667 in East Asians and 676 in South Asians) were identified. Baseline diabetes status was statistically significantly associated with an increased risk of death from any cancer (HR 1.26; 95% CI 1.21, 1.31). Significant positive associations with diabetes were observed for cancers of the colorectum (HR 1.41; 95% CI 1.26, 1.57), liver (HR 2.05; 95% CI 1.77, 2.38), bile duct (HR 1.41; 95% CI 1.04, 1.92), gallbladder (HR 1.33; 95% CI 1.10, 1.61), pancreas (HR 1.53; 95% CI 1.32, 1.77), breast (HR 1.72; 95% CI 1.34, 2.19), endometrium (HR 2.73; 95% CI 1.53, 4.85), ovary (HR 1.60; 95% CI 1.06, 2.42), prostate (HR 1.41; 95% CI 1.09, 1.82), kidney (HR 1.84; 95% CI 1.28, 2.64) and thyroid (HR 1.99; 95% CI 1.03, 3.86), as well as lymphoma (HR 1.39; 95% CI 1.04, 1.86). Diabetes was not statistically significantly associated with the risk of death from leukaemia and cancers of the bladder, cervix, oesophagus, stomach and lung. Diabetes was associated with a 26% increased risk of death from any cancer in Asians. The pattern of associations with specific cancers suggests the need for better control (prevention, detection, management) of the growing epidemic of diabetes (as well as obesity), in order to

  5. A genome-wide association study of upper aerodigestive tract cancers conducted within the INHANCE consortium.

    PubMed

    McKay, James D; Truong, Therese; Gaborieau, Valerie; Chabrier, Amelie; Chuang, Shu-Chun; Byrnes, Graham; Zaridze, David; Shangina, Oxana; Szeszenia-Dabrowska, Neonila; Lissowska, Jolanta; Rudnai, Peter; Fabianova, Eleonora; Bucur, Alexandru; Bencko, Vladimir; Holcatova, Ivana; Janout, Vladimir; Foretova, Lenka; Lagiou, Pagona; Trichopoulos, Dimitrios; Benhamou, Simone; Bouchardy, Christine; Ahrens, Wolfgang; Merletti, Franco; Richiardi, Lorenzo; Talamini, Renato; Barzan, Luigi; Kjaerheim, Kristina; Macfarlane, Gary J; Macfarlane, Tatiana V; Simonato, Lorenzo; Canova, Cristina; Agudo, Antonio; Castellsagué, Xavier; Lowry, Ray; Conway, David I; McKinney, Patricia A; Healy, Claire M; Toner, Mary E; Znaor, Ariana; Curado, Maria Paula; Koifman, Sergio; Menezes, Ana; Wünsch-Filho, Victor; Neto, José Eluf; Garrote, Leticia Fernández; Boccia, Stefania; Cadoni, Gabriella; Arzani, Dario; Olshan, Andrew F; Weissler, Mark C; Funkhouser, William K; Luo, Jingchun; Lubiński, Jan; Trubicka, Joanna; Lener, Marcin; Oszutowska, Dorota; Schwartz, Stephen M; Chen, Chu; Fish, Sherianne; Doody, David R; Muscat, Joshua E; Lazarus, Philip; Gallagher, Carla J; Chang, Shen-Chih; Zhang, Zuo-Feng; Wei, Qingyi; Sturgis, Erich M; Wang, Li-E; Franceschi, Silvia; Herrero, Rolando; Kelsey, Karl T; McClean, Michael D; Marsit, Carmen J; Nelson, Heather H; Romkes, Marjorie; Buch, Shama; Nukui, Tomoko; Zhong, Shilong; Lacko, Martin; Manni, Johannes J; Peters, Wilbert H M; Hung, Rayjean J; McLaughlin, John; Vatten, Lars; Njølstad, Inger; Goodman, Gary E; Field, John K; Liloglou, Triantafillos; Vineis, Paolo; Clavel-Chapelon, Francoise; Palli, Domenico; Tumino, Rosario; Krogh, Vittorio; Panico, Salvatore; González, Carlos A; Quirós, J Ramón; Martínez, Carmen; Navarro, Carmen; Ardanaz, Eva; Larrañaga, Nerea; Khaw, Kay-Tee; Key, Timothy; Bueno-de-Mesquita, H Bas; Peeters, Petra H M; Trichopoulou, Antonia; Linseisen, Jakob; Boeing, Heiner; Hallmans, Göran; Overvad, Kim; Tjønneland, Anne; Kumle, Merethe; Riboli, Elio; Välk, Kristjan; Vooder, Tõnu; Voodern, Tõnu; Metspalu, Andres; Zelenika, Diana; Boland, Anne; Delepine, Marc; Foglio, Mario; Lechner, Doris; Blanché, Hélène; Gut, Ivo G; Galan, Pilar; Heath, Simon; Hashibe, Mia; Hayes, Richard B; Boffetta, Paolo; Lathrop, Mark; Brennan, Paul

    2011-03-01

    Genome-wide association studies (GWAS) have been successful in identifying common genetic variation involved in susceptibility to etiologically complex disease. We conducted a GWAS to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT) cancers. Genome-wide genotyping was carried out using the Illumina HumanHap300 beadchips in 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre UADT cancer studies, as well as 4,821 generic controls. The 19 top-ranked variants were investigated further in an additional 6,514 UADT cancer cases and 7,892 controls of European descent from an additional 13 UADT cancer studies participating in the INHANCE consortium. Five common variants presented evidence for significant association in the combined analysis (p ≤ 5 × 10⁻⁷). Two novel variants were identified, a 4q21 variant (rs1494961, p = 1×10⁻⁸) located near DNA repair related genes HEL308 and FAM175A (or Abraxas) and a 12q24 variant (rs4767364, p =2 × 10⁻⁸) located in an extended linkage disequilibrium region that contains multiple genes including the aldehyde dehydrogenase 2 (ALDH2) gene. Three remaining variants are located in the ADH gene cluster and were identified previously in a candidate gene study involving some of these samples. The association between these three variants and UADT cancers was independently replicated in 5,092 UADT cancer cases and 6,794 controls non-overlapping samples presented here (rs1573496-ADH7, p = 5 × 10⁻⁸); rs1229984-ADH1B, p = 7 × 10⁻⁹; and rs698-ADH1C, p = 0.02). These results implicate two variants at 4q21 and 12q24 and further highlight three ADH variants in UADT cancer susceptibility.

  6. A Genome-Wide Association Study of Upper Aerodigestive Tract Cancers Conducted within the INHANCE Consortium

    PubMed Central

    McKay, James D.; Truong, Therese; Gaborieau, Valerie; Chabrier, Amelie; Chuang, Shu-Chun; Byrnes, Graham; Zaridze, David; Shangina, Oxana; Szeszenia-Dabrowska, Neonila; Lissowska, Jolanta; Rudnai, Peter; Fabianova, Eleonora; Bucur, Alexandru; Bencko, Vladimir; Holcatova, Ivana; Janout, Vladimir; Foretova, Lenka; Lagiou, Pagona; Trichopoulos, Dimitrios; Benhamou, Simone; Bouchardy, Christine; Ahrens, Wolfgang; Merletti, Franco; Richiardi, Lorenzo; Talamini, Renato; Barzan, Luigi; Kjaerheim, Kristina; Macfarlane, Gary J.; Macfarlane, Tatiana V.; Simonato, Lorenzo; Canova, Cristina; Agudo, Antonio; Castellsagué, Xavier; Lowry, Ray; Conway, David I.; McKinney, Patricia A.; Healy, Claire M.; Toner, Mary E.; Znaor, Ariana; Curado, Maria Paula; Koifman, Sergio; Menezes, Ana; Wünsch-Filho, Victor; Neto, José Eluf; Garrote, Leticia Fernández; Boccia, Stefania; Cadoni, Gabriella; Arzani, Dario; Olshan, Andrew F.; Weissler, Mark C.; Funkhouser, William K.; Luo, Jingchun; Lubiński, Jan; Trubicka, Joanna; Lener, Marcin; Oszutowska, Dorota; Schwartz, Stephen M.; Chen, Chu; Fish, Sherianne; Doody, David R.; Muscat, Joshua E.; Lazarus, Philip; Gallagher, Carla J.; Chang, Shen-Chih; Zhang, Zuo-Feng; Wei, Qingyi; Sturgis, Erich M.; Wang, Li-E; Franceschi, Silvia; Herrero, Rolando; Kelsey, Karl T.; McClean, Michael D.; Marsit, Carmen J.; Nelson, Heather H.; Romkes, Marjorie; Buch, Shama; Nukui, Tomoko; Zhong, Shilong; Lacko, Martin; Manni, Johannes J.; Peters, Wilbert H. M.; Hung, Rayjean J.; McLaughlin, John; Vatten, Lars; Njølstad, Inger; Goodman, Gary E.; Field, John K.; Liloglou, Triantafillos; Vineis, Paolo; Clavel-Chapelon, Francoise; Palli, Domenico; Tumino, Rosario; Krogh, Vittorio; Panico, Salvatore; González, Carlos A.; Quirós, J. Ramón; Martínez, Carmen; Navarro, Carmen; Ardanaz, Eva; Larrañaga, Nerea; Khaw, Kay-Tee; Key, Timothy; Bueno-de-Mesquita, H. Bas; Peeters, Petra H. M.; Trichopoulou, Antonia; Linseisen, Jakob; Boeing, Heiner; Hallmans, Göran; Overvad, Kim; Tjønneland, Anne; Kumle, Merethe; Riboli, Elio; Välk, Kristjan; Voodern, Tõnu; Metspalu, Andres; Zelenika, Diana; Boland, Anne; Delepine, Marc; Foglio, Mario; Lechner, Doris; Blanché, Hélène; Gut, Ivo G.; Galan, Pilar; Heath, Simon; Hashibe, Mia; Hayes, Richard B.; Boffetta, Paolo; Lathrop, Mark; Brennan, Paul

    2011-01-01

    Genome-wide association studies (GWAS) have been successful in identifying common genetic variation involved in susceptibility to etiologically complex disease. We conducted a GWAS to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT) cancers. Genome-wide genotyping was carried out using the Illumina HumanHap300 beadchips in 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre UADT cancer studies, as well as 4,821 generic controls. The 19 top-ranked variants were investigated further in an additional 6,514 UADT cancer cases and 7,892 controls of European descent from an additional 13 UADT cancer studies participating in the INHANCE consortium. Five common variants presented evidence for significant association in the combined analysis (p≤5×10−7). Two novel variants were identified, a 4q21 variant (rs1494961, p = 1×10−8) located near DNA repair related genes HEL308 and FAM175A (or Abraxas) and a 12q24 variant (rs4767364, p = 2×10−8) located in an extended linkage disequilibrium region that contains multiple genes including the aldehyde dehydrogenase 2 (ALDH2) gene. Three remaining variants are located in the ADH gene cluster and were identified previously in a candidate gene study involving some of these samples. The association between these three variants and UADT cancers was independently replicated in 5,092 UADT cancer cases and 6,794 controls non-overlapping samples presented here (rs1573496-ADH7, p = 5×10−8; rs1229984-ADH1B, p = 7×10−9; and rs698-ADH1C, p = 0.02). These results implicate two variants at 4q21 and 12q24 and further highlight three ADH variants in UADT cancer susceptibility. PMID:21437268

  7. ABO Blood Group Alleles and Prostate Cancer Risk: Results from the Breast and Prostate Cancer Cohort Consortium (BPC3)

    PubMed Central

    Markt, Sarah C.; Shui, Irene M.; Unger, Robert H.; Urun, Yuksel; Berg, Christine D.; Black, Amanda; Brennan, Paul; Bueno-de-Mesquita, H. Bas; Gapstur, Susan M.; Giovannucci, Edward; Haiman, Christopher; Henderson, Brian; Hoover, Robert N.; Hunter, David J.; Key, Timothy J.; Khaw, Kay-Tee; Canzian, Federico; Larranga, Nerea; Le Marchand, Loic; Ma, Jing; Naccarati, Alessio; Siddiq, Afshan; Stampfer, Meir J.; Stattin, Par; Stevens, Victoria L.; Stram, Daniel O.; Tjønneland, Anne; Travis, Ruth C.; Trichopoulos, Dimitrios; Ziegler, Regina G.; Lindstrom, Sara; Kraft, Peter; Mucci, Lorelei A.; Choueiri, Toni K.; Wilson, Kathryn M.

    2015-01-01

    Background ABO blood group has been associated with risk of cancers of the pancreas, stomach, ovary, kidney and skin, but has not been evaluated in relation to risk of aggressive prostate cancer. Methods We used three single nucleotide polymorphisms (SNPs) (rs8176746, rs505922, and rs8176704) to determine ABO genotype in 2,774 aggressive prostate cancer cases and 4,443 controls from the Breast and Prostate Cancer Cohort Consortium (BPC3). Unconditional logistic regression was used to calculate age and study adjusted odds ratios and 95% confidence intervals for the association between blood type, genotype and risk of aggressive prostate cancer (Gleason score ≥8 or locally advanced/metastatic disease (stage T3/T4/N1/M1). Results We found no association between ABO blood type and risk of aggressive prostate cancer (Type A: OR=0.97, 95% CI=0.87-1.08; Type B: OR=0.92, 95% CI=0.77-1.09; Type AB: OR=1.25, 95% CI=0.98-1.59, compared to Type O, respectively). Similarly, there was no association between ‘dose’ of A or B alleles and aggressive prostate cancer risk. Conclusions ABO blood type was not associated with risk of aggressive prostate cancer. PMID:26268879

  8. ABO blood group alleles and prostate cancer risk: Results from the breast and prostate cancer cohort consortium (BPC3).

    PubMed

    Markt, Sarah C; Shui, Irene M; Unger, Robert H; Urun, Yuksel; Berg, Christine D; Black, Amanda; Brennan, Paul; Bueno-de-Mesquita, H Bas; Gapstur, Susan M; Giovannucci, Edward; Haiman, Christopher; Henderson, Brian; Hoover, Robert N; Hunter, David J; Key, Timothy J; Khaw, Kay-Tee; Canzian, Federico; Larranga, Nerea; Le Marchand, Loic; Ma, Jing; Naccarati, Alessio; Siddiq, Afshan; Stampfer, Meir J; Stattin, Par; Stevens, Victoria L; Stram, Daniel O; Tjønneland, Anne; Travis, Ruth C; Trichopoulos, Dimitrios; Ziegler, Regina G; Lindstrom, Sara; Kraft, Peter; Mucci, Lorelei A; Choueiri, Toni K; Wilson, Kathryn M

    2015-11-01

    ABO blood group has been associated with risk of cancers of the pancreas, stomach, ovary, kidney, and skin, but has not been evaluated in relation to risk of aggressive prostate cancer. We used three single nucleotide polymorphisms (SNPs) (rs8176746, rs505922, and rs8176704) to determine ABO genotype in 2,774 aggressive prostate cancer cases and 4,443 controls from the Breast and Prostate Cancer Cohort Consortium (BPC3). Unconditional logistic regression was used to calculate age and study-adjusted odds ratios and 95% confidence intervals for the association between blood type, genotype, and risk of aggressive prostate cancer (Gleason score ≥8 or locally advanced/metastatic disease (stage T3/T4/N1/M1). We found no association between ABO blood type and risk of aggressive prostate cancer (Type A: OR = 0.97, 95%CI = 0.87-1.08; Type B: OR = 0.92, 95%CI =n0.77-1.09; Type AB: OR = 1.25, 95%CI = 0.98-1.59, compared to Type O, respectively). Similarly, there was no association between "dose" of A or B alleles and aggressive prostate cancer risk. ABO blood type was not associated with risk of aggressive prostate cancer. © 2015 Wiley Periodicals, Inc.

  9. Diabetes and other comorbidities in breast cancer survival by race/ethnicity: the California Breast Cancer Survivorship Consortium (CBCSC).

    PubMed

    Wu, Anna H; Kurian, Allison W; Kwan, Marilyn L; John, Esther M; Lu, Yani; Keegan, Theresa H M; Gomez, Scarlett Lin; Cheng, Iona; Shariff-Marco, Salma; Caan, Bette J; Lee, Valerie S; Sullivan-Halley, Jane; Tseng, Chiu-Chen; Bernstein, Leslie; Sposto, Richard; Vigen, Cheryl

    2015-02-01

    The role of comorbidities in survival of patients with breast cancer has not been well studied, particularly in non-white populations. We investigated the association of specific comorbidities with mortality in a multiethnic cohort of 8,952 breast cancer cases within the California Breast Cancer Survivorship Consortium (CBCSC), which pooled questionnaire and cancer registry data from five California-based studies. In total, 2,187 deaths (1,122 from breast cancer) were observed through December 31, 2010. Using multivariable Cox proportional hazards regression, we estimated HRs and 95% confidence intervals (CI) for overall and breast cancer-specific mortality associated with previous cancer, diabetes, high blood pressure (HBP), and myocardial infarction. Risk of breast cancer-specific mortality increased among breast cancer cases with a history of diabetes (HR, 1.48; 95% CI, 1.18-1.87) or myocardial infarction (HR, 1.94; 95% CI, 1.27-2.97). Risk patterns were similar across race/ethnicity (non-Latina white, Latina, African American, and Asian American), body size, menopausal status, and stage at diagnosis. In subgroup analyses, risk of breast cancer-specific mortality was significantly elevated among cases with diabetes who received neither radiotherapy nor chemotherapy (HR, 2.11; 95% CI, 1.32-3.36); no increased risk was observed among those who received both treatments (HR, 1.13; 95% CI, 0.70-1.84; P(interaction) = 0.03). A similar pattern was found for myocardial infarction by radiotherapy and chemotherapy (P(interaction) = 0.09). These results may inform future treatment guidelines for patients with breast cancer with a history of diabetes or myocardial infarction. Given the growing number of breast cancer survivors worldwide, we need to better understand how comorbidities may adversely affect treatment decisions and ultimately outcome. ©2014 American Association for Cancer Research.

  10. Screening and Early Detection of Gastric Cancer: East Versus West.

    PubMed

    Suh, Yun-Suhk; Yang, Han-Kwang

    2015-10-01

    Low ratio of mortality over incidence of gastric cancer in Asian countries including Korea and Japan could be explained by early detection after screening, different treatment strategy, or genetic disparity between the East and West. Early detection after screening program for gastric cancer and subsequent surgical treatment including appropriate lymph node dissection has been developed successfully in high risk areas such as East Asian countries. Even in countries with a low prevalence of gastric cancer, a specific screening program is recommended for any high-risk population. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Brief Report: Pediatric Cancer Burden and Treatment Resources Within the Pediatric IeDEA Consortium.

    PubMed

    Brown, Steven A; Abbas, Salma; Davies, Mary-Ann; Bunupuradah, Torsak; Sohn, Annette H; Technau, Karl-Günter; Renner, Lorna; Leroy, Valériane; Edmonds, Andrew; Yotebieng, Marcel; McGowan, Catherine C; Duda, Stephany N; Mofenson, Lynne; Musick, Beverly; Wools-Kaloustian, Kara

    2017-09-01

    The incidence and treatment of cancer in HIV-infected children from resource-limited settings has not been extensively studied. Develop and implement a cross-sectional survey to evaluate pediatric cancer burden, diagnostic modalities in use, and treatment availability as perceived by HIV clinic staff at regional International Epidemiology Databases to Evaluate AIDS (IeDEA) sites. IeDEA regional investigators developed a cross-sectional clinical site survey which included questions on the numbers and types of pediatric cancers observed, modalities used to treat identified cancers, and treatment options available at individual sites in the Asia-Pacific, Latin America, Central Africa, East Africa, West Africa, and Southern Africa regions. Kaposi sarcoma, non-Hodgkin lymphoma, and Burkitt lymphoma were reported by site personnel to be the most prevalent types of cancer in the pediatric HIV population. Survey results indicate that access to comprehensive cancer treatment modalities is very limited for children in these regions despite HIV care and treatment sites reporting that they diagnose pediatric cancers. Responses also showed that evaluating cancer in the pediatric HIV population is a challenge due to a lack of resources and varying treatment availability within regions. Further study is needed to increase our understanding of the changing epidemiology of cancer in HIV-infected pediatric populations. Increased financial and technical resources are critical to aid in the advancement of health services to support treatment of these children in resource-constrained settings.

  12. Diabetes and other comorbidities in breast cancer survival by race/ethnicity: The California Breast Cancer Survivorship Consortium (CBCSC)

    PubMed Central

    Wu, Anna H.; Kurian, Allison W.; Kwan, Marilyn L.; John, Esther M.; Lu, Yani; Keegan, Theresa H.M.; Gomez, Scarlett Lin; Cheng, Iona; Shariff-Marco, Salma; Caan, Bette J.; Lee, Valerie S.; Sullivan-Halley, Jane; Tseng, Chiu-Chen; Bernstein, Leslie; Sposto, Richard; Vigen, Cheryl

    2015-01-01

    Background The role of comorbidities in survival of breast cancer patients has not been well studied, particularly in non-white populations. Methods We investigated the association of specific comorbidities with mortality in a multiethnic cohort of 8,952 breast cancer cases within the California Breast Cancer Survivorship Consortium (CBCSC), which pooled questionnaire and cancer registry data from five California-based studies. In total, 2,187 deaths (1,122 from breast cancer) were observed through December 31, 2010. Using multivariable Cox proportional hazards regression, we estimated hazards ratios (HR) and 95% confidence intervals (CI) for overall and breast cancer-specific mortality associated with previous cancer, diabetes, high blood pressure (HBP), and myocardial infarction (MI). Results Risk of breast cancer-specific mortality increased among breast cancer cases with a history of diabetes (HR=1.48, 95% CI=1.18, 1.87) or MI (HR=1.94, 95% CI=1.27–2.97). Risk patterns were similar across race/ethnicity (non-Latina White, Latina, African American and Asian American), body size, menopausal status, and stage at diagnosis. In subgroup analyses, risk of breast cancer-specific mortality was significantly elevated among cases with diabetes who received neither radiation nor chemotherapy (HR=2.11, 95% CI=1.32–3.36); no increased risk was observed among those who received both treatments (HR=1.13, 95% CI= 0.70–1.84) (P interaction= 0.03). A similar pattern was found for MI by radiation and chemotherapy (P interaction=0.09). Conclusion These results may inform future treatment guidelines for breast cancer patients with a history of diabetes or MI. Impact Given the growing number of breast cancer survivors worldwide, we need to better understand how comorbidities may adversely affect treatment decisions and ultimately outcome. PMID:25425578

  13. International Lung Cancer Consortium: Pooled Analysis of Sequence Variants in DNA Repair and Cell Cycle Pathways

    PubMed Central

    Hung, Rayjean J.; Christiani, David C.; Risch, Angela; Popanda, Odilia; Haugen, Aage; Zienolddiny, Shan; Benhamou, Simone; Bouchardy, Christine; Lan, Qing; Spitz, Margaret R.; Wichmann, H.-Erich; LeMarchand, Loic; Vineis, Paolo; Matullo, Giuseppe; Kiyohara, Chikako; Zhang, Zuo-Feng; Pezeshki, Benhnaz; Harris, Curtis; Mechanic, Leah; Seow, Adeline; Ng, Daniel P.K.; Szeszenia-Dabrowska, Neonila; Zaridze, David; Lissowska, Jolanta; Rudnai, Peter; Fabianova, Eleonora; Mates, Dana; Foretova, Lenka; Janout, Vladimir; Bencko, Vladimir; Caporaso, Neil; Chen, Chu; Duell, Eric J.; Goodman, Gary; Field, John K.; Houlston, Richard S.; Hong, Yun-Chul; Landi, Maria Teresa; Lazarus, Philip; Muscat, Joshua; McLaughlin, John; Schwartz, Ann G.; Shen, Hongbing; Stucker, Isabelle; Tajima, Kazuo; Matsuo, Keitaro; Thun, Michael; Yang, Ping; Wiencke, John; Andrew, Angeline S.; Monnier, Stephanie; Boffetta, Paolo; Brennan, Paul

    2009-01-01

    Background The International Lung Cancer Consortium was established in 2004. To clarify the role of DNA repair genes in lung cancer susceptibility, we conducted a pooled analysis of genetic variants in DNA repair pathways, whose associations have been investigated by at least 3 individual studies. Methods Data from 14 studies were pooled for 18 sequence variants in 12 DNA repair genes, including APEX1, OGG1, XRCC1, XRCC2, XRCC3, ERCC1, XPD, XPF, XPG, XPA, MGMT, and TP53. The total number of subjects included in the analysis for each variant ranged from 2,073 to 13,955 subjects. Results Four of the variants were found to be weakly associated with lung cancer risk with borderline significance: these were XRCC3 T241M [heterozygote odds ratio (OR), 0.89; 95% confidence interval (95% CI), 0.79–0.99 and homozygote OR, 0.84; 95% CI, 0.71–1.00] based on 3,467 cases and 5,021 controls from 8 studies, XPD K751Q (heterozygote OR, 0.99; 95% CI, 0.89–1.10 and homozygote OR, 1.19; 95% CI, 1.02–1.39) based on 6,463 cases and 6,603 controls from 9 studies, and TP53 R72P (heterozygote OR, 1.14; 95% CI, 1.00–1.29 and homozygote OR, 1.20; 95% CI, 1.02–1.42) based on 3,610 cases and 5,293 controls from 6 studies. OGG1 S326C homozygote was suggested to be associated with lung cancer risk in Caucasians (homozygote OR, 1.34; 95% CI, 1.01–1.79) based on 2,569 cases and 4,178 controls from 4 studies but not in Asians. The other 14 variants did not exhibit main effects on lung cancer risk. Discussion In addition to data pooling, future priorities of International Lung Cancer Consortium include coordinated genotyping and multistage validation for ongoing genome-wide association studies. PMID:18990748

  14. Association of marijuana smoking with oropharyngeal and oral tongue cancers: pooled analysis from the INHANCE consortium.

    PubMed

    Marks, Morgan A; Chaturvedi, Anil K; Kelsey, Karl; Straif, Kurt; Berthiller, Julien; Schwartz, Stephen M; Smith, Elaine; Wyss, Annah; Brennan, Paul; Olshan, Andrew F; Wei, Qingyi; Sturgis, Erich M; Zhang, Zuo-Feng; Morgenstern, Hal; Muscat, Joshua; Lazarus, Philip; McClean, Michael; Chen, Chu; Vaughan, Thomas L; Wunsch-Filho, Victor; Curado, Maria Paula; Koifman, Sergio; Matos, Elena; Menezes, Ana; Daudt, Alexander W; Fernandez, Leticia; Posner, Marshall; Boffetta, Paolo; Lee, Yuan-Chin Amy; Hashibe, Mia; D'Souza, Gypsyamber

    2014-01-01

    The incidence of oropharyngeal and oral tongue cancers has increased over the last 20 years which parallels increased use of marijuana among individuals born after 1950. A pooled analysis was conducted comprising individual-level data from nine case-control studies from the United States and Latin America in the INHANCE consortium. Self-reported information on marijuana smoking, demographic, and behavioral factors was obtained from 1,921 oropharyngeal cases, 356 oral tongue cases, and 7,639 controls. Compared with never marijuana smokers, ever marijuana smokers had an elevated risk of oropharyngeal [adjusted OR (aOR), 1.24; 95% confidence interval (CI): 1.06-1.47] and a reduced risk of oral tongue cancer (aOR, 0.47; 95% CI, 0.29, 0.75). The risk of oropharyngeal cancer remained elevated among never tobacco and alcohol users. The risk of oral tongue cancer was reduced among never users of tobacco and alcohol. Sensitivity analysis adjusting for potential confounding by HPV exposure attenuated the association of marijuana use with oropharyngeal cancer (aOR, 0.99; 95% CI, 0.71-1.25), but had no effect on the oral tongue cancer association. These results suggest that the association of marijuana use with head and neck carcinoma may differ by tumor site. The associations of marijuana use with oropharyngeal and oral tongue cancer are consistent with both possible pro- and anticarcinogenic effects of cannabinoids. Additional work is needed to rule out various sources of bias, including residual confounding by HPV infection and misclassification of marijuana exposure.

  15. The California Breast Cancer Survivorship Consortium (CBCSC): Prognostic factors associated with racial/ethnic differences in breast cancer survival

    PubMed Central

    Wu, Anna H.; Gomez, Scarlett Lin; Vigen, Cheryl; Kwan, Marilyn L.; Keegan, Theresa H.M.; Lu, Yani; Shariff-Marco, Salma; Monroe, Kristine R.; Kurian, Allison W.; Cheng, Iona; Caan, Bette J.; Lee, Valerie S.; Roh, Janise M.; Sullivan-Halley, Jane; Henderson, Brian E.; Bernstein, Leslie; John, Esther M.; Sposto, Richard

    2014-01-01

    Racial/ethnic disparities in mortality among US breast cancer patients are well-documented. Our knowledge of the contribution of lifestyle factors to disease prognosis is based primarily on non-Latina Whites and is limited for Latina, African American and Asian American women. To address this knowledge gap, the California Breast Cancer Survivorship Consortium (CBCSC) harmonized and pooled interview information (e.g., demographics, family history of breast cancer, parity, smoking, alcohol consumption) from six California-based breast cancer studies and assembled corresponding cancer registry data (clinical characteristics, mortality), resulting in 12,210 patients (6,501 non-Latina Whites, 2,060 African Americans, 2,032 Latinas, 1,505 Asian Americans, 112 other race/ethnicity) diagnosed with primary invasive breast cancer between 1993 and 2007. In total, 3,047 deaths (1,570 breast cancer-specific) were observed with a mean (SD) follow-up of 8.3 (3.5) years. Cox-proportional hazards regression models were fit to data to estimate hazards ratios (HR) and 95% confidence intervals (CI) for overall and breast cancer-specific mortality. Compared with non-Latina Whites, the HR of breast cancer-specific mortality was 1.13 (95% CI, 0.97-1.33) for African Americans, 0.84 (95% CI, 0.70-1.00) for Latinas, and 0.60 (95% CI, 0.37-0.97) for Asian Americans after adjustment for age, tumor characteristics, and select lifestyle factors. The CBCSC represents a large and racially/ethnically diverse cohort of breast cancer patients from California. This cohort will enable analyses to jointly consider a variety of clinical, lifestyle, and contextual factors in attempting to explain the long-standing disparities in breast cancer outcomes. PMID:23864487

  16. Vigorous physical activity and risk of breast cancer in the African American breast cancer epidemiology and risk consortium.

    PubMed

    Gong, Zhihong; Hong, Chi-Chen; Bandera, Elisa V; Adams-Campbell, Lucile L; Troester, Melissa A; Park, Song-Yi; McInerney, Kathryn A; Zirpoli, Gary; Olshan, Andrew F; Palmer, Julie R; Ambrosone, Christine B; Rosenberg, Lynn

    2016-09-01

    The relationship between physical activity and breast cancer risk has been extensively studied among women of European descent, with most studies reporting inverse associations. However, data on American women of African ancestry (AA) and by tumor subtypes are sparse. Thus, we examined associations of vigorous exercise and breast cancer risk overall, and by estrogen receptor (ER) status, in the African American Breast Cancer Epidemiology and Risk Consortium. We pooled data from four large studies on 2482 ER+ cases, 1374 ER- cases, and 16,959 controls. Multivariable logistic regression was used to compute odds ratios (OR) and 95 % confidence intervals (CI) for the risk of breast cancer overall, and polytomous logistic regression was used to model the risk of ER+ and ER- cancer. Recent vigorous exercise was associated with a statistically significant, modestly decreased risk for breast cancer overall (OR 0.88, 95 % CI 0.81-0.96) and for ER+ cancer (OR 0.88, 95 % CI 0.80-0.98), but not for ER- cancer (OR 0.93, 95 % CI 0.82-1.06). Overall, there was no strong evidence of effect modification by age, menopausal status, body mass index, and parity. However, our data were suggestive of modification by family history, such that an inverse association was present among women without a family history but not among those with a relative affected by breast cancer. Results from this large pooled analysis provide evidence that vigorous physical activity is associated with a modestly reduced risk of breast cancer in AA women, specifically ER+ cancer.

  17. Tobacco and alcohol in relation to male breast cancer: an analysis of the male breast cancer pooling project consortium.

    PubMed

    Cook, Michael B; Guénel, Pascal; Gapstur, Susan M; van den Brandt, Piet A; Michels, Karin B; Casagrande, John T; Cooke, Rosie; Van Den Eeden, Stephen K; Ewertz, Marianne; Falk, Roni T; Gaudet, Mia M; Gkiokas, George; Habel, Laurel A; Hsing, Ann W; Johnson, Kenneth; Kolonel, Laurence N; La Vecchia, Carlo; Lynge, Elsebeth; Lubin, Jay H; McCormack, Valerie A; Negri, Eva; Olsson, Håkan; Parisi, Dominick; Petridou, Eleni Th; Riboli, Elio; Sesso, Howard D; Swerdlow, Anthony; Thomas, David B; Willett, Walter C; Brinton, Louise A

    2015-03-01

    The etiology of male breast cancer is poorly understood, partly due to its relative rarity. Although tobacco and alcohol exposures are known carcinogens, their association with male breast cancer risk remains ill-defined. The Male Breast Cancer Pooling Project consortium provided 2,378 cases and 51,959 controls for analysis from 10 case-control and 10 cohort studies. Individual participant data were harmonized and pooled. Unconditional logistic regression was used to estimate study design-specific (case-control/cohort) ORs and 95% confidence intervals (CI), which were then combined using fixed-effects meta-analysis. Cigarette smoking status, smoking pack-years, duration, intensity, and age at initiation were not associated with male breast cancer risk. Relations with cigar and pipe smoking, tobacco chewing, and snuff use were also null. Recent alcohol consumption and average grams of alcohol consumed per day were also not associated with risk; only one subanalysis of very high recent alcohol consumption (>60 g/day) was tentatively associated with male breast cancer (ORunexposed referent = 1.29; 95% CI, 0.97-1.71; OR>0-<7 g/day referent = 1.36; 95% CI, 1.04-1.77). Specific alcoholic beverage types were not associated with male breast cancer. Relations were not altered when stratified by age or body mass index. In this analysis of the Male Breast Cancer Pooling Project, we found little evidence that tobacco and alcohol exposures were associated with risk of male breast cancer. Tobacco and alcohol do not appear to be carcinogenic for male breast cancer. Future studies should aim to assess these exposures in relation to subtypes of male breast cancer. ©2014 American Association for Cancer Research.

  18. National Performance Benchmarks for Modern Diagnostic Digital Mammography: Update from the Breast Cancer Surveillance Consortium.

    PubMed

    Sprague, Brian L; Arao, Robert F; Miglioretti, Diana L; Henderson, Louise M; Buist, Diana S M; Onega, Tracy; Rauscher, Garth H; Lee, Janie M; Tosteson, Anna N A; Kerlikowske, Karla; Lehman, Constance D

    2017-04-01

    Purpose To establish contemporary performance benchmarks for diagnostic digital mammography with use of recent data from the Breast Cancer Surveillance Consortium (BCSC). Materials and Methods Institutional review board approval was obtained for active or passive consenting processes or to obtain a waiver of consent to enroll participants, link data, and perform analyses. Data were obtained from six BCSC registries (418 radiologists, 92 radiology facilities). Mammogram indication and assessments were prospectively collected for women undergoing diagnostic digital mammography and linked with cancer diagnoses from state cancer registries. The study included 401 548 examinations conducted from 2007 to 2013 in 265 360 women. Results Overall diagnostic performance measures were as follows: cancer detection rate, 34.7 per 1000 (95% confidence interval [CI]: 34.1, 35.2); abnormal interpretation rate, 12.6% (95% CI: 12.5%, 12.7%); positive predictive value (PPV) of a biopsy recommendation (PPV2), 27.5% (95% CI: 27.1%, 27.9%); PPV of biopsies performed (PPV3), 30.4% (95% CI: 29.9%, 30.9%); false-negative rate, 4.8 per 1000 (95% CI: 4.6, 5.0); sensitivity, 87.8% (95% CI: 87.3%, 88.4%); and specificity, 90.5% (95% CI: 90.4%, 90.6%). Among cancers detected, 63.4% were stage 0 or 1 cancers, 45.6% were minimal cancers, the mean size of invasive cancers was 21.2 mm, and 69.6% of invasive cancers were node negative. Performance metrics varied widely across diagnostic indications, with cancer detection rate (64.5 per 1000) and abnormal interpretation rate (18.7%) highest for diagnostic mammograms obtained to evaluate a breast problem with a lump. Compared with performance during the screen-film mammography era, diagnostic digital performance showed increased abnormal interpretation and cancer detection rates and decreasing PPVs, with less than 70% of radiologists within acceptable ranges for PPV2 and PPV3. Conclusion These performance measures can serve as national benchmarks that

  19. Tobacco and Alcohol in Relation to Male Breast Cancer: An Analysis of the Male Breast Cancer Pooling Project Consortium

    PubMed Central

    Cook, Michael B.; Guénel, Pascal; Gapstur, Susan M.; van den Brandt, Piet A.; Michels, Karin B.; Casagrande, John T.; Cooke, Rosie; Van Den Eeden, Stephen K.; Ewertz, Marianne; Falk, Roni T.; Gaudet, Mia M.; Gkiokas, George; Habel, Laurel A.; Hsing, Ann W.; Johnson, Kenneth; Kolonel, Laurence N.; La Vecchia, Carlo; Lynge, Elsebeth; Lubin, Jay H.; McCormack, Valerie A.; Negri, Eva; Olsson, Håkan; Parisi, Dominick; Petridou, Eleni Th.; Riboli, Elio; Sesso, Howard D.; Swerdlow, Anthony; Thomas, David B.; Willett, Walter C.; Brinton, Louise A.

    2015-01-01

    Background The etiology of male breast cancer is poorly understood, partly due to its relative rarity. Although tobacco and alcohol exposures are known carcinogens, their association with male breast cancer risk remains ill-defined. Methods The Male Breast Cancer Pooling Project consortium provided 2,378 cases and 51,959 controls for analysis from 10 case-control and 10 cohort studies. Individual participant data were harmonized and pooled. Unconditional logistic regression was used to estimate study design-specific (case-control/cohort) odds ratios (OR) and 95% confidence intervals (CI), which were then combined using fixed effects meta-analysis. Results Cigarette smoking status, smoking pack-years, duration, intensity, and age at initiation were not associated with male breast cancer risk. Relations with cigar and pipe smoking, tobacco chewing, and snuff use were also null. Recent alcohol consumption and average grams of alcohol consumed per day were also not associated with risk; only one sub-analysis of very high recent alcohol consumption (>60 grams/day) was tentatively associated with male breast cancer (ORunexposed referent=1.29, 95%CI:0.97–1.71; OR>0–<7 g/day referent=1.36, 95%CI:1.04–1.77). Specific alcoholic beverage types were not associated with male breast cancer. Relations were not altered when stratified by age or body mass index. Conclusions In this analysis of the Male Breast Cancer Pooling Project we found little evidence that tobacco and alcohol exposures were associated with risk of male breast cancer. Impact Tobacco and alcohol do not appear to be carcinogenic for male breast cancer. Future studies should aim to assess these exposures in relation to subtypes of male breast cancer. PMID:25515550

  20. RELATION OF ALLIUM VEGETABLES INTAKE WITH HEAD AND NECK CANCERS: EVIDENCE FROM THE INHANCE CONSORTIUM

    PubMed Central

    Galeone, Carlotta; Turati, Federica; Zhang, Zuo-Feng; Guercio, Valentina; Tavani, Alessandra; Serraino, Diego; Brennan, Paul; Fabianova, Eleonora; Lissowska, Jola; Mates, Dana; Rudnai, Peter; Shangina, Oxana; Szeszenia-Dabrowska, Neonila; Vaughan, Thomas L.; Kelsey, Karl; McClean, Michael; Levi, Fabio; Hayes, Richard B.; Purdue, Mark P.; Bosetti, Cristina; Brenner, Hermann; Pelucchi, Claudio; Lee, Yuan-Chin Amy; Hashibe, Mia; Boffetta, Paolo; La Vecchia, Carlo

    2015-01-01

    Scope Only a few studies analyzed the role of allium vegetables with reference to head and neck cancers (HNC), with mixed results. We investigated the potential favorable role of garlic and onion within the International Head and Neck Cancer Epidemiology (INHANCE) Consortium. Methods and results We analyzed pooled individual-level data from eight case-control studies, including 4590 cases and 7082 controls. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) for associations between garlic and onion intakes and HNC risk. Compared with no or low garlic use, the ORs of HNC were 0.95 (95% CI 0.71–1.27) for intermediate and 0.74 (95% CI 0.55–0.99) for high garlic use (p for trend= 0.02). The ORs of HNC for increasing categories of onion intake were 0.91 (95% CI 0.68–1.21) for >1 to ≤3 portions per week, and 0.83 (95% CI 0.60–1.13) for >3 portions per week (p for trend= 0.02), as compared to <1 portion per week. We found an inverse association between high onion intake and laryngeal cancer risk (OR=0.69; 95% CI 0.54–0.88), but no significant association for other subsites. Conclusions The results of this pooled-analysis support a possible moderate inverse association between garlic and onion intake and HNC risk. PMID:26018663

  1. Genetic variants of the DNA repair genes from Exome Aggregation Consortium (EXAC) database: significance in cancer.

    PubMed

    Das, Raima; Ghosh, Sankar Kumar

    2017-04-01

    DNA repair pathway is a primary defense system that eliminates wide varieties of DNA damage. Any deficiencies in them are likely to cause the chromosomal instability that leads to cell malfunctioning and tumorigenesis. Genetic polymorphisms in DNA repair genes have demonstrated a significant association with cancer risk. Our study attempts to give a glimpse of the overall scenario of the germline polymorphisms in the DNA repair genes by taking into account of the Exome Aggregation Consortium (ExAC) database as well as the Human Gene Mutation Database (HGMD) for evaluating the disease link, particularly in cancer. It has been found that ExAC DNA repair dataset (which consists of 228 DNA repair genes) comprises 30.4% missense, 12.5% dbSNP reported and 3.2% ClinVar significant variants. 27% of all the missense variants has the deleterious SIFT score of 0.00 and 6% variants carrying the most damaging Polyphen-2 score of 1.00, thus affecting the protein structure and function. However, as per HGMD, only a fraction (1.2%) of ExAC DNA repair variants was found to be cancer-related, indicating remaining variants reported in both the databases to be further analyzed. This, in turn, may provide an increased spectrum of the reported cancer linked variants in the DNA repair genes present in ExAC database. Moreover, further in silico functional assay of the identified vital cancer-associated variants, which is essential to get their actual biological significance, may shed some lights in the field of targeted drug development in near future. Copyright © 2017. Published by Elsevier B.V.

  2. Predictors of pretreatment CA125 at ovarian cancer diagnosis: a pooled analysis in the Ovarian Cancer Association Consortium.

    PubMed

    Babic, Ana; Cramer, Daniel W; Kelemen, Linda E; Köbel, Martin; Steed, Helen; Webb, Penelope M; Johnatty, Sharon E; deFazio, Anna; Lambrechts, Diether; Goodman, Marc T; Heitz, Florian; Matsuo, Keitaro; Hosono, Satoyo; Karlan, Beth Y; Jensen, Allan; Kjær, Susanne K; Goode, Ellen L; Pejovic, Tanja; Moffitt, Melissa; Høgdall, Estrid; Høgdall, Claus; McNeish, Iain; Terry, Kathryn L

    2017-05-01

    Cancer antigen 125 (CA125) is a glycoprotein expressed by epithelial cells of several normal tissue types and overexpressed by several epithelial cancers. Serum CA125 levels are mostly used as an aid in the diagnosis of ovarian cancer patients, to monitor response to treatment and detect cancer recurrence. Besides tumor characteristics, CA125 levels are also influenced by several epidemiologic factors, such as age, parity, and oral contraceptive use. Identifying factors that influence CA125 levels in ovarian cancer patients could aid in the interpretation of CA125 values for individuals. We evaluated predictors of pretreatment CA125 in 13 studies participating in the Ovarian Cancer Association Consortium. This analysis included a total of 5,091 women with invasive epithelial ovarian cancer with pretreatment CA125 measurements. We used probit scores to account for variability in CA125 between studies and linear regression to estimate the association between epidemiologic factors and tumor characteristics and pretreatment CA125 levels. In age-adjusted models, older age, history of pregnancy, history of tubal ligation, family history of breast cancer, and family history of ovarian cancer were associated with higher CA125 levels while endometriosis was associated with lower CA125 levels. After adjusting for tumor-related characteristics (stage, histology, grade), body mass index (BMI) higher than 30 kg/m(2) was associated with 10% (95% CI 2, 19%) higher CA125 levels, while race (non-white vs. white) was associated with 15% (95% CI 4, 27%) higher CA125 levels. Our results suggest that high BMI and race may influence CA125 levels independent of tumor characteristics. Validation is needed in studies that use a single assay for CA125 measurement and have a diverse study population.

  3. The INHANCE consortium: toward a better understanding of the causes and mechanisms of head and neck cancer.

    PubMed

    Winn, D M; Lee, Y-C A; Hashibe, M; Boffetta, P

    2015-09-01

    The International Head and Neck Cancer Epidemiology (INHANCE) consortium is a collaboration of research groups leading large epidemiology studies to improve the understanding of the causes and mechanisms of head and neck cancer. The consortium includes investigators of 35 studies who have pooled their data on 25 500 patients with head and neck cancer (i.e., cancers of the oral cavity, oropharynx, hypopharynx, and larynx) and 37 100 controls. The INHANCE analyses have confirmed that tobacco use and alcohol intake are key risk factors of these diseases and have provided precise estimates of risk and dose response, the benefit of quitting, and the hazard of smoking even a few cigarettes per day. Other risk factors include short height, lean body mass, low education and income, and a family history of head and neck cancer. Risk factors are generally similar for oral cavity, pharynx, and larynx, although the magnitude of risk may vary. Some major strengths of pooling data across studies include more precise estimates of risk and the ability to control for potentially confounding factors and to examine factors that may interact with each other. The INHANCE consortium provides evidence of the scientific productivity and discoveries that can be obtained from data pooling projects. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. 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

  5. Use of common analgesic medications and ovarian cancer survival: results from a pooled analysis in the Ovarian Cancer Association Consortium.

    PubMed

    Dixon, Suzanne C; Nagle, Christina M; Wentzensen, Nicolas; Trabert, Britton; Beeghly-Fadiel, Alicia; Schildkraut, Joellen M; Moysich, Kirsten B; deFazio, Anna; Risch, Harvey A; Rossing, Mary Anne; Doherty, Jennifer A; Wicklund, Kristine G; Goodman, Marc T; Modugno, Francesmary; Ness, Roberta B; Edwards, Robert P; Jensen, Allan; Kjær, Susanne K; Høgdall, Estrid; Berchuck, Andrew; Cramer, Daniel W; Terry, Kathryn L; Poole, Elizabeth M; Bandera, Elisa V; Paddock, Lisa E; Anton-Culver, Hoda; Ziogas, Argyrios; Menon, Usha; Gayther, Simon A; Ramus, Susan J; Gentry-Maharaj, Aleksandra; Pearce, Celeste Leigh; Wu, Anna H; Pike, Malcolm C; Webb, Penelope M

    2017-04-25

    Nonsteroidal anti-inflammatory drugs (NSAIDs) have been associated with improved survival in some cancers, but evidence for ovarian cancer is limited. Pooling individual-level data from 12 Ovarian Cancer Association Consortium studies, we evaluated the association between self-reported, pre-diagnosis use of common analgesics and overall/progression-free/disease-specific survival among 7694 women with invasive epithelial ovarian cancer (4273 deaths). Regular analgesic use (at least once per week) was not associated with overall survival (pooled hazard ratios, pHRs (95% confidence intervals): aspirin 0.96 (0.88-1.04); non-aspirin NSAIDs 0.97 (0.89-1.05); acetaminophen 1.01 (0.93-1.10)), nor with progression-free/disease-specific survival. There was however a survival advantage for users of any NSAIDs in studies clearly defining non-use as less than once per week (pHR=0.89 (0.82-0.98)). Although this study did not show a clear association between analgesic use and ovarian cancer survival, further investigation with clearer definitions of use and information about post-diagnosis use is warranted.

  6. A Collaborative Study of the Etiology of Breast Cancer Subtypes in African American Women: the AMBER Consortium

    PubMed Central

    Palmer, Julie R.; Ambrosone, Christine B.; Olshan, Andrew F.

    2014-01-01

    Purpose Breast cancer is a heterogeneous disease, with at least five intrinsic subtypes defined by molecular characteristics. Tumors that express the estrogen receptor (ER+) have better outcomes than ER− tumors, due in part to the success of hormonal therapies that target ER+ tumors. The incidence of ER− breast cancer, and the subset of ER− cancers that are basal-like, is about twice as high among African American (AA) women as among U.S. women of European descent (EA). This disparity appears to explain, in part, the disproportionately high mortality from breast cancer that occurs in AA women. Epidemiologic research on breast cancer in AA women lags behind research in EA women. Here, we review differences in the etiology of breast cancer subtypes among AA women and describe a new consortium of ongoing studies of breast cancer in AA women. Methods We combined samples and data from four large epidemiologic studies of breast cancer in AA women, two cohort and two case-control, creating the AMBER consortium. Tumor tissue is obtained and stored in tissue microarrays, with assays of molecular markers carried out at a pathology core. Genotyping, carried out centrally, includes a whole exome SNP array and over 180,000 custom SNPs for fine-mapping of GWAS loci and candidate pathways. Results To date, questionnaire data from 5,739 breast cancer cases and 14,273 controls have been harmonized. Genotyping of the first 3,200 cases and 3,700 controls is underway, with a total of 6,000 each expected by the end of the study period. Conclusions The new consortium will likely have sufficient statistical power to assess potential risk factors, both genetic and non-genetic in relation to specific subtypes of breast cancer in AA women. PMID:24343304

  7. Alcohol intake and risk of colorectal cancer: Results from the UK Dietary Cohort Consortium

    PubMed Central

    Park, J Y; Dahm, C C; Keogh, R H; Mitrou, P N; Cairns, B J; Greenwood, D C; Spencer, E A; Fentiman, I S; Shipley, M J; Brunner, E J; Cade, J E; Burley, V J; Mishra, G D; Kuh, D; Stephen, A M; White, I R; Luben, R N; Mulligan, A A; Khaw, K-T; Rodwell, S A

    2010-01-01

    Background: Epidemiological studies have suggested that excessive alcohol intake increases colorectal cancer (CRC) risk. However, findings regarding tumour subsites and sex differences have been inconsistent. Methods: We investigated the prospective associations between alcohol intake on overall and site- and sex-specific CRC risk. Analyses were conducted on 579 CRC cases and 1996 matched controls nested within the UK Dietary Cohort Consortium using standardised data obtained from food diaries as a main nutritional method and repeated using data from food frequency questionnaire (FFQ). Results: Compared with individuals in the lightest category of drinkers (>0–<5 g per day), the multivariable odds ratios of CRC were 1.16 (95% confidence interval (95% CI): 0.88, 1.53) for non-drinkers, 0.91 (95% CI: 0.67, 1.24) for drinkers with 5–<15 g per day, 0.90 (95% CI: 0.65, 1.25) for drinkers with 15–<30 g per day, 1.02 (95% CI: 0.66, 1.58) for drinkers with 30–<45 g per day and 1.19 (95% CI: 0.75, 1.91) for drinkers with ⩾45 g per day. No clear associations were observed between site-specific CRC risk and alcohol intake in either sex. Analyses using FFQ showed similar results. Conclusion: We found no significantly increased risk of CRC up to 30 g per day of alcohol intake within the UK Dietary Cohort Consortium. PMID:20648013

  8. Contribution of the neighborhood environment and obesity to breast cancer survival: the California Breast Cancer Survivorship Consortium.

    PubMed

    Cheng, Iona; Shariff-Marco, Salma; Koo, Jocelyn; Monroe, Kristine R; Yang, Juan; John, Esther M; Kurian, Allison W; Kwan, Marilyn L; Henderson, Brian E; Bernstein, Leslie; Lu, Yani; Sposto, Richard; Vigen, Cheryl; Wu, Anna H; Gomez, Scarlett Lin; Keegan, Theresa H M

    2015-08-01

    Little is known about neighborhood attributes that may influence opportunities for healthy eating and physical activity in relation to breast cancer mortality. We used data from the California Breast Cancer Survivorship Consortium and the California Neighborhoods Data System (CNDS) to examine the neighborhood environment, body mass index, and mortality after breast cancer. We studied 8,995 African American, Asian American, Latina, and non-Latina white women with breast cancer. Residential addresses were linked to the CNDS to characterize neighborhoods. We used multinomial logistic regression to evaluate the associations between neighborhood factors and obesity and Cox proportional hazards regression to examine associations between neighborhood factors and mortality. For Latinas, obesity was associated with more neighborhood crowding [quartile 4 (Q4) vs. Q1: OR, 3.24; 95% confidence interval (CI), 1.50-7.00]; breast cancer-specific mortality was inversely associated with neighborhood businesses (Q4 vs. Q1: HR, 0.46; 95% CI, 0.25-0.85) and positively associated with multifamily housing (Q3 vs. Q1: HR, 1.98; 95% CI, 1.20-3.26). For non-Latina whites, lower neighborhood socioeconomic status (SES) was associated with obesity [quintile 1 (Q1) vs. Q5: OR, 2.52; 95% CI, 1.31-4.84], breast cancer-specific (Q1 vs. Q5: HR, 2.75; 95% CI, 1.47-5.12), and all-cause (Q1 vs. Q5: HR, 1.75; 95% CI, 1.17-2.62) mortality. For Asian Americans, no associations were seen. For African Americans, lower neighborhood SES was associated with lower mortality in a nonlinear fashion. Attributes of the neighborhood environment were associated with obesity and mortality following breast cancer diagnosis, but these associations differed across racial/ethnic groups. ©2015 American Association for Cancer Research.

  9. Carotenoid intake and head and neck cancer: a pooled analysis in the International Head and Neck Cancer Epidemiology Consortium.

    PubMed

    Leoncini, Emanuele; Edefonti, Valeria; Hashibe, Mia; Parpinel, Maria; Cadoni, Gabriella; Ferraroni, Monica; Serraino, Diego; Matsuo, Keitaro; Olshan, Andrew F; Zevallos, Jose P; Winn, Deborah M; Moysich, Kirsten; Zhang, Zuo-Feng; Morgenstern, Hal; Levi, Fabio; Kelsey, Karl; McClean, Michael; Bosetti, Cristina; Schantz, Stimson; Yu, Guo-Pei; Boffetta, Paolo; Lee, Yuan-Chin Amy; Chuang, Shu-Chun; Decarli, Adriano; La Vecchia, Carlo; Boccia, Stefania

    2016-04-01

    Food and nutrition play an important role in head and neck cancer (HNC) etiology; however, the role of carotenoids remains largely undefined. We explored the relation of HNC risk with the intake of carotenoids within the International Head and Neck Cancer Epidemiology Consortium. We pooled individual-level data from 10 case-control studies conducted in Europe, North America, and Japan. The analysis included 18,207 subjects (4414 with oral and pharyngeal cancer, 1545 with laryngeal cancer, and 12,248 controls), categorized by quintiles of carotenoid intake from natural sources. Comparing the highest with the lowest quintile, the risk reduction associated with total carotenoid intake was 39 % (95 % CI 29-47 %) for oral/pharyngeal cancer and 39 % (95 % CI 24-50 %) for laryngeal cancer. Intakes of β-carotene equivalents, β-cryptoxanthin, lycopene, and lutein plus zeaxanthin were associated with at least 18 % reduction in the rate of oral and pharyngeal cancer (95 % CI 6-29 %) and 17 % reduction in the rate of laryngeal cancer (95 % CI 0-32 %). The overall protective effect of carotenoids on HNC was stronger for subjects reporting greater alcohol consumption (p < 0.05). The odds ratio for the combined effect of low carotenoid intake and high alcohol or tobacco consumption versus high carotenoid intake and low alcohol or tobacco consumption ranged from 7 (95 % CI 5-9) to 33 (95 % CI 23-49). A diet rich in carotenoids may protect against HNC. Persons with both low carotenoid intake and high tobacco or alcohol are at substantially higher risk of HNC.

  10. Anthropometric Measures, Body Mass Index and Pancreatic Cancer: a Pooled Analysis from the Pancreatic Cancer Cohort Consortium (PanScan)

    PubMed Central

    Arslan, Alan A.; Helzlsouer, Kathy J.; Kooperberg, Charles; Shu, Xiao-Ou; Steplowski, Emily; Bueno-de-Mesquita, H. Bas; Fuchs, Charles S.; Gross, Myron D.; Jacobs, Eric J.; LaCroix, Andrea Z.; Petersen, Gloria M.; Stolzenberg-Solomon, Rachael Z.; Zheng, Wei; Albanes, Demetrius; Amundadottir, Laufey; Bamlet, William R.; Barricarte, Aurelio; Bingham, Sheila A.; Boeing, Heiner; Boutron-Ruault, Marie-Christine; Buring, Julie E.; Chanock, Stephen J.; Clipp, Sandra; Gaziano, J. Michael; Giovannucci, Edward L.; Hankinson, Susan E.; Hartge, Patricia; Hoover, Robert N.; Hunter, David J.; Hutchinson, Amy; Jacobs, Kevin B.; Kraft, Peter; Lynch, Shannon M.; Manjer, Jonas; Manson, JoAnn E.; McTiernan, Anne; McWilliams, Robert R.; Mendelsohn, Julie B.; Michaud, Dominique S.; Palli, Domenico; Rohan, Thomas E.; Slimani, Nadia; Thomas, Gilles; Tjønneland, Anne; Tobias, Geoffrey S.; Trichopoulos, Dimitrios; Virtamo, Jarmo; Wolpin, Brian M.; Yu, Kai; Zeleniuch-Jacquotte, Anne; Patel, Alpa V.

    2010-01-01

    Background Pooled data were analyzed from the NCI Pancreatic Cancer Cohort Consortium (PanScan) to study the association between pre-diagnostic anthropometric measures and risk of pancreatic cancer. Methods PanScan applied a nested case-control study design and included 2,170 cases and 2,209 controls. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using unconditional logistic regression for cohort-specific quartiles of body mass index (BMI), weight, height, waist circumference, and waist-to-hip ratio (WHR), as well as conventional BMI categories: underweight (<18.5 kg/m2), normal (18.5-24.9 kg/m2), overweight (25.0-29.9 kg/m2), obese (30.0-34.9 kg/m2), and severely obese (≥35.0 kg/m2). Models were adjusted for potential confounders. Results Among all subjects, a positive association between increasing BMI and risk of pancreatic cancer was observed (adjusted OR for the highest vs. lowest BMI quartile = 1.33, 95% CI = 1.12-1.58, Ptrend < 0.001). Among men, the adjusted OR for pancreatic cancer for the highest vs. lowest quartile of BMI was 1.33 (95% CI = 1.04-1.69, Ptrend <0.03). Among women, the adjusted OR for pancreatic cancer for the highest quartile of BMI was 1.34 (95% CI = 1.05-1.70, Ptrend = 0.01). Increased WHR was associated with increased risk of pancreatic cancer among women (adjusted OR for the highest vs. lowest quartile = 1.87, 95% CI = 1.31-2.69, Ptrend = 0.003) but less so in men. Conclusion The findings provide strong support for a positive association between BMI and pancreatic cancer risk. In addition, centralized fat distribution may increase pancreatic cancer risk, especially in women. PMID:20458087

  11. Multiple Novel Prostate Cancer Predisposition Loci Confirmed by an International Study: The PRACTICAL Consortium

    PubMed Central

    Kote-Jarai, Zsofia; Easton, Douglas F.; Stanford, Janet L.; Ostrander, Elaine A.; Schleutker, Johanna; Ingles, Sue A.; Schaid, Daniel; Thibodeau, Stephen; Dörk, Thilo; Neal, David; Cox, Angela; Maier, Christiane; Vogel, Walter; Guy, Michelle; Muir, Kenneth; Lophatananon, Artitaya; Kedda, Mary-Anne; Spurdle, Amanda; Steginga, Suzanne; John, Esther M.; Giles, Graham; Hopper, John; Chappuis, Pierre O.; Hutter, Pierre; Foulkes, William D.; Hamel, Nancy; Salinas, Claudia A.; Koopmeiners, Joseph S.; Karyadi, Danielle M.; Johanneson, Bo; Wahlfors, Tiina; Tammela, Teuvo L.; Stern, Mariana C.; Corral, Roman; McDonnell, Shannon K.; Schürmann, Peter; Meyer, Andreas; Kuefer, Rainer; Leongamornlert, Daniel A.; Tymrakiewicz, Malgorzata; Liu, Jo-fen; O'Mara, Tracy; Gardiner, R.A. (Frank); Aitken, Joanne; Joshi, Amit D.; Severi, Gianluca; English, Dallas R.; Southey, Melissa; Edwards, Stephen M.; Amin Al Olama, Ali; Eeles, Rosalind A.

    2009-01-01

    A recent genome-wide association study found that genetic variants on chromosomes 3, 6, 7, 10, 11, 19 and X were associated with prostate cancer risk. We evaluated the most significant single-nucleotide polymorphisms (SNP) in these loci using a worldwide consortium of 13 groups (PRACTICAL). Blood DNA from 7,370 prostate cancer cases and 5,742 male controls was analyzed by genotyping assays. Odds ratios (OR) associated with each genotype were estimated using unconditional logistic regression. Six of the seven SNPs showed clear evidence of association with prostate cancer (P = 0.0007-P = 10−17). For each of these six SNPs, the estimated per-allele OR was similar to those previously reported and ranged from 1.12 to 1.29. One SNP on 3p12 (rs2660753) showed a weaker association than previously reported [per-allele OR, 1.08 (95% confidence interval, 1.00-1.16; P = 0.06) versus 1.18 (95% confidence interval, 1.06-1.31)]. The combined risks associated with each pair of SNPs were consistent with a multiplicative risk model. Under this model, and in combination with previously reported SNPs on 8q and 17q, these loci explain 16% of the familial risk of the disease, and men in the top 10% of the risk distribution have a 2.1-fold increased risk relative to general population rates. This study provides strong confirmation of these susceptibility loci in multiple populations and shows that they make an important contribution to prostate cancer risk prediction. PMID:18708398

  12. Coordinating centers in cancer epidemiology research: the Asia Cohort Consortium coordinating center.

    PubMed

    Rolland, Betsy; Smith, Briana R; Potter, John D

    2011-10-01

    Although it is tacitly recognized that a good coordinating center (CC) is essential to the success of any multisite collaborative project, very little study has been done on what makes a CC successful, why some CCs fail, or how to build a CC that meets the needs of a given project. Moreover, very little published guidance is available, as few CCs outside the clinical trial realm write about their work. The Asia Cohort Consortium (ACC) is a collaborative cancer epidemiology research project that has made strong scientific and organizational progress over the past 3 years by focusing its CC on the following activities: collaboration development; operations management; statistical and data management; and communications infrastructure and tool development. Our hope is that, by sharing our experience building the ACC CC, we can begin a conversation about what it means to run a CC for multi-institutional collaboration in cancer epidemiology, help other collaborative projects solve some of the issues associated with collaborative research, and learn from others. ©2011 AACR

  13. Diet and the Risk of Head and Neck Cancer: A Pooled Analysis in the INHANCE Consortium

    PubMed Central

    Chuang, Shu-Chun; Jenab, Mazda; Heck, Julia E.; Bosetti, Cristina; Talamini, Renato; Matsuo, Keitaro; Castellsague, Xavier; Franceschi, Silvia; Herrero, Rolando; Winn, Deborah M.; La Vecchia, Carlo; Morgenstern, Hal; Zhang, Zuo-Feng; Levi, Fabio; Dal Maso, Luigino; Kelsey, Karl; McClean, Michael D.; Vaughan, Thomas; Lazarus, Philip; Muscat, Joshua; Ramroth, Heribert; Chen, Chu; Schwartz, Stephen M.; Eluf-Neto, Jose; Hayes, Richard B.; Purdue, Mark; Boccia, Stefania; Cadoni, Gabriella; Zaridze, David; Koifman, Sergio; Curado, Maria Paula; Ahrens, Wolfgang; Benhamou, Simone; Matos, Elena; Lagiou, Pagona; Szeszenia-Dabrowska, Neonilla; Olshan, Andrew F.; Fernandez, Leticia; Menezes, Ana; Agudo, Antonio; Daudt, Alexander W.; Merletti, Franco; Macfarlane, Gary J.; Kjaerheim, Kristina; Mates, Dana; Holcatova, Ivana; Schantz, Stimson; Yu, Guo-Pei; Simonato, Lorenzo; Brenner, Hermann; Mueller, Heiko; Conway, David I.; Thomson, Peter; Fabianova, Eleonora; Znaor, Ariana; Rudnai, Peter; Healy, Claire M.; Ferro, Gilles; Brennan, Paul; Boffetta, Paolo; Hashibe, Mia

    2013-01-01

    We investigated the association between diet and head and neck cancer (HNC) risk using data from the International Head and Neck Cancer Epidemiology (INHANCE) Consortium. The INHANCE pooled data included 22 case-control studies with 14,520 cases and 22,737 controls. Center-specific quartiles among the controls were used for food groups and frequencies per week were used for single food items. A dietary pattern score combining high fruit and vegetable intake and low red meat intake, was created. Odds ratios (OR) and 95% confidence intervals (CI) for the dietary items on the risk of HNC were estimated with a two-stage random effects logistic regression model. An inverse association was observed for higher frequency intake of fruit (4th vs. 1st quartile OR=0.52, 95% CI=0.43–0.62, ptrend<0.01) and vegetables (OR=0.66, 95% CI=0.49–0.90, ptrend=0.01). Intake of red meat (OR=1.40, 95% CI=1.13–1.74, ptrend=0.13) and processed meat (OR=1.37, 95% CI=1.14–1.65, ptrend<0.01) were positively associated with HNC risk. Higher dietary pattern scores, reflecting high fruit/vegetable and low red meat intake, were associated with reduced HNC risk (per score increment OR=0.90, 95% CI=0.84–0.97). PMID:22037906

  14. Coordinating Centers in Cancer-Epidemiology Research: The Asia Cohort Consortium Coordinating Center

    PubMed Central

    Rolland, Betsy; Smith, Briana R; Potter, John D

    2011-01-01

    Although it is tacitly recognized that a good Coordinating Center (CC) is essential to the success of any multi-site collaborative project, very little study has been done on what makes a CC successful, why some CCs fail, or how to build a CC that meets the needs of a given project. Moreover, very little published guidance is available, as few CCs outside the clinical-trial realm write about their work. The Asia Cohort Consortium (ACC) is a collaborative cancer-epidemiology research project that has made strong scientific and organizational progress over the past three years by focusing its CC on the following activities: collaboration development; operations management; statistical and data management; and communications infrastructure and tool development. Our hope is that, by sharing our experience building the ACC CC, we can begin a conversation about what it means to run a coordinating center for multi-institutional collaboration in cancer epidemiology, help other collaborative projects solve some of the issues associated with collaborative research, and learn from others. PMID:21803842

  15. Correlates of circulating 25-hydroxyvitamin D: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers.

    PubMed

    McCullough, Marjorie L; Weinstein, Stephanie J; Freedman, D Michal; Helzlsouer, Kathy; Flanders, W Dana; Koenig, Karen; Kolonel, Laurence; Laden, Francine; Le Marchand, Loic; Purdue, Mark; Snyder, Kirk; Stevens, Victoria L; Stolzenberg-Solomon, Rachael; Virtamo, Jarmo; Yang, Gong; Yu, Kai; Zheng, Wei; Albanes, Demetrius; Ashby, Jason; Bertrand, Kimberly; Cai, Hui; Chen, Yu; Gallicchio, Lisa; Giovannucci, Edward; Jacobs, Eric J; Hankinson, Susan E; Hartge, Patricia; Hartmuller, Virginia; Harvey, Chinonye; Hayes, Richard B; Horst, Ronald L; Shu, Xiao-Ou

    2010-07-01

    Low vitamin D status is common globally and is associated with multiple disease outcomes. Understanding the correlates of vitamin D status will help guide clinical practice, research, and interpretation of studies. Correlates of circulating 25-hydroxyvitamin D (25(OH)D) concentrations measured in a single laboratory were examined in 4,723 cancer-free men and women from 10 cohorts participating in the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers, which covers a worldwide geographic area. Demographic and lifestyle characteristics were examined in relation to 25(OH)D using stepwise linear regression and polytomous logistic regression. The prevalence of 25(OH)D concentrations less than 25 nmol/L ranged from 3% to 36% across cohorts, and the prevalence of 25(OH)D concentrations less than 50 nmol/L ranged from 29% to 82%. Seasonal differences in circulating 25(OH)D were most marked among whites from northern latitudes. Statistically significant positive correlates of 25(OH)D included male sex, summer blood draw, vigorous physical activity, vitamin D intake, fish intake, multivitamin use, and calcium supplement use. Significant inverse correlates were body mass index, winter and spring blood draw, history of diabetes, sedentary behavior, smoking, and black race/ethnicity. Correlates varied somewhat within season, race/ethnicity, and sex. These findings help identify persons at risk for low vitamin D status for both clinical and research purposes.

  16. National Performance Benchmarks for Modern Screening Digital Mammography: Update from the Breast Cancer Surveillance Consortium.

    PubMed

    Lehman, Constance D; Arao, Robert F; Sprague, Brian L; Lee, Janie M; Buist, Diana S M; Kerlikowske, Karla; Henderson, Louise M; Onega, Tracy; Tosteson, Anna N A; Rauscher, Garth H; Miglioretti, Diana L

    2017-04-01

    Purpose To establish performance benchmarks for modern screening digital mammography and assess performance trends over time in U.S. community practice. Materials and Methods This HIPAA-compliant, institutional review board-approved study measured the performance of digital screening mammography interpreted by 359 radiologists across 95 facilities in six Breast Cancer Surveillance Consortium (BCSC) registries. The study included 1 682 504 digital screening mammograms performed between 2007 and 2013 in 792 808 women. Performance measures were calculated according to the American College of Radiology Breast Imaging Reporting and Data System, 5th edition, and were compared with published benchmarks by the BCSC, the National Mammography Database, and performance recommendations by expert opinion. Benchmarks were derived from the distribution of performance metrics across radiologists and were presented as 50th (median), 10th, 25th, 75th, and 90th percentiles, with graphic presentations using smoothed curves. Results Mean screening performance measures were as follows: abnormal interpretation rate (AIR), 11.6 (95% confidence interval [CI]: 11.5, 11.6); cancers detected per 1000 screens, or cancer detection rate (CDR), 5.1 (95% CI: 5.0, 5.2); sensitivity, 86.9% (95% CI: 86.3%, 87.6%); specificity, 88.9% (95% CI: 88.8%, 88.9%); false-negative rate per 1000 screens, 0.8 (95% CI: 0.7, 0.8); positive predictive value (PPV) 1, 4.4% (95% CI: 4.3%, 4.5%); PPV2, 25.6% (95% CI: 25.1%, 26.1%); PPV3, 28.6% (95% CI: 28.0%, 29.3%); cancers stage 0 or 1, 76.9%; minimal cancers, 57.7%; and node-negative invasive cancers, 79.4%. Recommended CDRs were achieved by 92.1% of radiologists in community practice, and 97.1% achieved recommended ranges for sensitivity. Only 59.0% of radiologists achieved recommended AIRs, and only 63.0% achieved recommended levels of specificity. Conclusion The majority of radiologists in the BCSC surpass cancer detection recommendations for screening

  17. History of thyroid disease and survival of ovarian cancer patients: results from the Ovarian Cancer Association Consortium, a brief report.

    PubMed

    Minlikeeva, Albina N; Freudenheim, Jo L; Cannioto, Rikki A; Eng, Kevin H; Szender, J Brian; Mayor, Paul; Etter, John L; Cramer, Daniel W; Diergaarde, Brenda; Doherty, Jennifer A; Dörk, Thilo; Edwards, Robert; deFazio, Anna; Friel, Grace; Goodman, Marc T; Hillemanns, Peter; Høgdall, Estrid; Jensen, Allan; Jordan, Susan J; Karlan, Beth Y; Kjær, Susanne K; Klapdor, Rüdiger; Matsuo, Keitaro; Mizuno, Mika; Nagle, Christina M; Odunsi, Kunle; Paddock, Lisa; Rossing, Mary Anne; Schildkraut, Joellen M; Schmalfeldt, Barbara; Segal, Brahm H; Starbuck, Kristen; Terry, Kathryn L; Webb, Penelope M; Zsiros, Emese; Ness, Roberta B; Modugno, Francesmary; Bandera, Elisa V; Chang-Claude, Jenny; Moysich, Kirsten B

    2017-09-26

    Findings from in vitro studies suggest that increased exposure to thyroid hormones can influence progression of ovarian tumours. However, epidemiologic evidence on this topic is limited. We pooled data from 11 studies from the Ovarian Cancer Association Consortium. Using multivariate Cox proportional hazards models, we estimated associations between hyper- and hypothyroidism and medications prescribed for these conditions with 5-year all-cause survival among women diagnosed with invasive ovarian cancer. Overall, there was a nonsignificant association with history of hyperthyroidism (n=160 cases) and mortality (HR=1.22; 95% CI=0.97-1.53). Furthermore, diagnosis of hyperthyroidism within the 5 years before ovarian cancer diagnosis was associated with an increased risk of death (HR=1.94; 95% CI=1.19-3.18). A more modest association was observed with history of hypothyroidism (n=624 cases) and mortality (HR=1.16; 95% CI=1.03-1.31). Neither duration of hypothyroidism nor use of thyroid medications was associated with survival. In this large study of women with ovarian cancer, we found that recent history of hyperthyroidism and overall history of hypothyroidism were associated with worse 5-year survival.

  18. Factors associated with oxidative stress and cancer risk in the Breast and Prostate Cancer Cohort Consortium (BPC3)

    PubMed Central

    Blein, Sophie; Berndt, Sonja; Joshi, Amit D.; Campa, Daniele; Ziegler, Regina G.; Riboli, Elio; Cox, David G.; Gaudet, Mia M.; Stevens, Victoria L.; Diver, W. Ryan; Gapstur, Susan M.; Chanock, Stephen J.; Hoover, Robert N.; Yeager, Meredith; Albanes, Demetrius; Virtamo, Jarmo; Crawford, E. David; Isaacs, Claudine; Berg, Christine; Trichopoulos, Dimitrios; Panico, Salvatore; Peeters, Petra H.; Johansson, Mattias; Khaw, Kay-Tee; Kraft, Peter; Hunter, David J.; Lindström, Sara; Ma, Jing; Stampfer, Meir; Gaziano, J. Michael; Giovannucci, Edward; Willett, Walter H.; Hankinson, Susan E.; Lee, I-Min; Buring, Julie; Henderson, Brian; Le Marchand, Loïc; Kolonel, Laurence; Haiman, Christopher J.

    2015-01-01

    Both endogenous factors (genomic variations) and exogenous factors (environmental exposures, lifestyle) impact the balance of reactive oxygen species (ROS). Variants of the ND3 (rs2853826; G10398A) gene of the mitochondrial genome, manganese superoxide dismutase (MnSOD; rs4880 Val16Ala) and glutathione peroxidase (GPX-1; rs1050450 Pro198Leu) are purported to have functional effects on regulation of ROS balance. In this study, we examined associations of breast and prostate cancer risk and survival with these variants, and interactions between rs4880 - rs1050450 and alcohol consumption - rs2853826. Nested case-control studies were conducted in the Breast and Prostate Cancer Cohort Consortium (BPC3), consisting of nine cohorts. The analyses included over 10726 post-menopausal breast and 7532 prostate cancer cases with matched controls. Logistic regression models were used to evaluate associations with risk, and proportional hazard models were used for survival outcomes. We did not observe significant interactions between polymorphisms in MnSOD and GPX-1, or between mitochondrial polymorphisms and alcohol intake and risk of either breast (p-interaction of 0.34 and 0.98 respectively) or prostate cancer (p-interaction of 0.49 and 0.50 respectively). We observed a weak inverse association between prostate cancer risk and GPX-1 Leu198Leu carriers (OR 0.87, 95% CI 0.79 – 0.97, p = 0.01). Overall survival among women with breast cancer was inversely associated with G10398 carriers who consumed alcohol (HR 0.66 95% CI 0.49 – 0.88). Given the high power in our study, it is unlikely that interactions tested have more than moderate effects on breast or prostate cancer risk. Observed associations need both further epidemiological and biological confirmation. PMID:24437375

  19. Contribution of the Neighborhood Environment and Obesity to Breast Cancer Survival: The California Breast Cancer Survivorship Consortium

    PubMed Central

    Cheng, Iona; Shariff-Marco, Salma; Koo, Jocelyn; Monroe, Kristine R.; Yang, Juan; John, Esther M.; Kurian, Allison W.; Kwan, Marilyn L.; Henderson, Brian E.; Bernstein, Leslie; Lu, Yani; Sposto, Richard; Vigen, Cheryl; Wu, Anna H.; Gomez, Scarlett Lin; Keegan, Theresa H.M.

    2015-01-01

    Little is known about neighborhood attributes that may influence opportunities for healthy eating and physical activity in relation to breast cancer mortality. We used data from the California Breast Cancer Survivorship Consortium and the California Neighborhoods Data System to examine the neighborhood environment, body mass index, and mortality after breast cancer. We studied 8,995 African American, Asian American, Latina, and non-Latina White women with breast cancer. Residential addresses were linked to the CNDS to characterize neighborhoods. We used multinomial logistic regression to evaluate the associations between neighborhood factors and obesity, and Cox proportional hazards regression to examine associations between neighborhood factors and mortality. For Latinas, obesity was associated with more neighborhood crowding (Quartile 4 (Q4) vs. Q1: Odds Ratio (OR)=3.24; 95% Confidence Interval (CI): 1.50-7.00); breast cancer-specific mortality was inversely associated with neighborhood businesses (Q4 vs. Q1: Hazard Ratio (HR)=0.46; 95% CI: 0.25-0.85) and positively associated with multi-family housing (Q3 vs. Q1: HR=1.98; 95% CI: 1.20-3.26). For non-Latina Whites, lower neighborhood socioeconomic status (SES) was associated with obesity (Quintile 1 (Q1) vs. Q5: OR=2.52; 95% CI: 1.31-4.84), breast cancer-specific (Q1 vs. Q5: HR=2.75; 95% CI: 1.47-5.12), and all-cause (Q1 vs. Q5: HR=1.75; 95% CI: 1.17-2.62) mortality. For Asian Americans, no associations were seen. For African Americans, lower neighborhood SES was associated with lower mortality in a nonlinear fashion. Attributes of the neighborhood environment were associated with obesity and mortality following breast cancer diagnosis, but these associations differed across racial/ethnic groups. PMID:26063477

  20. Interactions Between Genetic Variants and Breast Cancer Risk Factors in the Breast and Prostate Cancer Cohort Consortium

    PubMed Central

    Campa, Daniele; Kaaks, Rudolf; Le Marchand, Loïc; Haiman, Christopher A.; Travis, Ruth C.; Buring, Julie E.; Chanock, Stephen J.; Diver, W. Ryan; Dostal, Lucie; Fournier, Agnes; Hankinson, Susan E.; Henderson, Brian E.; Hoover, Robert N.; Isaacs, Claudine; Johansson, Mattias; Kolonel, Laurence N.; Kraft, Peter; Lee, I-Min; McCarty, Catherine A.; Overvad, Kim; Panico, Salvatore; Peeters, Petra H.M.; Riboli, Elio; Sanchez, Maria José; Schumacher, Fredrick R.; Skeie, Guri; Stram, Daniel O.; Thun, Michael J.; Trichopoulos, Dimitrios; Zhang, Shumin; Ziegler, Regina G.; Hunter, David J.; Lindström, Sara

    2011-01-01

    Background Recently, several genome-wide association studies have identified various genetic susceptibility loci for breast cancer. Relatively little is known about the possible interactions between these loci and the established risk factors for breast cancer. Methods To assess interactions between single-nucleotide polymorphisms (SNPs) and established risk factors, we prospectively collected DNA samples and questionnaire data from 8576 breast cancer case subjects and 11 892 control subjects nested within the National Cancer Institute’s Breast and Prostate Cancer Cohort Consortium (BPC3). We genotyped 17 germline SNPs (FGFR2-rs2981582, FGFR2-rs3750817, TNRC9-rs3803662, 2q35-rs13387042, MAP3K1-rs889312, 8q24-rs13281615, CASP8-rs1045485, LSP1-rs3817198, COL1A1-rs2075555, COX11-rs6504950, RNF146-rs2180341, 6q25-rs2046210, SLC4A7-rs4973768, NOTCH2-rs11249433, 5p12-rs4415084, 5p12-rs10941679, RAD51L1-rs999737), and odds ratios were estimated by logistic regression to confirm previously reported associations with breast cancer risk. We performed likelihood ratio test to assess interactions between 17 SNPs and nine established risk factors (age at menarche, parity, age at menopause, use of hormone replacement therapy, family history, height, body mass index, smoking status, and alcohol consumption), and a correction for multiple testing of 153 tests (adjusted P value threshold = .05/153 = 3 × 10−4) was done. Case–case comparisons were performed for possible differential associations of polymorphisms by subgroups of tumor stage, estrogen and progesterone receptor status, and age at diagnosis. All statistical tests were two-sided. Results We confirmed the association of 14 SNPs with breast cancer risk (Ptrend = 2.57 × 10−3 –3.96 × 10−19). Three SNPs (LSP1-rs3817198, COL1A1-rs2075555, and RNF146-rs2180341) did not show association with breast cancer risk. After accounting for multiple testing, no statistically significant interactions were detected between

  1. Common genetic determinants of breast-cancer risk in East Asian women: a collaborative study of 23 637 breast cancer cases and 25 579 controls

    PubMed Central

    Zheng, Wei; Zhang, Ben; Cai, Qiuyin; Sung, Hyuna; Michailidou, Kyriaki; Shi, Jiajun; Choi, Ji-Yeob; Long, Jirong; Dennis, Joe; Humphreys, Manjeet K.; Wang, Qin; Lu, Wei; Gao, Yu-Tang; Li, Chun; Cai, Hui; Park, Sue K.; Yoo, Keun-Young; Noh, Dong-Young; Han, Wonshik; Dunning, Alison M.; Benitez, Javier; Vincent, Daniel; Bacot, Francois; Tessier, Daniel; Kim, Sung-Won; Lee, Min Hyuk; Lee, Jong Won; Lee, Jong-Young; Xiang, Yong-Bing; Zheng, Ying; Wang, Wenjin; Ji, Bu-Tian; Matsuo, Keitaro; Ito, Hidemi; Iwata, Hiroji; Tanaka, Hideo; Wu, Anna H.; Tseng, Chiu-chen; Van Den Berg, David; Stram, Daniel O.; Teo, Soo Hwang; Yip, Cheng Har; Kang, In Nee; Wong, Tien Y.; Shen, Chen-Yang; Yu, Jyh-Cherng; Huang, Chiun-Sheng; Hou, Ming-Feng; Hartman, Mikael; Miao, Hui; Lee, Soo Chin; Putti, Thomas Choudary; Muir, Kenneth; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Sangrajrang, Suleeporn; Shen, Hongbing; Chen, Kexin; Wu, Pei-Ei; Ren, Zefang; Haiman, Christopher A.; Sueta, Aiko; Kim, Mi Kyung; Khoo, Ui Soon; Iwasaki, Motoki; Pharoah, Paul D.P.; Wen, Wanqing; Hall, Per; Shu, Xiao-Ou; Easton, Douglas F.; Kang, Daehee

    2013-01-01

    In a consortium including 23 637 breast cancer patients and 25 579 controls of East Asian ancestry, we investigated 70 single-nucleotide polymorphisms (SNPs) in 67 independent breast cancer susceptibility loci recently identified by genome-wide association studies (GWASs) conducted primarily in European-ancestry populations. SNPs in 31 loci showed an association with breast cancer risk at P < 0.05 in a direction consistent with that reported previously. Twenty-one of them remained statistically significant after adjusting for multiple comparisons with the Bonferroni-corrected significance level of <0.0015. Eight of the 70 SNPs showed a significantly different association with breast cancer risk by estrogen receptor (ER) status at P < 0.05. With the exception of rs2046210 at 6q25.1, the seven other SNPs showed a stronger association with ER-positive than ER-negative cancer. This study replicated all five genetic risk variants initially identified in Asians and provided evidence for associations of breast cancer risk in the East Asian population with nearly half of the genetic risk variants initially reported in GWASs conducted in European descendants. Taken together, these common genetic risk variants explain ∼10% of excess familial risk of breast cancer in Asian populations. PMID:23535825

  2. Associations between hormone receptor expression and ovarian cancer survival: an Ovarian Tumor Tissue Analysis consortium study

    PubMed Central

    Sieh, Weiva; Köbel, Martin; Longacre, Teri A.; Bowtell, David D.; deFazio, Anna; Goodman, Marc T.; Høgdall, Estrid; Deen, Suha; Wentzensen, Nicolas; Moysich, Kirsten B.; Brenton, James D.; Clarke, Blaise; Menon, Usha; Gilks, C. Blake; Kim, Andre; Madore, Jason; Fereday, Sian; George, Joshy; Galletta, Laura; Lurie, Galina; Wilkens, Lynne R.; Carney, Michael E.; Thompson, Pamela J.; Matsuno, Rayna K.; Kjær, Susanne Krüger; Jensen, Allan; Høgdall, Claus; Kalli, Kimberly R.; Fridley, Brooke L.; Keeney, Gary L.; Vierkant, Robert A.; Cunningham, Julie M.; Brinton, Louise A.; Yang, Hannah P.; Sherman, Mark E.; Garcia-Closas, Montserrat; Lissowska, Jolanta; Odunsi, Kunle; Morrison, Carl; Lele, Shashikant; Bshara, Wiam; Sucheston, Lara; Jimenez-Linan, Mercedes; Blows, Fiona M.; Alsop, Jennifer; Mack, Marie; McGuire, Valerie; Rothstein, Joseph H.; Rosen, Barry P.; Bernardini, Marcus Q.; Mackay, Helen; Oza, Amit; Wozniak, Eva L.; Benjamin, Elizabeth; Gentry-Maharaj, Aleksandra; Gayther, Simon A.; Tinker, Anna V.; Prentice, Leah M.; Chow, Christine; Anglesio, Michael S.; Johnatty, Sharon E.; Chenevix-Trench, Georgia; Whittemore, Alice S.; Pharoah, Paul D. P.; Goode, Ellen L.; Huntsman, David G.; Ramus, Susan J.

    2014-01-01

    Background Ovarian cancer is a lethal disease comprised of distinct histopathological types. There are few established biomarkers of ovarian cancer prognosis, in part because subtype-specific associations may have been obscured in studies combining all subtypes. We examined whether progesterone receptor (PR) and estrogen receptor (ER) protein expression were associated with subtype-specific survival in the international Ovarian Tumor Tissue Analysis (OTTA) consortium. Methods PR and ER were assessed by central immunohistochemical analysis of tissue microarrays for 2933 women with invasive epithelial ovarian cancer from 12 study sites. Negative, weak, and strong expression were defined as positive staining in <1%, 1–50%, and ≥50% of tumor cell nuclei, respectively. Hazard ratios (HRs) for ovarian cancer death were estimated using Cox regression stratified by site and adjusted for age, stage, and grade. Results PR expression was associated with improved survival for endometrioid (EC; p<0·0001) and high-grade serous carcinoma (HGSC; p=0·0006), and ER expression was associated with improved EC survival (p<0·0001); no significant associations were found for mucinous, clear cell, or low-grade serous carcinoma. EC patients with hormone receptor (PR and/or ER) positive (weak or strong) versus negative tumors had significantly reduced risk of dying from their disease, independent of clinical factors (HR, 0·33; 95% CI, 0·21–0·51; p<0·0001). HGSC patients with strong versus weak or negative tumor PR expression had significantly reduced risk of dying from their disease, independent of clinical factors (HR, 0·71; 95% CI, 0·55–0·91; p=0·0061). Interpretation PR and ER are prognostic biomarkers for endometrioid and high-grade serous ovarian cancers. Clinical trials, stratified by subtype and biomarker status, are needed to determine whether hormone receptor status predicts response to endocrine therapy, and can guide personalized treatment for ovarian cancer

  3. Gene-environment interactions involving functional variants: Results from the Breast Cancer Association Consortium.

    PubMed

    Barrdahl, Myrto; Rudolph, Anja; Hopper, John L; Southey, Melissa C; Broeks, Annegien; Fasching, Peter A; Beckmann, Matthias W; Gago-Dominguez, Manuela; Castelao, J Esteban; Guénel, Pascal; Truong, Thérèse; Bojesen, Stig E; Gapstur, Susan M; Gaudet, Mia M; Brenner, Hermann; Arndt, Volker; Brauch, Hiltrud; Hamann, Ute; Mannermaa, Arto; Lambrechts, Diether; Jongen, Lynn; Flesch-Janys, Dieter; Thoene, Kathrin; Couch, Fergus J; Giles, Graham G; Simard, Jacques; Goldberg, Mark S; Figueroa, Jonine; Michailidou, Kyriaki; Bolla, Manjeet K; Dennis, Joe; Wang, Qin; Eilber, Ursula; Behrens, Sabine; Czene, Kamila; Hall, Per; Cox, Angela; Cross, Simon; Swerdlow, Anthony; Schoemaker, Minouk J; Dunning, Alison M; Kaaks, Rudolf; Pharoah, Paul D P; Schmidt, Marjanka; Garcia-Closas, Montserrat; Easton, Douglas F; Milne, Roger L; Chang-Claude, Jenny

    2017-11-01

    Investigating the most likely causal variants identified by fine-mapping analyses may improve the power to detect gene-environment interactions. We assessed the interplay between 70 single nucleotide polymorphisms identified by genetic fine-scale mapping of susceptibility loci and 11 epidemiological breast cancer risk factors in relation to breast cancer. Analyses were conducted on up to 58,573 subjects (26,968 cases and 31,605 controls) from the Breast Cancer Association Consortium, in one of the largest studies of its kind. Analyses were carried out separately for estrogen receptor (ER) positive (ER+) and ER negative (ER-) disease. The Bayesian False Discovery Probability (BFDP) was computed to assess the noteworthiness of the results. Four potential gene-environment interactions were identified as noteworthy (BFDP < 0.80) when assuming a true prior interaction probability of 0.01. The strongest interaction result in relation to overall breast cancer risk was found between CFLAR-rs7558475 and current smoking (ORint  = 0.77, 95% CI: 0.67-0.88, pint  = 1.8 × 10(-4) ). The interaction with the strongest statistical evidence was found between 5q14-rs7707921 and alcohol consumption (ORint =1.36, 95% CI: 1.16-1.59, pint  = 1.9 × 10(-5) ) in relation to ER- disease risk. The remaining two gene-environment interactions were also identified in relation to ER- breast cancer risk and were found between 3p21-rs6796502 and age at menarche (ORint  = 1.26, 95% CI: 1.12-1.43, pint =1.8 × 10(-4) ) and between 8q23-rs13267382 and age at first full-term pregnancy (ORint  = 0.89, 95% CI: 0.83-0.95, pint  = 5.2 × 10(-4) ). While these results do not suggest any strong gene-environment interactions, our results may still be useful to inform experimental studies. These may in turn, shed light on the potential interactions observed. © 2017 The Authors International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.

  4. Low penetrance breast cancer susceptibility loci are associated with specific breast tumor subtypes: findings from the Breast Cancer Association Consortium

    PubMed Central

    Broeks, Annegien; Schmidt, Marjanka K.; Sherman, Mark E.; Couch, Fergus J.; Hopper, John L.; Dite, Gillian S.; Apicella, Carmel; Smith, Letitia D.; Hammet, Fleur; Southey, Melissa C.; Van ’t Veer, Laura J.; de Groot, Renate; Smit, Vincent T.H.B.M.; Fasching, Peter A.; Beckmann, Matthias W.; Jud, Sebastian; Ekici, Arif B.; Hartmann, Arndt; Hein, Alexander; Schulz-Wendtland, Ruediger; Burwinkel, Barbara; Marme, Frederik; Schneeweiss, Andreas; Sinn, Hans-Peter; Sohn, Christof; Tchatchou, Sandrine; Bojesen, Stig E.; Nordestgaard, Børge G.; Flyger, Henrik; Ørsted, David D.; Kaur-Knudsen, Diljit; Milne, Roger L.; Pérez, Jose I. Arias; Zamora, Pilar; Rodríguez, Primitiva Menéndez; Benítez, Javier; Brauch, Hiltrud; Justenhoven, Christina; Ko, Yon-Dschun; Hamann, Ute; Fischer, Hans-Peter; Brüning, Thomas; Pesch, Beate; Chang-Claude, Jenny; Wang-Gohrke, Shan; Bremer, Michael; Karstens, Johann H.; Hillemanns, Peter; Dörk, Thilo; Nevanlinna, Heli A.; Heikkinen, Tuomas; Heikkilä, Päivi; Blomqvist, Carl; Aittomäki, Kristiina; Aaltonen, Kirsimari; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kosma, Veli-Matti; Kauppinen, Jaana M.; Kataja, Vesa; Auvinen, Päivi; Eskelinen, Matti; Soini, Ylermi; Chenevix-Trench, Georgia; Spurdle, Amanda B.; Beesley, Jonathan; Chen, Xiaoqing; Holland, Helene; Lambrechts, Diether; Claes, Bart; Vandorpe, Thijs; Neven, Patrick; Wildiers, Hans; Flesch-Janys, Dieter; Hein, Rebecca; Löning, Thomas; Kosel, Matthew; Fredericksen, Zachary S.; Wang, Xianshu; Giles, Graham G.; Baglietto, Laura; Severi, Gianluca; McLean, Catriona; Haiman, Christopher A.; Henderson, Brian E.; Le Marchand, Loic; Kolonel, Laurence N.; Grenaker Alnæs, Grethe; Kristensen, Vessela; Børresen-Dale, Anne-Lise; Hunter, David J.; Hankinson, Susan E.; Andrulis, Irene L.; Marie Mulligan, Anna; O'Malley, Frances P.; Devilee, Peter; Huijts, Petra E.A.; Tollenaar, Rob A.E.M.; Van Asperen, Christi J.; Seynaeve, Caroline S.; Chanock, Stephen J.; Lissowska, Jolanta; Brinton, Louise; Peplonska, Beata; Figueroa, Jonine; Yang, Xiaohong R.; Hooning, Maartje J.; Hollestelle, Antoinette; Oldenburg, Rogier A.; Jager, Agnes; Kriege, Mieke; Ozturk, Bahar; van Leenders, Geert J.L.H.; Hall, Per; Czene, Kamila; Humphreys, Keith; Liu, Jianjun; Cox, Angela; Connley, Daniel; Cramp, Helen E.; Cross, Simon S.; Balasubramanian, Sabapathy P.; Reed, Malcolm W.R.; Dunning, Alison M.; Easton, Douglas F.; Humphreys, Manjeet K.; Caldas, Carlos; Blows, Fiona; Driver, Kristy; Provenzano, Elena; Lubinski, Jan; Jakubowska, Anna; Huzarski, Tomasz; Byrski, Tomasz; Cybulski, Cezary; Gorski, Bohdan; Gronwald, Jacek; Brennan, Paul; Sangrajrang, Suleeporn; Gaborieau, Valerie; Shen, Chen-Yang; Hsiung, Chia-Ni; Yu, Jyh-Cherng; Chen, Shou-Tung; Hsu, Giu-Cheng; Hou, Ming-Feng; Huang, Chiun-Sheng; Anton-Culver, Hoda; Ziogas, Argyrios; Pharoah, Paul D.P.; Garcia-Closas, Montserrat

    2011-01-01

    Breast cancers demonstrate substantial biological, clinical and etiological heterogeneity. We investigated breast cancer risk associations of eight susceptibility loci identified in GWAS and two putative susceptibility loci in candidate genes in relation to specific breast tumor subtypes. Subtypes were defined by five markers (ER, PR, HER2, CK5/6, EGFR) and other pathological and clinical features. Analyses included up to 30 040 invasive breast cancer cases and 53 692 controls from 31 studies within the Breast Cancer Association Consortium. We confirmed previous reports of stronger associations with ER+ than ER− tumors for six of the eight loci identified in GWAS: rs2981582 (10q26) (P-heterogeneity = 6.1 × 10−18), rs3803662 (16q12) (P = 3.7 × 10−5), rs13281615 (8q24) (P = 0.002), rs13387042 (2q35) (P = 0.006), rs4973768 (3p24) (P = 0.003) and rs6504950 (17q23) (P = 0.002). The two candidate loci, CASP8 (rs1045485, rs17468277) and TGFB1 (rs1982073), were most strongly related with the risk of PR negative tumors (P = 5.1 × 10−6 and P = 4.1 × 10−4, respectively), as previously suggested. Four of the eight loci identified in GWAS were associated with triple negative tumors (P ≤ 0.016): rs3803662 (16q12), rs889312 (5q11), rs3817198 (11p15) and rs13387042 (2q35); however, only two of them (16q12 and 2q35) were associated with tumors with the core basal phenotype (P ≤ 0.002). These analyses are consistent with different biological origins of breast cancers, and indicate that tumor stratification might help in the identification and characterization of novel risk factors for breast cancer subtypes. This may eventually result in further improvements in prevention, early detection and treatment. PMID:21596841

  5. 11th Annual NIH Pain Consortium Symposium on Advances in Pain Research | Division of Cancer Prevention

    Cancer.gov

    The NIH Pain Consortium will convene the 11th Annual NIH Pain Consortium Symposium on Advances in Pain Research, featuring keynote speakers and expert panel sessions on Innovative Models and Methods. The first keynote address will be delivered by David J. Clark, MD, PhD, Stanford University entitled “Challenges of Translational Pain Research: What Makes a Good Model?” |

  6. Polymorphisms in DNA repair genes, smoking, and bladder cancer risk: findings from the International Consortium of Bladder Cancer

    PubMed Central

    Stern, Mariana C.; Lin, Jie; Figueroa, Jonine D.; Kelsey, Karl T.; Kiltie, Anne E.; Yuan, Jian-Min; Matullo, Giuseppe; Fletcher, Tony; Benhamou, Simone; Taylor, Jack A.; Placidi, Donatella; Zhang, Zuo-Feng; Steineck, Gunnar; Rothman, Nathaniel; Kogevinas, Manolis; Silverman, Debra; Malats, Nuria; Chanock, Stephen; Wu, Xifeng; Karagas, Margaret R.; Andrew, Angeline S.; Nelson, Heather H.; Bishop, D. Timothy; Sak, Sei Chung; Choudhury, Ananya; Barrett, Jennifer H; Elliot, Faye; Corral, Román; Joshi, Amit D.; Gago-Dominguez, Manuela; Cortessis, Victoria K.; Xiang, Yong-Bing; Vineis, Paolo; Sacerdote, Carlotta; Guarrera, Simonetta; Polidoro, Silvia; Allione, Alessandra; Gurzau, Eugen; Koppova, Kvetoslava; Kumar, Rajiv; Rudnai, Peter; Porru, Stefano; Carta, Angela; Campagna, Marcello; Arici, Cecilia; Park, SungShim Lani; Garcia-Closas, Montserrat

    2009-01-01

    Tobacco smoking is the most important and well-established bladder cancer risk factor, and a rich source of chemical carcinogens and reactive oxygen species that can induce damage to DNA in urothelial cells. Therefore, common variation in DNA repair genes might modify bladder cancer risk. In this study we present results from meta- and pooled analyses conducted as part of the International Consortium of Bladder Cancer. We included data on 10 single nucleotide polymorphisms corresponding to 7 DNA repair genes from 13 studies. Pooled- and meta-analyses included 5,282 cases and 5,954 controls of non-Latino white origin. We found evidence for weak but consistent associations with ERCC2 D312N (rs1799793) (per allele OR = 1.10; 95% CI = 1.01–1.19; p = 0.021), NBN E185Q (rs1805794) (per allele OR = 1.09; 95% CI = 1.01–1.18; p = 0.028), and XPC A499V (rs2228000) (per allele OR = 1.10; 95% CI = 1.00–1.21, p = 0.044). The association with NBN E185Q was limited to ever smokers (interaction p = 0.002), and was strongest for the highest levels of smoking dose and smoking duration. Overall, our study provides the strongest evidence to date for a role of common variants in DNA repair genes in bladder carcinogenesis. PMID:19706757

  7. De-Risking Immunotherapy: Report of a Consensus Workshop of the Cancer Immunotherapy Consortium of the Cancer Research Institute.

    PubMed

    Mellman, Ira; Hubbard-Lucey, Vanessa M; Tontonoz, Matthew J; Kalos, Michael D; Chen, Daniel S; Allison, James P; Drake, Charles G; Levitsky, Hy; Lonberg, Nils; van der Burg, Sjoerd H; Fearon, Douglas T; Wherry, E John; Lowy, Israel; Vonderheide, Robert H; Hwu, Patrick

    2016-04-01

    With the recent FDA approvals of pembrolizumab and nivolumab, and a host of additional immunomodulatory agents entering clinical development each year, the field of cancer immunotherapy is changing rapidly. Strategies that can assist researchers in choosing the most promising drugs and drug combinations to move forward through clinical development are badly needed in order to reduce the likelihood of late-stage clinical trial failures. On October 5, 2014, the Cancer Immunotherapy Consortium of the Cancer Research Institute, a collaborative think tank composed of stakeholders from academia, industry, regulatory agencies, and patient interest groups, met to discuss strategies for de-risking immunotherapy development, with a focus on integrating preclinical and clinical studies, and conducting smarter early-phase trials, particularly for combination therapies. Several recommendations were made, including making better use of clinical data to inform preclinical research, obtaining adequate tissues for biomarker studies, and choosing appropriate clinical trial endpoints to identify promising drug candidates and combinations in nonrandomized early-phase trials.

  8. Family history of cancer and risk of Pancreatic Cancer: A Pooled Analysis from the Pancreatic Cancer Cohort Consortium (PanScan)

    PubMed Central

    Jacobs, Eric J.; Chanock, Stephen J.; Fuchs, Charles S.; LaCroix, Andrea; McWilliams, Robert R.; Steplowski, Emily; Stolzenberg-Solomon, Rachael Z.; Arslan, Alan A.; Bueno-de-Mesquita, H. Bas; Gross, Myron; Helzlsouer, Kathy; Petersen, Gloria; Zheng, Wei; Agalliu, Ilir; Allen, Naomi E.; Amundadottir, Laufey; Boutron-Ruault, Marie-Christine; Buring, Julie E.; Canzian, Federico; Clipp, Sandra; Dorronsoro, Miren; Gaziano, J. Michael; Giovannucci, Edward L.; Hankinson, Susan E.; Hartge, Patricia; Hoover, Robert N.; Hunter, David J.; Jacobs, Kevin B.; Jenab, Mazda; Kraft, Peter; Kooperberg, Charles; Lynch, Shannon M.; Sund, Malin; Mendelsohn, Julie B.; Mouw, Tracy; Newton, Christina C.; Overvad, Kim; Palli, Domenico; Peeters, Petra H.M.; Rajkovic, Aleksandar; Shu, Xiao-Ou; Thomas, Gilles; Tobias, Geoffrey S.; Trichopoulos, Dimitrios; Virtamo, Jarmo; Wactawski-Wende, Jean; Wolpin, Brian M.; Yu, Kai; Zeleniuch-Jacquotte, Anne

    2010-01-01

    A family history of pancreatic cancer has consistently been associated with increased risk of pancreatic cancer. However, uncertainty remains about the strength of this association. Results from previous studies suggest a family history of select cancers (i.e. ovarian, breast, and colorectal) could also be associated, although not as strongly, with increased risk of pancreatic cancer. We examined the association between a family history of five types of cancer (pancreas, prostate, ovarian, breast, and colorectal) and risk of pancreatic cancer using data from a collaborative nested case-control study conducted by the Pancreatic Cancer Cohort Consortium. Cases and controls were from cohort studies from the United States, Europe, and China, and a case-control study from the Mayo Clinic. Analyses of family history of pancreatic cancer included 1,183 cases and 1,205 controls. A family history of pancreatic cancer in a parent, sibling, or child was associated with increased risk of pancreatic cancer (multivariate-adjusted OR = 1.76, 95% CI 1.19–2.61). A family history of prostate cancer was also associated with increased risk (OR = 1.45, 95% CI 1.12–1.89). There were no statistically significant associations with a family history of ovarian cancer (OR = 0.82, 95% CI 0.52–1.31), breast cancer (OR = 1.21, 95% CI 0.97–1.51), or colorectal cancer (OR = 1.17, 95% CI 0.93–1.47). Our results confirm a moderate sized association between a family history of pancreatic cancer and risk of pancreatic cancer and also provide evidence for an association with a family history of prostate cancer worth further study. PMID:20049842

  9. Multiple myeloma and family history of lymphohaematopoietic cancers: Results from the International Multiple Myeloma Consortium.

    PubMed

    Schinasi, Leah H; Brown, Elizabeth E; Camp, Nicola J; Wang, Sophia S; Hofmann, Jonathan N; Chiu, Brian C; Miligi, Lucia; Beane Freeman, Laura E; de Sanjose, Silvia; Bernstein, Leslie; Monnereau, Alain; Clavel, Jacqueline; Tricot, Guido J; Atanackovic, Djordje; Cocco, Pierluigi; Orsi, Laurent; Dosman, James A; McLaughlin, John R; Purdue, Mark P; Cozen, Wendy; Spinelli, John J; de Roos, Anneclaire J

    2016-10-01

    Family clusters of multiple myeloma (MM) suggest disease heritability. Nevertheless, patterns of inheritance and the importance of genetic versus environmental risk factors in MM aetiology remain unclear. We pooled data from eleven case-control studies from the International Multiple Myeloma Consortium to characterize the association of MM risk with having a first-degree relative with a history of a lympho-haematapoietic cancer. Unconditional logistic regression models, adjusted for study, sex, age and education level, were used to estimate associations between MM risk and having a first-degree relative with a history of non-Hodgkin lymphoma, Hodgkin lymphoma, leukaemia or MM. Sex, African American race/ethnicity and age were explored as effect modifiers. A total of 2843 cases and 11 470 controls were included. MM risk was elevated in association with having a first-degree relative with any lympho-haematapoietic cancer (Odds Ratio (OR) = 1·29, 95% Confidence Interval (CI): 1·08-1·55). The association was particularly strong for having a first-degree relative with MM (OR = 1·90, 95% CI: 1·26-2·87), especially among men (OR = 4·13, 95% CI: 2·17-7·85) and African Americans (OR = 5·52, 95% CI: 1·87-16·27).These results support the hypothesis that genetic inheritance plays a role in MM aetiology. Future studies are warranted to characterize interactions of genetic markers with environmental exposures.

  10. The second annual conference of International ovarian cancer consortium and the symposium on tumor microenvironment and therapeutic resistance

    PubMed Central

    Isidoro, Ciro; Song, Yong Sang; Surh, Young-Joon; Dhanasekaran, Danny N.

    2016-01-01

    The second Annual Meeting of the International Ovarian Cancer Consortium (IOCC) was held in conjunction with the Symposium on Tumor Microenvironment and Therapeutic Resistance at the Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, and USA. A brief welcoming event along with the banquet on Aug 16th was followed by the eight thematic scientific sessions from August 16 to 18, 2015. Forty-three lectures, organized in eight sessions, were discussed in front of an audience of more than hundred attendees. Emphasis was put on oncogene signaling in cancer genesis and progression, new approaches in Precision Medicine and therapy of ovarian cancer, the role of tumor microenvironment in carcinogenesis, and preventive/curative potential of natural products. In this meeting-report, we highlight the findings and the perspectives in cancer biology and therapeutic strategies that emerged during the conference.

  11. Plasma carotenoid- and retinol-weighted multi-SNP scores and risk of breast cancer in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium

    PubMed Central

    Hendrickson, Sara J.; Lindström, Sara; Eliassen, A. Heather; Rosner, Bernard A.; Chen, Constance; Barrdahl, Myrto; Brinton, Louise; Buring, Julie; Canzian, Federico; Chanock, Stephen; Clavel-Chapelon, Françoise; Figueroa, Jonine D.; Gapstur, Susan M.; Garcia-Closas, Montserrat; Gaudet, Mia M.; Haiman, Christopher A.; Hazra, Aditi; Henderson, Brian; Hoover, Robert; Hüsing, Anika; Johansson, Mattias; Kaaks, Rudolf; Khaw, Kay-Tee; Kolonel, Laurence N.; Marchand, Loic Le; Lissowska, Jolanta; Lund, Eiliv; McCullough, Marjorie L.; Peplonska, Beata; Riboli, Elio; Sacerdote, Carlotta; Sánchez, María-José; Tjønneland, Anne; Trichopoulos, Dimitrios; van Gils, Carla H.; Yeager, Meredith; Kraft, Peter; Hunter, David J; Ziegler, Regina G.; Willett, Walter C.

    2013-01-01

    Background Dietary and circulating carotenoids have been inversely associated with breast cancer risk, but observed associations may be due to confounding. Single nucleotide polymorphisms (SNPs) in β-carotene 15,15′-monooxygenase 1 (BCMO1), a gene encoding the enzyme involved in the first step of synthesizing vitamin A from dietary carotenoids, have been associated with circulating carotenoid concentrations and may serve as unconfounded surrogates for those biomarkers. We determined associations between variants in BCMO1 and breast cancer risk in a large cohort consortium. Methods We used unconditional logistic regression to test four SNPs in BCMO1 for associations with breast cancer risk in 9,226 cases and 10,420 controls from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3). We also tested weighted multi-SNP scores composed of the two SNPs with strong, confirmed associations with circulating carotenoid concentrations. Results Neither the individual SNPs nor the weighted multi-SNP scores were associated with breast cancer risk (odds ratio (95% confidence interval) comparing extreme quintiles of weighted multi-SNP scores =1.04 (0.94–1.16) for β-carotene, 1.08 (0.98–1.20) for α-carotene, 1.04 (0.94–1.16) for β-cryptoxanthin, 0.95 (0.87–1.05) for lutein/zeaxanthin, and 0.92 (0.83–1.02) for retinol). Furthermore, no associations were observed when stratifying by estrogen receptor status, but power was limited. Conclusions Our results do not support an association between SNPs associated with circulating carotenoid concentrations and breast cancer risk. Impact Future studies will need additional genetic surrogates and/or sample sizes at least three times larger to contribute evidence of a causal link between carotenoids and breast cancer. PMID:23515144

  12. [Developments in cancer management by innovative genomics. 2006 report of the National Cancer Consortium].

    PubMed

    Tímár, József; Kásler, Miklós; Kátai, József; Soós, Miklós; Mathiasz, Dóra; Romány, Anna; Patthy, László; Kovács, Gábor; Józsa, Adrienn; Szilák, László; Forrai, Tamás

    2006-01-01

    Research on developing molecular diagnostics for hereditary cancers resulted in establishing diagnostic services for familiar polyposis and non-polyposis patients (mutation determination of APC, MYH, STK11, SMAD4, MLH1, MSH2). In familiar testicular cancers the role of gr/gr gene on Y chromosome was identified. Molecular diagnostic tool was established to monitor the progression of follicular lymphoma using Bcl-2/IgH fusion sequences. Molecular diagnostic tools were developed to monitor circulating endothelial precursor cells (CEP) as well and the technique was tested in lung cancer patients. In malignant melanoma we have tested several potential novel markers among which ryanodine receptor seems to be a promising one, while the functional P2X7 receptor may serve as a therapeutic target. We have determined the tyrosine kinase "kinome" profile of HER-2-amplified breast cancers. Furthermore, the "kinome" profile was found to be characteristic for head and neck cancers of various anatomical location. Based on previous studies on the anti-migratory and antimetastatic potential of low-molecular-weight heparins, we have identified short heparin-derived oligosaccharides with maintained antimetastatic- but non-anticoagulant potentials. Pharmacogenomic studies on the role of polymorphism of the serine-hydroxymethyl-transferase (SHMT) gene in the efficacy of 5-FU and FOLFIRI protocols of colorectal cancer patients revealed a significant effect resulting in altered overall survival as well.

  13. Genotype-Derived ABO Blood Group Alleles and the Risk of Pancreatic Cancer: Data from the Pancreatic Cancer Cohort Consortium

    PubMed Central

    Wolpin, Brian M.; Kraft, Peter; Gross, Myron; Helzlsouer, Kathy; Bueno-de-Mesquita, H. Bas; Steplowski, Emily; Stolzenberg-Solomon, Rachael Z.; Arslan, Alan A.; Jacobs, Eric J.; LaCroix, Andrea; Petersen, Gloria; Zheng, Wei; Albanes, Demetrius; Allen, Naomi E.; Amundadottir, Laufey; Anderson, Garnet; Boutron-Ruault, Marie-Christine; Buring, Julie E.; Canzian, Federico; Chanock, Stephen J.; Clipp, Sandra; Gaziano, J. Michael; Giovannucci, Edward L.; Hallmans, Göran; Hankinson, Susan E.; Hoover, Robert N.; Hunter, David J.; Hutchinson, Amy; Jacobs, Kevin; Kooperberg, Charles; Lynch, Shannon M.; Mendelsohn, Julie B.; Michaud, Dominique S.; Overvad, Kim; Patel, Alpa V.; Rajkovic, Aleksandar; Sanchéz, Maria-José; Shu, Xiao-Ou; Slimani, Nadia; Thomas, Gilles; Tobias, Geoffrey S.; Trichopoulos, Dimitrios; Vineis, Paolo; Virtamo, Jarmo; Wactawski-Wende, Jean; Yu, Kai; Zeleniuch-Jacquotte, Anne; Hartge, Patricia; Fuchs, Charles S.

    2009-01-01

    A recent genome-wide association study (PanScan) identified significant associations at the ABO gene locus with pancreatic cancer risk; however, the mechanisms underlying these associations and the influence of specific ABO genotypes remain unknown. We determined ABO genotypes (OO, AO, AA, AB, BO, BB) in 1534 cases and 1583 controls from 12 prospective cohort studies participating in PanScan. We also grouped participants by genotype-derived serologic blood type (O, A, AB, B). Adjusted odds ratios (ORs) for pancreatic cancer by ABO alleles were calculated using logistic regression. Compared to blood type O, the ORs for pancreatic cancer in subjects with types A, AB, and B were 1.38 (95% confidence interval [CI], 1.18-1.62), 1.47 (95% CI, 1.07-2.02), and 1.53 (95% CI, 1.21-1.92), respectively. The incidence rates (cases per 100,000 subjects per year) for blood types O, A, AB, and B were 28.9, 39.9, 41.8, and 44.5. An increase in risk was noted with the addition of each non-O allele. Compared to OO, subjects with AO and AA had ORs of 1.33 (95% CI, 1.13-1.58) and 1.61 (95% CI, 1.22-2.18), while subjects with BO and BB had ORs of 1.45 (95% CI, 1.14-1.85) and 2.42 (1.28-4.57). The population attributable fraction for non-O blood type was 19.5%. In a joint model with smoking, current smokers with non-O blood type had an adjusted OR of 2.68 (95% CI, 2.03-3.54), compared with non-smokers with blood type O. Among participants in a large prospective cohort consortium, ABO genotypes were significantly associated with pancreatic cancer risk. PMID:20103627

  14. The role of oral hygiene in head and neck cancer: results from International Head and Neck Cancer Epidemiology (INHANCE) consortium.

    PubMed

    Hashim, D; Sartori, S; Brennan, P; Curado, M P; Wünsch-Filho, V; Divaris, K; Olshan, A F; Zevallos, J P; Winn, D M; Franceschi, S; Castellsagué, X; Lissowska, J; Rudnai, P; Matsuo, K; Morgenstern, H; Chen, C; Vaughan, T L; Hofmann, J N; D'Souza, G; Haddad, R I; Wu, H; Lee, Y-C; Hashibe, M; Vecchia, C La; Boffetta, P

    2016-08-01

    Poor oral hygiene has been proposed to contribute to head and neck cancer (HNC) risk, although causality and independency of some indicators are uncertain. This study investigates the relationship of five oral hygiene indicators with incident HNCs. In a pooled analysis of 8925 HNC cases and 12 527 controls from 13 studies participating in the International Head and Neck Cancer Epidemiology Consortium, comparable data on good oral hygiene indicators were harmonized. These included: no denture wear, no gum disease (or bleeding), <5 missing teeth, tooth brushing at least daily, and visiting a dentist ≥once a year. Logistic regression was used to estimate the effects of each oral hygiene indicator and cumulative score on HNC risk, adjusting for tobacco smoking and alcohol consumption. Inverse associations with any HNC, in the hypothesized direction, were observed for <5 missing teeth [odds ratio (OR) = 0.78; 95% confidence interval (CI) 0.74, 0.82], annual dentist visit (OR = 0.82; 95% CI 0.78, 0.87), daily tooth brushing (OR = 0.83, 95% CI 0.79, 0.88), and no gum disease (OR = 0.94; 95% CI 0.89, 0.99), and no association was observed for wearing dentures. These associations were relatively consistent across specific cancer sites, especially for tooth brushing and dentist visits. The population attributable fraction for ≤ 2 out of 5 good oral hygiene indicators was 8.9% (95% CI 3.3%, 14%) for oral cavity cancer. Good oral hygiene, as characterized by few missing teeth, annual dentist visits, and daily tooth brushing, may modestly reduce the risk of HNC. © The Author 2016. 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.

  15. The role of oral hygiene in head and neck cancer: results from International Head and Neck Cancer Epidemiology (INHANCE) consortium

    PubMed Central

    Hashim, D.; Sartori, S.; Brennan, P.; Curado, M. P.; Wünsch-Filho, V.; Divaris, K.; Olshan, A. F.; Zevallos, J. P.; Winn, D. M.; Franceschi, S.; Castellsagué, X.; Lissowska, J.; Rudnai, P.; Matsuo, K.; Morgenstern, H.; Chen, C.; Vaughan, T. L.; Hofmann, J. N.; D'Souza, G.; Haddad, R. I.; Wu, H.; Lee, Y.-C.; Hashibe, M.; Vecchia, C. La; Boffetta, P.

    2016-01-01

    Background Poor oral hygiene has been proposed to contribute to head and neck cancer (HNC) risk, although causality and independency of some indicators are uncertain. This study investigates the relationship of five oral hygiene indicators with incident HNCs. Methods In a pooled analysis of 8925 HNC cases and 12 527 controls from 13 studies participating in the International Head and Neck Cancer Epidemiology Consortium, comparable data on good oral hygiene indicators were harmonized. These included: no denture wear, no gum disease (or bleeding), <5 missing teeth, tooth brushing at least daily, and visiting a dentist ≥once a year. Logistic regression was used to estimate the effects of each oral hygiene indicator and cumulative score on HNC risk, adjusting for tobacco smoking and alcohol consumption. Results Inverse associations with any HNC, in the hypothesized direction, were observed for <5 missing teeth [odds ratio (OR) = 0.78; 95% confidence interval (CI) 0.74, 0.82], annual dentist visit (OR = 0.82; 95% CI 0.78, 0.87), daily tooth brushing (OR = 0.83, 95% CI 0.79, 0.88), and no gum disease (OR = 0.94; 95% CI 0.89, 0.99), and no association was observed for wearing dentures. These associations were relatively consistent across specific cancer sites, especially for tooth brushing and dentist visits. The population attributable fraction for ≤ 2 out of 5 good oral hygiene indicators was 8.9% (95% CI 3.3%, 14%) for oral cavity cancer. Conclusion Good oral hygiene, as characterized by few missing teeth, annual dentist visits, and daily tooth brushing, may modestly reduce the risk of HNC. PMID:27234641

  16. Obesity and mortality after breast cancer by race/ethnicity: The California Breast Cancer Survivorship Consortium.

    PubMed

    Kwan, Marilyn L; John, Esther M; Caan, Bette J; Lee, Valerie S; Bernstein, Leslie; Cheng, Iona; Gomez, Scarlett Lin; Henderson, Brian E; Keegan, Theresa H M; Kurian, Allison W; Lu, Yani; Monroe, Kristine R; Roh, Janise M; Shariff-Marco, Salma; Sposto, Richard; Vigen, Cheryl; Wu, Anna H

    2014-01-01

    We investigated body size and survival by race/ethnicity in 11,351 breast cancer patients diagnosed from 1993 to 2007 with follow-up through 2009 by using data from questionnaires and the California Cancer Registry. We calculated hazard ratios and 95% confidence intervals from multivariable Cox proportional hazard model-estimated associations of body size (body mass index (BMI) (weight (kg)/height (m)(2)) and waist-hip ratio (WHR)) with breast cancer-specific and all-cause mortality. Among 2,744 ascertained deaths, 1,445 were related to breast cancer. Being underweight (BMI <18.5) was associated with increased risk of breast cancer mortality compared with being normal weight in non-Latina whites (hazard ratio (HR) = 1.91, 95% confidence interval (CI): 1.14, 3.20), whereas morbid obesity (BMI ≥ 40) was suggestive of increased risk (HR = 1.43, 95% CI: 0.84, 2.43). In Latinas, only the morbidly obese were at high risk of death (HR = 2.26, 95% CI: 1.23, 4.15). No BMI-mortality associations were apparent in African Americans and Asian Americans. High WHR (quartile 4 vs. quartile 1) was associated with breast cancer mortality in Asian Americans (HR = 2.21, 95% CI: 1.21, 4.03; P for trend = 0.01), whereas no associations were found in African Americans, Latinas, or non-Latina whites. For all-cause mortality, even stronger BMI and WHR associations were observed. The impact of obesity and body fat distribution on breast cancer patients' risk of death may vary across racial/ethnic groups.

  17. East meets West: ethnic differences in prostate cancer epidemiology between East Asians and Caucasians.

    PubMed

    Kimura, Tomomi

    2012-09-01

    Prostate cancer is the most prevalent cancer in males in Western countries. The reported incidence in Asia is much lower than that in African Americans and European Caucasians. Although the lack of systematic prostate cancer screening system in Asian countries explains part of the difference, this alone cannot fully explain the lower incidence in Asian immigrants in the United States and west-European countries compared to the black and non-Hispanic white in those countries, nor the somewhat better prognosis in Asian immigrants with prostate cancer in the United States. Soy food consumption, more popular in Asian populations, is associated with a 25% to 30% reduced risk of prostate cancer. Prostate-specific antigen(PSA) is the only established and routinely implemented clinical biomarker for prostate cancer detection and disease status. Other biomarkers, such as urinary prostate cancer antigen 3 RNA, may increase accuracy of prostate cancer screening compared to PSA alone. Several susceptible loci have been identified in genetic linkage analyses in populations of countries in the West, and approximately 30 genetic polymorphisms have been reported to modestly increase the prostate cancer risk in genome-wide association studies. Most of the identified polymorphisms are reproducible regardless of ethnicity. Somatic mutations in the genomes of prostate tumors have been repeatedly reported to include deletion and gain of the 8p and 8q chromosomal regions, respectively; epigenetic gene silencing of glutathione S-transferase Pi(GSTP1); as well as mutations in androgen receptor gene. However, the molecular mechanisms underlying carcinogenesis, aggressiveness, and prognosis of prostate cancer remain largely unknown. Gene-gene and/or gene-environment interactions still need to be learned. In this review, the differences in PSA screening practice, reported incidence and prognosis of prostate cancer, and genetic factors between the populations in East and West factors are

  18. East meets West: ethnic differences in prostate cancer epidemiology between East Asians and Caucasians

    PubMed Central

    Kimura, Tomomi

    2012-01-01

    Prostate cancer is the most prevalent cancer in males in Western countries. The reported incidence in Asia is much lower than that in African Americans and European Caucasians. Although the lack of systematic prostate cancer screening system in Asian countries explains part of the difference, this alone cannot fully explain the lower incidence in Asian immigrants in the United States and west-European countries compared to the black and non-Hispanic white in those countries, nor the somewhat better prognosis in Asian immigrants with prostate cancer in the United States. Soy food consumption, more popular in Asian populations, is associated with a 25% to 30% reduced risk of prostate cancer. Prostate-specific antigen (PSA) is the only established and routinely implemented clinical biomarker for prostate cancer detection and disease status. Other biomarkers, such as urinary prostate cancer antigen 3 RNA, may increase accuracy of prostate cancer screening compared to PSA alone. Several susceptible loci have been identified in genetic linkage analyses in populations of countries in the West, and approximately 30 genetic polymorphisms have been reported to modestly increase the prostate cancer risk in genome-wide association studies. Most of the identified polymorphisms are reproducible regardless of ethnicity. Somatic mutations in the genomes of prostate tumors have been repeatedly reported to include deletion and gain of the 8p and 8q chromosomal regions, respectively; epigenetic gene silencing of glutathione S-transferase Pi (GSTP1); as well as mutations in androgen receptor gene. However, the molecular mechanisms underlying carcinogenesis, aggressiveness, and prognosis of prostate cancer remain largely unknown. Gene-gene and/or gene-environment interactions still need to be learned. In this review, the differences in PSA screening practice, reported incidence and prognosis of prostate cancer, and genetic factors between the populations in East and West factors are

  19. Associations of body mass index, smoking, and alcohol consumption with prostate cancer mortality in the Asia Cohort Consortium.

    PubMed

    Fowke, Jay H; McLerran, Dale F; Gupta, Prakash C; He, Jiang; Shu, Xiao-Ou; Ramadas, Kunnambath; Tsugane, Shoichiro; Inoue, Manami; Tamakoshi, Akiko; Koh, Woon-Puay; Nishino, Yoshikazu; Tsuji, Ichiro; Ozasa, Kotaro; Yuan, Jian-Min; Tanaka, Hideo; Ahn, Yoon-Ok; Chen, Chien-Jen; Sugawara, Yumi; Yoo, Keun-Young; Ahsan, Habibul; Pan, Wen-Harn; Pednekar, Mangesh; Gu, Dongfeng; Xiang, Yong-Bing; Sauvaget, Catherine; Sawada, Norie; Wang, Renwei; Kakizaki, Masako; Tomata, Yasutake; Ohishi, Waka; Butler, Lesley M; Oze, Isao; Kim, Dong-Hyun; You, San-Lin; Park, Sue K; Parvez, Faruque; Chuang, Shao-Yuan; Chen, Yu; Lee, Jung Eun; Grant, Eric; Rolland, Betsy; Thornquist, Mark; Feng, Ziding; Zheng, Wei; Boffetta, Paolo; Sinha, Rashmi; Kang, Daehee; Potter, John D

    2015-09-01

    Many potentially modifiable risk factors for prostate cancer are also associated with prostate cancer screening, which may induce a bias in epidemiologic studies. We investigated the associations of body mass index (weight (kg)/height (m)(2)), smoking, and alcohol consumption with risk of fatal prostate cancer in Asian countries where prostate cancer screening is not widely utilized. Analysis included 18 prospective cohort studies conducted during 1963-2006 across 6 countries in southern and eastern Asia that are part of the Asia Cohort Consortium. Body mass index, smoking, and alcohol intake were determined by questionnaire at baseline, and cause of death was ascertained through death certificates. Analysis included 522,736 men aged 54 years, on average, at baseline. During 4.8 million person-years of follow-up, there were 634 prostate cancer deaths (367 prostate cancer deaths across the 11 cohorts with alcohol data). In Cox proportional hazards analyses of all cohorts in the Asia Cohort Consortium, prostate cancer mortality was not significantly associated with obesity (body mass index >25: hazard ratio (HR) = 1.08, 95% confidence interval (CI): 0.85, 1.36), ever smoking (HR = 1.00, 95% CI: 0.84, 1.21), or heavy alcohol intake (HR = 1.00, 95% CI: 0.74, 1.35). Differences in prostate cancer screening and detection probably contribute to differences in the association of obesity, smoking, or alcohol intake with prostate cancer risk and mortality between Asian and Western populations and thus require further investigation.

  20. Associations of Body Mass Index, Smoking, and Alcohol Consumption With Prostate Cancer Mortality in the Asia Cohort Consortium

    PubMed Central

    Fowke, Jay H.; McLerran, Dale F.; Gupta, Prakash C.; He, Jiang; Shu, Xiao-Ou; Ramadas, Kunnambath; Tsugane, Shoichiro; Inoue, Manami; Tamakoshi, Akiko; Koh, Woon-Puay; Nishino, Yoshikazu; Tsuji, Ichiro; Ozasa, Kotaro; Yuan, Jian-Min; Tanaka, Hideo; Ahn, Yoon-Ok; Chen, Chien-Jen; Sugawara, Yumi; Yoo, Keun-Young; Ahsan, Habibul; Pan, Wen-Harn; Pednekar, Mangesh; Gu, Dongfeng; Xiang, Yong-Bing; Sauvaget, Catherine; Sawada, Norie; Wang, Renwei; Kakizaki, Masako; Tomata, Yasutake; Ohishi, Waka; Butler, Lesley M.; Oze, Isao; Kim, Dong-Hyun; You, San-Lin; Park, Sue K.; Parvez, Faruque; Chuang, Shao-Yuan; Chen, Yu; Lee, Jung Eun; Grant, Eric; Rolland, Betsy; Thornquist, Mark; Feng, Ziding; Zheng, Wei; Boffetta, Paolo; Sinha, Rashmi; Kang, Daehee; Potter, John D.

    2015-01-01

    Many potentially modifiable risk factors for prostate cancer are also associated with prostate cancer screening, which may induce a bias in epidemiologic studies. We investigated the associations of body mass index (weight (kg)/height (m)2), smoking, and alcohol consumption with risk of fatal prostate cancer in Asian countries where prostate cancer screening is not widely utilized. Analysis included 18 prospective cohort studies conducted during 1963–2006 across 6 countries in southern and eastern Asia that are part of the Asia Cohort Consortium. Body mass index, smoking, and alcohol intake were determined by questionnaire at baseline, and cause of death was ascertained through death certificates. Analysis included 522,736 men aged 54 years, on average, at baseline. During 4.8 million person-years of follow-up, there were 634 prostate cancer deaths (367 prostate cancer deaths across the 11 cohorts with alcohol data). In Cox proportional hazards analyses of all cohorts in the Asia Cohort Consortium, prostate cancer mortality was not significantly associated with obesity (body mass index >25: hazard ratio (HR) = 1.08, 95% confidence interval (CI): 0.85, 1.36), ever smoking (HR = 1.00, 95% CI: 0.84, 1.21), or heavy alcohol intake (HR = 1.00, 95% CI: 0.74, 1.35). Differences in prostate cancer screening and detection probably contribute to differences in the association of obesity, smoking, or alcohol intake with prostate cancer risk and mortality between Asian and Western populations and thus require further investigation. PMID:26243736

  1. Oncofertility Consortium

    MedlinePlus

    ... Oncofertility Consortium Conference November 14-16, 2017 in Chicago, Illinois Register for the Oncofertility Conference Call the ... Consortium 303 E Superior Street, Suite 10-121 Chicago, IL, 60611 (312) 503-2504 Social Media Parking ...

  2. Obesity and survival among women with ovarian cancer: results from the Ovarian Cancer Association Consortium

    PubMed Central

    Nagle, C M; Dixon, S C; Jensen, A; Kjaer, S K; Modugno, F; deFazio, A; Fereday, S; Hung, J; Johnatty, S E; Fasching, P A; Beckmann, M W; Lambrechts, D; Vergote, I; Van Nieuwenhuysen, E; Lambrechts, S; Risch, H A; Rossing, M A; Doherty, J A; Wicklund, K G; Chang-Claude, J; Goodman, M T; Ness, R B; Moysich, K; Heitz, F; du Bois, A; Harter, P; Schwaab, I; Matsuo, K; Hosono, S; Goode, E L; Vierkant, R A; Larson, M C; Fridley, B L; Høgdall, C; Schildkraut, J M; Weber, R P; Cramer, D W; Terry, K L; Bandera, E V; Paddock, L; Rodriguez-Rodriguez, L; Wentzensen, N; Yang, H P; Brinton, L A; Lissowska, J; Høgdall, E; Lundvall, L; Whittemore, A; McGuire, V; Sieh, W; Rothstein, J; Sutphen, R; Anton-Culver, H; Ziogas, A; Pearce, C L; Wu, A H; Webb, P M

    2015-01-01

    Background: Observational studies have reported a modest association between obesity and risk of ovarian cancer; however, whether it is also associated with survival and whether this association varies for the different histologic subtypes are not clear. We undertook an international collaborative analysis to assess the association between body mass index (BMI), assessed shortly before diagnosis, progression-free survival (PFS), ovarian cancer-specific survival and overall survival (OS) among women with invasive ovarian cancer. Methods: We used original data from 21 studies, which included 12 390 women with ovarian carcinoma. We combined study-specific adjusted hazard ratios (HRs) using random-effects models to estimate pooled HRs (pHR). We further explored associations by histologic subtype. Results: Overall, 6715 (54%) deaths occurred during follow-up. A significant OS disadvantage was observed for women who were obese (BMI: 30–34.9, pHR: 1.10 (95% confidence intervals (CIs): 0.99–1.23); BMI: ⩾35, pHR: 1.12 (95% CI: 1.01–1.25)). Results were similar for PFS and ovarian cancer-specific survival. In analyses stratified by histologic subtype, associations were strongest for women with low-grade serous (pHR: 1.12 per 5 kg m−2) and endometrioid subtypes (pHR: 1.08 per 5 kg m−2), and more modest for the high-grade serous (pHR: 1.04 per 5 kg m−2) subtype, but only the association with high-grade serous cancers was significant. Conclusions: Higher BMI is associated with adverse survival among the majority of women with ovarian cancer. PMID:26151456

  3. Obesity and survival among women with ovarian cancer: results from the Ovarian Cancer Association Consortium.

    PubMed

    Nagle, C M; Dixon, S C; Jensen, A; Kjaer, S K; Modugno, F; deFazio, A; Fereday, S; Hung, J; Johnatty, S E; Fasching, P A; Beckmann, M W; Lambrechts, D; Vergote, I; Van Nieuwenhuysen, E; Lambrechts, S; Risch, H A; Rossing, M A; Doherty, J A; Wicklund, K G; Chang-Claude, J; Goodman, M T; Ness, R B; Moysich, K; Heitz, F; du Bois, A; Harter, P; Schwaab, I; Matsuo, K; Hosono, S; Goode, E L; Vierkant, R A; Larson, M C; Fridley, B L; Høgdall, C; Schildkraut, J M; Weber, R P; Cramer, D W; Terry, K L; Bandera, E V; Paddock, L; Rodriguez-Rodriguez, L; Wentzensen, N; Yang, H P; Brinton, L A; Lissowska, J; Høgdall, E; Lundvall, L; Whittemore, A; McGuire, V; Sieh, W; Rothstein, J; Sutphen, R; Anton-Culver, H; Ziogas, A; Pearce, C L; Wu, A H; Webb, P M

    2015-09-01

    Observational studies have reported a modest association between obesity and risk of ovarian cancer; however, whether it is also associated with survival and whether this association varies for the different histologic subtypes are not clear. We undertook an international collaborative analysis to assess the association between body mass index (BMI), assessed shortly before diagnosis, progression-free survival (PFS), ovarian cancer-specific survival and overall survival (OS) among women with invasive ovarian cancer. We used original data from 21 studies, which included 12 390 women with ovarian carcinoma. We combined study-specific adjusted hazard ratios (HRs) using random-effects models to estimate pooled HRs (pHR). We further explored associations by histologic subtype. Overall, 6715 (54%) deaths occurred during follow-up. A significant OS disadvantage was observed for women who were obese (BMI: 30-34.9, pHR: 1.10 (95% confidence intervals (CIs): 0.99-1.23); BMI: ⩾35, pHR: 1.12 (95% CI: 1.01-1.25)). Results were similar for PFS and ovarian cancer-specific survival. In analyses stratified by histologic subtype, associations were strongest for women with low-grade serous (pHR: 1.12 per 5 kg m(-2)) and endometrioid subtypes (pHR: 1.08 per 5 kg m(-2)), and more modest for the high-grade serous (pHR: 1.04 per 5 kg m(-2)) subtype, but only the association with high-grade serous cancers was significant. Higher BMI is associated with adverse survival among the majority of women with ovarian cancer.

  4. Obesity and Mortality After Breast Cancer by Race/Ethnicity: The California Breast Cancer Survivorship Consortium

    PubMed Central

    Kwan, Marilyn L.; John, Esther M.; Caan, Bette J.; Lee, Valerie S.; Bernstein, Leslie; Cheng, Iona; Gomez, Scarlett Lin; Henderson, Brian E.; Keegan, Theresa H.M.; Kurian, Allison W.; Lu, Yani; Monroe, Kristine R.; Roh, Janise M.; Shariff-Marco, Salma; Sposto, Richard; Vigen, Cheryl; Wu, Anna H.

    2014-01-01

    We investigated body size and survival by race/ethnicity in 11,351 breast cancer patients diagnosed from 1993 to 2007 with follow-up through 2009 by using data from questionnaires and the California Cancer Registry. We calculated hazard ratios and 95% confidence intervals from multivariable Cox proportional hazard model–estimated associations of body size (body mass index (BMI) (weight (kg)/height (m)2) and waist-hip ratio (WHR)) with breast cancer–specific and all-cause mortality. Among 2,744 ascertained deaths, 1,445 were related to breast cancer. Being underweight (BMI <18.5) was associated with increased risk of breast cancer mortality compared with being normal weight in non-Latina whites (hazard ratio (HR) = 1.91, 95% confidence interval (CI): 1.14, 3.20), whereas morbid obesity (BMI ≥40) was suggestive of increased risk (HR = 1.43, 95% CI: 0.84, 2.43). In Latinas, only the morbidly obese were at high risk of death (HR = 2.26, 95% CI: 1.23, 4.15). No BMI–mortality associations were apparent in African Americans and Asian Americans. High WHR (quartile 4 vs. quartile 1) was associated with breast cancer mortality in Asian Americans (HR = 2.21, 95% CI: 1.21, 4.03; P for trend = 0.01), whereas no associations were found in African Americans, Latinas, or non-Latina whites. For all-cause mortality, even stronger BMI and WHR associations were observed. The impact of obesity and body fat distribution on breast cancer patients' risk of death may vary across racial/ethnic groups. PMID:24107615

  5. Multi-institutional oncogenic driver mutation analysis in lung adenocarcinoma: The Lung Cancer Mutation Consortium experience

    PubMed Central

    Dias-Santagata, Dora; Wistuba, Ignacio I.; Chen, Heidi; Fujimoto, Junya; Kugler, Kelly; Franklin, Wilbur A.; Iafrate, A. John; Ladanyi, Marc; Kris, Mark G.; Johnson, Bruce E.; Bunn, Paul A.; Minna, John D.; Kwiatkowski, David J.

    2015-01-01

    Introduction Molecular genetic analyses of lung adenocarcinoma have recently become standard of care for treatment selection. The Lung Cancer Mutation Consortium was formed to enable collaborative multi-institutional analyses of 10 potential oncogenic driver mutations. Technical aspects of testing, and clinicopathologic correlations are presented. Methods Mutation testing in at least one of 8 genes (EGFR, KRAS, ERBB2, AKT1, BRAF, MEK1, NRAS, PIK3CA) using SNaPshot, mass spectrometry, Sanger sequencing +/− PNA and/or sizing assays, along with ALK and/or MET FISH were performed in 6 labs on 1007 patients from 14 institutions. Results 1007 specimens had mutation analysis performed, and 733 specimens had all 10 genes analyzed. Mutation identification rates did not vary by analytic method. Biopsy and cytology specimens were inadequate for testing in 26% and 35% of cases compared to 5% of surgical specimens. Among the 1007 cases with mutation analysis performed, EGFR, KRAS, ALK, and ERBB2 alterations were detected in 22, 25, 8.5, and 2.4% of cases, respectively. EGFR mutations were highly associated with female sex, Asian race, and never smoking status; and less strongly associated with stage IV disease, presence of bone metastases, and absence of adrenal metastases. ALK rearrangements were strongly associated with never smoking status, and more weakly associated with presence of liver metastases. ERBB2 mutations were strongly associated with Asian race and never smoking status. Two mutations were seen in 2.7% of samples, all but one of which involved one or more of PIK3CA, ALK or MET. Conclusion Multi-institutional molecular analysis across multiple platforms, sample types, and institutions can yield consistent results and novel clinicopathological observations. PMID:25738220

  6. Cancer patient and survivor research from the cancer information service research consortium: a preview of three large randomized trials and initial lessons learned.

    PubMed

    Marcus, Alfred C; Diefenbach, Michael A; Stanton, Annette L; Miller, Suzanne M; Fleisher, Linda; Raich, Peter C; Morra, Marion E; Perocchia, Rosemarie Slevin; Tran, Zung Vu; Bright, Mary Anne

    2013-01-01

    The authors describe 3 large randomized trials from the Cancer Information Service Research Consortium. Three web-based multimedia programs are being tested to help newly diagnosed prostate (Project 1) and breast cancer patients (Project 2) make informed treatment decisions and breast cancer patients prepare for life after treatment (Project 3). Project 3 also tests a telephone callback intervention delivered by a cancer information specialist. All participants receive standard print material specific to each project. Preliminary results from the 2-month follow-up interviews are reported for the initial wave of enrolled participants, most of whom were recruited from the Cancer Information Service (1-800-4-CANCER) telephone information program (Project 1: n =208; Project 2: n =340; Project 3: n =792). Self-reported use of the multimedia program was 51%, 52%, and 67% for Projects 1, 2, and 3, respectively. Self-reported use of the print materials (read all, most, or some) was 90%, 85%, and 83% for Projects 1, 2, and 3, respectively. The callback intervention was completed by 92% of Project 3 participants. Among those using the Cancer Information Service Research Consortium interventions, perceived usefulness and benefit was high, and more than 90% reported that they would recommend them to other cancer patients. The authors present 5 initial lessons learned that may help inform future cancer communications research.

  7. Association of Type 2 Diabetes Susceptibility Variants With Advanced Prostate Cancer Risk in the Breast and Prostate Cancer Cohort Consortium

    PubMed Central

    Machiela, Mitchell J.; Lindström, Sara; Allen, Naomi E.; Haiman, Christopher A.; Albanes, Demetrius; Barricarte, Aurelio; Berndt, Sonja I.; Bueno-de-Mesquita, H. Bas; Chanock, Stephen; Gaziano, J. Michael; Gapstur, Susan M.; Giovannucci, Edward; Henderson, Brian E.; Jacobs, Eric J.; Kolonel, Laurence N.; Krogh, Vittorio; Ma, Jing; Stampfer, Meir J.; Stevens, Victoria L.; Stram, Daniel O.; Tjønneland, Anne; Travis, Ruth; Willett, Walter C.; Hunter, David J.; Le Marchand, Loic; Kraft, Peter

    2012-01-01

    Observational studies have found an inverse association between type 2 diabetes (T2D) and prostate cancer (PCa), and genome-wide association studies have found common variants near 3 loci associated with both diseases. The authors examined whether a genetic background that favors T2D is associated with risk of advanced PCa. Data from the National Cancer Institute's Breast and Prostate Cancer Cohort Consortium, a genome-wide association study of 2,782 advanced PCa cases and 4,458 controls, were used to evaluate whether individual single nucleotide polymorphisms or aggregations of these 36 T2D susceptibility loci are associated with PCa. Ten T2D markers near 9 loci (NOTCH2, ADCY5, JAZF1, CDKN2A/B, TCF7L2, KCNQ1, MTNR1B, FTO, and HNF1B) were nominally associated with PCa (P < 0.05); the association for single nucleotide polymorphism rs757210 at the HNF1B locus was significant when multiple comparisons were accounted for (adjusted P = 0.001). Genetic risk scores weighted by the T2D log odds ratio and multilocus kernel tests also indicated a significant relation between T2D variants and PCa risk. A mediation analysis of 9,065 PCa cases and 9,526 controls failed to produce evidence that diabetes mediates the association of the HNF1B locus with PCa risk. These data suggest a shared genetic component between T2D and PCa and add to the evidence for an interrelation between these diseases. PMID:23193118

  8. Genetic susceptibility to pancreatic cancer and its functional characterisation: the PANcreatic Disease ReseArch (PANDoRA) consortium.

    PubMed

    Campa, Daniele; Rizzato, Cosmeri; Capurso, Gabriele; Giese, Nathalia; Funel, Niccola; Greenhalf, William; Soucek, Pavel; Gazouli, Maria; Pezzilli, Raffaele; Pasquali, Claudio; Talar-Wojnarowska, Renata; Cantore, Maurizio; Andriulli, Angelo; Scarpa, Aldo; Jamroziak, Krzysztof; Delle Fave, Gianfranco; Costello, Eithne; Khaw, Kay-Tee; Heller, Anette; Key, Tim J; Theodoropoulos, George; Malecka-Panas, Ewa; Mambrini, Andrea; Bambi, Franco; Landi, Stefano; Pedrazzoli, Sergio; Bassi, Claudio; Pacetti, Paola; Piepoli, Ada; Tavano, Francesca; di Sebastiano, Pierluigi; Vodickova, Ludmila; Basso, Daniela; Plebani, Mario; Fogar, Paola; Büchler, Markus W; Bugert, Peter; Vodicka, Pavel; Boggi, Ugo; Neoptolemos, John P; Werner, Jens; Canzian, Federico

    2013-02-01

    Pancreatic cancer is the fourth leading cause of cancer deaths in the European Union and in the USA, but little is known about its genetic susceptibility. The PANcreatic Disease ReseArch (PANDoRA) consortium was established to unite the efforts of different research groups; its aim is to create a large bio-database to uncover new genetic factors for pancreatic cancer risk, response to treatment, and patient survival. So far 2220 cases of pancreatic adenocarcinoma, a smaller number of cases of endocrine pancreatic tumours (n=86), chronic pancreatitis (n=272) and 3847 healthy controls have been collected. As a collective effort of the consortium, SNPs associated with pancreatic adenocarcinoma risk from a genome-wide association study performed in Caucasians were replicated. The possibility that the same genetic polymorphisms may influence patient survival as well was also addressed. This collective effort is particularly important for pancreatic cancer because it is a relatively rare disease for which little is known about aetiopathogenesis and risk factors. The recruitment of additional collaborators and partner institutions is continuously on-going. Copyright © 2012 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  9. Oral fenretinide in biochemically recurrent prostate cancer: a California cancer consortium phase II trial.

    PubMed

    Cheung, Eric; Pinski, Jacek; Dorff, Tanya; Groshen, Susan; Quinn, David I; Reynolds, C Patrick; Maurer, Barry J; Lara, Primo N; Tsao-Wei, Denice D; Twardowski, Przemyslaw; Chatta, Gurkamal; McNamara, Mark; Gandara, David R

    2009-01-01

    Fenretinide is a synthetic retinoid that is cytotoxic to a variety of cancers. We conducted a phase II trial of oral fenretinide in patients with biochemically recurrent prostate cancer. Eligible patients had histologically confirmed prostate cancer and a confirmed rising prostate-specific antigen (PSA) >or= 2 ng/mL following either radical prostatectomy and/or pelvic radiation therapy, without clinical or radiographic evidence of metastasis. The primary endpoint was PSA response, which was defined as a confirmed decrease by >or=50%, and >or=5 ng/mL, from the pretreatment value. Treatment comprised oral fenretinide 900 mg/m2 twice daily for 1 week, every 3 weeks, for 1 year. After a median follow-up of 17.7 months, out of 23 patients, 7 (30%) patients had PSA stable disease (SD), 11 (48%) patients had PSA progression within 3 months, 4 patients had minimal increases over 3 months that did not qualify as SD or progression (17%), and one patient (4%) was not evaluable. Median time to PSA progression was 4.6 months (95% CI, 3.2-8.2 months). Observed grade 3 toxicities included fatigue, pain, hypermagnesemia, a rise in lipase, and nyctalopia. Although well-tolerated, oral fenretinide did not meet prespecified PSA criteria for response in biochemically recurrent prostate cancer; however, 30% of patients had SD, which suggests modest single-agent clinical activity. The role of different formulations of fenretinide, which might allow for higher serum concentrations of the drug, is currently under investigation.

  10. Association between air pollution and mammographic breast density in the Breast Cancer Surveilance Consortium.

    PubMed

    Yaghjyan, Lusine; Arao, Robert; Brokamp, Cole; O'Meara, Ellen S; Sprague, Brian L; Ghita, Gabriela; Ryan, Patrick

    2017-04-06

    Mammographic breast density is a well-established strong risk factor for breast cancer. The environmental contributors to geographic variation in breast density in urban and rural areas are poorly understood. We examined the association between breast density and exposure to ambient air pollutants (particulate matter <2.5 μm in diameter (PM2.5) and ozone (O3)) in a large population-based screening registry. Participants included women undergoing mammography screening at imaging facilities within the Breast Cancer Surveillance Consortium (2001-2009). We included women aged ≥40 years with known residential zip codes before the index mammogram (n = 279,967). Breast density was assessed using the American College of Radiology's Breast Imaging-Reporting and Data System (BI-RADS) four-category breast density classification. PM2.5 and O3 estimates for grids across the USA (2001-2008) were obtained from the US Environmental Protection Agency Hierarchical Bayesian Model (HBM). For the majority of women (94%), these estimates were available for the year preceding the mammogram date. Association between exposure to air pollutants and density was estimated using polytomous logistic regression, adjusting for potential confounders. Women with extremely dense breasts had higher mean PM2.5 and lower O3 exposures than women with fatty breasts (8.97 vs. 8.66 ug/m(3) and 33.70 vs. 35.82 parts per billion (ppb), respectively). In regression analysis, women with heterogeneously dense vs. scattered fibroglandular breasts were more likely to have higher exposure to PM2.5 (fourth vs. first quartile odds ratio (OR) = 1.19, 95% confidence interval (CI) 1.16 - 1.23). Women with extremely dense vs. scattered fibroglandular breasts were less likely to have higher levels of ozone exposure (fourth vs. first quartile OR = 0.80, 95% CI 0.73-0.87). Exposure to PM2.5 and O3 may in part explain geographical variation in mammographic density. Further studies are warranted to

  11. Paclitaxel Plus Oxaliplatin for Recurrent or Metastatic Cervical Cancer: A New York Cancer Consortium Study

    PubMed Central

    Kuo, Dennis Yi-Shin; Blank, Stephanie V.; Christo, Paul J.; Kim, Mimi; Caputo, Thomas A.; Pothuri, Bhavana; Hershman, Dawn; Goldman, Noah; Ivy, Percy S.; Runowicz, Carolyn D.; Muggia, Franco; Goldberg, Gary L.; Einstein, Mark H.

    2009-01-01

    Objective Survival in women with recurrent or metastatic cervical cancer remains poor. More effective and less toxic regimens are needed. Cisplatin is an effective radiosensitizer, but its single agent activity in recurrent cervical cancer, especially after prior cisplatin exposure, is disappointing, with a response rate of only 13%. Oxaliplatin has preclinical activity in cisplatin-resistant tumors and may have synergic activity when combined with paclitaxel. Our objective is determine the efficacy and toxicity of paclitaxel and oxaliplatin in patients with recurrent or metastatic cervical cancer. Methods Patients with histologic confirmation of primary metastatic or recurrent cervical cancer not amenable to surgical management were eligible. Treatment consisted of paclitaxel 175 mg/m2 IV and oxaliplatin 130 mg/m2 IV every 21 days. The primary endpoints were toxicity, recorded every cycle, and response, determined by RECIST criteria were assessed every 9 weeks, with subsequent confirmation as required. Sample size determinations were made using a Simon's two-stage design with a projected overall response proportion of 13% with cisplatin alone. Survival rates were calculated with Kaplan-Meier methods. Results Of the 35 patients enrolled, 32 were evaluable. The median age was 56(27-78); 30 had had prior radiation (23 concomitant with cisplatin). Patients completed a mean of 4.2 cycles (1-11). There were 2 complete and 5 partial responses for a total response rate of 7/32 (22%; 95% CI: 9.3%-40.0%). Eight patients had stable disease for an overall clinical benefit rate of 15/32 (47%; 95% CI: 29.1% - 65.3%). The mean time to best response was 13.5 weeks (95% C.I.: 10.6, 16.4). The mean progression-free survival was 21 weeks (95% C.I.: 14.7, 27.2) and mean overall survival was 52.1weeks (95% C.I.: 39.4, 64.8). A total of 135 cycles were administered. There were 28 (20.1%) grade 3/4 hematologic toxicities and 46 (34.1%) grade 3/4 non-hematologic toxicities, which were

  12. Circulating 25-Hydroxyvitamin D and the Risk of Rarer Cancers: Design and Methods of the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers

    PubMed Central

    Gallicchio, Lisa; Helzlsouer, Kathy J.; Chow, Wong-Ho; Freedman, D. Michal; Hankinson, Susan E.; Hartge, Patricia; Hartmuller, Virginia; Harvey, Chinonye; Hayes, Richard B.; Horst, Ronald L.; Koenig, Karen L.; Kolonel, Laurence N.; Laden, Francine; McCullough, Marjorie L.; Parisi, Dominick; Purdue, Mark P.; Shu, Xiao-Ou; Snyder, Kirk; Stolzenberg-Solomon, Rachael Z.; Tworoger, Shelley S.; Varanasi, Arti; Virtamo, Jarmo; Wilkens, Lynne R.; Xiang, Yong-Bing; Yu, Kai; Zeleniuch-Jacquotte, Anne; Zheng, Wei; Abnet, Christian C.; Albanes, Demetrius; Bertrand, Kimberly; Weinstein, Stephanie J.

    2010-01-01

    The Cohort Consortium Vitamin D Pooling Project of Rarer Cancers (VDPP), a consortium of 10 prospective cohort studies from the United States, Finland, and China, was formed to examine the associations between circulating 25-hydroxyvitamin D (25(OH)D) concentrations and the risk of rarer cancers. Cases (total n = 5,491) included incident primary endometrial (n = 830), kidney (n = 775), ovarian (n = 516), pancreatic (n = 952), and upper gastrointestinal tract (n = 1,065) cancers and non-Hodgkin lymphoma (n = 1,353) diagnosed in the participating cohorts. At least 1 control was matched to each case on age, date of blood collection (1974–2006), sex, and race/ethnicity (n = 6,714). Covariate data were obtained from each cohort in a standardized manner. The majority of the serum or plasma samples were assayed in a central laboratory using a direct, competitive chemiluminescence immunoassay on the DiaSorin LIAISON platform (DiaSorin, Inc., Stillwater, Minnesota). Masked quality control samples included serum standards from the US National Institute of Standards and Technology. Conditional logistic regression analyses were conducted using clinically defined cutpoints, with 50–<75 nmol/L as the reference category. Meta-analyses were also conducted using inverse-variance weights in random-effects models. This consortium approach permits estimation of the association between 25(OH)D and several rarer cancers with high accuracy and precision across a wide range of 25(OH)D concentrations. PMID:20562188

  13. East-West Symposium on nasopharyngeal cancer

    SciTech Connect

    Liu, F.-F. . E-mail: Fei-Fei.Liu@rmp.uhn.on.ca; Frappier, Lori; Kim, John; O'Sullivan, Brian; Hui, Angela; Bastianutto, Carlo

    2007-03-01

    Background: To achieve greater understanding of the epidemiology, pathogenesis, molecular oncology, diagnostic, and therapeutic aspects of nasopharyngeal cancer (NPC), an international meeting was held in June 2005, Toronto, Canada. Results: Further insights were obtained into the role of EBV in NPC development, with its diverse effects ranging from proliferative signals via NF-kB, to immunesuppression, to angiogenic gene regulation. Subsequently, multiple pathways are dysregulated in NPC as revealed by expression array analyses, including apoptosis, integrin, and B-catenin cascades. Advances have been made in the diagnosis and monitoring of NPC, using transoral brushings and plasma levels of EBV transcripts, which may not directly correlate with the number of circulating tumor cells, but is nevertheless informative in predicting and tracking disease response. Many novel therapies have promising results, particularly in the areas of immunotherapies, and the exploration of molecularly targeted approaches such as cetuximab or histone deacetylase inhibitors. Conclusions: The results from large randomized trials and meta-analyses have consistently demonstrated the benefit of concurrent chemotherapy with curative radiation therapy, but at a cost of greater acute and late-tissue toxicities. Further advances are required to achieve an improved understanding on the inter-relationship between environmental and genetic determinants in NPC development, to reduce the global burden of this disease. At the same time, novel therapeutic approaches are necessary to increase curability of NPC, but with reduced long-term toxicities.

  14. Unifying screening processes within the PROSPR consortium: a conceptual model for breast, cervical, and colorectal cancer screening.

    PubMed

    Beaber, Elisabeth F; Kim, Jane J; Schapira, Marilyn M; Tosteson, Anna N A; Zauber, Ann G; Geiger, Ann M; Kamineni, Aruna; Weaver, Donald L; Tiro, Jasmin A

    2015-06-01

    General frameworks of the cancer screening process are available, but none directly compare the process in detail across different organ sites. This limits the ability of medical and public health professionals to develop and evaluate coordinated screening programs that apply resources and population management strategies available for one cancer site to other sites. We present a trans-organ conceptual model that incorporates a single screening episode for breast, cervical, and colorectal cancers into a unified framework based on clinical guidelines and protocols; the model concepts could be expanded to other organ sites. The model covers four types of care in the screening process: risk assessment, detection, diagnosis, and treatment. Interfaces between different provider teams (eg, primary care and specialty care), including communication and transfer of responsibility, may occur when transitioning between types of care. Our model highlights across each organ site similarities and differences in steps, interfaces, and transitions in the screening process and documents the conclusion of a screening episode. This model was developed within the National Cancer Institute-funded consortium Population-based Research Optimizing Screening through Personalized Regimens (PROSPR). PROSPR aims to optimize the screening process for breast, cervical, and colorectal cancer and includes seven research centers and a statistical coordinating center. Given current health care reform initiatives in the United States, this conceptual model can facilitate the development of comprehensive quality metrics for cancer screening and promote trans-organ comparative cancer screening research. PROSPR findings will support the design of interventions that improve screening outcomes across multiple cancer sites.

  15. NCI Cohort Consortium

    Cancer.gov

    The NCI Cohort Consortium is an extramural-intramural partnership formed by the National Cancer Institute to address the need for large-scale collaborations to pool the large quantity of data and biospecimens necessary to conduct a wide range of cancer studies.

  16. Population Burden of Betel Quid Abuse and Its Relation to Oral Premalignant Disorders in South, Southeast, and East Asia: An Asian Betel-Quid Consortium Study

    PubMed Central

    Lee, Chien-Hung; Min-Shan Ko, Albert; Warnakulasuriya, Saman; Ling, Tian-You; Sunarjo; Rajapakse, Palandage Sunethra; Zain, Rosnah Binti; Ibrahim, Salah Osman; Zhang, Shan-Shan; Wu, Han-Jiang; Liu, Lin; Kuntoro; Utomo, Budi; Warusavithana, Supun Amila; Razak, Ishak Abdul; Abdullah, Norlida; Shrestha, Prashanta; Shieh, Tien-Yu; Yen, Cheng-Fang

    2012-01-01

    Objectives. We investigated the population burden of betel quid abuse and its related impact on oral premalignant disorders (OPDs) in South, Southeast, and East Asia. Methods. The Asian Betel-Quid Consortium conducted a multistage sampling of 8922 representative participants from Taiwan, Mainland China, Malaysia, Indonesia, Nepal, and Sri Lanka. Participants received an interviewer-administered survey and were examined for oral mucosal disorders. Results. The prevalence of betel quid abuse was 0.8% to 46.3% across 6 Asian populations. The abuse frequency was over 40.5% for current chewers, with the highest proportion in Nepalese and Southeast Asian chewers (76.9%−99.6%). Tobacco-added betel quid conferred higher abuse rates (74.4%−99.6%) among Malaysian, Indonesian, and Sri Lankan men than did tobacco-free betel quid (21.8%−89.1%). Gender, lower education level, younger age at chewing initiation, and clustering of familial betel quid use significantly contributed to higher abuse rates. Indonesian betel quid abusers showed the highest prevalence of OPDs and had a greater risk of OPDs than did nonabusers. Conclusions. Betel quid abuse is high in regions of Asia where it is customarily practiced, and such abuse correlates highly with OPDs. By recognizing abuse-associated factors, health policies and preventive frameworks can be effectively constructed to combat these oral preneoplasms. PMID:22390524

  17. Lung cancer and DNA repair genes: multilevel association analysis from the International Lung Cancer Consortium

    PubMed Central

    Kazma, Rémi; Babron, Marie-Claude; Gaborieau, Valérie; Génin, Emmanuelle; Brennan, Paul; Hung, Rayjean J.; McLaughlin, John R.; Krokan, Hans E.; Elvestad, Maiken B.; Skorpen, Frank; Anderssen, Endre; Vooder, Tõnu; Välk, Kristjan; Metspalu, Andres; Field, John K.; Lathrop, Mark; Sarasin, Alain; Benhamou, Simone

    2012-01-01

    Lung cancer (LC) is the leading cause of cancer-related death worldwide and tobacco smoking is the major associated risk factor. DNA repair is an important process, maintaining genome integrity and polymorphisms in DNA repair genes may contribute to susceptibility to LC. To explore the role of DNA repair genes in LC, we conducted a multilevel association study with 1655 single nucleotide polymorphisms (SNPs) in 211 DNA repair genes using 6911 individuals pooled from four genome-wide case–control studies. Single SNP association corroborates previous reports of association with rs3131379, located on the gene MSH5 (P = 3.57 × 10-5) and returns a similar risk estimate. The effect of this SNP is modulated by histological subtype. On the log-additive scale, the odds ratio per allele is 1.04 (0.84–1.30) for adenocarcinomas, 1.52 (1.28–1.80) for squamous cell carcinomas and 1.31 (1.09–1.57) for other histologies (heterogeneity test: P = 9.1 × 10−3). Gene-based association analysis identifies three repair genes associated with LC (P < 0.01): UBE2N, structural maintenance of chromosomes 1L2 and POLB. Two additional genes (RAD52 and POLN) are borderline significant. Pathway-based association analysis identifies five repair pathways associated with LC (P < 0.01): chromatin structure, DNA polymerases, homologous recombination, genes involved in human diseases with sensitivity to DNA-damaging agents and Rad6 pathway and ubiquitination. This first international pooled analysis of a large dataset unravels the role of specific DNA repair pathways in LC and highlights the importance of accounting for gene and pathway effects when studying LC. PMID:22382497

  18. Variant ABO Blood Group Alleles, Secretor Status and Risk of Pancreatic Cancer: Results from the Pancreatic Cancer Cohort Consortium

    PubMed Central

    Wolpin, Brian M.; Kraft, Peter; Xu, Mousheng; Steplowski, Emily; Olsson, Martin L.; Arslan, Alan A.; Bueno-de-Mesquita, H. Bas; Gross, Myron; Helzlsouer, Kathy; Jacobs, Eric J.; LaCroix, Andrea; Petersen, Gloria; Stolzenberg-Solomon, Rachael Z.; Zheng, Wei; Albanes, Demetrius; Allen, Naomi E.; Amundadottir, Laufey; Austin, Melissa A.; Boutron-Ruault, Marie-Christine; Buring, Julie E.; Canzian, Federico; Chanock, Stephen J.; Gaziano, J. Michael; Giovannucci, Edward L.; Hallmans, Göran; Hankinson, Susan E.; Hoover, Robert N.; Hunter, David J.; Hutchinson, Amy; Jacobs, Kevin B.; Kooperberg, Charles; Mendelsohn, Julie B.; Michaud, Dominique S.; Overvad, Kim; Patel, Alpa V.; Sanchéz, Maria-José; Sansbury, Leah; Shu, Xiao-Ou; Slimani, Nadia; Tobias, Geoffrey S.; Trichopoulos, Dimitrios; Vineis, Paolo; Visvanathan, Kala; Virtamo, Jarmo; Wactawski-Wende, Jean; Watters, Joanne; Yu, Kai; Zeleniuch-Jacquotte, Anne; Hartge, Patricia; Fuchs, Charles S.

    2010-01-01

    Background Subjects with non-O ABO blood group alleles have increased risk of pancreatic cancer. Glycosyltransferase activity is greater for the A1 versus A2 variant, while O01 and O02 variants are nonfunctioning. We hypothesized: (1) A1 allele would confer greater risk than A2 allele, (2) protective effect of the O allele would be equivalent for O01 and O02 variants, (3) secretor phenotype would modify the association with risk. Methods We determined ABO variants and secretor phenotype from single nucleotide polymorphisms in ABO and FUT2 genes in 1533 cases and 1582 controls from 12 prospective cohort studies. Adjusted odds ratios (ORs) for pancreatic cancer were calculated using logistic regression. Results An increased risk was observed in participants with A1, but not A2 alleles. Compared to subjects with genotype O/O, genotypes A2/O, A2/A1, A1/O, and A1/A1 had ORs of 0.96 (95% confidence interval [CI], 0.72–1.26), 1.46 (95%CI, 0.98–2.17), 1.48 (95%CI, 1.23–1.78), and 1.71 (95%CI, 1.18–2.47). Risk was similar for O01 and O02 variant O alleles. Compared to O01/O01, the ORs for each additional allele of O02, A1, and A2 were 1.00 (95%CI, 0.87–1.14), 1.38 (95%CI, 1.20–1.58), and 0.96 (95%CI, 0.77–1.20); P-value, O01 versus O02=0.94, A1 versus A2=0.004. Secretor phenotype was not an effect modifier (P-interaction=0.63). Conclusions Among participants in a large prospective cohort consortium, ABO allele subtypes corresponding to increased glycosyltransferase activity were associated with increased pancreatic cancer risk. Impact These data support the hypothesis that ABO glycosyltransferase activity influences pancreatic cancer risk, rather than actions of other nearby genes on chromosome 9q34. PMID:20971884

  19. History of hypertension, heart disease, and diabetes and ovarian cancer patient survival: evidence from the ovarian cancer association consortium.

    PubMed

    Minlikeeva, Albina N; Freudenheim, Jo L; Cannioto, Rikki A; Szender, J Brian; Eng, Kevin H; Modugno, Francesmary; Ness, Roberta B; LaMonte, Michael J; Friel, Grace; Segal, Brahm H; Odunsi, Kunle; Mayor, Paul; Zsiros, Emese; Schmalfeldt, Barbara; Klapdor, Rüdiger; Dӧrk, Thilo; Hillemanns, Peter; Kelemen, Linda E; Kӧbel, Martin; Steed, Helen; de Fazio, Anna; Jordan, Susan J; Nagle, Christina M; Risch, Harvey A; Rossing, Mary Anne; Doherty, Jennifer A; Goodman, Marc T; Edwards, Robert; Matsuo, Keitaro; Mizuno, Mika; Karlan, Beth Y; Kjær, Susanne K; Høgdall, Estrid; Jensen, Allan; Schildkraut, Joellen M; Terry, Kathryn L; Cramer, Daniel W; Bandera, Elisa V; Paddock, Lisa E; Kiemeney, Lambertus A; Massuger, Leon F; Kupryjanczyk, Jolanta; Berchuck, Andrew; Chang-Claude, Jenny; Diergaarde, Brenda; Webb, Penelope M; Moysich, Kirsten B

    2017-05-01

    Survival following ovarian cancer diagnosis is generally low; understanding factors related to prognosis could be important to optimize treatment. The role of previously diagnosed comorbidities and use of medications for those conditions in relation to prognosis for ovarian cancer patients has not been studied extensively, particularly according to histological subtype. Using pooled data from fifteen studies participating in the Ovarian Cancer Association Consortium, we examined the associations between history of hypertension, heart disease, diabetes, and medications taken for these conditions and overall survival (OS) and progression-free survival (PFS) among patients diagnosed with invasive epithelial ovarian carcinoma. We used Cox proportional hazards regression models adjusted for age and stage to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) overall and within strata of histological subtypes. History of diabetes was associated with increased risk of mortality (n = 7,674; HR = 1.12; 95% CI = 1.01-1.25). No significant mortality associations were observed for hypertension (n = 6,482; HR = 0.95; 95% CI = 0.88-1.02) or heart disease (n = 4,252; HR = 1.05; 95% CI = 0.87-1.27). No association of these comorbidities was found with PFS in the overall study population. However, among patients with endometrioid tumors, hypertension was associated with lower risk of progression (n = 339, HR = 0.54; 95% CI = 0.35-0.84). Comorbidity was not associated with OS or PFS for any of the other histological subtypes. Ever use of beta blockers, oral antidiabetic medications, and insulin was associated with increased mortality, HR = 1.20; 95% CI = 1.03-1.40, HR = 1.28; 95% CI = 1.05-1.55, and HR = 1.63; 95% CI = 1.20-2.20, respectively. Ever use of diuretics was inversely associated with mortality, HR = 0.71; 95% CI = 0.53-0.94. Histories of hypertension, diabetes, and use of diuretics

  20. Interactions between breast cancer susceptibility loci and menopausal hormone therapy in relationship to breast cancer in the Breast and Prostate Cancer Cohort Consortium.

    PubMed

    Gaudet, Mia M; Barrdahl, Myrto; Lindström, Sara; Travis, Ruth C; Auer, Paul L; Buring, Julie E; Chanock, Stephen J; Eliassen, A Heather; Gapstur, Susan M; Giles, Graham G; Gunter, Marc; Haiman, Christopher; Hunter, David J; Joshi, Amit D; Kaaks, Rudolf; Khaw, Kay-Tee; Lee, I-Min; Le Marchand, Loic; Milne, Roger L; Peeters, Petra H M; Sund, Malin; Tamimi, Rulla; Trichopoulou, Antonia; Weiderpass, Elisabete; Yang, Xiaohong R; Prentice, Ross L; Feigelson, Heather Spencer; Canzian, Federico; Kraft, Peter

    2016-02-01

    Current use of menopausal hormone therapy (MHT) has important implications for postmenopausal breast cancer risk, and observed associations might be modified by known breast cancer susceptibility loci. To provide the most comprehensive assessment of interactions of prospectively collected data on MHT and 17 confirmed susceptibility loci with invasive breast cancer risk, a nested case-control design among eight cohorts within the NCI Breast and Prostate Cancer Cohort Consortium was used. Based on data from 13,304 cases and 15,622 controls, multivariable-adjusted logistic regression analyses were used to estimate odds ratios (OR) and 95 % confidence intervals (CI). Effect modification of current and past use was evaluated on the multiplicative scale. P values <1.5 × 10(-3) were considered statistically significant. The strongest evidence of effect modification was observed for current MHT by 9q31-rs865686. Compared to never users of MHT with the rs865686 GG genotype, the association between current MHT use and breast cancer risk for the TT genotype (OR 1.79, 95 % CI 1.43-2.24; P interaction = 1.2 × 10(-4)) was less than expected on the multiplicative scale. There are no biological implications of the sub-multiplicative interaction between MHT and rs865686. Menopausal hormone therapy is unlikely to have a strong interaction with the common genetic variants associated with invasive breast cancer.

  1. Interaction between tobacco and alcohol use and the risk of head and neck cancer: pooled analysis in the INHANCE consortium

    PubMed Central

    Hashibe, Mia; Brennan, Paul; Chuang, Shu-chun; Boccia, Stefania; Castellsague, Xavier; Chen, Chu; Curado, Maria Paula; Maso, Luigino Dal; Daudt, Alexander W.; Fabianova, Eleonora; Fernandez, Leticia; Wünsch-Filho, Victor; Franceschi, Silvia; Hayes, Richard B.; Herrero, Rolando; Kelsey, Karl; Koifman, Sergio; La Vecchia, Carlo; Lazarus, Philip; Levi, Fabio; Lence, Juan J.; Mates, Dana; Matos, Elena; Menezes, Ana; McClean, Michael D.; Muscat, Joshua; Eluf-Neto, Jose; Olshan, Andrew F.; Purdue, Mark; Rudnai, Peter; Schwartz, Stephen M.; Smith, Elaine; Sturgis, Erich M.; Szeszenia-Dabrowska, Neonilia; Talamini, Renato; Wei, Qingyi; Winn, Deborah M.; Shangina, Oxana; Pilarska, Agnieszka; Zhang, Zuo-Feng; Ferro, Gilles; Berthiller, Julien; Boffetta, Paolo

    2011-01-01

    Background The magnitude of risk conferred by the interaction between tobacco and alcohol use on the risk of head and neck cancers is not clear, since studies have used various methods to quantify the excess head and neck cancer burden. Methods We analyzed individual-level pooled data from 17 European and American case-control studies (11,221 cases and 16,168 controls) participating in the International Head and Neck Cancer Epidemiology (INHANCE) consortium. We estimated the multiplicative interaction parameter (ψ) and population attributable risks (PAR). Results A greater than multiplicative joint effect between ever tobacco and alcohol use was observed for head and neck cancer risk (ψ=2.15, 95%CI=1.53–3.04). The PAR for tobacco or alcohol was 72% (95%CI=61%–79%) for head and neck cancer, of which 4% was due to alcohol alone, 33% was due tobacco alone and 35% was due to tobacco and alcohol combined. The total PAR differed by subsite (64% for oral cavity cancer, 72% for pharyngeal cancer, 89% for laryngeal cancer), by sex (74% for men, 57% for women) by age (33% for cases <45 years, 73% for cases >60 years) and by region (84% in Europe, 51% in North America, 83% in Latin America). Conclusions Our results confirm that the joint effect between tobacco and alcohol use is greater than multiplicative on head and neck cancer risk. However, a substantial proportion of head and neck cancers cannot be attributed to tobacco or alcohol use, particularly for oral cavity cancer, for head and neck cancer among women and among young onset cases. PMID:19190158

  2. Overview of childhood cancers at a regional cancer centre in North-East India.

    PubMed

    Hazarika, Munlima; Krishnatreya, Manigreeva; Bhuyan, Cidananda; Saikia, Bhargab Jyoti; Kataki, Amal Chandra; Nandy, Pintu; Hazarika, Monalisha; Roy, Partha Sarathi

    2014-01-01

    Childhood cancers are relatively uncommon in comparison to adult cancers. There is no literature available to shed light on clinic-pathological types and patterns of care for childhood cancers in our population in North-East India. In this analysis we therefore tried to determine the common childhood cancers diagnosed in our institute, clinical profile of the patients, types of treatment and compliance, and median survival estimates. Leukemia was most common, followed by retinoblastoma, central nervous system tumours and lymphomas. Ascertaining the clinic-pathological profile of childhood cancers in our population is essential for allocation and management of resources for this small but important group of patients.

  3. Associations of breast cancer risk factors with tumor subtypes: a pooled analysis from the Breast Cancer Association Consortium studies.

    PubMed

    Yang, Xiaohong R; Chang-Claude, Jenny; Goode, Ellen L; Couch, Fergus J; Nevanlinna, Heli; Milne, Roger L; Gaudet, Mia; Schmidt, Marjanka K; Broeks, Annegien; Cox, Angela; Fasching, Peter A; Hein, Rebecca; Spurdle, Amanda B; Blows, Fiona; Driver, Kristy; Flesch-Janys, Dieter; Heinz, Judith; Sinn, Peter; Vrieling, Alina; Heikkinen, Tuomas; Aittomäki, Kristiina; Heikkilä, Päivi; Blomqvist, Carl; Lissowska, Jolanta; Peplonska, Beata; Chanock, Stephen; Figueroa, Jonine; Brinton, Louise; Hall, Per; Czene, Kamila; Humphreys, Keith; Darabi, Hatef; Liu, Jianjun; Van 't Veer, Laura J; van Leeuwen, Flora E; Andrulis, Irene L; Glendon, Gord; Knight, Julia A; Mulligan, Anna Marie; O'Malley, Frances P; Weerasooriya, Nayana; John, Esther M; Beckmann, Matthias W; Hartmann, Arndt; Weihbrecht, Sebastian B; Wachter, David L; Jud, Sebastian M; Loehberg, Christian R; Baglietto, Laura; English, Dallas R; Giles, Graham G; McLean, Catriona A; Severi, Gianluca; Lambrechts, Diether; Vandorpe, Thijs; Weltens, Caroline; Paridaens, Robert; Smeets, Ann; Neven, Patrick; Wildiers, Hans; Wang, Xianshu; Olson, Janet E; Cafourek, Victoria; Fredericksen, Zachary; Kosel, Matthew; Vachon, Celine; Cramp, Helen E; Connley, Daniel; Cross, Simon S; Balasubramanian, Sabapathy P; Reed, Malcolm W R; Dörk, Thilo; Bremer, Michael; Meyer, Andreas; Karstens, Johann H; Ay, Aysun; Park-Simon, Tjoung-Won; Hillemanns, Peter; Arias Pérez, Jose Ignacio; Menéndez Rodríguez, Primitiva; Zamora, Pilar; Benítez, Javier; Ko, Yon-Dschun; Fischer, Hans-Peter; Hamann, Ute; Pesch, Beate; Brüning, Thomas; Justenhoven, Christina; Brauch, Hiltrud; Eccles, Diana M; Tapper, William J; Gerty, Sue M; Sawyer, Elinor J; Tomlinson, Ian P; Jones, Angela; Kerin, Michael; Miller, Nicola; McInerney, Niall; Anton-Culver, Hoda; Ziogas, Argyrios; Shen, Chen-Yang; Hsiung, Chia-Ni; Wu, Pei-Ei; Yang, Show-Lin; Yu, Jyh-Cherng; Chen, Shou-Tung; Hsu, Giu-Cheng; Haiman, Christopher A; Henderson, Brian E; Le Marchand, Loic; Kolonel, Laurence N; Lindblom, Annika; Margolin, Sara; Jakubowska, Anna; Lubiński, Jan; Huzarski, Tomasz; Byrski, Tomasz; Górski, Bohdan; Gronwald, Jacek; Hooning, Maartje J; Hollestelle, Antoinette; van den Ouweland, Ans M W; Jager, Agnes; Kriege, Mieke; Tilanus-Linthorst, Madeleine M A; Collée, Margriet; Wang-Gohrke, Shan; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Mononen, Kari; Grip, Mervi; Hirvikoski, Pasi; Winqvist, Robert; Mannermaa, Arto; Kosma, Veli-Matti; Kauppinen, Jaana; Kataja, Vesa; Auvinen, Päivi; Soini, Ylermi; Sironen, Reijo; Bojesen, Stig E; Ørsted, David Dynnes; Kaur-Knudsen, Diljit; Flyger, Henrik; Nordestgaard, Børge G; Holland, Helene; Chenevix-Trench, Georgia; Manoukian, Siranoush; Barile, Monica; Radice, Paolo; Hankinson, Susan E; Hunter, David J; Tamimi, Rulla; Sangrajrang, Suleeporn; Brennan, Paul; McKay, James; Odefrey, Fabrice; Gaborieau, Valerie; Devilee, Peter; Huijts, P E A; Tollenaar, R A E M; Seynaeve, C; Dite, Gillian S; Apicella, Carmel; Hopper, John L; Hammet, Fleur; Tsimiklis, Helen; Smith, Letitia D; Southey, Melissa C; Humphreys, Manjeet K; Easton, Douglas; Pharoah, Paul; Sherman, Mark E; Garcia-Closas, Montserrat

    2011-02-02

    Previous studies have suggested that breast cancer risk factors are associated with estrogen receptor (ER) and progesterone receptor (PR) expression status of the tumors. We pooled tumor marker and epidemiological risk factor data from 35,568 invasive breast cancer case patients from 34 studies participating in the Breast Cancer Association Consortium. Logistic regression models were used in case-case analyses to estimate associations between epidemiological risk factors and tumor subtypes, and case-control analyses to estimate associations between epidemiological risk factors and the risk of developing specific tumor subtypes in 12 population-based studies. All statistical tests were two-sided. In case-case analyses, of the epidemiological risk factors examined, early age at menarche (≤12 years) was less frequent in case patients with PR(-) than PR(+) tumors (P = .001). Nulliparity (P = 3 × 10(-6)) and increasing age at first birth (P = 2 × 10(-9)) were less frequent in ER(-) than in ER(+) tumors. Obesity (body mass index [BMI] ≥ 30 kg/m(2)) in younger women (≤50 years) was more frequent in ER(-)/PR(-) than in ER(+)/PR(+) tumors (P = 1 × 10(-7)), whereas obesity in older women (>50 years) was less frequent in PR(-) than in PR(+) tumors (P = 6 × 10(-4)). The triple-negative (ER(-)/PR(-)/HER2(-)) or core basal phenotype (CBP; triple-negative and cytokeratins [CK]5/6(+) and/or epidermal growth factor receptor [EGFR](+)) accounted for much of the heterogeneity in parity-related variables and BMI in younger women. Case-control analyses showed that nulliparity, increasing age at first birth, and obesity in younger women showed the expected associations with the risk of ER(+) or PR(+) tumors but not triple-negative (nulliparity vs parity, odds ratio [OR] = 0.94, 95% confidence interval [CI] = 0.75 to 1.19, P = .61; 5-year increase in age at first full-term birth, OR = 0.95, 95% CI = 0.86 to 1.05, P = .34; obesity in younger women, OR = 1.36, 95% CI = 0.95 to 1

  4. High-throughput automated scoring of Ki67 in breast cancer tissue microarrays from the Breast Cancer Association Consortium.

    PubMed

    Abubakar, Mustapha; Howat, William J; Daley, Frances; Zabaglo, Lila; McDuffus, Leigh-Anne; Blows, Fiona; Coulson, Penny; Raza Ali, H; Benitez, Javier; Milne, Roger; Brenner, Herman; Stegmaier, Christa; Mannermaa, Arto; Chang-Claude, Jenny; Rudolph, Anja; Sinn, Peter; Couch, Fergus J; Tollenaar, Rob A E M; Devilee, Peter; Figueroa, Jonine; Sherman, Mark E; Lissowska, Jolanta; Hewitt, Stephen; Eccles, Diana; Hooning, Maartje J; Hollestelle, Antoinette; Wm Martens, John; Hm van Deurzen, Carolien; Investigators, kConFab; Bolla, Manjeet K; Wang, Qin; Jones, Michael; Schoemaker, Minouk; Broeks, Annegien; van Leeuwen, Flora E; Van't Veer, Laura; Swerdlow, Anthony J; Orr, Nick; Dowsett, Mitch; Easton, Douglas; Schmidt, Marjanka K; Pharoah, Paul D; Garcia-Closas, Montserrat

    2016-07-01

    Automated methods are needed to facilitate high-throughput and reproducible scoring of Ki67 and other markers in breast cancer tissue microarrays (TMAs) in large-scale studies. To address this need, we developed an automated protocol for Ki67 scoring and evaluated its performance in studies from the Breast Cancer Association Consortium. We utilized 166 TMAs containing 16,953 tumour cores representing 9,059 breast cancer cases, from 13 studies, with information on other clinical and pathological characteristics. TMAs were stained for Ki67 using standard immunohistochemical procedures, and scanned and digitized using the Ariol system. An automated algorithm was developed for the scoring of Ki67, and scores were compared to computer assisted visual (CAV) scores in a subset of 15 TMAs in a training set. We also assessed the correlation between automated Ki67 scores and other clinical and pathological characteristics. Overall, we observed good discriminatory accuracy (AUC = 85%) and good agreement (kappa = 0.64) between the automated and CAV scoring methods in the training set. The performance of the automated method varied by TMA (kappa range= 0.37-0.87) and study (kappa range = 0.39-0.69). The automated method performed better in satisfactory cores (kappa = 0.68) than suboptimal (kappa = 0.51) cores (p-value for comparison = 0.005); and among cores with higher total nuclei counted by the machine (4,000-4,500 cells: kappa = 0.78) than those with lower counts (50-500 cells: kappa = 0.41; p-value = 0.010). Among the 9,059 cases in this study, the correlations between automated Ki67 and clinical and pathological characteristics were found to be in the expected directions. Our findings indicate that automated scoring of Ki67 can be an efficient method to obtain good quality data across large numbers of TMAs from multicentre studies. However, robust algorithm development and rigorous pre- and post-analytical quality control procedures are

  5. Associations of Breast Cancer Risk Factors With Tumor Subtypes: A Pooled Analysis From the Breast Cancer Association Consortium Studies

    PubMed Central

    Chang-Claude, Jenny; Goode, Ellen L.; Couch, Fergus J.; Nevanlinna, Heli; Milne, Roger L.; Gaudet, Mia; Schmidt, Marjanka K.; Broeks, Annegien; Cox, Angela; Fasching, Peter A.; Hein, Rebecca; Spurdle, Amanda B.; Blows, Fiona; Driver, Kristy; Flesch-Janys, Dieter; Heinz, Judith; Sinn, Peter; Vrieling, Alina; Heikkinen, Tuomas; Aittomäki, Kristiina; Heikkilä, Päivi; Blomqvist, Carl; Lissowska, Jolanta; Peplonska, Beata; Chanock, Stephen; Figueroa, Jonine; Brinton, Louise; Hall, Per; Czene, Kamila; Humphreys, Keith; Darabi, Hatef; Liu, Jianjun; Van ‘t Veer, Laura J.; van Leeuwen, Flora E.; Andrulis, Irene L.; Glendon, Gord; Knight, Julia A.; Mulligan, Anna Marie; O’Malley, Frances P.; Weerasooriya, Nayana; John, Esther M.; Beckmann, Matthias W.; Hartmann, Arndt; Weihbrecht, Sebastian B.; Wachter, David L.; Jud, Sebastian M.; Loehberg, Christian R.; Baglietto, Laura; English, Dallas R.; Giles, Graham G.; McLean, Catriona A.; Severi, Gianluca; Lambrechts, Diether; Vandorpe, Thijs; Weltens, Caroline; Paridaens, Robert; Smeets, Ann; Neven, Patrick; Wildiers, Hans; Wang, Xianshu; Olson, Janet E.; Cafourek, Victoria; Fredericksen, Zachary; Kosel, Matthew; Vachon, Celine; Cramp, Helen E.; Connley, Daniel; Cross, Simon S.; Balasubramanian, Sabapathy P.; Reed, Malcolm W. R.; Dörk, Thilo; Bremer, Michael; Meyer, Andreas; Karstens, Johann H.; Ay, Aysun; Park-Simon, Tjoung-Won; Hillemanns, Peter; Arias Pérez, Jose Ignacio; Rodríguez, Primitiva Menéndez; Zamora, Pilar; Benítez, Javier; Ko, Yon-Dschun; Fischer, Hans-Peter; Hamann, Ute; Pesch, Beate; Brüning, Thomas; Justenhoven, Christina; Brauch, Hiltrud; Eccles, Diana M.; Tapper, William J.; Gerty, Sue M.; Sawyer, Elinor J.; Tomlinson, Ian P.; Jones, Angela; Kerin, Michael; Miller, Nicola; McInerney, Niall; Anton-Culver, Hoda; Ziogas, Argyrios; Shen, Chen-Yang; Hsiung, Chia-Ni; Wu, Pei-Ei; Yu, Jyh-Cherng; Chen, Shou-Tung; Hsu, Giu-Cheng; Haiman, Christopher A.; Henderson, Brian E.; Le Marchand, Loic; Kolonel, Laurence N.; Lindblom, Annika; Margolin, Sara; Jakubowska, Anna; Lubiński, Jan; Huzarski, Tomasz; Byrski, Tomasz; Górski, Bohdan; Gronwald, Jacek; Hooning, Maartje J.; Hollestelle, Antoinette; van den Ouweland, Ans M. W.; Jager, Agnes; Kriege, Mieke; Tilanus-Linthorst, Madeleine M. A.; Collée, Margriet; Wang-Gohrke, Shan; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Mononen, Kari; Grip, Mervi; Hirvikoski, Pasi; Winqvist, Robert; Mannermaa, Arto; Kosma, Veli-Matti; Kauppinen, Jaana; Kataja, Vesa; Auvinen, Päivi; Soini, Ylermi; Sironen, Reijo; Bojesen, Stig E.; Dynnes Ørsted, David; Kaur-Knudsen, Diljit; Flyger, Henrik; Nordestgaard, Børge G.; Holland, Helene; Chenevix-Trench, Georgia; Manoukian, Siranoush; Barile, Monica; Radice, Paolo; Hankinson, Susan E.; Hunter, David J.; Tamimi, Rulla; Sangrajrang, Suleeporn; Brennan, Paul; McKay, James; Odefrey, Fabrice; Gaborieau, Valerie; Devilee, Peter; Huijts, P.E.A.; Tollenaar, RAEM.; Seynaeve, C.; Dite, Gillian S.; Apicella, Carmel; Hopper, John L.; Hammet, Fleur; Tsimiklis, Helen; Smith, Letitia D.; Southey, Melissa C.; Humphreys, Manjeet K.; Easton, Douglas; Pharoah, Paul; Sherman, Mark E.; Garcia-Closas, Montserrat

    2011-01-01

    Background Previous studies have suggested that breast cancer risk factors are associated with estrogen receptor (ER) and progesterone receptor (PR) expression status of the tumors. Methods We pooled tumor marker and epidemiological risk factor data from 35 568 invasive breast cancer case patients from 34 studies participating in the Breast Cancer Association Consortium. Logistic regression models were used in case–case analyses to estimate associations between epidemiological risk factors and tumor subtypes, and case–control analyses to estimate associations between epidemiological risk factors and the risk of developing specific tumor subtypes in 12 population-based studies. All statistical tests were two-sided. Results In case–case analyses, of the epidemiological risk factors examined, early age at menarche (≤12 years) was less frequent in case patients with PR− than PR+ tumors (P = .001). Nulliparity (P = 3 × 10−6) and increasing age at first birth (P = 2 × 10−9) were less frequent in ER− than in ER+ tumors. Obesity (body mass index [BMI] ≥ 30 kg/m2) in younger women (≤50 years) was more frequent in ER−/PR− than in ER+/PR+ tumors (P = 1 × 10−7), whereas obesity in older women (>50 years) was less frequent in PR− than in PR+ tumors (P = 6 × 10−4). The triple-negative (ER−/PR−/HER2−) or core basal phenotype (CBP; triple-negative and cytokeratins [CK]5/6+ and/or epidermal growth factor receptor [EGFR]+) accounted for much of the heterogeneity in parity-related variables and BMI in younger women. Case–control analyses showed that nulliparity, increasing age at first birth, and obesity in younger women showed the expected associations with the risk of ER+ or PR+ tumors but not triple-negative (nulliparity vs parity, odds ratio [OR] = 0.94, 95% confidence interval [CI] = 0.75 to 1.19, P = .61; 5-year increase in age at first full-term birth, OR = 0.95, 95% CI = 0.86 to 1.05, P = .34; obesity in younger women, OR = 1.36, 95

  6. High‐throughput automated scoring of Ki67 in breast cancer tissue microarrays from the Breast Cancer Association Consortium

    PubMed Central

    Howat, William J; Daley, Frances; Zabaglo, Lila; McDuffus, Leigh‐Anne; Blows, Fiona; Coulson, Penny; Raza Ali, H; Benitez, Javier; Milne, Roger; Brenner, Herman; Stegmaier, Christa; Mannermaa, Arto; Chang‐Claude, Jenny; Rudolph, Anja; Sinn, Peter; Couch, Fergus J; Tollenaar, Rob A.E.M.; Devilee, Peter; Figueroa, Jonine; Sherman, Mark E; Lissowska, Jolanta; Hewitt, Stephen; Eccles, Diana; Hooning, Maartje J; Hollestelle, Antoinette; WM Martens, John; HM van Deurzen, Carolien; Investigators, kConFab; Bolla, Manjeet K; Wang, Qin; Jones, Michael; Schoemaker, Minouk; Broeks, Annegien; van Leeuwen, Flora E; Van't Veer, Laura; Swerdlow, Anthony J; Orr, Nick; Dowsett, Mitch; Easton, Douglas; Schmidt, Marjanka K; Pharoah, Paul D; Garcia‐Closas, Montserrat

    2016-01-01

    Abstract Automated methods are needed to facilitate high‐throughput and reproducible scoring of Ki67 and other markers in breast cancer tissue microarrays (TMAs) in large‐scale studies. To address this need, we developed an automated protocol for Ki67 scoring and evaluated its performance in studies from the Breast Cancer Association Consortium. We utilized 166 TMAs containing 16,953 tumour cores representing 9,059 breast cancer cases, from 13 studies, with information on other clinical and pathological characteristics. TMAs were stained for Ki67 using standard immunohistochemical procedures, and scanned and digitized using the Ariol system. An automated algorithm was developed for the scoring of Ki67, and scores were compared to computer assisted visual (CAV) scores in a subset of 15 TMAs in a training set. We also assessed the correlation between automated Ki67 scores and other clinical and pathological characteristics. Overall, we observed good discriminatory accuracy (AUC = 85%) and good agreement (kappa = 0.64) between the automated and CAV scoring methods in the training set. The performance of the automated method varied by TMA (kappa range= 0.37–0.87) and study (kappa range = 0.39–0.69). The automated method performed better in satisfactory cores (kappa = 0.68) than suboptimal (kappa = 0.51) cores (p‐value for comparison = 0.005); and among cores with higher total nuclei counted by the machine (4,000–4,500 cells: kappa = 0.78) than those with lower counts (50–500 cells: kappa = 0.41; p‐value = 0.010). Among the 9,059 cases in this study, the correlations between automated Ki67 and clinical and pathological characteristics were found to be in the expected directions. Our findings indicate that automated scoring of Ki67 can be an efficient method to obtain good quality data across large numbers of TMAs from multicentre studies. However, robust algorithm development and rigorous pre‐ and post

  7. Spatial and Temporal Variation in Fine Particulate Matter Mass and Chemical Composition: The Middle East Consortium for Aerosol Research Study

    PubMed Central

    Abdeen, Ziad; Heo, Jongbae; Wu, Bo; Shpund, Jacob; Vanger, Arye; Sharf, Geula; Moise, Tamar; Brenner, Shmuel; Nassar, Khaled; Saleh, Rami; Al-Mahasneh, Qusai M.; Sarnat, Jeremy A.; Schauer, James J.

    2014-01-01

    Ambient fine particulate matter (PM2.5) samples were collected from January to December 2007 to investigate the sources and chemical speciation in Palestine, Jordan, and Israel. The 24-h PM2.5 samples were collected on 6-day intervals at eleven urban and rural sites simultaneously. Major chemical components including metals, ions, and organic and elemental carbon were analyzed. The mass concentrations of PM2.5 across the 11 sites varied from 20.6 to 40.3 μg/m3, with an average of 28.7 μg/m3. Seasonal variation of PM2.5 concentrations was substantial, with higher average concentrations (37.3 μg/m3) in the summer (April–June) months compared to winter (October–December) months (26.0 μg/m3) due mainly to high contributions of sulfate and crustal components. PM2.5 concentrations in the spring were greatly impacted by regional dust storms. Carbonaceous mass was the most abundant component, contributing 40% to the total PM2.5 mass averaged across the eleven sites. Crustal components averaged 19.1% of the PM2.5 mass and sulfate, ammonium, and nitrate accounted for 16.2%, 6.4%, and 3.7%, respectively, of the total PM2.5 mass. The results of this study demonstrate the need to better protect the health and welfare of the residents on both sides of the Jordan River in the Middle East. PMID:25045751

  8. Spatial and temporal variation in fine particulate matter mass and chemical composition: the Middle East Consortium for Aerosol Research Study.

    PubMed

    Abdeen, Ziad; Qasrawi, Radwan; Heo, Jongbae; Wu, Bo; Shpund, Jacob; Vanger, Arye; Sharf, Geula; Moise, Tamar; Brenner, Shmuel; Nassar, Khaled; Saleh, Rami; Al-Mahasneh, Qusai M; Sarnat, Jeremy A; Schauer, James J

    2014-01-01

    Ambient fine particulate matter (PM2.5) samples were collected from January to December 2007 to investigate the sources and chemical speciation in Palestine, Jordan, and Israel. The 24-h PM2.5 samples were collected on 6-day intervals at eleven urban and rural sites simultaneously. Major chemical components including metals, ions, and organic and elemental carbon were analyzed. The mass concentrations of PM2.5 across the 11 sites varied from 20.6 to 40.3 μg/m(3), with an average of 28.7 μg/m(3). Seasonal variation of PM2.5 concentrations was substantial, with higher average concentrations (37.3 μg/m(3)) in the summer (April-June) months compared to winter (October-December) months (26.0 μg/m(3)) due mainly to high contributions of sulfate and crustal components. PM2.5 concentrations in the spring were greatly impacted by regional dust storms. Carbonaceous mass was the most abundant component, contributing 40% to the total PM2.5 mass averaged across the eleven sites. Crustal components averaged 19.1% of the PM2.5 mass and sulfate, ammonium, and nitrate accounted for 16.2%, 6.4%, and 3.7%, respectively, of the total PM2.5 mass. The results of this study demonstrate the need to better protect the health and welfare of the residents on both sides of the Jordan River in the Middle East.

  9. Smokeless Tobacco Use and the Risk of Head and Neck Cancer: Pooled Analysis of US Studies in the INHANCE Consortium.

    PubMed

    Wyss, Annah B; Hashibe, Mia; Lee, Yuan-Chin Amy; Chuang, Shu-Chun; Muscat, Joshua; Chen, Chu; Schwartz, Stephen M; Smith, Elaine; Zhang, Zuo-Feng; Morgenstern, Hal; Wei, Qingyi; Li, Guojun; Kelsey, Karl T; McClean, Michael; Winn, Deborah M; Schantz, Stimson; Yu, Guo-Pei; Gillison, Maura L; Zevallos, Jose P; Boffetta, Paolo; Olshan, Andrew F

    2016-10-15

    Previous studies on smokeless tobacco use and head and neck cancer (HNC) have found inconsistent and often imprecise estimates, with limited control for cigarette smoking. Using pooled data from 11 US case-control studies (1981-2006) of oral, pharyngeal, and laryngeal cancers (6,772 cases and 8,375 controls) in the International Head and Neck Cancer Epidemiology (INHANCE) Consortium, we applied hierarchical logistic regression to estimate odds ratios and 95% confidence intervals for ever use, frequency of use, and duration of use of snuff and chewing tobacco separately for never and ever cigarette smokers. Ever use (versus never use) of snuff was strongly associated with HNC among never cigarette smokers (odds ratio (OR) = 1.71, 95% confidence interval (CI): 1.08, 2.70), particularly for oral cavity cancers (OR = 3.01, 95% CI: 1.63, 5.55). Although ever (versus never) tobacco chewing was weakly associated with HNC among never cigarette smokers (OR = 1.20, 95% CI: 0.81, 1.77), analyses restricted to cancers of the oral cavity showed a stronger association (OR = 1.81, 95% CI: 1.04, 3.17). Few or no associations between each type of smokeless tobacco and HNC were observed among ever cigarette smokers, possibly reflecting residual confounding by smoking. Smokeless tobacco use appears to be associated with HNC, especially oral cancers, with snuff being more strongly associated than chewing tobacco.

  10. Polymorphisms in Stromal Genes and Susceptibility to Serous Epithelial Ovarian Cancer: A Report from the Ovarian Cancer Association Consortium

    PubMed Central

    Amankwah, Ernest K.; Wang, Qinggang; Schildkraut, Joellen M.; Tsai, Ya-Yu; Ramus, Susan J.; Fridley, Brooke L.; Beesley, Jonathan; Johnatty, Sharon E.; Webb, Penelope M.; Chenevix-Trench, Georgia; Dale, Laura C.; Lambrechts, Diether; Amant, Frederic; Despierre, Evelyn; Vergote, Ignace; Gayther, Simon A.; Gentry-Maharaj, Aleksandra; Menon, Usha; Chang-Claude, Jenny; Wang-Gohrke, Shan; Anton-Culver, Hoda; Ziogas, Argyrios; Dörk, Thilo; Dürst, Matthias; Antonenkova, Natalia; Bogdanova, Natalia; Brown, Robert; Flanagan, James M.; Kaye, Stanley B.; Paul, James; Bützow, Ralf; Nevanlinna, Heli; Campbell, Ian; Eccles, Diana M.; Karlan, Beth Y.; Gross, Jenny; Walsh, Christine; Pharoah, Paul D. P.; Song, Honglin; Krüger Kjær, Susanne; Høgdall, Estrid; Høgdall, Claus; Lundvall, Lene; Nedergaard, Lotte; Kiemeney, Lambertus A. L. M.; Massuger, Leon F. A. G.; van Altena, Anne M.; Vermeulen, Sita H. H. M.; Le, Nhu D.; Brooks-Wilson, Angela; Cook, Linda S.; Phelan, Catherine M.; Cunningham, Julie M.; Vachon, Celine M.; Vierkant, Robert A.; Iversen, Edwin S.; Berchuck, Andrew; Goode, Ellen L.; Sellers, Thomas A.; Kelemen, Linda E.

    2011-01-01

    Alterations in stromal tissue components can inhibit or promote epithelial tumorigenesis. Decorin (DCN) and lumican (LUM) show reduced stromal expression in serous epithelial ovarian cancer (sEOC). We hypothesized that common variants in these genes associate with risk. Associations with sEOC among Caucasians were estimated with odds ratios (OR) among 397 cases and 920 controls in two U.S.-based studies (discovery set), 436 cases and 1,098 controls in Australia (replication set 1) and a consortium of 15 studies comprising 1,668 cases and 4,249 controls (replication set 2). The discovery set and replication set 1 (833 cases and 2,013 controls) showed statistically homogeneous (Pheterogeneity≥0.48) decreased risks of sEOC at four variants: DCN rs3138165, rs13312816 and rs516115, and LUM rs17018765 (OR = 0.6 to 0.9; Ptrend = 0.001 to 0.03). Results from replication set 2 were statistically homogeneous (Pheterogeneity≥0.13) and associated with increased risks at DCN rs3138165 and rs13312816, and LUM rs17018765: all ORs = 1.2; Ptrend≤0.02. The ORs at the four variants were statistically heterogeneous across all 18 studies (Pheterogeneity≤0.03), which precluded combining. In post-hoc analyses, interactions were observed between each variant and recruitment period (Pinteraction≤0.003), age at diagnosis (Pinteraction = 0.04), and year of diagnosis (Pinteraction = 0.05) in the five studies with available information (1,044 cases, 2,469 controls). We conclude that variants in DCN and LUM are not directly associated with sEOC, and that confirmation of possible effect modification of the variants by non-genetic factors is required. PMID:21637745

  11. One Thousand Genomes Imputation in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium Aggressive Prostate Cancer Genome-wide Association Study

    PubMed Central

    Machiela, Mitchell J.; Chen, Constance; Liang, Liming; Diver, W. Ryan; Stevens, Victoria L.; Tsilidis, Konstantinos K.; Haiman, Christopher A.; Chanock, Stephen J.; Hunter, David J.; Kraft, Peter

    2014-01-01

    BACKGROUND Genotype imputation substantially increases available markers for analysis in genome-wide association studies (GWAS) by leveraging linkage disequilibrium from a reference panel. We sought to (i) investigate the performance of imputation from the August 2010 release of the 1000 Genomes Project (1000GP) in an existing GWAS of prostate cancer, (ii) look for novel associations with prostate cancer risk, (iii) fine-map known prostate cancer susceptibility regions using an approximate Bayesian framework and stepwise regression, and (iv) compare power and efficiency of imputation and de novo sequencing. METHODS We used 2,782 aggressive prostate cancer cases and 4,458 controls from the NCI Breast and Prostate Cancer Cohort Consortium aggressive prostate cancer GWAS to infer 5.8 million well-imputed autosomal single nucleotide polymorphisms. RESULTS Imputation quality, as measured by correlation between imputed and true allele counts, was higher among common variants than rare variants. We found no novel prostate cancer associations among a subset of 1.2 million well-imputed low-frequency variants. At a genome-wide sequencing cost of $2,500, imputation from SNP arrays is a more powerful strategy than sequencing for detecting disease associations of SNPs with minor allele frequencies above 1%. CONCLUSIONS 1000GP imputation provided dense coverage of previously-identified prostate cancer susceptibility regions, highlighting its potential as an inexpensive first-pass approach to fine-mapping in regions such as 5p15 and 8q24. Our study shows 1000GP imputation can accurately identify low-frequency variants and stresses the importance of large sample size when studying these variants. PMID:23255287

  12. One thousand genomes imputation in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium aggressive prostate cancer genome-wide association study.

    PubMed

    Machiela, Mitchell J; Chen, Constance; Liang, Liming; Diver, W Ryan; Stevens, Victoria L; Tsilidis, Konstantinos K; Haiman, Christopher A; Chanock, Stephen J; Hunter, David J; Kraft, Peter

    2013-05-01

    Genotype imputation substantially increases available markers for analysis in genome-wide association studies (GWAS) by leveraging linkage disequilibrium from a reference panel. We sought to (i) investigate the performance of imputation from the August 2010 release of the 1000 Genomes Project (1000GP) in an existing GWAS of prostate cancer, (ii) look for novel associations with prostate cancer risk, (iii) fine-map known prostate cancer susceptibility regions using an approximate Bayesian framework and stepwise regression, and (iv) compare power and efficiency of imputation and de novo sequencing. We used 2,782 aggressive prostate cancer cases and 4,458 controls from the NCI Breast and Prostate Cancer Cohort Consortium aggressive prostate cancer GWAS to infer 5.8 million well-imputed autosomal single nucleotide polymorphisms (SNPs). Imputation quality, as measured by correlation between imputed and true allele counts, was higher among common variants than rare variants. We found no novel prostate cancer associations among a subset of 1.2 million well-imputed low-frequency variants. At a genome-wide sequencing cost of $2,500, imputation from SNP arrays is a more powerful strategy than sequencing for detecting disease associations of SNPs with minor allele frequencies (MAF) above 1%. 1000GP imputation provided dense coverage of previously identified prostate cancer susceptibility regions, highlighting its potential as an inexpensive first-pass approach to fine mapping in regions such as 5p15 and 8q24. Our study shows 1000GP imputation can accurately identify low-frequency variants and stresses the importance of large sample size when studying these variants. Copyright © 2012 Wiley Periodicals, Inc.

  13. Sequence variants of estrogen receptor beta and risk of prostate cancer in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium.

    PubMed

    Chen, Yen-Ching; Kraft, Peter; Bretsky, Philip; Ketkar, Shamika; Hunter, David J; Albanes, Demetrius; Altshuler, David; Andriole, Gerald; Berg, Christine D; Boeing, Heiner; Burtt, Noel; Bueno-de-Mesquita, Bas; Cann, Howard; Canzian, Federico; Chanock, Stephen; Dunning, Alison; Feigelson, Heather S; Freedman, Matthew; Gaziano, J Michael; Giovannucci, Edward; Sánchez, Maria-Jose; Haiman, Christopher A; Hallmans, Göran; Hayes, Richard B; Henderson, Brian E; Hirschhorn, Joel; Kaaks, Rudolf; Key, Timothy J; Kolonel, Laurence N; LeMarchand, Loic; Ma, Jing; Overvad, Kim; Palli, Domenico; Pharaoh, Paul; Pike, Malcolm; Riboli, Eliot; Rodriguez, Carmen; Setiawan, V Wendy; Stampfer, Meir; Stram, Daniel O; Thomas, Gilles; Thun, Michael J; Travis, Ruth C; Virtamo, Jarmo; Trichopoulou, Antonia; Wacholder, Sholom; Weinstein, Stephanie J

    2007-10-01

    Estrogen receptor beta (ESR2) may play a role in modulating prostate carcinogenesis through the regulation of genes related to cell proliferation and apoptosis. We conducted nested case-control studies in the Breast and Prostate Cancer Cohort Consortium (BPC3) that pooled 8,323 prostate cancer cases and 9,412 controls from seven cohorts. Whites were the predominant ethnic group. We characterized genetic variation in ESR2 by resequencing exons in 190 breast and prostate cancer cases and genotyping a dense set of single nucleotide polymorphisms (SNP) spanning the locus in a multiethnic panel of 349 cancer-free subjects. We selected four haplotype-tagging SNPs (htSNP) to capture common ESR2 variation in Whites; these htSNPs were then genotyped in all cohorts. Conditional logistic regression models were used to assess the association between sequence variants of ESR2 and the risk of prostate cancer. We also investigated the effect modification by age, body mass index, and family history, as well as the association between sequence variants of ESR2 and advanced-stage (>or=T3b, N1, or M1) and high-grade (Gleason sum >or=8) prostate cancer, respectively. The four tag SNPs in ESR2 were not significantly associated with prostate cancer risk, individually. The global test for the influence of any haplotype on the risk of prostate cancer was not significant (P = 0.31). However, we observed that men carrying two copies of one of the variant haplotypes (TACC) had a 1.46-fold increased risk of prostate cancer (99% confidence interval, 1.06-2.01) compared with men carrying zero copies of this variant haplotype. No SNPs or haplotypes were associated with advanced stage or high grade of prostate cancer. In our analysis focused on genetic variation common in Whites, we observed little evidence for any substantial association of inherited variation in ESR2 with risk of prostate cancer. A nominally significant (P < 0.01) association between the TACC haplotype and prostate cancer risk

  14. Genetic variations in vitamin D-related pathways and breast cancer risk in African American women in the AMBER consortium.

    PubMed

    Yao, Song; Haddad, Stephen A; Hu, Qiang; Liu, Song; Lunetta, Kathryn L; Ruiz-Narvaez, Edward A; Hong, Chi-Chen; Zhu, Qianqian; Sucheston-Campbell, Lara; Cheng, Ting-Yuan David; Bensen, Jeannette T; Johnson, Candace S; Trump, Donald L; Haiman, Christopher A; Olshan, Andrew F; Palmer, Julie R; Ambrosone, Christine B

    2016-05-01

    Studies of genetic variations in vitamin D-related pathways and breast cancer risk have been conducted mostly in populations of European ancestry, and only sparsely in African Americans (AA), who are known for a high prevalence of vitamin D deficiency. We analyzed 24,445 germline variants in 63 genes from vitamin D-related pathways in the African American Breast Cancer Epidemiology and Risk (AMBER) consortium, including 3,663 breast cancer cases and 4,687 controls. Odds ratios (OR) were derived from logistic regression models for overall breast cancer, by estrogen receptor (ER) status (1,983 ER positive and 1,098 ER negative), and for case-only analyses of ER status. None of the three vitamin D-related pathways were associated with breast cancer risk overall or by ER status. Gene-level analyses identified associations with risk for several genes at a nominal p ≤ 0.05, particularly for ER- breast cancer, including rs4647707 in DDB2. In case-only analyses, vitamin D metabolism and signaling pathways were associated with ER- cancer (pathway-level p = 0.02), driven by a single gene CASR (gene-level p = 0.001). The top SNP in CASR was rs112594756 (p = 7 × 10(-5), gene-wide corrected p = 0.01), followed by a second signal from a nearby SNP rs6799828 (p = 1 × 10(-4), corrected p = 0.03). In summary, several variants in vitamin D pathways were associated with breast cancer risk in AA women. In addition, CASR may be related to tumor ER status, supporting a role of vitamin D or calcium in modifying breast cancer phenotypes.

  15. Genetic variations in vitamin D-related pathways and breast cancer risk in African American women in the AMBER consortium

    PubMed Central

    Yao, Song; Haddad, Stephen A.; Hu, Qiang; Liu, Song; Lunetta, Kathryn L.; Ruiz-Narvaez, Edward A.; Hong, Chi-Chen; Zhu, Qianqian; Sucheston-Campbell, Lara; Cheng, Ting-Yuan David; Bensen, Jeannette T.; Johnson, Candace S.; Trump, Donald L.; Haiman, Christopher A.; Olshan, Andrew F.; Palmer, Julie R.; Ambrosone, Christine B.

    2016-01-01

    Studies of genetic variations in vitamin D-related pathways and breast cancer risk have been conducted mostly in populations of European ancestry, and only sparsely in African Americans (AA), who are known for a high prevalence of vitamin D deficiency. We analyzed 24,445 germline variants in 63 genes from vitamin D-related pathways in the African American Breast Cancer Epidemiology and Risk (AMBER) consortium, including 3,663 breast cancer cases and 4,687 controls. Odds ratios (OR) were derived from logistic regression models for overall breast cancer, by estrogen receptor (ER) status (1,983 ER positive and 1,098 ER negative), and for case-only analyses of ER status. None of the three vitamin D-related pathways were associated with breast cancer risk overall or by ER status. Gene-level analyses identified associations with risk for several genes at a nominal p ≤ 0.05, particularly for ER− breast cancer, including rs4647707 in DDB2. In case-only analyses, vitamin D metabolism and signaling pathways were associated with ER− cancer (pathway-level p = 0.02), driven by a single gene CASR (gene-level p = 0.001). The top SNP in CASR was rs112594756 (p = 7 × 10−5, gene-wide corrected p = 0.01), followed by a second signal from a nearby SNP rs6799828 (p = 1 × 10−4, corrected p = 0.03). In summary, several variants in vitamin D pathways were associated with breast cancer risk in AA women. In addition, CASR may be related to tumor ER status, supporting a role of vitamin D or calcium in modifying breast cancer phenotypes. PMID:26650177

  16. Pathway analyses identify TGFBR2 as potential breast cancer susceptibility gene: results from a consortium study among Asians.

    PubMed

    Ma, Xiangyu; Beeghly-Fadiel, Alicia; Lu, Wei; Shi, Jiajun; Xiang, Yong-Bing; Cai, Qiuyin; Shen, Hongbing; Shen, Chen-Yang; Ren, Zefang; Matsuo, Keitaro; Khoo, Ui Soon; Iwasaki, Motoki; Long, Jirong; Zhang, Ben; Ji, Bu-Tian; Zheng, Ying; Wang, Wenjing; Hu, Zhibin; Liu, Yao; Wu, Pei-Ei; Shieh, Ya-Lan; Wang, Shenming; Xie, Xiaoming; Ito, Hidemi; Kasuga, Yoshio; Chan, Kelvin Y K; Iwata, Hiroji; Tsugane, Shoichiro; Gao, Yu-Tang; Shu, Xiao Ou; Moses, Harold L; Zheng, Wei

    2012-07-01

    The TGF-β signaling pathway plays a significant role in the carcinogenic process of breast cancer. We systematically evaluated associations of common variants in TGF-β signaling pathway genes with breast cancer risk using a multistage, case-control study among Asian women. In the first stage, 341 single-nucleotide polymorphisms with minor allele frequencies ≥ 0.05 across 11 genes were evaluated among 2,926 cases and 2,380 controls recruited as a part of the Shanghai Breast Cancer Genetics Study (SBCGS). In the second stage, 20 SNPs with promising associations were evaluated among an additional 1,890 cases and 2,000 controls from the SBCGS. One variant, TGFBR2 rs1078985, had highly consistent and significant associations with breast cancer risk among participants in both study stages, as well as promising results from in silico analysis. Additional genotyping was carried out among 2,475 cases and 2,343 controls from the SBCGS, as well as among 5,077 cases and 5,384 controls from six studies in the Asian Breast Cancer Consortium (stage III). Pooled analysis of all data indicated that minor allele homozygotes (GG) of TGFBR2 rs1078985 had a 24% reduced risk of breast cancer compared with major allele carriers (AG or AA; OR, 0.76; 95% CI, 0.65-0.89; P = 8.42 × 10(-4)). These findings support a role for common genetic variation in TGF-β signaling pathway genes, specifically in TGFBR2, in breast cancer susceptibility. These findings may provide new insights into the etiology of breast cancer as well as future potential therapeutic targets. ©2012 AACR

  17. Unifying Screening Processes Within the PROSPR Consortium: A Conceptual Model for Breast, Cervical, and Colorectal Cancer Screening

    PubMed Central

    Kim, Jane J.; Schapira, Marilyn M.; Tosteson, Anna N. A.; Zauber, Ann G.; Geiger, Ann M.; Kamineni, Aruna; Weaver, Donald L.; Tiro, Jasmin A.

    2015-01-01

    General frameworks of the cancer screening process are available, but none directly compare the process in detail across different organ sites. This limits the ability of medical and public health professionals to develop and evaluate coordinated screening programs that apply resources and population management strategies available for one cancer site to other sites. We present a trans-organ conceptual model that incorporates a single screening episode for breast, cervical, and colorectal cancers into a unified framework based on clinical guidelines and protocols; the model concepts could be expanded to other organ sites. The model covers four types of care in the screening process: risk assessment, detection, diagnosis, and treatment. Interfaces between different provider teams (eg, primary care and specialty care), including communication and transfer of responsibility, may occur when transitioning between types of care. Our model highlights across each organ site similarities and differences in steps, interfaces, and transitions in the screening process and documents the conclusion of a screening episode. This model was developed within the National Cancer Institute–funded consortium Population-based Research Optimizing Screening through Personalized Regimens (PROSPR). PROSPR aims to optimize the screening process for breast, cervical, and colorectal cancer and includes seven research centers and a statistical coordinating center. Given current health care reform initiatives in the United States, this conceptual model can facilitate the development of comprehensive quality metrics for cancer screening and promote trans-organ comparative cancer screening research. PROSPR findings will support the design of interventions that improve screening outcomes across multiple cancer sites. PMID:25957378

  18. Risk of second primary cancers after testicular cancer in East and West Germany: a focus on contralateral testicular cancers.

    PubMed

    Rusner, Carsten; Streller, Brigitte; Stegmaier, Christa; Trocchi, Pietro; Kuss, Oliver; McGlynn, Katherine A; Trabert, Britton; Stang, Andreas

    2014-01-01

    Testicular cancer survival rates improved dramatically after cisplatin-based therapy was introduced in the 1970s. However, chemotherapy and radiation therapy are potentially carcinogenic. The purpose of this study was to estimate the risk of developing second primary cancers including the risk associated with primary histologic type (seminoma and non-seminoma) among testicular cancer survivors in Germany. We identified 16 990 and 1401 cases of testicular cancer in population-based cancer registries of East Germany (1961-1989 and 1996-2008) and Saarland (a federal state in West Germany; 1970-2008), respectively. We estimated the risk of a second primary cancer using standardized incidence ratios (SIRs) with 95% confidence intervals (95% CIs). To determine trends, we plotted model-based estimated annual SIRs. In East Germany, a total of 301 second primary cancers of any location were observed between 1961 and 1989 (SIR: 1.9; 95% CI: 1.7-2.1), and 159 cancers (any location) were observed between 1996 and 2008 (SIR: 1.7; 95% CI: 1.4-2.0). The SIRs for contralateral testicular cancer were increased in the registries with a range from 6.0 in Saarland to 13.9 in East Germany. The SIR for seminoma, in particular, was higher in East Germany compared to the other registries. We observed constant trends in the model-based SIRs for contralateral testicular cancers. The majority of reported SIRs of other cancer sites including histology-specific risks showed low precisions of estimated effects, likely due to small sample sizes. Testicular cancer patients are at increased risk especially for cancers of the contralateral testis and should receive intensive follow-ups.

  19. Underusers of mammogram screening: stage of adoption in five U.S. subpopulations. The NCI Breast Cancer Screening Consortium.

    PubMed

    Stoddard, A M; Rimer, B K; Lane, D; Fox, S A; Lipkus, I; Luckmann, R; Avrunin, J S; Sprachman, S; Costanza, M; Urban, N

    1998-01-01

    The purpose of this report is to describe the characteristics of women ages 50 to 80 who do not follow commonly accepted mammography screening guidelines. It provides unique understanding of the robustness of characteristics of underusers across five different U.S. subpopulations. The data are from the baseline surveys of the five studies of the NCI Breast Cancer Screening Consortium. Stage of adoption of mammography screening and other characteristics of underusers are presented. Polytomous logistic regression analysis was used to explore multivariable associations with stage of adoption in each study site. The five samples studied by the Consortium range in size from 259 to 4,477 women (n = 11,292). The relationship of the perceptions of the pros and cons of mammography with stage of adoption was strikingly similar across the five samples. Other variables consistently associated with stage were a recent receipt of a breast physical examination and recommendation for mammography by a physician. The findings suggest a need to encourage regular screening through effective communication from a health care provider. Intervention messages should be designed to increase the pros of mammography, decrease the cons, and highlight these differentially according to the woman's stage of adoption.

  20. The global cancer genomics consortium's symposium: new era of molecular medicine and epigenetic cancer medicine - cross section of genomics and epigenetics

    PubMed Central

    Toi, Masakazu; Pillai, M. Radhakrishna; Gupta, Sudeep; Badwe, Rajendra; Carmo-Fonseca, Maria; Costa, Luis; Chow, Louis WC; Knapp, Stefan; Kumar, Rakesh

    2015-01-01

    The Global Cancer Genomics Consortium (GCGC) colleagues continue to function together as an interactive multidisciplinary team of cancer biologists and oncologists with interests in genomics and building a bidirectional bridge between cancer clinics and laboratories while taking advantage of shared resources among its member scientists. The GCGC includes member scientists from six institutions in Lisbon, United Kingdom, Japan, India and United States, and was formed in December 2010 for a period of five years. Driven by valuable lessons learned from the previous symposiums, the fourth GCGC Symposium focused on a cross section of genomic and epigenetic cancer medicine and it's for this reason we chose the conference theme - New Era of Molecular Medicine and Epigenetic Cancer Medicine: Cross Section of Genomics and Epigenetics. This year's symposium was co-organized by the Organization for Oncology and Translational Research (OOTR) at the Shiran Hall, Kyoto University, Kyoto, Japan, from November 14 and 15, 2014. The symposium attracted around 80 participants from 14 countries, and counted with 23 invited platform speakers. Scientific sessions included eight platform sessions and one poster session, and three plenary lectures. The symposium focused on cancer stem cells and self-renewal, cancer transcriptome, tumor heterogeneity, tumor biology, breast cancer genomics, targeted therapeutics and personalized medicine. The issues of cancer stem cells and tumor heterogeneity were echoed in most of the scientific presentations. The meeting concluded with an oral presentation by the best poster awardee and closing remarks by meeting co-chairs.

  1. Current Status of the Management of Hereditary Breast and Ovarian Cancer in Asia: First Report by the Asian BRCA Consortium.

    PubMed

    Nakamura, Seigo; Kwong, Ava; Kim, Sung-Won; Iau, Philip; Patmasiriwat, Pimpicha; Dofitas, Rodney; Aryandono, Teguh; Hu, Zhen; Huang, Chiun-Sheng; Ginsburg, Ophira; Rashid, Muhammad Usman; Sarin, Rajiv; Teo, Soo-Hwang

    2016-01-01

    BRCA1/BRCA2 mutations are associated with an increased lifetime risk for hereditary breast and ovarian cancer (HBOC). Compared with the Western developed countries, genetic testing and risk assessment for HBOC in Asia are less available, thus prohibiting the appropriate surveillance, clinical strategies and cancer management. The current status of HBOC management in 14 Asian countries, including genetic counselling/testing uptakes and clinical management options, was reviewed. We analysed how economic factors, healthcare and legal frameworks, and cultural issues affect the genetic service availability in Asia. In 2012, only an estimated 4,000 breast cancer cases from 14 Asian countries have benefited from genetic services. Genetic testing costs and the absence of their adoption into national healthcare systems are the main economic barriers for approaching genetic services. Training programmes, regional accredited laboratories and healthcare professionals are not readily available in most of the studied countries. A lack of legal frameworks against genetic discrimination and a lack of public awareness of cancer risk assessment also provide challenges to HBOC management in Asia. The Asian BRCA Consortium reports the current disparities in genetic services for HBOC in Asia and urges the policy makers, healthcare sectors and researchers to address the limitations in HBOC management. © 2015 S. Karger AG, Basel.

  2. Biology and etiology of young-onset breast cancers among premenopausal African American women: results from the AMBER Consortium.

    PubMed

    Chollet-Hinton, Lynn; Olshan, Andrew F; Nichols, Hazel B; Anders, Carey K; Lund, Jennifer L; Allott, Emma H; Bethea, Traci N; Hong, Chi-Chen; Cohen, Stephanie M; Khoury, Thaer; Zirpoli, Gary R; Borges, Virginia F; Rosenberg, Lynn A; Bandera, Elisa V; Ambrosone, Christine B; Palmer, Julie R; Troester, Melissa A

    2017-09-13

    African American (AA) women have higher incidence of aggressive, young-onset (<40 years) breast cancers. Young- and older-onset disease may have distinct tumor biologies and etiologies; however, studies investigating age differences among AA women have been rare and generally underpowered. We examined tumor characteristics and breast cancer risk factors associated with premenopausal young (<40) vs. older (≥40) AA women's breast cancer in the African American Breast Cancer Epidemiology and Risk Consortium (2,008 cases and 5,144 controls). Unconditional logistic regression models assessed heterogeneity of tumor biology and risk factor associations by age, overall and by estrogen receptor status. Premenopausal AA women <40 years had higher frequency of poorer-prognosis tumor characteristics compared to older women, including negative estrogen and progesterone receptor status, triple-negative subtype, high grade, higher stage, and larger tumors. Adiposity (i.e., waist-to-hip ratio) and family history of breast cancer were more strongly associated with young-onset disease (case-control OR=1.46, 95% CI=1.04,2.05; OR=3.10, 95% CI=2.08,4.63, respectively) compared to older-onset disease (OR=1.11, 95% CI=0.91,1.35; OR=1.57, 95% CI=1.26,1.94). Breastfeeding showed a slight inverse risk association among young women (OR=0.70, 95% CI=0.43,1.16). Oral contraceptive use was associated with increased risk regardless of age. Considering various cutpoints for young age (<40, <45, <50), age-related heterogeneity was greatest when <40 was used. Among premenopausal AA women, diagnosis before age 40 is associated with more aggressive breast tumor biology and some etiologic differences. Modifiable risk factors including breastfeeding, adiposity, and oral contraceptive use may be important targets for mitigating harms of young-onset breast cancer. Copyright ©2017, American Association for Cancer Research.

  3. OBESITY, BODY FAT DISTRIBUTION, AND RISK OF BREAST CANCER SUBTYPES IN AFRICAN AMERICAN WOMEN PARTICIPATING IN THE AMBER CONSORTIUM

    PubMed Central

    Bandera, Elisa V.; Chandran, Urmila; Hong, Chi-Chen; Troester, Melissa A.; Bethea, Traci N.; Adams-Campbell, Lucile L.; Haiman, Christopher A.; Park, Song-Yi; Olshan, Andrew F.; Ambrosone, Christine B.; Palmer, Julie R.; Rosenberg, Lynn

    2015-01-01

    Purpose African American (AA) women are more likely than white women to be obese and to be diagnosed with ER- and triple negative (TN) breast cancer, but few studies have evaluated the impact of obesity and body fat distribution on breast cancer subtypes in AA women. We evaluated these associations in the AMBER Consortium by pooling data from four large studies. Methods Cases were categorized according to hormone receptor status as ER+, ER-, and TN (ER-, PR-, and HER2-) based on pathology data. A total of 2,104 ER+ cases, 1,070 ER- cases (including 491 TN cases), and 12,060 controls were included. Odds ratios (OR) and 95% confidence intervals (CI) were computed using logistic regression, taking into account breast cancer risk factors. Results In postmenopausal women, higher recent (most proximal value to diagnosis/index date) BMI was associated with increased risk of ER+ cancer (OR: 1.31; 95% CI: 1.02–1.67 for BMI≥35 vs <25 kg/m2) and with decreased risk of TN tumors (OR: 0.60; 95% CI: 0.39–0.93 for BMI≥35 vs. <25). High young adult BMI was associated with decreased premenopausal ER+ cancer and all subtypes of postmenopausal cancer, and high recent waist-to-hip ratio (WHR) with increased risk of pre-menopausal ER+ tumors (OR: 1.35; 95% CI: 1.01–1.80) and all tumor subtypes combined in postmenopausal women (OR: 1.26; 95% CI: 1.02–1.56). Conclusions The impact of general and central obesity varies by menopausal status and hormone receptor subtype in AA women. Our findings imply different mechanisms for associations of adiposity with TN and ER+ breast cancers. PMID:25809092

  4. Obesity, body fat distribution, and risk of breast cancer subtypes in African American women participating in the AMBER Consortium.

    PubMed

    Bandera, Elisa V; Chandran, Urmila; Hong, Chi-Chen; Troester, Melissa A; Bethea, Traci N; Adams-Campbell, Lucile L; Haiman, Christopher A; Park, Song-Yi; Olshan, Andrew F; Ambrosone, Christine B; Palmer, Julie R; Rosenberg, Lynn

    2015-04-01

    African American (AA) women are more likely than white women to be obese and to be diagnosed with ER- and triple-negative (TN) breast cancer, but few studies have evaluated the impact of obesity and body fat distribution on breast cancer subtypes in AA women. We evaluated these associations in the AMBER Consortium by pooling data from four large studies. Cases were categorized according to hormone receptor status as ER+, ER-, and TN (ER-, PR-, and HER2-) based on pathology data. A total of 2104 ER+ cases, 1070 ER- cases (including 491 TN cases), and 12,060 controls were included. Odds ratios (OR) and 95 % confidence intervals (CI) were computed using logistic regression, taking into account breast cancer risk factors. In postmenopausal women, higher recent (most proximal value to diagnosis/index date) BMI was associated with increased risk of ER+ cancer (OR 1.31; 95 % CI 1.02-1.67 for BMI ≥ 35 vs. <25 kg/m(2)) and with decreased risk of TN tumors (OR 0.60; 95 % CI 0.39-0.93 for BMI ≥ 35 vs. <25). High young adult BMI was associated with decreased premenopausal ER+ cancer and all subtypes of postmenopausal cancer, and high recent waist-to-hip ratio with increased risk of premenopausal ER+ tumors (OR 1.35; 95 % CI 1.01-1.80) and all tumor subtypes combined in postmenopausal women (OR 1.26; 95 % CI 1.02-1.56). The impact of general and central obesity varies by menopausal status and hormone receptor subtype in AA women. Our findings imply different mechanisms for associations of adiposity with TN and ER+ breast cancers.

  5. Vitamin or mineral supplement intake and the risk of head and neck cancer: pooled analysis in the INHANCE consortium

    PubMed Central

    Li, Qian; Chuang, Shu-chun; Neto, Jose Eluf; Menezes, Ana; Matos, Elena; Koifman, Sergio; Wünsch-Filho, Victor; Fernandez, Leticia; Daudt, Alexander W.; Curado, Maria Paula; Winn, Deborah M.; Franceschi, Silvia; Herrero, Rolando; Castellsague, Xavier; Morgenstern, Hal; Zhang, Zuo-Feng; Lazarus, Philip; Muscat, Joshua; McClean, Michael; Kelsey, Karl T.; Hayes, Richard B.; Purdue, Mark P.; Schwartz, Stephen M.; Chen, Chu; Benhamou, Simone; Olshan, Andrew F.; Yu, Guopei; Schantz, Stimson; Ferro, Gilles; Brennan, Paul; Boffetta, Paolo; Hashibe, Mia

    2012-01-01

    To investigate the potential role of vitamin or mineral supplementation on the risk of head and neck cancer (HNC), we analyzed individual-level pooled data from 12 case-control studies (7,002 HNC cases and 8,383 controls) participating in the International Head and Neck Cancer Epidemiology consortium. There were a total of 2,028 oral cavity cancer, 2,465 pharyngeal cancer, and 874 unspecified oral/pharynx cancer, 1,329 laryngeal cancer and 306 overlapping HNC cases. Odds ratios (OR) and 95% confidence intervals (CIs) for self reported ever use of any vitamins, multivitamins, vitamin A, vitamin C, vitamin E, and calcium, beta-carotene, iron, selenium, and zinc supplements were assessed. We further examined frequency, duration and cumulative exposure of each vitamin or mineral when possible and stratified by smoking and drinking status. All ORs were adjusted for age, sex, race/ethnicity, study center, education level, and pack-years of smoking, frequency of alcohol drinking and fruit/vegetable intake. A decreased risk of HNC was observed with ever use of vitamin C (OR=0.76, 95% CI=0.59-0.96) and with ever use of calcium supplement (OR=0.64, 95% CI=0.42-0.97). The inverse association with HNC risk was also observed for 10 or more years of vitamin C use (OR=0.72, 95% CI=0.54-0.97) and more than 365 tablets of cumulative calcium intake (OR=0.36, 95% CI=0.16-0.83), but linear trends were not observed for the frequency or duration of any supplement intake. We did not observe any strong associations between vitamin or mineral supplement intake and the risk of head and neck cancer. PMID:22173631

  6. Cancer Patient and Survivor Research from the Cancer Information Service Research Consortium: A Preview of Three Large Randomized Trials and Initial Lessons Learned

    PubMed Central

    MARCUS, ALFRED C.; DIEFENBACH, MICHAEL A.; STANTON, ANNETTE L.; MILLER-HALEGOUA, SUZANNE N.; FLEISHER, LINDA; RAICH, PETER C.; MORRA, MARION E.; PEROCCHIA, ROSEMARIE SLEVIN; TRAN, ZUNG VU; BRIGHT, MARY ANNE

    2014-01-01

    Three large randomized trials are described from the Cancer Information Service Research Consortium (CISRC). Three web-based multimedia programs are being tested to help newly diagnosed prostate (Project 1) and breast cancer patients (Project 2) make informed treatment decisions and breast cancer patients prepare for life after treatment (Project 3). Project 3 is also testing a telephone callback intervention delivered by a cancer information specialist. All participants receive standard print material specific to each project. Preliminary results from the two-month follow-up interviews are reported for the initial wave of enrolled participants, most of whom were recruited from the Cancer Information Service (1-800-4-CANCER) telephone information program (Project 1 = 208, Project 2 = 340, Project 3 = 792). Self-reported use of the multimedia program was 51%, 52% and 67% for Projects 1–3, respectively. Self-reported use of the print materials (read all, most or some) was 90%, 85% and 83% for Projects 1–3, respectively. The callback intervention was completed by 92% of Project 3 participants. Among those using the CISRC interventions, perceived utility and benefit was high, and more than 90% would recommend them to other cancer patients. Five initial lessons learned are presented that may help inform future cancer communications research. PMID:23448232

  7. Dietary fiber intake and head and neck cancer risk: A pooled analysis in the International Head and Neck Cancer Epidemiology consortium.

    PubMed

    Kawakita, Daisuke; Lee, Yuan-Chin Amy; Turati, Federica; Parpinel, Maria; Decarli, Adriano; Serraino, Diego; Matsuo, Keitaro; Olshan, Andrew F; Zevallos, Jose P; Winn, Deborah M; Moysich, Kirsten; Zhang, Zuo-Feng; Morgenstern, Hal; Levi, Fabio; Kelsey, Karl; McClean, Michael; Bosetti, Cristina; Garavello, Werner; Schantz, Stimson; Yu, Guo-Pei; Boffetta, Paolo; Chuang, Shu-Chun; Hashibe, Mia; Ferraroni, Monica; La Vecchia, Carlo; Edefonti, Valeria

    2017-11-01

    The possible role of dietary fiber in the etiology of head neck cancers (HNCs) is unclear. We used individual-level pooled data from ten case-control studies (5959 cases and 12,248 controls) participating in the International Head and Neck Cancer Epidemiology (INHANCE) consortium, to examine the association between fiber intake and cancer of the oral cavity/pharynx and larynx. Odds Ratios (ORs) and their 95% Confidence Intervals (CIs) were estimated using unconditional multiple logistic regression applied to quintile categories of non-alcohol energy-adjusted fiber intake and adjusted for tobacco and alcohol use and other known or putative confounders. Fiber intake was inversely associated with oral and pharyngeal cancer combined (OR for 5th vs. 1st quintile category = 0.49, 95% CI: 0.40-0.59; p for trend <0.001) and with laryngeal cancer (OR = 0.66, 95% CI: 0.54-0.82, p for trend <0.001). There was, however, appreciable heterogeneity of the estimated effect across studies for oral and pharyngeal cancer combined. Nonetheless, inverse associations were consistently observed for the subsites of oral and pharyngeal cancers and within most strata of the considered covariates, for both cancer sites. Our findings from a multicenter large-scale pooled analysis suggest that, although in the presence of between-study heterogeneity, a greater intake of fiber may lower HNC risk. © 2017 UICC.

  8. Folate intake and the risk of oral cavity and pharyngeal cancer: a pooled analysis within the INHANCE Consortium

    PubMed Central

    Galeone, Carlotta; Edefonti, Valeria; Parpinel, Maria; Leoncini, Emanuele; Matsuo, Keitaro; Talamini, Renato; Olshan, Andrew F.; Zevallos, Jose P.; Winn, Deborah M.; Jayaprakash, Vijayvel; Moysich, Kirsten; Zhang, Zuo-Feng; Morgenstern, Hal; Levi, Fabio; Bosetti, Cristina; Kelsey, Karl; McClean, Michael; Schantz, Stimson; Yu, Guo-Pei; Boffetta, Paolo; Lee, Yuan-Chin Amy; Hashibe, Mia; La Vecchia, Carlo; Boccia, Stefania

    2014-01-01

    There are suggestions of an inverse association between folate intake and serum folate levels and the risk of oral cavity and pharyngeal cancers (OPC), but most studies are limited in sample size, with only few reporting information on the source of dietary folate. This study aims to investigate the association between folate intake and the risk of OPC within the International Head and Neck Cancer Epidemiology (INHANCE) Consortium. We analyzed pooled individual-level data from 10 case-control studies participating in the INHANCE consortium, including 5,127 cases and 13,249 controls. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were estimated for the associations between total folate intake (natural, fortification and supplementation) and natural folate only, and OPC risk. We found an inverse association between total folate intake and overall OPC risk (the adjusted OR for the highest versus the lowest quintile was 0.65, 95% CI: 0.43–0.99), with a stronger association for oral cavity (OR=0.57, 95% CI: 0.43–0.75). A similar inverse association, though somewhat weaker, was observed for folate intake from natural sources only (OR=0.64, 95% CI: 0.45–0.91). The highest OPC risk was observed in heavy alcohol drinkers with low folate intake as compared to never/light drinkers with high folate (OR=4.05, 95% CI: 3.43–4.79); the attributable proportion due to interaction was 11.1%(95% CI: 1.4–20.8%). The present project of a large pool of case-control studies supports a protective effect total folate intake on OPC risk. PMID:24974959

  9. Vitamin C intake from diary recordings and risk of breast cancer in the UK Dietary Cohort Consortium.

    PubMed

    Hutchinson, J; Lentjes, M A H; Greenwood, D C; Burley, V J; Cade, J E; Cleghorn, C L; Threapleton, D E; Key, T J; Cairns, B J; Keogh, R H; Dahm, C C; Brunner, E J; Shipley, M J; Kuh, D; Mishra, G; Stephen, A M; Bhaniani, A; Borgulya, G; Khaw, K T

    2012-05-01

    Vitamin C intake has been inversely associated with breast cancer risk in case-control studies, but not in meta-analyses of cohort studies using Food Frequency Questionnaires, which can over-report fruit and vegetable intake, the main source of vitamin C. This is the first study to investigate associations between vitamin C intake and breast cancer risk using food diaries. Estimated dietary vitamin C intake was derived from 4-7 day food diaries pooled from five prospective studies in the UK Dietary Cohort Consortium. This nested case-control study of 707 incident breast cancer cases and 2144 matched controls examined breast cancer risk in relation to dietary vitamin C intake using conditional logistic regression adjusting for relevant covariates. Additionally, total vitamin C intake from supplements and diet was analysed in three cohorts. No evidence of associations was observed between breast cancer risk and vitamin C intake analysed for dietary vitamin C intake (odds ratios (OR)=0.98 per 60 mg/day, 95% confidence interval (CI): 0.88-1.09, P (trend)=0.7), dietary vitamin C density (OR=0.97 per 60 mg/day, 95% CI: 0.87-1.07, P (trend)=0.5 ) or total vitamin C intake (OR=1.01 per 60 mg/day, 95% CI: 0.99-1.03, P (trend)=0.3). Additionally, there was no significant association for post-menopausal women (OR=1.02 per 60 mg/day, 95% CI: 0.99-1.05, P (trend)=0.3). This pooled analysis of individual UK women found no evidence of significant associations between breast cancer incidence and dietary or total vitamin C intake derived uniquely from detailed diary recordings.

  10. Alcohol and lung cancer risk among never smokers: A pooled analysis from the international lung cancer consortium and the SYNERGY study.

    PubMed

    Fehringer, Gordon; Brenner, Darren R; Zhang, Zuo-Feng; Lee, Yuan-Chin Amy; Matsuo, Keitaro; Ito, Hidemi; Lan, Qing; Vineis, Paolo; Johansson, Mattias; Overvad, Kim; Riboli, Elio; Trichopoulou, Antonia; Sacerdote, Carlotta; Stucker, Isabelle; Boffetta, Paolo; Brennan, Paul; Christiani, David C; Hong, Yun-Chul; Landi, Maria Teresa; Morgenstern, Hal; Schwartz, Ann G; Wenzlaff, Angela S; Rennert, Gad; McLaughlin, John R; Harris, Curtis C; Olivo-Marston, Susan; Orlow, Irene; Park, Bernard J; Zauderer, Marjorie; Barros Dios, Juan M; Ruano Raviña, Alberto; Siemiatycki, Jack; Koushik, Anita; Lazarus, Philip; Fernández-Somoano, Ana; Tardon, Adonina; Le Marchand, Loic; Brenner, Hermann; Saum, Kai-Uwe; Duell, Eric J; Andrew, Angeline S; Szeszenia-Dabrowska, Neonila; Lissowska, Jolanta; Zaridze, David; Rudnai, Peter; Fabianova, Eleonora; Mates, Dana; Foretova, Lenka; Janout, Vladimir; Bencko, Vladimir; Holcatova, Ivana; Pesatori, Angela Cecilia; Consonni, Dario; Olsson, Ann; Straif, Kurt; Hung, Rayjean J

    2017-05-01

    It is not clear whether alcohol consumption is associated with lung cancer risk. The relationship is likely confounded by smoking, complicating the interpretation of previous studies. We examined the association of alcohol consumption and lung cancer risk in a large pooled international sample, minimizing potential confounding of tobacco consumption by restricting analyses to never smokers. Our study included 22 case-control and cohort studies with a total of 2548 never-smoking lung cancer patients and 9362 never-smoking controls from North America, Europe and Asia within the International Lung Cancer Consortium (ILCCO) and SYNERGY Consortium. Alcohol consumption was categorized into amounts consumed (grams per day) and also modelled as a continuous variable using restricted cubic splines for potential non-linearity. Analyses by histologic sub-type were included. Associations by type of alcohol consumed (wine, beer and liquor) were also investigated. Alcohol consumption was inversely associated with lung cancer risk with evidence most strongly supporting lower risk for light and moderate drinkers relative to non-drinkers (>0-4.9 g per day: OR = 0.80, 95% CI = 0.70-0.90; 5-9.9 g per day: OR = 0.82, 95% CI = 0.69-0.99; 10-19.9 g per day: OR = 0.79, 95% CI = 0.65-0.96). Inverse associations were found for consumption of wine and liquor, but not beer. The results indicate that alcohol consumption is inversely associated with lung cancer risk, particularly among subjects with low to moderate consumption levels, and among wine and liquor drinkers, but not beer drinkers. Although our results should have no relevant bias from the confounding effect of smoking we cannot preclude that confounding by other factors contributed to the observed associations. Confounding in relation to the non-drinker reference category may be of particular importance.

  11. PTGS2 and IL6 genetic variation and risk of breast and prostate cancer: results from the Breast and Prostate Cancer Cohort Consortium (BPC3)

    PubMed Central

    Dossus, Laure; Kaaks, Rudolf; Canzian, Federico; Albanes, Demetrius; Berndt, Sonja I.; Boeing, Heiner; Buring, Julie; Chanock, Stephen J.; Clavel-Chapelon, Francoise; Feigelson, Heather Spencer; Gaziano, John M.; Giovannucci, Edward; Gonzalez, Carlos; Haiman, Christopher A.; Hallmans, Göran; Hankinson, Susan E.; Hayes, Richard B.; Henderson, Brian E.; Hoover, Robert N.; Hunter, David J.; Khaw, Kay-Tee; Kolonel, Laurence N.; Kraft, Peter; Ma, Jing; Le Marchand, Loic; Lund, Eiliv; Peeters, Petra H.M.; Stampfer, Meir; Stram, Dan O.; Thomas, Gilles; Thun, Michael J.; Tjonneland, Anne; Trichopoulos, Dimitrios; Tumino, Rosario; Riboli, Elio; Virtamo, Jarmo; Weinstein, Stephanie J.; Yeager, Meredith; Ziegler, Regina G.; Cox, David G.

    2010-01-01

    Genes involved in the inflammation pathway have been associated with cancer risk. Genetic variants in the interleukin-6 (IL6) and prostaglandin-endoperoxide synthase-2 (PTGS2, encoding for the COX-2 enzyme) genes, in particular, have been related to several cancer types, including breast and prostate cancers. We conducted a study within the Breast and Prostate Cancer Cohort Consortium to examine the association between IL6 and PTGS2 polymorphisms and breast and prostate cancer risk. Twenty-seven polymorphisms, selected by pairwise tagging, were genotyped on 6292 breast cancer cases and 8135 matched controls and 8008 prostate cancer cases and 8604 matched controls. The large sample sizes and comprehensive single nucleotide polymorphism tagging in this study gave us excellent power to detect modest effects for common variants. After adjustment for multiple testing, none of the associations examined remained statistically significant at P = 0.01. In analyses not adjusted for multiple testing, one IL6 polymorphism (rs6949149) was marginally associated with breast cancer risk (TT versus GG, odds ratios (OR): 1.32; 99% confidence intervals (CI): 1.00–1.74, Ptrend = 0.003) and two were marginally associated with prostate cancer risk (rs6969502-AA versus rs6969502-GG, OR: 0.87, 99% CI: 0.75–1.02; Ptrend = 0.002 and rs7805828-AA versus rs7805828-GG, OR: 1.11, 99% CI: 0.99–1.26; Ptrend = 0.007). An increase in breast cancer risk was observed for the PTGS2 polymorphism rs7550380 (TT versus GG, OR: 1.38, 99% CI: 1.04–1.83). No association was observed between PTGS2 polymorphisms and prostate cancer risk. In conclusion, common genetic variation in these two genes might play at best a limited role in breast and prostate cancers. PMID:19965896

  12. Vitamin E intake from natural sources and head and neck cancer risk: a pooled analysis in the International Head and Neck Cancer Epidemiology consortium

    PubMed Central

    Edefonti, V; Hashibe, M; Parpinel, M; Ferraroni, M; Turati, F; Serraino, D; Matsuo, K; Olshan, A F; Zevallos, J P; Winn, D M; Moysich, K; Zhang, Z-F; Morgenstern, H; Levi, F; Kelsey, K; McClean, M; Bosetti, C; Schantz, S; Yu, G-P; Boffetta, P; Chuang, S-C; A Lee, Y-C; La Vecchia, C; Decarli, A

    2015-01-01

    Background: Evidence for the possible effect of vitamin E on head and neck cancers (HNCs) is limited. Methods: We used individual-level pooled data from 10 case–control studies (5959 cases and 12 248 controls) participating in the International Head and Neck Cancer Epidemiology (INHANCE) consortium to assess the association between vitamin E intake from natural sources and cancer of the oral cavity/pharynx and larynx. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression models applied to quintile categories of nonalcohol energy-adjusted vitamin E intake. Results: Intake of vitamin E was inversely related to oral/pharyngeal cancer (OR for the fifth vs the first quintile category=0.59, 95% CI: 0.49–0.71; P for trend <0.001) and to laryngeal cancer (OR=0.67, 95% CI: 0.54–0.83, P for trend <0.001). There was, however, appreciable heterogeneity of the estimated effect across studies for oral/pharyngeal cancer. Inverse associations were generally observed for the anatomical subsites of oral and pharyngeal cancer and within covariate strata for both sites. Conclusion: Our findings suggest that greater vitamin E intake from foods may lower HNC risk, although we were not able to explain the heterogeneity observed across studies or rule out certain sources of bias. PMID:25989276

  13. Vitamin E intake from natural sources and head and neck cancer risk: a pooled analysis in the International Head and Neck Cancer Epidemiology consortium.

    PubMed

    Edefonti, V; Hashibe, M; Parpinel, M; Ferraroni, M; Turati, F; Serraino, D; Matsuo, K; Olshan, A F; Zevallos, J P; Winn, D M; Moysich, K; Zhang, Z-F; Morgenstern, H; Levi, F; Kelsey, K; McClean, M; Bosetti, C; Schantz, S; Yu, G-P; Boffetta, P; Chuang, S-C; A Lee, Y-C; La Vecchia, C; Decarli, A

    2015-06-30

    Evidence for the possible effect of vitamin E on head and neck cancers (HNCs) is limited. We used individual-level pooled data from 10 case-control studies (5959 cases and 12 248 controls) participating in the International Head and Neck Cancer Epidemiology (INHANCE) consortium to assess the association between vitamin E intake from natural sources and cancer of the oral cavity/pharynx and larynx. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression models applied to quintile categories of non-alcohol energy-adjusted vitamin E intake. Intake of vitamin E was inversely related to oral/pharyngeal cancer (OR for the fifth vs the first quintile category=0.59, 95% CI: 0.49-0.71; P for trend <0.001) and to laryngeal cancer (OR=0.67, 95% CI: 0.54-0.83, P for trend <0.001). There was, however, appreciable heterogeneity of the estimated effect across studies for oral/pharyngeal cancer. Inverse associations were generally observed for the anatomical subsites of oral and pharyngeal cancer and within covariate strata for both sites. Our findings suggest that greater vitamin E intake from foods may lower HNC risk, although we were not able to explain the heterogeneity observed across studies or rule out certain sources of bias.

  14. A Novel Cross-Disciplinary Multi-Institute Approach to Translational Cancer Research: Lessons Learned from Pennsylvania Cancer Alliance Bioinformatics Consortium (PCABC)

    PubMed Central

    Patel, Ashokkumar A.; Gilbertson, John R.; Showe, Louise C.; London, Jack W.; Ross, Eric; Ochs, Michael F.; Carver, Joseph; Lazarus, Andrea; Parwani, Anil V.; Dhir, Rajiv; Beck, J. Robert; Liebman, Michael; Garcia, Fernando U.; Prichard, Jeff; Wilkerson, Myra; Herberman, Ronald B.; Becich, Michael J.

    2007-01-01

    Background: The Pennsylvania Cancer Alliance Bioinformatics Consortium (PCABC, http://www.pcabc.upmc.edu) is one of the first major project-based initiatives stemming from the Pennsylvania Cancer Alliance that was funded for four years by the Department of Health of the Commonwealth of Pennsylvania. The objective of this was to initiate a prototype biorepository and bioinformatics infrastructure with a robust data warehouse by developing a statewide data model (1) for bioinformatics and a repository of serum and tissue samples; (2) a data model for biomarker data storage; and (3) a public access website for disseminating research results and bioinformatics tools. The members of the Consortium cooperate closely, exploring the opportunity for sharing clinical, genomic and other bioinformatics data on patient samples in oncology, for the purpose of developing collaborative research programs across cancer research institutions in Pennsylvania. The Consortium’s intention was to establish a virtual repository of many clinical specimens residing in various centers across the state, in order to make them available for research. One of our primary goals was to facilitate the identification of cancer-specific biomarkers and encourage collaborative research efforts among the participating centers. Methods: The PCABC has developed unique partnerships so that every region of the state can effectively contribute and participate. It includes over 80 individuals from 14 organizations, and plans to expand to partners outside the State. This has created a network of researchers, clinicians, bioinformaticians, cancer registrars, program directors, and executives from academic and community health systems, as well as external corporate partners - all working together to accomplish a common mission. The various sub-committees have developed a common IRB protocol template, common data elements for standardizing data collections for three organ sites, intellectual property

  15. Role of race in oncogenic driver prevalence and outcomes in lung adenocarcinoma: Results from the Lung Cancer Mutation Consortium.

    PubMed

    Steuer, Conor E; Behera, Madhusmita; Berry, Lynne; Kim, Sungjin; Rossi, Michael; Sica, Gabriel; Owonikoko, Taofeek K; Johnson, Bruce E; Kris, Mark G; Bunn, Paul A; Khuri, Fadlo R; Garon, Edward B; Ramalingam, Suresh S

    2016-03-01

    The discovery of oncogenic drivers has ushered in a new era for lung cancer, but the role of these mutations in different racial/ethnic minorities has been understudied. The Lung Cancer Mutation Consortium 1 (LCMC1) database was investigated to evaluate the frequency and impact of oncogenic drivers in lung adenocarcinomas in the racial/ethnic minority patient population. Patients with metastatic lung adenocarcinomas from 14 US sites were enrolled in the LCMC1. Tumor samples were collected from 2009 through 2012 with multiplex genotyping performed on 10 oncogenic drivers (KRAS, epidermal growth factor receptor [EGFR], anaplastic lymphoma kinase (ALK) rearrangements, ERBB2 [formerly human epidermal growth factor receptor 2], BRAF, PIK3CA, MET amplification, NRAS, MEK1, and AKT1). Patients were classified as white, Asian, African American (AA), or Latino. The driver mutation frequency, the treatments, and the survival from diagnosis were determined. One thousand seven patients were included. Whites represented the majority (n = 838); there were 60 AAs, 48 Asians, and 28 Latinos. Asian patients had the highest rate of oncogenic drivers with 81% (n = 39), and they were followed by Latinos with 68% (n = 19), whites with 61% (n = 511), and AAs with 53% (n = 32). For AAs, the EGFR mutation frequency was 22%, the KRAS frequency was 17%, and the ALK frequency was 4%. Asian patients were most likely to receive targeted therapies (51% vs 27% for AAs). There were no significant differences in overall survival. Differences were observed in the prevalence of oncogenic drivers in lung adenocarcinomas and in subsequent treatments among racial groups. The lowest frequency of drivers was seen for AA patients; however, more than half of AA patients had a driver, and those treated with targeted therapy had outcomes similar to those of other races. Cancer 2016;122:766-772. © 2015 American Cancer Society. © 2015 American Cancer Society.

  16. Challenges in initiating and conducting personalized cancer therapy trials: perspectives from WINTHER, a Worldwide Innovative Network (WIN) Consortium trial.

    PubMed

    Rodon, J; Soria, J C; Berger, R; Batist, G; Tsimberidou, A; Bresson, C; Lee, J J; Rubin, E; Onn, A; Schilsky, R L; Miller, W H; Eggermont, A M; Mendelsohn, J; Lazar, V; Kurzrock, R

    2015-08-01

    Advances in 'omics' technology and targeted therapeutic molecules are together driving the incorporation of molecular-based diagnostics into the care of patients with cancer. There is an urgent need to assess the efficacy of therapy determined by molecular matching of patients with particular targeted therapies. WINTHER is a clinical trial that uses cutting edge genomic and transcriptomic assays to guide treatment decisions. Through the lens of this ambitious multinational trial (five countries, six sites) coordinated by the Worldwide Innovative Networking Consortium for personalized cancer therapy, we discovered key challenges in initiation and conduct of a prospective, omically driven study. To date, the time from study concept to activation has varied between 19 months at Gustave Roussy Cancer Campus in France to 30 months at the Segal Cancer Center, McGill University (Canada). It took 3+ years to be able to activate US sites due to national regulatory hurdles. Access to medications proposed by the molecular analysis remains a major challenge, since their availability through active clinical trials is highly variable over time within sites and across the network. Rules regarding the off-label use of drugs, or drugs not yet approved at all in some countries, pose a further challenge, and many biopharmaceutical companies lack a simple internal mechanism to supply the drugs even if they wish to do so. These various obstacles should be addressed to test and then implement precision medicine in cancer. © 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.

  17. A case-control analysis of oral contraceptive use and breast cancer subtypes in the African American Breast Cancer Epidemiology and Risk Consortium.

    PubMed

    Bethea, Traci N; Rosenberg, Lynn; Hong, Chi-Chen; Troester, Melissa A; Lunetta, Kathryn L; Bandera, Elisa V; Schedin, Pepper; Kolonel, Laurence N; Olshan, Andrew F; Ambrosone, Christine B; Palmer, Julie R

    2015-02-21

    Recent oral contraceptive (OC) use has been consistently associated with increased risk of breast cancer, but evidence on specific breast cancer subtypes is sparse. We investigated recency and duration of OC use in relation to molecular subtypes of breast cancer in a pooled analysis of data from the African American Breast Cancer Epidemiology and Risk Consortium. The study included 1,848 women with estrogen receptor-positive (ER+) breast cancer, 1,043 with ER-negative (ER-) breast cancer (including 494 triple negative (TN) tumors, which do not have receptors for estrogen, progesterone, and human epidermal growth factor 2), and 10,044 controls. Multivariable polytomous logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for exposure categories relative to never use, controlling for potential confounding variables. OC use within the previous 5 years was associated with increased risk of ER+ (OR 1.46, 95% CI 1.18 to 1.81), ER- (OR 1.57, 95% CI 1.22 to 1.43), and TN (OR 1.78, 95% CI 1.25 to 2.53) breast cancer. The risk declined after cessation of use but was apparent for ER+ cancer for 15 to 19 years after cessation and for ER- breast cancer for an even longer interval after cessation. Long duration of use was also associated with increased risk of each subtype, particularly ER-. Our results suggest that OC use, particularly recent use of long duration, is associated with an increased risk of ER+, ER-, and TN breast cancer in African American women. Research into mechanisms that explain these findings, especially the association with ER- breast cancer, is needed.

  18. Exposure to secondhand tobacco smoke and lung cancer by histological type: a pooled analysis of the International Lung Cancer Consortium (ILCCO)

    PubMed Central

    Kim, Claire H; Lee, Yuan-Chin Amy; Hung, Rayjean J; McNallan, Sheila R; Cote, Michele L; Lim, Wei-Yen; Chang, Shen-Chih; Kim, Jin Hee; Ugolini, Donatella; Chen, Ying; Liloglou, Triantafillos; Andrew, Angeline S; Onega, Tracy; Duell, Eric J; Field, John K; Lazarus, Philip; Le Marchand, Loic; Neri, Monica; Vineis, Paolo; Kiyohara, Chikako; Hong, Yun-Chul; Morgenstern, Hal; Matsuo, Keitaro; Tajima, Kazuo; Christiani, David C; McLaughlin, John R; Bencko, Vladimir; Holcatova, Ivana; Boffetta, Paolo; Brennan, Paul; Fabianova, Eleonora; Foretova, Lenka; Janout, Vladimir; Lissowska, Jolanta; Mates, Dana; Rudnai, Peter; Szeszenia-Dabrowska, Neonila; Mukeria, Anush; Zaridze, David; Seow, Adeline; Schwartz, Ann G; Yang, Ping; Zhang, Zuo-Feng

    2014-01-01

    While the association between exposure to secondhand smoke and lung cancer risk is well established, few studies with sufficient power have examined the association by histological type. In this study, we evaluated the secondhand smoke-lung cancer relationship by histological type based on pooled data from 18 case-control studies in the International Lung Cancer Consortium (ILCCO), including 2,504 cases and 7,276 controls who were never smokers and 10,184 cases and 7,176 controls who were ever smokers. We used multivariable logistic regression, adjusting for age, sex, race/ethnicity, smoking status, pack-years of smoking, and study. Among never smokers, the odds ratios (OR) comparing those ever exposed to secondhand smoke with those never exposed were 1.31 (95% CI: 1.17–1.45) for all histological types combined, 1.26 (95% CI: 1.10–1.44) for adenocarcinoma, 1.41 (95% CI: 0.99–1.99) for squamous cell carcinoma, 1.48 (95% CI: 0.89–2.45) for large cell lung cancer, and 3.09 (95% CI: 1.62–5.89) for small cell lung cancer. The estimated association with secondhand smoke exposure was greater for small cell lung cancer than for non-small cell lung cancers (OR=2.11, 95% CI: 1.11–4.04). This analysis is the largest to date investigating the relation between exposure to secondhand smoke and lung cancer. Our study provides more precise estimates of the impact of secondhand smoke on the major histological types of lung cancer, indicates the association with secondhand smoke is stronger for small cell lung cancer than for the other histological types, and suggests the importance of intervention against exposure to secondhand smoke in lung cancer prevention. PMID:24615328

  19. Exposure to secondhand tobacco smoke and lung cancer by histological type: a pooled analysis of the International Lung Cancer Consortium (ILCCO).

    PubMed

    Kim, Claire H; Lee, Yuan-Chin Amy; Hung, Rayjean J; McNallan, Sheila R; Cote, Michele L; Lim, Wei-Yen; Chang, Shen-Chih; Kim, Jin Hee; Ugolini, Donatella; Chen, Ying; Liloglou, Triantafillos; Andrew, Angeline S; Onega, Tracy; Duell, Eric J; Field, John K; Lazarus, Philip; Le Marchand, Loic; Neri, Monica; Vineis, Paolo; Kiyohara, Chikako; Hong, Yun-Chul; Morgenstern, Hal; Matsuo, Keitaro; Tajima, Kazuo; Christiani, David C; McLaughlin, John R; Bencko, Vladimir; Holcatova, Ivana; Boffetta, Paolo; Brennan, Paul; Fabianova, Eleonora; Foretova, Lenka; Janout, Vladimir; Lissowska, Jolanta; Mates, Dana; Rudnai, Peter; Szeszenia-Dabrowska, Neonila; Mukeria, Anush; Zaridze, David; Seow, Adeline; Schwartz, Ann G; Yang, Ping; Zhang, Zuo-Feng

    2014-10-15

    While the association between exposure to secondhand smoke and lung cancer risk is well established, few studies with sufficient power have examined the association by histological type. In this study, we evaluated the secondhand smoke-lung cancer relationship by histological type based on pooled data from 18 case-control studies in the International Lung Cancer Consortium (ILCCO), including 2,504 cases and 7,276 control who were never smokers and 10,184 cases and 7,176 controls who were ever smokers. We used multivariable logistic regression, adjusting for age, sex, race/ethnicity, smoking status, pack-years of smoking, and study. Among never smokers, the odds ratios (OR) comparing those ever exposed to secondhand smoke with those never exposed were 1.31 (95% CI: 1.17-1.45) for all histological types combined, 1.26 (95% CI: 1.10-1.44) for adenocarcinoma, 1.41 (95% CI: 0.99-1.99) for squamous cell carcinoma, 1.48 (95% CI: 0.89-2.45) for large cell lung cancer, and 3.09 (95% CI: 1.62-5.89) for small cell lung cancer. The estimated association with secondhand smoke exposure was greater for small cell lung cancer than for nonsmall cell lung cancers (OR=2.11, 95% CI: 1.11-4.04). This analysis is the largest to date investigating the relation between exposure to secondhand smoke and lung cancer. Our study provides more precise estimates of the impact of secondhand smoke on the major histological types of lung cancer, indicates the association with secondhand smoke is stronger for small cell lung cancer than for the other histological types, and suggests the importance of intervention against exposure to secondhand smoke in lung cancer prevention. © 2014 UICC.

  20. Variation in Screening Abnormality Rates and Follow-Up of Breast, Cervical and Colorectal Cancer Screening within the PROSPR Consortium.

    PubMed

    Tosteson, Anna N A; Beaber, Elisabeth F; Tiro, Jasmin; Kim, Jane; McCarthy, Anne Marie; Quinn, Virginia P; Doria-Rose, V Paul; Wheeler, Cosette M; Barlow, William E; Bronson, Mackenzie; Garcia, Michael; Corley, Douglas A; Haas, Jennifer S; Halm, Ethan A; Kamineni, Aruna; Rutter, Carolyn M; Tosteson, Tor D; Trentham-Dietz, Amy; Weaver, Donald L

    2016-04-01

    Primary care providers and health systems have prominent roles in guiding effective cancer screening. To characterize variation in screening abnormality rates and timely initial follow-up for common cancer screening tests. Population-based cohort undergoing screening in 2011, 2012, or 2013 at seven research centers comprising the National Cancer Institute-sponsored Population-based Research Optimizing Screening through Personalized Regimens (PROSPR) consortium. Adults undergoing mammography with or without digital breast tomosynthesis (n = 97,683 ages 40-75 years), fecal occult blood or fecal immunochemical tests (n = 759,553 ages 50-75 years), or Papanicolaou with or without human papillomavirus tests (n = 167,330 ages 21-65 years). Breast, colorectal, or cervical cancer screening. Abnormality rates per 1000 screens; percentage with timely initial follow-up (within 90 days, except 9-month window for BI-RADS 3). Primary care clinic-level variation in percentage with screening abnormality and percentage with timely initial follow-up. There were 10,248/97,683 (104.9 per 1000) abnormal breast cancer screens, 35,847/759,553 (47.2 per 1000) FOBT/FIT-positive colorectal cancer screens, and 13,266/167,330 (79.3 per 1000) abnormal cervical cancer screens. The percentage with timely follow-up was 93.2 to 96.7 % for breast centers, 46.8 to 68.7  % for colorectal centers, and 46.6 % for the cervical cancer screening center (low-grade squamous intraepithelial lesions or higher). The primary care clinic variation (25th to 75th percentile) was smaller for the percentage with an abnormal screen (breast, 8.5-10.3 %; colorectal, 3.0-4.8 %; cervical, 6.3-9.9 %) than for the percentage with follow-up within 90 days (breast, 90.2-95.8 %; colorectal, 43.4-52.0 %; cervical, 29.6-61.4 %). Variation in both the rate of screening abnormalities and their initial follow-up was evident across organ sites and primary care clinics. This highlights an opportunity for improving the delivery of

  1. Replication of five prostate cancer loci identified in an Asian population--results from the NCI Breast and Prostate Cancer Cohort Consortium (BPC3).

    PubMed

    Lindström, Sara; Schumacher, Fredrick R; Campa, Daniele; Albanes, Demetrius; Andriole, Gerald; Berndt, Sonja I; Bueno-de-Mesquita, H Bas; Chanock, Stephen J; Diver, W Ryan; Ganziano, J Michael; Gapstur, Susan M; Giovannucci, Edward; Haiman, Christopher A; Henderson, Brian; Hunter, David J; Johansson, Mattias; Kolonel, Laurence N; Le Marchand, Loic; Ma, Jing; Stampfer, Meir; Stevens, Victoria L; Trichopoulos, Dimitrios; Virtamo, Jarmo; Willett, Walter C; Yeager, Meredith; Hsing, Ann W; Kraft, Peter

    2012-01-01

    A recent genome-wide association study (GWAS) of prostate cancer in a Japanese population identified five novel regions not previously discovered in other ethnicities. In this study, we attempt to replicate these five loci in a series of nested prostate cancer case-control studies of European ancestry. We genotyped five single-nucleotide polymorphism (SNP): rs13385191 (chromosome 2p24), rs12653946 (5p15), rs1983891 (6p21), rs339331 (6p22), and rs9600079 (13q22), in 7,956 prostate cancer cases and 8,148 controls from a series of nested case-control studies within the National cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3). We tested each SNP for association with prostate cancer risk and assessed whether associations differed with respect to disease severity and age of onset. Four SNPs (rs13385191, rs12653946, rs1983891, and rs339331) were significantly associated with prostate cancer risk (P values ranging from 0.01 to 1.1 × 10(-5)). Allele frequencies and ORs were overall lower in our population of European descent than in the discovery Asian population. SNP rs13385191 (C2orf43) was only associated with low-stage disease (P = 0.009, case-only test). No other SNP showed association with disease severity or age of onset. We did not replicate the 13q22 SNP, rs9600079 (P = 0.62). Four SNPs associated with prostate cancer risk in an Asian population are also associated with prostate cancer risk in men of European descent. This study illustrates the importance of evaluation of prostate cancer risk markers across ethnic groups.

  2. Increased risk of lung cancer in individuals with a family history of the disease: A pooled analysis from the International Lung Cancer Consortium

    PubMed Central

    Coté, Michele L.; Liu, Mei; Bonassi, Stefano; Neri, Monica; Schwartz, Ann G.; Christiani, David C.; Spitz, Margaret R.; Muscat, Joshua E.; Rennert, Gad; Aben, Katja K.; Andrew, Angeline S.; Bencko, Vladimir; Bickeböller, Heike; Boffetta, Paolo; Brennan, Paul; Brenner, Hermann; Duell, Eric J.; Fabianova, Eleonora; Field, John K.; Foretova, Lenka; Friis, Søren; Harris, Curtis C.; Holcatova, Ivana; Hong, Yun-Chul; Isla, Dolores; Janout, Vladimir; Kiemeney, Lambertus A.; Kiyohara, Chikako; Lan, Qing; Lazarus, Philip; Lissowska, Jolanta; Marchand, Loic Le; Mates, Dana; Matsuo, Keitaro; Mayordomo, Jose I.; McLaughlin, John R.; Morgenstern, Hal; Müeller, Heiko; Orlow, Irene; Park, Bernard J.; Pinchev, Mila; Raji, Olaide Y.; Rennert, Hedy S.; Rudnai, Peter; Seow, Adeline; Stucker, Isabelle; Szeszenia-Dabrowska, Neonila; Teare, M. Dawn; Tjønnelan, Anne; Ugolini, Donatella; van der Heijden, Henricus F.M.; Wichmann, Erich; Wiencke, John K.; Woll, Penella J.; Yang, Ping; Zaridze, David; Zhang, Zuo-Feng; Etzel, Carol J.; Hung, Rayjean J.

    2012-01-01

    Background and Methods Familial aggregation of lung cancer exists after accounting for cigarette smoking. However, the extent to which family history affects risk by smoking status, histology, relative type and ethnicity is not well described. This pooled analysis included 24 case-control studies in the International Lung Cancer Consortium. Each study collected age of onset/interview, gender, race/ethnicity, cigarette smoking, histology and first-degree family history of lung cancer. Data from 24,380 lung cancer cases and 23,305 healthy controls were analyzed. Unconditional logistic regression models and generalized estimating equations were used to estimate odds ratios and 95% confidence intervals. Results Individuals with a first-degree relative with lung cancer had a 1.51-fold increase in risk of lung cancer, after adjustment for smoking and other potential confounders(95% CI: 1.39, 1.63). The association was strongest for those with a family history in a sibling, after adjustment (OR=1.82, 95% CI: 1.62, 2.05). No modifying effect by histologic type was found. Never smokers showed a lower association with positive familial history of lung cancer (OR=1.25, 95% CI: 1.03, 1.52), slightly stronger for those with an affected sibling (OR=1.44, 95% CI: 1.07, 1.93), after adjustment. Conclusions The increased risk among never smokers and similar magnitudes of the effect of family history on lung cancer risk across histological types suggests familial aggregation of lung cancer is independent of those associated with cigarette smoking. While the role of genetic variation in the etiology of lung cancer remains to be fully characterized, family history assessment is immediately available and those with a positive history represent a higher risk group. PMID:22436981

  3. COGENT (COlorectal cancer GENeTics): an international consortium to study the role of polymorphic variation on the risk of colorectal cancer

    PubMed Central

    Tomlinson, I P M; Dunlop, M; Campbell, H; Zanke, B; Gallinger, S; Hudson, T; Koessler, T; Pharoah, P D; Niittymäkix, I; Tuupanenx, S; Aaltonen, L A; Hemminki, K; Lindblom, A; Försti, A; Sieber, O; Lipton, L; van Wezel, T; Morreau, H; Wijnen, J T; Devilee, P; Matsuda, K; Nakamura, Y; Castellví-Bel, S; Ruiz-Ponte, C; Castells, A; Carracedo, A; Ho, J W C; Sham, P; Hofstra, R M W; Vodicka, P; Brenner, H; Hampe, J; Schafmayer, C; Tepel, J; Schreiber, S; Völzke, H; Lerch, M M; Schmidt, C A; Buch, S; Moreno, V; Villanueva, C M; Peterlongo, P; Radice, P; Echeverry, M M; Velez, A; Carvajal-Carmona, L; Scott, R; Penegar, S; Broderick, P; Tenesa, A; Houlston, R S

    2009-01-01

    It is now recognised that a part of the inherited risk of colorectal cancer (CRC) can be explained by the co-inheritance of low-penetrance genetic variants. The accumulated experience to date in identifying these variants has served to highlight difficulties in conducting statistically and methodologically rigorous studies and follow-up analyses. The COGENT (COlorectal cancer GENeTics) consortium includes 20 research groups in Europe, Australia, the Americas, China and Japan. The overarching goal of COGENT is to identify and characterise low-penetrance susceptibility variants for CRC through association-based analyses. In this study, we review the rationale for identifying low-penetrance variants for CRC and our proposed strategy for establishing COGENT. PMID:19920828

  4. Prostate cancer in East Asia: evolving trend over the last decade

    PubMed Central

    Zhu, Yao; Wang, Hong-Kai; Qu, Yuan-Yuan; Ye, Ding-Wei

    2015-01-01

    Prostate cancer is now becoming an emerging health priority in East Asia. Most of our current knowledge on Prostate cancer has been generated from studies conducted in Western population; however, there is considerable heterogeneity of Prostate cancer between East and West. In this article, we reviewed epidemiologic trends, risk factors, disease characteristics and management of Prostate cancer in East Asian population over the last decade. Growing evidence from East Asia suggests an important role of genetic and environmental risk factors interactions in the carcinogenesis of Prostate cancer. Exposure to westernized diet and life style and improvement in health care in combination contribute substantially to the increasing epidemic in this region. Diagnostic and treatment guidelines in East Asia are largely based on Western knowledge. Although there is a remarkable improvement in the outcome over the last decade, ample evidence suggests an inneglectable difference in diagnostic accuracy, treatment efficacy and adverse events between different populations. The knowledge from western countries should be calibrated in the Asian setting to provide a better race-based treatment approach. In this review, we intend to reveal the evolving trend of Prostate cancer in the last decade, in order to gain evidence to improve Prostate cancer prevention and control in East Asia. PMID:25080928

  5. Replication of five prostate cancer loci identified in an Asian population – Results from the NCI Breast and Prostate Cancer Cohort Consortium (BPC3)

    PubMed Central

    Lindstrom, Sara; Schumacher, Fredrick R.; Campa, Daniele; Albanes, Demetrius; Andriole, Gerald; Berndt, Sonja I.; Bueno-de-Mesquita, H. Bas; Chanock, Stephen J.; Diver, W. Ryan; Ganziano, J. Michael; Gapstur, Susan M.; Giovannucci, Edward; Haiman, Christopher A.; Henderson, Brian; Hunter, David J; Johansson, Mattias; Kolonel, Laurence N.; Le Marchand, Loic; Ma, Jing; Stampfer, Meir; Stevens, Victoria L.; Trichopoulos, Dimitrios; Virtamo, Jarmo; Willett, Walter C.; Yeager, Meredith; Hsing, Ann W.; Kraft, Peter

    2011-01-01

    Background A recent Genome-Wide Association Study (GWAS) of prostate cancer in a Japanese population identified five novel regions not previously discovered in other ethnicities. In this study, we attempt to replicate these five loci in a series of nested prostate cancer case-control studies of European ancestry. Methods We genotyped five SNPs: rs13385191 (chromosome 2p24), rs12653946 (5p15), rs1983891 (6p21), rs339331 (6p22) and rs9600079 (13q22), in 7,956 prostate cancer cases and 8,148 controls from a series of nested case-control studies within the NCI Breast and Prostate Cancer Cohort Consortium (BPC3). We tested each SNP for association with prostate cancer risk and assessed if associations differed with respect to disease severity and age of onset. Results Four SNPs (rs13385191, rs12653946, rs1983891 and rs339331) were significantly associated with prostate cancer risk (p-values ranging from 0.01 to 1.1×10-5). Allele frequencies and odds ratios were overall lower in our population of European descent compared to the discovery Asian population. SNP rs13385191 (C2orf43) was only associated with low-stage disease (p=0.009, case-only test). No other SNP showed association with disease severity or age of onset. We did not replicate the 13q22 SNP, rs9600079 (p=0.62). Conclusions Four SNPs associated with prostate cancer risk in an Asian population are also associated with prostate cancer risk in men of European descent. Impact This study illustrates the importance of evaluation of prostate cancer risk markers across ethnic groups. PMID:22056501

  6. Mouthwash use and cancer of the head and neck: a pooled analysis from the International Head and Neck Cancer Epidemiology Consortium.

    PubMed

    Boffetta, Paolo; Hayes, Richard B; Sartori, Samantha; Lee, Yuan-Chin A; Muscat, Joshua; Olshan, Andrew; Winn, Deborah M; Castellsagué, Xavier; Zhang, Zuo-Feng; Morgenstern, Hal; Chen, Chu; Schwartz, Stephen M; Vaughan, Thomas L; Wunsch-Filho, Victor; Purdue, Mark; Koifman, Sergio; Curado, Maria P; Vilensky, Marta; Gillison, Maura; Fernandez, Leticia; Menezes, Ana; Daudt, Alexander W; Schantz, Stimson; Yu, Guopei; D'Souza, Gypsyamber; Haddad, Robert I; La Vecchia, Carlo; Hashibe, Mia

    2016-07-01

    Most mouthwashes contain alcohol, a known cause of head and neck cancer (oral cavity, pharynx, larynx), likely through the carcinogenic activity of acetaldehyde, formed in the oral cavity from alcohol. We carried out a pooled analysis of 8981 cases of head and neck cancer and 10 090 controls from 12 case-control studies with comparable information on mouthwash use in the International Head and Neck Cancer Epidemiology Consortium. Logistic regression was used to assess the association of mouthwash use with cancers of the oral cavity, oropharynx, hypopharynx, and larynx, adjusting for study, age, sex, pack-years of tobacco smoking, number of alcoholic drinks/day, and education. Compared with never users of mouthwash, the odds ratio (OR) of all head and neck cancers was 1.01 [95% confidence interval (CI): 0.94-1.08] for ever users, based on 12 studies. The corresponding ORs of cancer of the oral cavity and oropharynx were 1.11 (95% CI: 1.00-1.23) and 1.28 (95% CI: 1.06-1.56), respectively. OR for all head and neck cancer was 1.15 (95% CI: 1.01-1.30) for use for more than 35 years, based on seven studies (P for linear trend=0.01), and OR 1.31 (95% CI: 1.09-1.58) for use more than one per day, based on five studies (P for linear trend <0.001). Although limited by the retrospective nature of the study and the limited ability to assess risks of mouthwash use in nonusers of tobacco and alcohol, this large investigation shows potential risks for head and neck cancer subsites and in long-term and frequent users of mouthwash. This pooled analysis provides the most precise estimate of the association between mouthwash use and head and neck cancer.

  7. Genetic variation in the vitamin d pathway in relation to risk of prostate cancer--results from the breast and prostate cancer cohort consortium.

    PubMed

    Mondul, Alison M; Shui, Irene M; Yu, Kai; Travis, Ruth C; Stevens, Victoria L; Campa, Daniele; Schumacher, Frederick R; Ziegler, Regina G; Bueno-de-Mesquita, H Bas; Berndt, Sonja; Crawford, E D; Gapstur, Susan M; Gaziano, J Michael; Giovannucci, Edward; Haiman, Christopher A; Henderson, Brian E; Hunter, David J; Johansson, Mattias; Key, Timothy J; Le Marchand, Loïc; Lindström, Sara; McCullough, Marjorie L; Navarro, Carmen; Overvad, Kim; Palli, Domenico; Purdue, Mark; Stampfer, Meir J; Weinstein, Stephanie J; Willett, Walter C; Yeager, Meredith; Chanock, Stephen J; Trichopoulos, Dimitrios; Kolonel, Laurence N; Kraft, Peter; Albanes, Demetrius

    2013-04-01

    Studies suggest that vitamin D status may be associated with prostate cancer risk although the direction and strength of this association differs between experimental and observational studies. Genome-wide association studies have identified genetic variants associated with 25-hydroxyvitamin D [25(OH)D] status. We examined prostate cancer risk in relation to single-nucleotide polymorphisms (SNP) in four genes shown to predict circulating levels of 25(OH)D. SNP markers localized to each of four genes (GC, CYP24A1, CYP2R1, and DHCR7) previously associated with 25(OH)D were genotyped in 10,018 cases and 11,052 controls from the National Cancer Institute (NCI) Breast and Prostate Cancer Cohort Consortium. Logistic regression was used to estimate the individual and cumulative association between genetic variants and risk of overall and aggressive prostate cancer. We observed a decreased risk of aggressive prostate cancer among men with the allele in rs6013897 near CYP24A1 associated with lower serum 25(OH)D [per A allele, OR, 0.86; 95% confidence interval (CI), 0.80-0.93; Ptrend = 0.0002) but an increased risk for nonaggressive disease (per A allele: OR, 1.10; 95% CI, 1.04-1.17; Ptrend = 0.002). Examination of a polygenic score of the four SNPs revealed statistically significantly lower risk of aggressive prostate cancer among men with a greater number of low vitamin D alleles (OR for 6-8 vs. 0-1 alleles, 0.66; 95% CI, 0.44-0.98; Ptrend = 0.003). In this large, pooled analysis, genetic variants related to lower 25(OH)D levels were associated with a decreased risk of aggressive prostate cancer. Our genetic findings do not support a protective association between loci known to influence vitamin D levels and prostate cancer risk.

  8. Analysis of Xq27-28 linkage in the international consortium for prostate cancer genetics (ICPCG) families.

    PubMed

    Bailey-Wilson, Joan E; Childs, Erica J; Cropp, Cheryl D; Schaid, Daniel J; Xu, Jianfeng; Camp, Nicola J; Cannon-Albright, Lisa A; Farnham, James M; George, Asha; Powell, Isaac; Carpten, John D; Giles, Graham G; Hopper, John L; Severi, Gianluca; English, Dallas R; Foulkes, William D; Mæhle, Lovise; Møller, Pål; Eeles, Rosalind; Easton, Douglas; Guy, Michelle; Edwards, Steve; Badzioch, Michael D; Whittemore, Alice S; Oakley-Girvan, Ingrid; Hsieh, Chih-Lin; Dimitrov, Latchezar; Stanford, Janet L; Karyadi, Danielle M; Deutsch, Kerry; McIntosh, Laura; Ostrander, Elaine A; Wiley, Kathleen E; Isaacs, Sarah D; Walsh, Patrick C; Thibodeau, Stephen N; McDonnell, Shannon K; Hebbring, Scott; Lange, Ethan M; Cooney, Kathleen A; Tammela, Teuvo L J; Schleutker, Johanna; Maier, Christiane; Bochum, Sylvia; Hoegel, Josef; Grönberg, Henrik; Wiklund, Fredrik; Emanuelsson, Monica; Cancel-Tassin, Geraldine; Valeri, Antoine; Cussenot, Olivier; Isaacs, William B

    2012-06-19

    Genetic variants are likely to contribute to a portion of prostate cancer risk. Full elucidation of the genetic etiology of prostate cancer is difficult because of incomplete penetrance and genetic and phenotypic heterogeneity. Current evidence suggests that genetic linkage to prostate cancer has been found on several chromosomes including the X; however, identification of causative genes has been elusive. Parametric and non-parametric linkage analyses were performed using 26 microsatellite markers in each of 11 groups of multiple-case prostate cancer families from the International Consortium for Prostate Cancer Genetics (ICPCG). Meta-analyses of the resultant family-specific linkage statistics across the entire 1,323 families and in several predefined subsets were then performed. Meta-analyses of linkage statistics resulted in a maximum parametric heterogeneity lod score (HLOD) of 1.28, and an allele-sharing lod score (LOD) of 2.0 in favor of linkage to Xq27-q28 at 138 cM. In subset analyses, families with average age at onset less than 65 years exhibited a maximum HLOD of 1.8 (at 138 cM) versus a maximum regional HLOD of only 0.32 in families with average age at onset of 65 years or older. Surprisingly, the subset of families with only 2-3 affected men and some evidence of male-to-male transmission of prostate cancer gave the strongest evidence of linkage to the region (HLOD = 3.24, 134 cM). For this subset, the HLOD was slightly increased (HLOD = 3.47 at 134 cM) when families used in the original published report of linkage to Xq27-28 were excluded. Although there was not strong support for linkage to the Xq27-28 region in the complete set of families, the subset of families with earlier age at onset exhibited more evidence of linkage than families with later onset of disease. A subset of families with 2-3 affected individuals and with some evidence of male to male disease transmission showed stronger linkage signals. Our results suggest that the genetic basis

  9. Analysis of Xq27-28 linkage in the international consortium for prostate cancer genetics (ICPCG) families

    PubMed Central

    2012-01-01

    Background Genetic variants are likely to contribute to a portion of prostate cancer risk. Full elucidation of the genetic etiology of prostate cancer is difficult because of incomplete penetrance and genetic and phenotypic heterogeneity. Current evidence suggests that genetic linkage to prostate cancer has been found on several chromosomes including the X; however, identification of causative genes has been elusive. Methods Parametric and non-parametric linkage analyses were performed using 26 microsatellite markers in each of 11 groups of multiple-case prostate cancer families from the International Consortium for Prostate Cancer Genetics (ICPCG). Meta-analyses of the resultant family-specific linkage statistics across the entire 1,323 families and in several predefined subsets were then performed. Results Meta-analyses of linkage statistics resulted in a maximum parametric heterogeneity lod score (HLOD) of 1.28, and an allele-sharing lod score (LOD) of 2.0 in favor of linkage to Xq27-q28 at 138 cM. In subset analyses, families with average age at onset less than 65 years exhibited a maximum HLOD of 1.8 (at 138 cM) versus a maximum regional HLOD of only 0.32 in families with average age at onset of 65 years or older. Surprisingly, the subset of families with only 2–3 affected men and some evidence of male-to-male transmission of prostate cancer gave the strongest evidence of linkage to the region (HLOD = 3.24, 134 cM). For this subset, the HLOD was slightly increased (HLOD = 3.47 at 134 cM) when families used in the original published report of linkage to Xq27-28 were excluded. Conclusions Although there was not strong support for linkage to the Xq27-28 region in the complete set of families, the subset of families with earlier age at onset exhibited more evidence of linkage than families with later onset of disease. A subset of families with 2–3 affected individuals and with some evidence of male to male disease transmission showed stronger linkage

  10. Alcohol consumption and gastric cancer risk-A pooled analysis within the StoP project consortium.

    PubMed

    Rota, Matteo; Pelucchi, Claudio; Bertuccio, Paola; Matsuo, Keitaro; Zhang, Zuo-Feng; Ito, Hidemi; Hu, Jinfu; Johnson, Kenneth C; Palli, Domenico; Ferraroni, Monica; Yu, Guo-Pei; Muscat, Joshua; Lunet, Nuno; Peleteiro, Bárbara; Ye, Weimin; Song, Huan; Zaridze, David; Maximovitch, Dmitry; Guevara, Marcela; Fernández-Villa, Tania; Vioque, Jesus; Navarrete-Muñoz, Eva M; Wolk, Alicja; Orsini, Nicola; Bellavia, Andrea; Håkansson, Niclas; Mu, Lina; Persiani, Roberto; Kurtz, Robert C; Lagiou, Areti; Lagiou, Pagona; Galeone, Carlotta; Bonzi, Rossella; Boffetta, Paolo; Boccia, Stefania; Negri, Eva; La Vecchia, Carlo

    2017-11-15

    An association between heavy alcohol drinking and gastric cancer risk has been recently reported, but the issue is still open to discussion and quantification. We investigated the role of alcohol drinking on gastric cancer risk in the "Stomach cancer Pooling (StoP) Project," a consortium of epidemiological studies. A total of 9,669 cases and 25,336 controls from 20 studies from Europe, Asia and North America were included. We estimated summary odds-ratios (ORs) and the corresponding 95% confidence intervals (CIs) by pooling study-specific ORs using random-effects meta-regression models. Compared with abstainers, drinkers of up to 4 drinks/day of alcohol had no increase in gastric cancer risk, while the ORs were 1.26 (95% CI, 1.08-1.48) for heavy (>4 to 6 drinks/day) and 1.48 (95% CI 1.29-1.70) for very heavy (>6 drinks/day) drinkers. The risk for drinkers of >4 drinks/day was higher in never smokers (OR 1.87, 95% CI 1.35-2.58) as compared with current smokers (OR 1.14, 95% CI 0.93-1.40). Somewhat stronger associations emerged with heavy drinking in cardia (OR 1.61, 95% CI 1.11-2.34) than in non-cardia (OR 1.28, 95% CI 1.13-1.45) gastric cancers, and in intestinal-type (OR 1.54, 95% CI 1.20-1.97) than in diffuse-type (OR 1.29, 95% CI 1.05-1.58) cancers. The association was similar in strata of H. pylori infected (OR = 1.52, 95% CI 1.16-2.00) and noninfected subjects (OR = 1.69, 95% CI 0.95-3.01). Our collaborative pooled-analysis provides definite, more precise quantitative evidence than previously available of an association between heavy alcohol drinking and gastric cancer risk. © 2017 UICC.

  11. Ovarian Cancer and Reproductive System Biology: A Harvard Stem Cell Institution Consortium

    DTIC Science & Technology

    2010-12-01

    involving Lin28A /B and the tumor suppressor microRNA let-7 for roles in ovarian and germ cell tumor initiation and maintenance; and 6) performing...Cancer - The Lin28A /let-7 pathway in ovarian and reproductive system cancers It was also agreed that Stephen Cannistra would serve as a scientific...murine models of ovarian and germ cell cancers; 5) testing a novel genetic pathway involving Lin28A /B and the tumor suppressor microRNA let-7 for roles

  12. Regional Cancer Registries – 20 Years and Growing

    Cancer.gov

    The NCI, Center for Global Health (CGH), the University of California at Irvine, the Middle East Cancer Consortium, and the International Agency for Research on Cancer partnered in support of the training course, held in Ankara, Turkey this past October, on The Uses of Cancer Registry Data in Cancer Control Research.

  13. Development of the Ovarian Cancer Cohort Consortium: Risk Factor Associations by Heterogeneity of Disease

    DTIC Science & Technology

    2015-10-01

    primary ovarian cancer risk factors (e.g., oral contraceptive use, parity) by histology are complete and a manuscript is drafted and sent to co...associations of known and putative ovarian cancer risk factors, including (but not limited to) age, oral contraceptive use, tubal ligation, parity...duration, and type), use of oral contraceptives (ever/never, duration), tubal ligation, parity, hysterectomy status, oophorectomy status, age at menarche

  14. Parity, Lactation, and Breast Cancer Subtypes in African American Women: Results from the AMBER Consortium

    PubMed Central

    Viscidi, Emma; Troester, Melissa A.; Hong, Chi-Chen; Schedin, Pepper; Bethea, Traci N.; Bandera, Elisa V.; Borges, Virginia; McKinnon, Craig; Haiman, Christopher A.; Lunetta, Kathryn; Kolonel, Laurence N.; Rosenberg, Lynn; Olshan, Andrew F.; Ambrosone, Christine B.

    2014-01-01

    Background African American (AA) women have a disproportionately high incidence of estrogen receptor–negative (ER-) breast cancer, a subtype with a largely unexplained etiology. Because childbearing patterns also differ by race/ethnicity, with higher parity and a lower prevalence of lactation in AA women, we investigated the relation of parity and lactation to risk of specific breast cancer subtypes. Methods Questionnaire data from two cohort and two case-control studies of breast cancer in AA women were combined and harmonized. Case patients were classified as ER+ (n = 2446), ER- (n = 1252), or triple negative (ER-, PR-, HER2-; n = 567) based on pathology data; there were 14180 control patients. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated in polytomous logistic regression analysis with adjustment for study, age, reproductive and other risk factors. Results ORs for parity relative to nulliparity was 0.92 (95% CI = 0.81 to 1.03) for ER+, 1.33 (95% CI = 1.11 to 1.59) for ER-, and 1.37 (95% CI = 1.06 to 1.70) for triple-negative breast cancer. Lactation was associated with a reduced risk of ER- (OR = 0.81, 95% CI = 0.69 to 0.95) but not ER+ cancer. ER- cancer risk increased with each additional birth in women who had not breastfed, with an OR of 1.68 (95% CI = 1.15 to 2.44) for 4 or more births relative to one birth with lactation. Conclusions The findings suggest that parous women who have not breastfed are at increased risk of ER- and triple-negative breast cancer. Promotion of lactation may be an effective tool for reducing occurrence of the subtypes that contribute disproportionately to breast cancer mortality. PMID:25224496

  15. Circulating vitamin D, vitamin D-related genetic variation, and risk of fatal prostate cancer in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium.

    PubMed

    Shui, Irene M; Mondul, Alison M; Lindström, Sara; Tsilidis, Konstantinos K; Travis, Ruth C; Gerke, Travis; Albanes, Demetrius; Mucci, Lorelei A; Giovannucci, Edward; Kraft, Peter

    2015-06-15

    Evidence from experimental animal and cell line studies supports a beneficial role for vitamin D in prostate cancer (PCa). Although the results from human studies have been mainly null for overall PCa risk, there may be a benefit for survival. This study assessed the associations of circulating 25-hydroxyvitamin D (25(OH)D) and common variations in key vitamin D-related genes with fatal PCa. In a large cohort consortium, 518 fatal cases and 2986 controls with 25(OH)D data were identified. Genotyping information for 91 single-nucleotide polymorphisms (SNPs) in 7 vitamin D-related genes (vitamin D receptor, group-specific component, cytochrome P450 27A1 [CYP27A1], CYP27B1, CYP24A1, CYP2R1, and retinoid X receptor α) was available for 496 fatal cases and 3577 controls. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations of 25(OH)D and SNPs with fatal PCa. The study also tested for 25(OH)D-SNP interactions among 264 fatal cases and 1169 controls. No statistically significant relationship was observed between 25(OH)D and fatal PCa (OR for extreme quartiles, 0.86; 95% CI, 0.65-1.14; P for trend = .22) or the main effects of the SNPs and fatal PCa. There was evidence suggesting that associations of several SNPs, including 5 related to circulating 25(OH)D, with fatal PCa were modified by 25(OH)D. Individually, these associations did not remain significant after multiple testing; however, the P value for the set-based test for CYP2R1 was .002. Statistically significant associations were not observed for either 25(OH)D or vitamin D-related SNPs with fatal PCa. The effect modification of 25(OH)D associations by biologically plausible genetic variation may deserve further exploration. © 2015 American Cancer Society.

  16. Genetic Variation in the Vitamin D Pathway in Relation to Risk of Prostate Cancer – Results from Breast and Prostate Cancer Cohort Consortium (BPC3)

    PubMed Central

    Mondul, Alison M.; Shui, Irene M.; Yu, Kai; Travis, Ruth C.; Stevens, Victoria L.; Campa, Daniele; Schumacher, Frederick R.; Ziegler, Regina G.; Bueno-de-Mesquita, H. Bas; Berndt, Sonja; Crawford, E. D.; Gapstur, Susan M.; Gaziano, J. Michael; Giovannucci, Edward; Haiman, Christopher A.; Henderson, Brian E.; Hunter, David J.; Johansson, Mattias; Key, Timothy J.; Le Marchand, Loic; Lindström, Sara; McCullough, Marjorie L.; Navarro, Carmen; Overvad, Kim; Palli, Domenico; Purdue, Mark; Stampfer, Meir J.; Weinstein, Stephanie J.; Willett, Walter C.; Yeager, Meredith; Chanock, Stephen J.; Trichopoulos, Dimitrios; Kolonel, Laurence N.; Kraft, Peter; Albanes, Demetrius

    2013-01-01

    Background Studies suggest that vitamin D status may be associated with prostate cancer risk, although the direction and strength of this association differs between experimental and observational studies. Genome-wide association studies have identified genetic variants associated with 25-hydroxyvitamin D (25(OH)D) status. We examined prostate cancer risk in relation to SNPs in four genes shown to predict circulating levels of 25(OH)D. Methods SNP markers localized to each of four genes (GC, CYP24A1, CYP2R1, and DHCR7) previously associated with 25(OH)D were genotyped in 10,018 cases and 11,052 controls from the NCI Breast and Prostate Cancer Cohort Consortium. Logistic regression was used to estimate the individual and cumulative association between genetic variants and risk of overall and aggressive prostate cancer. Results We observed a decreased risk of aggressive prostate cancer among men with the allele in rs6013897 near CYP24A1 associated with lower serum 25(OH)D (per A allele, OR=0.86, 95%CI=0.80–0.93, p-trend=0.0002), but an increased risk for non-aggressive disease (per a allele: OR=1.10, 95%CI=1.04–1.17, p-trend=0.002). Examination of a polygenic score of the four SNPs revealed statistically significantly lower risk of aggressive prostate cancer among men with a greater number of low vitamin D alleles (OR for 6–8 vs. 0–1 alleles = 0.66, 95% CI = 0.44 – 0.98; p-trend=0.003). Conclusions In this large, pooled analysis, genetic variants related to lower 25(OH)D were associated with a decreased risk of aggressive prostate cancer. Impact Our genetic findings do not support a protective association between loci known to influence vitamin D levels and prostate cancer risk. PMID:23377224

  17. Insulin-like growth factor pathway genes and blood concentrations, dietary protein, and risk of prostate cancer in the NCI Breast and Prostate Cancer Cohort Consortium (BPC3)

    PubMed Central

    Tsilidis, Konstantinos K; Travis, Ruth C; Appleby, Paul N; Allen, Naomi E; Lindström, Sara; Albanes, Demetrius; Ziegler, Regina G; McCullough, Marjorie L; Siddiq, Afshan; Barricarte, Aurelio; Berndt, Sonja I; Bueno-de-Mesquita, H Bas; Chanock, Stephen J; Crawford, E David; Diver, W Ryan; Gapstur, Susan M; Giovannucci, Edward; Gu, Fangyi; Haiman, Christopher A; Hayes, Richard B; Hunter, David J; Johansson, Mattias; Kaaks, Rudolf; Kolonel, Laurence N; Kraft, Peter; Le Marchand, Loic; Overvad, Kim; Polidoro, Silvia; Riboli, Elio; Schumacher, Fredrick R; Stevens, Victoria L; Trichopoulos, Dimitrios; Virtamo, Jarmo; Willett, Walter C; Key, Timothy J

    2013-01-01

    It has been hypothesized that a high intake of dairy protein may increase prostate cancer risk by increasing the production of insulin-like growth factor 1 (IGF-1). Several single nucleotide polymorphisms (SNPs) have been weakly associated with circulating concentrations of IGF-1 and IGF binding protein 3 (IGFBP-3), but none of these SNPs was associated with risk of prostate cancer. We examined whether an association between 16 SNPs associated with circulating IGF-1 or IGFBP-3 concentrations and prostate cancer exists within subgroups defined by dietary protein intake in 5,253 cases and 4,963 controls of European ancestry within the NCI Breast and Prostate Cancer Cohort Consortium (BPC3). The BPC3 includes nested case-control studies within large North-American and European cohorts. Per allele odds ratios for prostate cancer for the SNPs were compared across tertiles of protein intake, which was expressed as the percentage of energy derived from total, animal, dairy or plant protein sources, using conditional logistic regression models. Total, animal, dairy and plant protein intakes were significantly positively associated with blood IGF-1 (P<0.01), but not with IGFBP-3 concentrations (P>0.10) or with risk of prostate cancer (P>0.20). After adjusting for multiple testing, the SNP-prostate cancer associations did not differ by intakes of protein, although two interactions by intake of plant protein were of marginal statistical significance (SSTR5 (somatostatin receptor 5) -rs197056 [uncorrected P for interaction, 0.001]; SSTR5-rs197057 [uncorrected P for interaction, 0.002]). We found no strong evidence that the associations between 16 IGF pathway SNPs and prostate cancer differed by intakes of dietary protein. PMID:23341348

  18. Nutrient-based dietary patterns and the risk of head and neck cancer: a pooled analysis in the International Head and Neck Cancer Epidemiology consortium

    PubMed Central

    Edefonti, V.; Hashibe, M.; Ambrogi, F.; Parpinel, M.; Bravi, F.; Talamini, R.; Levi, F.; Yu, G.; Morgenstern, H.; Kelsey, K.; McClean, M.; Schantz, S.; Zhang, Z.; Chuang, S.; Boffetta, P.; La Vecchia, C.; Decarli, A.

    2012-01-01

    Background The association between dietary patterns and head and neck cancer has rarely been addressed. Patients and methods We used individual-level pooled data from five case–control studies (2452 cases and 5013 controls) participating in the International Head and Neck Cancer Epidemiology consortium. A posteriori dietary patterns were identified through a principal component factor analysis carried out on 24 nutrients derived from study-specific food-frequency questionnaires. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using unconditional logistic regression models on quintiles of factor scores. Results We identified three major dietary patterns named ‘animal products and cereals’, ‘antioxidant vitamins and fiber’, and ‘fats’. The ‘antioxidant vitamins and fiber’ pattern was inversely related to oral and pharyngeal cancer (OR = 0.57, 95% CI 0.43–0.76 for the highest versus the lowest score quintile). The ‘animal products and cereals’ pattern was positively associated with laryngeal cancer (OR = 1.54, 95% CI 1.12–2.11), whereas the ‘fats’ pattern was inversely associated with oral and pharyngeal cancer (OR = 0.78, 95% CI 0.63–0.97) and positively associated with laryngeal cancer (OR = 1.69, 95% CI 1.22–2.34). Conclusions These findings suggest that diets rich in animal products, cereals, and fats are positively related to laryngeal cancer, and those rich in fruit and vegetables inversely related to oral and pharyngeal cancer. PMID:22123733

  19. Common genetic variants in prostate cancer risk prediction – Results from the NCI Breast and Prostate Cancer Cohort Consortium (BPC3)

    PubMed Central

    Lindström, Sara; Schumacher, Fredrick R.; Cox, David; Travis, Ruth C.; Albanes, Demetrius; Allen, Naomi E.; Andriole, Gerald; Berndt, Sonja I.; Boeing, Heiner; Bueno-de-Mesquita, H. Bas; Crawford, E. David; Diver, W. Ryan; Ganziano, J. Michael; Giles, Graham G.; Giovannucci, Edward; Gonzalez, Carlos A.; Henderson, Brian; Hunter, David J.; Johansson, Mattias; Kolonel, Laurence N.; Ma, Jing; Le Marchand, Loic; Pala, Valeria; Stampfer, Meir; Stram, Daniel O.; Thun, Michael J.; Tjonneland, Anne; Trichopoulos, Dimitrios; Virtamo, Jarmo; Weinstein, Stephanie J.; Willett, Walter C.; Yeager, Meredith; Hayes, Richard B.; Severi, Gianluca; Haiman, Christopher A.; Chanock, Stephen J.; Kraft, Peter

    2012-01-01

    Background One of the goals of personalized medicine is to generate individual risk profiles that could identify individuals in the population that exhibit high risk. The discovery of more than two-dozen independent SNP markers in prostate cancer has raised the possibility for such risk stratification. In this study, we evaluated the discriminative and predictive ability for prostate cancer risk models incorporating 25 common prostate cancer genetic markers, family history of prostate cancer and age. Methods We fit a series of risk models and estimated their performance in 7,509 prostate cancer cases and 7,652 controls within the NCI Breast and Prostate Cancer Cohort Consortium (BPC3). We also calculated absolute risks based on SEER incidence data. Results The best risk model (C-statistic=0.642) included individual genetic markers and family history of prostate cancer. We observed a decreasing trend in discriminative ability with advancing age (P=0.009), with highest accuracy in men younger than 60 years (C-statistic=0.679). The absolute ten-year risk for 50-year old men with a family history ranged from 1.6% (10th percentile of genetic risk) to 6.7% (90th percentile of genetic risk). For men without family history, the risk ranged from 0.8% (10th percentile) to 3.4% (90th percentile). Conclusions Our results indicate that incorporating genetic information and family history in prostate cancer risk models can be particularly useful for identifying younger men that might benefit from PSA screening. Impact Although adding genetic risk markers improves model performance, the clinical utility of these genetic risk models is limited. PMID:22237985

  20. Polymorphism in the GALNT1 Gene and Epithelial Ovarian Cancer in Non-Hispanic White Women: The Ovarian Cancer Association Consortium

    PubMed Central

    Phelan, Catherine M.; Tsai, Ya-Yu; Goode, Ellen L.; Vierkant, Robert A.; Fridley, Brooke L.; Beesley, Jonathan; Chen, Xiao Qing; Webb, Penelope M.; Chanock, Stephen; Cramer, Daniel W.; Moysich, Kirsten; Edwards, Robert P.; Chang-Claude, Jenny; Garcia-Closas, Montserrat; Yang, Hannah; Wang-Gohrke, Shan; Hein, Rebecca; Green, Adele C.; Lissowska, Jolanta; Carney, Michael E.; Lurie, Galina; Wilkens, Lynne R.; Ness, Roberta B.; Pearce, Celeste Leigh; Wu, Anna H.; Van Den Berg, David J.; Stram, Daniel O.; Terry, Kathryn L.; Whiteman, David C.; Whittemore, Alice S.; DiCioccio, Richard A.; McGuire, Valerie; Doherty, Jennifer A.; Rossing, Mary Anne; Anton-Culver, Hoda; Ziogas, Argyrios; Hogdall, Claus; Hogdall, Estrid; Kjaer, Susanne Krüger; Blaakaer, Jan; Quaye, Lydia; Ramus, Susan J.; Jacobs, Ian; Song, Honglin; Pharoah, Paul D.P.; Iversen, Edwin S.; Marks, Jeffrey R.; Pike, Malcolm C.; Gayther, Simon A.; Cunningham, Julie M.; Goodman, Marc T.; Schildkraut, Joellen M.; Chenevix-Trench, Georgia; Berchuck, Andrew; Sellers, Thomas A.

    2010-01-01

    Aberrant glycosylation is a well-described hallmark of cancer. In a previous ovarian cancer case control study that examined polymorphisms in 26 glycosylation-associated genes, we found strong statistical evidence (P = 0.00017) that women who inherited two copies of a single-nucleotide polymorphism in the UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyltransferase, GALNT1, had decreased ovarian cancer risk. The current study attempted to replicate this observation. The GALNT1 single-nucleotide polymorphism rs17647532 was genotyped in 6,965 cases and 8,377 controls from 14 studies forming the Ovarian Cancer Association Consortium. The fixed effects estimate per rs17647532 allele was null (odds ratio, 0.99; 95% confidence interval, 0.92–1.07). When a recessive model was fit, the results were unchanged. Test for hetero geneity of the odds ratios revealed consistency across the 14 replication sites but significant differences compared with the original study population (P = 0.03). This study underscores the need for replication of putative findings in genetic association studies. PMID:20142253

  1. CYP19A1 genetic variation in relation to prostate cancer risk and circulating sex hormone concentrations in men from the Breast and Prostate Cancer Cohort Consortium

    PubMed Central

    Travis, Ruth C.; Schumacher, Fredrick; Hirschhorn, Joel N.; Kraft, Peter; Allen, Naomi E.; Albanes, Demetrius; Berglund, Goran; Berndt, Sonja I.; Boeing, Heiner; Bueno-de-Mesquita, H. Bas; Calle, Eugenia E.; Chanock, Stephen; Dunning, Alison M.; Hayes, Richard; Feigelson, Heather Spencer; Gaziano, J. Michael; Giovannucci, Edward; Haiman, Christopher A.; Henderson, Brian E.; Kaaks, Rudolf; Kolonel, Laurence N.; Ma, Jing; Rodriguez, Laudina; Riboli, Elio; Stampfer, Meir; Stram, Daniel O.; Thun, Michael J.; Tjønneland, Anne; Trichopoulos, Dimitrios; Vineis, Paolo; Virtamo, Jarmo; Le Marchand, Loïc; Hunter, David J.

    2009-01-01

    Sex hormones, in particular the androgens, are important for the growth of the prostate gland and have been implicated in prostate cancer carcinogenesis, yet the determinants of endogenous steroid hormone levels remain poorly understood. Twin studies suggest a heritable component for circulating concentrations of sex hormones, although epidemiological evidence linking steroid hormone gene variants to prostate cancer is limited. Here we report on findings from a comprehensive study of genetic variation at the CYP19A1 locus in relation to prostate cancer risk and to circulating steroid hormone concentrations in men by the Breast and Prostate Cancer Cohort Consortium (BPC3), a large collaborative prospective study. The BPC3 systematically characterised variation in CYP19A1 by targeted resequencing and dense genotyping; selected haplotype-tagging single nucleotide polymorphisms (htSNPs) that efficiently predict common variants in U.S. and European whites, Latinos, Japanese Americans, and Native Hawaiians; and genotyped these htSNPs in 8,166 prostate cancer cases and 9,079 study-, age-, and ethnicity-matched controls. CYP19A1 htSNPs, two common missense variants and common haplotypes were not significantly associated with risk of prostate cancer. However, several htSNPs in linkage disequilibrium blocks 3 and 4 were significantly associated with a 5–10% difference in estradiol concentrations in men (association per copy of the two-SNP haplotype rs749292–rs727479 (A–A) versus noncarriers; P=1 × 10−5), and withinverse, although less marked changes, in free testosterone concentrations. These results suggest that although germline variation in CYP19A1 characterised by the htSNPs produces measurable differences in sex hormone concentrations in men, they do not substantially influence risk for prostate cancer. PMID:19789370

  2. Natural vitamin C intake and the risk of head and neck cancer: A pooled analysis in the International Head and Neck Cancer Epidemiology Consortium.

    PubMed

    Edefonti, Valeria; Hashibe, Mia; Parpinel, Maria; Turati, Federica; Serraino, Diego; Matsuo, Keitaro; Olshan, Andrew F; Zevallos, Jose P; Winn, Deborah M; Moysich, Kirsten; Zhang, Zuo-Feng; Morgenstern, Hal; Levi, Fabio; Kelsey, Karl; McClean, Michael; Bosetti, Cristina; Galeone, Carlotta; Schantz, Stimson; Yu, Guo-Pei; Boffetta, Paolo; Amy Lee, Yuan-Chin; Chuang, Shu-Chun; La Vecchia, Carlo; Decarli, Adriano

    2015-07-15

    Evidence of associations between single nutrients and head and neck cancer (HNC) is still more limited and less consistent than that for fruit and vegetables. However, clarification of the protective mechanisms of fruit and vegetables is important to our understanding of HNC etiology. We investigated the association between vitamin C intake from natural sources and cancer of the oral cavity/pharynx and larynx using individual-level pooled data from ten case-control studies (5,959 cases and 12,248 controls) participating in the International Head and Neck Cancer Epidemiology (INHANCE) consortium. After harmonization of study-specific exposure information via the residual method, adjusted odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using unconditional multiple logistic regression models on quintile categories of 'non-alcohol energy-adjusted' vitamin C intake. In the presence of heterogeneity of the estimated ORs among studies, we derived those estimates from generalized linear mixed models. Higher intakes of vitamin C were inversely related to oral and pharyngeal (OR = 0.54, 95% CI: 0.45-0.65, for the fifth quintile category versus the first one, p for trend<0.001) and laryngeal cancers (OR = 0.52, 95% CI: 0.40-0.68, p for trend = 0.006), although in the presence of heterogeneity among studies for both sites. Inverse associations were consistently observed for the anatomical subsites of oral and pharyngeal cancer, and across strata of age, sex, education, body mass index, tobacco, and alcohol, for both cancer sites. The inverse association of vitamin C intake from foods with HNC may reflect a protective effect on these cancers; however, we cannot rule out other explanations. © 2014 UICC.

  3. Cancer control programs in East Asia: evidence from the international literature.

    PubMed

    Moore, Malcolm A

    2014-07-01

    Cancer is a major cause of mortality and morbidity throughout the world, including the countries of North-East and South-East Asia. Assessment of burden through cancer registration, determination of risk and protective factors, early detection and screening, clinical practice, interventions for example in vaccination, tobacco cessation efforts and palliative care all should be included in comprehensive cancer control programs. The degree to which this is possible naturally depends on the resources available at local, national and international levels. The present review concerns elements of cancer control programs established in China, Taiwan, Korea, and Japan in North-East Asia, Viet Nam, Thailand, Malaysia, and Indonesia as representative larger countries of South-East Asia for comparison, using the published literature as a guide. While major advances have been made, there are still areas which need more attention, especially in South-East Asia, and international cooperation is essential if standard guidelines are to be generated to allow effective cancer control efforts throughout the Far East.

  4. Cancer Control Programs in East Asia: Evidence From the International Literature

    PubMed Central

    Moore, Malcolm A.

    2014-01-01

    Cancer is a major cause of mortality and morbidity throughout the world, including the countries of North-East and South-East Asia. Assessment of burden through cancer registration, determination of risk and protective factors, early detection and screening, clinical practice, interventions for example in vaccination, tobacco cessation efforts and palliative care all should be included in comprehensive cancer control programs. The degree to which this is possible naturally depends on the resources available at local, national and international levels. The present review concerns elements of cancer control programs established in China, Taiwan, Korea, and Japan in North-East Asia, Viet Nam, Thailand, Malaysia, and Indonesia as representative larger countries of South-East Asia for comparison, using the published literature as a guide. While major advances have been made, there are still areas which need more attention, especially in South-East Asia, and international cooperation is essential if standard guidelines are to be generated to allow effective cancer control efforts throughout the Far East. PMID:25139165

  5. Estrogen receptor beta rs1271572 polymorphism and invasive ovarian carcinoma risk: pooled analysis within the Ovarian Cancer Association Consortium.

    PubMed

    Lurie, Galina; Wilkens, Lynne R; Thompson, Pamela J; Shvetsov, Yurii B; Matsuno, Rayna K; Carney, Michael E; Palmieri, Rachel T; Wu, Anna H; Pike, Malcolm C; Pearce, Celeste L; Menon, Usha; Gentry-Maharaj, Aleksandra; Gayther, Simon A; Ramus, Susan J; Whittemore, Alice S; McGuire, Valerie; Sieh, Weiva; Pharoah, Paul D P; Song, Honglin; Gronwald, Jacek; Jakubowska, Anna; Cybulski, Cezary; Lubinski, Jan; Schildkraut, Joellen M; Berchuck, Andrew; Krüger Kjær, Susanne; Høgdall, Estrid; Fasching, Peter A; Beckmann, Matthias W; Ekici, Arif B; Hein, Alexander; Chenevix-Trench, Georgia; Webb, Penelope M; Beesley, Jonathan; Goodman, Marc T

    2011-01-01

    The association of ovarian carcinoma risk with the polymorphism rs1271572 in the estrogen receptor beta (ESR2) gene was examined in 4946 women with primary invasive ovarian carcinoma and 6582 controls in a pooled analysis of ten case-control studies within the Ovarian Cancer Association Consortium (OCAC). All participants were non-Hispanic white women. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression adjusted for site and age. Women with the TT genotype were at increased risk of ovarian carcinoma compared to carriers of the G allele (OR = 1.10; 95%; CI: 1.01-1.21; p = 0.04); the OR was 1.09 (CI: 0.99-1.20; p = 0.07) after excluding data from the center (Hawaii) that nominated this SNP for OCAC genotyping A stronger association of rs1271572 TT versus GT/GG with risk was observed among women aged ≤50 years versus older women (OR = 1.35; CI: 1.12-1.62; p = 0.002; p for interaction = 0.02) that remained statistically significant after excluding Hawaii data (OR = 1.34; CI: 1.11-1.61; p = 0.009). No heterogeneity of the association was observed by study, menopausal status, gravidity, parity, use of contraceptive or menopausal hormones, tumor histological type, or stage at diagnosis. This pooled analysis suggests that rs1271572 might influence the risk of ovarian cancer, in particular among younger women.

  6. Estrogen Receptor Beta rs1271572 Polymorphism and Invasive Ovarian Carcinoma Risk: Pooled Analysis within the Ovarian Cancer Association Consortium

    PubMed Central

    Lurie, Galina; Wilkens, Lynne R.; Thompson, Pamela J.; Shvetsov, Yurii B.; Matsuno, Rayna K.; Carney, Michael E.; Palmieri, Rachel T.; Wu, Anna H.; Pike, Malcolm C.; Pearce, Celeste L.; Menon, Usha; Gentry-Maharaj, Aleksandra; Gayther, Simon A.; Ramus, Susan J.; Whittemore, Alice S.; McGuire, Valerie; Sieh, Weiva; Pharoah, Paul D. P.; Song, Honglin; Gronwald, Jacek; Jakubowska, Anna; Cybulski, Cezary; Lubinski, Jan; Schildkraut, Joellen M.; Berchuck, Andrew; Krüger Kjær, Susanne; Høgdall, Estrid; Fasching, Peter A.; Beckmann, Matthias W.; Ekici, Arif B.; Hein, Alexander; Chenevix-Trench, Georgia; Webb, Penelope M.; Beesley, Jonathan; Goodman, Marc T.

    2011-01-01

    The association of ovarian carcinoma risk with the polymorphism rs1271572 in the estrogen receptor beta (ESR2) gene was examined in 4946 women with primary invasive ovarian carcinoma and 6582 controls in a pooled analysis of ten case-control studies within the Ovarian Cancer Association Consortium (OCAC). All participants were non-Hispanic white women. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression adjusted for site and age. Women with the TT genotype were at increased risk of ovarian carcinoma compared to carriers of the G allele (OR = 1.10; 95%; CI: 1.01–1.21; p = 0.04); the OR was 1.09 (CI: 0.99–1.20; p = 0.07) after excluding data from the center (Hawaii) that nominated this SNP for OCAC genotyping A stronger association of rs1271572 TT versus GT/GG with risk was observed among women aged ≤50 years versus older women (OR = 1.35; CI: 1.12–1.62; p = 0.002; p for interaction = 0.02) that remained statistically significant after excluding Hawaii data (OR = 1.34; CI: 1.11–1.61; p = 0.009). No heterogeneity of the association was observed by study, menopausal status, gravidity, parity, use of contraceptive or menopausal hormones, tumor histological type, or stage at diagnosis. This pooled analysis suggests that rs1271572 might influence the risk of ovarian cancer, in particular among younger women. PMID:21673961

  7. Development of the Ovarian Cancer Cohort Consortium: Risk Factor Associations by Heterogeneity of Disease

    DTIC Science & Technology

    2014-10-01

    postmenopausal hormone use, family history of ovarian cancer, BMI, height, analgesic use, and lifetime ovulatory cycles , differ by histologic...index, height, analgesic use, and lifetime ovulatory cycles , differ by (a) histologic subtype, (b) tumor dominance (as a surrogate for cell of origin...values ᝾ or >60 MENARCHE AND MENOPAUSE VARIABLES AGEMENARCHE Age in years when menstrual periods began .=unknown, or values ɝ or

  8. Genome-wide linkage analysis of 1233 prostate cancer pedigrees from the International Consortium for Prostate Cancer Genetics using novel sumLINK and sumLOD analyses

    PubMed Central

    Christensen, G. Bryce; Baffoe-Bonnie, Agnes B.; George, Asha; Powell, Isaac; Bailey-Wilson, Joan E.; Carpten, John D.; Giles, Graham G.; Hopper, John L.; Severi, Gianluca; English, Dallas R.; Foulkes, William D.; Maehle, Lovise; Moller, Pal; Eeles, Ros; Easton, Douglas; Badzioch, Michael D.; Whittemore, Alice S.; Oakley-Girvan, Ingrid; Hsieh, Chih-Lin; Dimitrov, Latchezar; Xu, Jianfeng; Stanford, Janet L.; Johanneson, Bo; Deutsch, Kerry; McIntosh, Laura; Ostrander, Elaine A.; Wiley, Kathleen E.; Isaacs, Sarah D.; Walsh, Patrick C.; Isaacs, William B.; Thibodeau, Stephen N.; McDonnell, Shannon K.; Hebbring, Scott; Schaid, Daniel J.; Lange, Ethan M.; Cooney, Kathleen A.; Tammela, Teuvo L.J.; Schleutker, Johanna; Paiss, Thomas; Maier, Christiane; Grönberg, Henrik; Wiklund, Fredrik; Emanuelsson, Monica; Farnham, James M.; Cannon-Albright, Lisa A.; Camp, Nicola J.

    2012-01-01

    Background Prostate cancer is generally believed to have a strong inherited component, but the search for susceptibility genes has been hindered by the effects of genetic heterogeneity. The recently developed sumLINK and sumLOD statistics are powerful tools for linkage analysis in the presence of heterogeneity. Methods We performed a secondary analysis of 1233 prostate cancer pedigrees from the International Consortium for Prostate Cancer Genetics (ICPCG) using two novel statistics, the sumLINK and sumLOD. For both statistics, dominant and recessive genetic models were considered. False discovery rate (FDR) analysis was conducted to assess the effects of multiple testing. Results Our analysis identified significant linkage evidence at chromosome 22q12, confirming previous findings by the initial conventional analyses of the same ICPCG data. Twelve other regions were identified with genomewide suggestive evidence for linkage. Seven regions (1q23, 5q11, 5q35, 6p21, 8q12, 11q13, 20p11-q11) are near loci previously identified in the initial ICPCG pooled data analysis or the subset of aggressive prostate cancer (PC) pedigrees. Three other regions (1p12, 8p23, 19q13) confirm loci reported by others, and two (2p24, 6q27) are novel susceptibility loci. FDR testing indicates that over 70% of these results are likely true positive findings. Statistical recombinant mapping narrowed regions to an average of 9 cM. Conclusions Our results represent genomic regions with the greatest consistency of positive linkage evidence across a very large collection of high-risk prostate cancer pedigrees using new statistical tests that deal powerfully with heterogeneity. These regions are excellent candidates for further study to identify prostate cancer predisposition genes. PMID:20333727

  9. Interactions between household air pollution and GWAS-identified lung cancer susceptibility markers in the Female Lung Cancer Consortium in Asia (FLCCA).

    PubMed

    Hosgood, H Dean; Song, Minsun; Hsiung, Chao Agnes; Yin, Zhihua; Shu, Xiao-Ou; Wang, Zhaoming; Chatterjee, Nilanjan; Zheng, Wei; Caporaso, Neil; Burdette, Laurie; Yeager, Meredith; Berndt, Sonja I; Landi, Maria Teresa; Chen, Chien-Jen; Chang, Gee-Chen; Hsiao, Chin-Fu; Tsai, Ying-Huang; Chien, Li-Hsin; Chen, Kuan-Yu; Huang, Ming-Shyan; Su, Wu-Chou; Chen, Yuh-Min; Chen, Chung-Hsing; Yang, Tsung-Ying; Wang, Chih-Liang; Hung, Jen-Yu; Lin, Chien-Chung; Perng, Reury-Perng; Chen, Chih-Yi; Chen, Kun-Chieh; Li, Yao-Jen; Yu, Chong-Jen; Chen, Yi-Song; Chen, Ying-Hsiang; Tsai, Fang-Yu; Kim, Christopher; Seow, Wei Jie; Bassig, Bryan A; Wu, Wei; Guan, Peng; He, Qincheng; Gao, Yu-Tang; Cai, Qiuyin; Chow, Wong-Ho; Xiang, Yong-Bing; Lin, Dongxin; Wu, Chen; Wu, Yi-Long; Shin, Min-Ho; Hong, Yun-Chul; Matsuo, Keitaro; Chen, Kexin; Wong, Maria Pik; Lu, Dara; Jin, Li; Wang, Jiu-Cun; Seow, Adeline; Wu, Tangchun; Shen, Hongbing; Fraumeni, Joseph F; Yang, Pan-Chyr; Chang, I-Shou; Zhou, Baosen; Chanock, Stephen J; Rothman, Nathaniel; Lan, Qing

    2015-03-01

    We previously carried out a multi-stage genome-wide association study (GWAS) on lung cancer among never smokers in the Female Lung Cancer Consortium in Asia (FLCCA) (6,609 cases, 7,457 controls) that identified novel susceptibility loci at 10q25.2, 6q22.2, and 6p21.32, and confirmed two previously identified loci at 5p15.33 and 3q28. Household air pollution (HAP) attributed to solid fuel burning for heating and cooking, is the leading cause of the overall disease burden in Southeast Asia, and is known to contain lung carcinogens. To evaluate the gene-HAP interactions associated with lung cancer in loci independent of smoking, we analyzed data from studies participating in FLCCA with fuel use information available (n = 3; 1,731 cases; 1,349 controls). Coal use was associated with a 30% increased risk of lung cancer (OR 1.3, 95% CI 1.0-1.6). Among the five a priori SNPs identified by our GWAS, two showed a significant interaction with coal use (HLA Class II rs2395185, p = 0.02; TP63 rs4488809 (rs4600802), p = 0.04). The risk of lung cancer associated with coal exposure varied with the respective alleles for these two SNPs. Our observations provide evidence that genetic variation in HLA Class II and TP63 may modify the association between HAP and lung cancer risk. The roles played in the cell cycle and inflammation pathways by the proteins encoded by these two genes provide biological plausibility for these interactions; however, additional replication studies are needed in other non-smoking populations.

  10. Circulating Vitamin D, Vitamin D-related genetic variation, and risk of fatal prostate cancer in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium

    PubMed Central

    Shui, Irene M; Mondul, Alison M.; Lindström, Sara; Tsilidis, Konstantinos K.; Travis, Ruth C.; Gerke, Travis; Albanes, Demetrius; Mucci, Lorelei A; Giovannucci, Edward; Kraft, Peter

    2015-01-01

    Background Evidence from animal and cell line experimental studies support a beneficial role for vitamin D in prostate cancer (PCa). While the results from human studies have been mainly null for overall PCa risk, there may be a benefit for survival. We assessed the associations of circulating 25-hydroxyvitamin D [25(OH)D] and common variation in key vitamin D-related genes with fatal PCa. Methods In a large cohort consortium, we identified 518 fatal cases and 2986 controls with 25(OH)D data. Genotyping information for 91 single nucleotide polymorphisms (SNPs) in 7 vitamin D-related genes (VDR, GC, CYP27A1, CYP27B1, CYP24A1, CYP2R1, RXRA) was available for 496 fatal cases and 3577 controls. We used unconditional logistic regression to calculate odd ratios (OR) and 95% confidence intervals (CI) for the associations of 25(OH)D and SNPs with fatal PCa. We also tested for 25(OH)D-SNP interactions among 264 fatal cases and 1169 controls. Results We observed no statistically significant relationship between 25(OH)D and fatal PCa [OR(95% CI)extreme quartiles=0.86(0.65-1.14); p-trend=0.22] or the main effects of the SNPs and fatal PCa. There was suggestive evidence that associations of several SNPs (including 5 related to circulating 25(OH)D) with fatal PCa were modified by 25(OH)D. Individually these associations would not remain significant after considering multiple testing; however the p-value for the set-based test for CYP2R1 was 0.002. Conclusions In our study, we did not observe statistically significant associations for either 25(OH)D or vitamin D-related SNPs with fatal PCa. Effect modification of 25(OH)D associations by biologically plausible genetic variation may deserve further exploration. PMID:25731953

  11. Animal models of human prostate cancer: The Consensus Report of the New York Meeting of the Mouse Models of Human Cancers Consortium Prostate Pathology Committee

    PubMed Central

    Ittmann, Michael; Huang, Jiaoti; Radaelli, Enrico; Martin, Philip; Signoretti, Sabina; Sullivan, Ruth; Simons, Brian W.; Ward, Jerrold M.; Robinson, Brian D.; Chu, Gerald C.; Loda, Massimo; Thomas, George; Borowsky, Alexander; Cardiff, Robert D.

    2013-01-01

    Animal models, particularly mouse models, play a central role in the study of the etiology, prevention and treatment of human prostate cancer (PCa). While tissue culture models are extremely useful in understanding the biology of PCa, they cannot recapitulate the complex cellular interactions within the tumor microenvironment that play a key role in cancer initiation and progression. The NCI Mouse Models of Human Cancers Consortium convened a group of human and veterinary pathologists to review the current animal models of PCa and make recommendations regarding the pathological analysis of these models. Over 40 different models with 439 samples were reviewed including genetically engineered mouse models, xenograft, rat and canine models. Numerous relevant models have been developed over the last 15 years and each approach has strengths and weaknesses. Analysis of multiple genetically engineered models has shown that reactive stroma formation is present in all the models developing invasive carcinomas. In addition, numerous models with multiple genetic alterations display aggressive phenotypes characterized by sarcomatoid carcinomas and metastases, which is presumably a histological manifestation of epithelial-mesenchymal transition. The significant progress in development of improved models of PCa has already accelerated our understanding the complex biology of PCa and promises to enhance development of new approaches to prevention, detection and treatment of this common malignancy. PMID:23610450

  12. Role of common genetic variants in ovarian cancer susceptibility and outcome: progress to date from the Ovarian Cancer Association Consortium (OCAC).

    PubMed

    Bolton, K L; Ganda, C; Berchuck, A; Pharaoh, P D P; Gayther, S A

    2012-04-01

    In this article, we review the current knowledge of the inherited genetics of epithelial ovarian cancer (EOC) susceptibility and clinical outcome. We focus on recent developments in identifying low-penetrance susceptibility genes and the role of the Ovarian Cancer Association Consortium (OCAC) in these discoveries. The OCAC was established to facilitate large-scale replication analyses for reported genetic associations for EOC. Since its inception, the OCAC has conducted both candidate gene and genome-wide association studies (GWAS); the latter has identified six established loci for EOC susceptibility, most of which showed stronger association with the serous histological subtype. Future GWAS and sequencing studies are likely to result in the discovery of additional susceptibility loci and may result in established associations with clinical outcome. Additional rare and uncommon ovarian cancer loci will likely be uncovered from high-throughput next-generation sequencing studies. Applying these novel findings to establish improved preventative and clinical intervention strategies will be one of the major challenges of future work. © 2012 The Association for the Publication of the Journal of Internal Medicine.

  13. Replication of Lung Cancer Susceptibility Loci at Chromosomes 15q25, 5p15, and 6p21: A Pooled Analysis From the International Lung Cancer Consortium

    PubMed Central

    Truong, Therese; Hung, Rayjean J.; Amos, Christopher I.; Wu, Xifeng; Bickeböller, Heike; Rosenberger, Albert; Sauter, Wiebke; Illig, Thomas; Wichmann, H.-Erich; Risch, Angela; Dienemann, Hendrik; Kaaks, Rudolph; Yang, Ping; Jiang, Ruoxiang; Wiencke, John K.; Wrensch, Margaret; Hansen, Helen; Kelsey, Karl T.; Matsuo, Keitaro; Tajima, Kazuo; Schwartz, Ann G.; Wenzlaff, Angie; Seow, Adeline; Ying, Chen; Staratschek-Jox, Andrea; Nürnberg, Peter; Stoelben, Erich; Wolf, Jürgen; Lazarus, Philip; Muscat, Joshua E.; Gallagher, Carla J.; Zienolddiny, Shanbeh; Haugen, Aage; van der Heijden, Henricus F. M.; Kiemeney, Lambertus A.; Isla, Dolores; Mayordomo, Jose Ignacio; Rafnar, Thorunn; Stefansson, Kari; Zhang, Zuo-Feng; Chang, Shen-Chih; Kim, Jin Hee; Hong, Yun-Chul; Duell, Eric J.; Andrew, Angeline S.; Lejbkowicz, Flavio; Rennert, Gad; Müller, Heiko; Brenner, Hermann; Le Marchand, Loïc; Benhamou, Simone; Bouchardy, Christine; Teare, M. Dawn; Xue, Xiaoyan; McLaughlin, John; Liu, Geoffrey; McKay, James D.; Spitz, Margaret R.

    2010-01-01

    Background Genome-wide association studies have identified three chromosomal regions at 15q25, 5p15, and 6p21 as being associated with the risk of lung cancer. To confirm these associations in independent studies and investigate heterogeneity of these associations within specific subgroups, we conducted a coordinated genotyping study within the International Lung Cancer Consortium based on independent studies that were not included in previous genome-wide association studies. Methods Genotype data for single-nucleotide polymorphisms at chromosomes 15q25 (rs16969968, rs8034191), 5p15 (rs2736100, rs402710), and 6p21 (rs2256543, rs4324798) from 21 case–control studies for 11 645 lung cancer case patients and 14 954 control subjects, of whom 85% were white and 15% were Asian, were pooled. Associations between the variants and the risk of lung cancer were estimated by logistic regression models. All statistical tests were two-sided. Results Associations between 15q25 and the risk of lung cancer were replicated in white ever-smokers (rs16969968: odds ratio [OR] = 1.26, 95% confidence interval [CI] = 1.21 to 1.32, Ptrend = 2 × 10−26), and this association was stronger for those diagnosed at younger ages. There was no association in never-smokers or in Asians between either of the 15q25 variants and the risk of lung cancer. For the chromosome 5p15 region, we confirmed statistically significant associations in whites for both rs2736100 (OR = 1.15, 95% CI = 1.10 to 1.20, Ptrend = 1 × 10−10) and rs402710 (OR = 1.14, 95% CI = 1.09 to 1.19, Ptrend = 5 × 10−8) and identified similar associations in Asians (rs2736100: OR = 1.23, 95% CI = 1.12 to 1.35, Ptrend = 2 × 10−5; rs402710: OR = 1.15, 95% CI = 1.04 to 1.27, Ptrend = .007). The associations between the 5p15 variants and lung cancer differed by histology; odds ratios for rs2736100 were highest in adenocarcinoma and for rs402710 were highest in adenocarcinoma and squamous cell carcinomas. This pattern was

  14. Report from the Fifth National Cancer Institute Mouse Models of Human Cancers Consortium Nervous System Tumors Workshop

    PubMed Central

    Gutmann, David H.; Stiles, Charles D.; Lowe, Scott W.; Bollag, Gideon E.; Furnari, Frank B.; Charest, Al

    2011-01-01

    Cancers of the nervous system are clinically challenging tumors that present with varied histopathologies and genetic etiologies. While the prognosis for the most malignant of these tumors is essentially unchanged despite decades of basic and translational science research, the past few years have witnessed the identification of numerous targetable molecular alterations in these cancers. With the advent of advanced genomic sequencing methodologies and the development of accurate small-animal models of these nervous system cancers, we are now ideally positioned to develop personalized therapies that target the unique cellular and molecular changes that define their formation and drive their continued growth. Recently, the National Cancer Institute convened a workshop to advance our understanding of nervous system cancer mouse models and to inform clinical trials by reconsidering these neoplasms as complex biological systems characterized by heterogeneity at all levels. PMID:21727208

  15. Risk Analysis of Prostate Cancer in PRACTICAL, a Multinational Consortium, Using 25 Known Prostate Cancer Susceptibility Loci.

    PubMed

    Amin Al Olama, Ali; Benlloch, Sara; Antoniou, Antonis C; Giles, Graham G; Severi, Gianluca; Neal, David E; Hamdy, Freddie C; Donovan, Jenny L; Muir, Kenneth; Schleutker, Johanna; Henderson, Brian E; Haiman, Christopher A; Schumacher, Fredrick R; Pashayan, Nora; Pharoah, Paul D P; Ostrander, Elaine A; Stanford, Janet L; Batra, Jyotsna; Clements, Judith A; Chambers, Suzanne K; Weischer, Maren; Nordestgaard, Børge G; Ingles, Sue A; Sorensen, Karina D; Orntoft, Torben F; Park, Jong Y; Cybulski, Cezary; Maier, Christiane; Doerk, Thilo; Dickinson, Joanne L; Cannon-Albright, Lisa; Brenner, Hermann; Rebbeck, Timothy R; Zeigler-Johnson, Charnita; Habuchi, Tomonori; Thibodeau, Stephen N; Cooney, Kathleen A; Chappuis, Pierre O; Hutter, Pierre; Kaneva, Radka P; Foulkes, William D; Zeegers, Maurice P; Lu, Yong-Jie; Zhang, Hong-Wei; Stephenson, Robert; Cox, Angela; Southey, Melissa C; Spurdle, Amanda B; FitzGerald, Liesel; Leongamornlert, Daniel; Saunders, Edward; Tymrakiewicz, Malgorzata; Guy, Michelle; Dadaev, Tokhir; Little, Sarah J; Govindasami, Koveela; Sawyer, Emma; Wilkinson, Rosemary; Herkommer, Kathleen; Hopper, John L; Lophatonanon, Aritaya; Rinckleb, Antje E; Kote-Jarai, Zsofia; Eeles, Rosalind A; Easton, Douglas F

    2015-07-01

    Genome-wide association studies have identified multiple genetic variants associated with prostate cancer risk which explain a substantial proportion of familial relative risk. These variants can be used to stratify individuals by their risk of prostate cancer. We genotyped 25 prostate cancer susceptibility loci in 40,414 individuals and derived a polygenic risk score (PRS). We estimated empirical odds ratios (OR) for prostate cancer associated with different risk strata defined by PRS and derived age-specific absolute risks of developing prostate cancer by PRS stratum and family history. The prostate cancer risk for men in the top 1% of the PRS distribution was 30.6 (95% CI, 16.4-57.3) fold compared with men in the bottom 1%, and 4.2 (95% CI, 3.2-5.5) fold compared with the median risk. The absolute risk of prostate cancer by age of 85 years was 65.8% for a man with family history in the top 1% of the PRS distribution, compared with 3.7% for a man in the bottom 1%. The PRS was only weakly correlated with serum PSA level (correlation = 0.09). Risk profiling can identify men at substantially increased or reduced risk of prostate cancer. The effect size, measured by OR per unit PRS, was higher in men at younger ages and in men with family history of prostate cancer. Incorporating additional newly identified loci into a PRS should improve the predictive value of risk profiles. We demonstrate that the risk profiling based on SNPs can identify men at substantially increased or reduced risk that could have useful implications for targeted prevention and screening programs. ©2015 American Association for Cancer Research.

  16. Sexual behaviours and the risk of head and neck cancers: a pooled analysis in the International Head and Neck Cancer Epidemiology (INHANCE) consortium

    PubMed Central

    Heck, Julia E; Berthiller, Julien; Vaccarella, Salvatore; Winn, Deborah M; Smith, Elaine M; Shan'gina, Oxana; Schwartz, Stephen M; Purdue, Mark P; Pilarska, Agnieszka; Eluf-Neto, Jose; Menezes, Ana; McClean, Michael D; Matos, Elena; Koifman, Sergio; Kelsey, Karl T; Herrero, Rolando; Hayes, Richard B; Franceschi, Silvia; Wünsch-Filho, Victor; Fernández, Leticia; Daudt, Alexander W; Curado, Maria Paula; Chen, Chu; Castellsagué, Xavier; Ferro, Gilles; Brennan, Paul; Boffetta, Paolo; Hashibe, Mia

    2010-01-01

    Background Sexual contact may be the means by which head and neck cancer patients are exposed to human papillomavirus (HPV). Methods We undertook a pooled analysis of four population-based and four hospital-based case–control studies from the International Head and Neck Cancer Epidemiology (INHANCE) consortium, with participants from Argentina, Australia, Brazil, Canada, Cuba, India, Italy, Spain, Poland, Puerto Rico, Russia and the USA. The study included 5642 head and neck cancer cases and 6069 controls. We calculated odds ratios (ORs) of associations between cancer and specific sexual behaviours, including practice of oral sex, number of lifetime sexual partners and oral sex partners, age at sexual debut, a history of same-sex contact and a history of oral–anal contact. Findings were stratified by sex and disease subsite. Results Cancer of the oropharynx was associated with having a history of six or more lifetime sexual partners [OR = 1.25, 95% confidence interval (CI) 1.01, 1.54] and four or more lifetime oral sex partners (OR = 2.25, 95% CI 1.42, 3.58). Cancer of the tonsil was associated with four or more lifetime oral sex partners (OR = 3.36, 95 % CI 1.32, 8.53), and, among men, with ever having oral sex (OR = 1.59, 95% CI 1.09, 2.33) and with an earlier age at sexual debut (OR = 2.36, 95% CI 1.37, 5.05). Cancer of the base of the tongue was associated with ever having oral sex among women (OR = 4.32, 95% CI 1.06, 17.6), having two sexual partners in comparison with only one (OR = 2.02, 95% CI 1.19, 3.46) and, among men, with a history of same-sex sexual contact (OR = 8.89, 95% CI 2.14, 36.8). Conclusions Sexual behaviours are associated with cancer risk at the head and neck cancer subsites that have previously been associated with HPV infection. PMID:20022926

  17. PROSPECT Eligibility and Clinical Outcomes: Results From the Pan-Canadian Rectal Cancer Consortium.

    PubMed

    Bossé, Dominick; Mercer, Jamison; Raissouni, Soundouss; Dennis, Kristopher; Goodwin, Rachel; Jiang, Di; Powell, Erin; Kumar, Aalok; Lee-Ying, Richard; Price-Hiller, Julie; Heng, Daniel Y C; Tang, Patricia A; MacLean, Anthony; Cheung, Winson Y; Vickers, Michael M

    2016-09-01

    The PROSPECT trial (N1048) is evaluating the selective use of chemoradiation in patients with cT2N1 and cT3N0-1 rectal cancer undergoing sphincter-sparing low anterior resection. We evaluated outcomes of PROSPECT-eligible and -ineligible patients from a multi-institutional database. Data from patients with locally advanced rectal cancer who received chemoradiation and low anterior resection from 2005 to 2014 were retrospectively collected from 5 Canadian centers. Overall survival, disease-free survival (DFS), recurrence-free survival (RFS), and time to local recurrence (LR) were estimated using the Kaplan-Meier method, and a multivariate analysis was performed adjusting for prognostic factors. A total of 566 (37%) of 1531 patients met the PROSPECT eligibility criteria. Eligible patients were more likely to have better PS (P = .0003) and negative circumferential resection margin (P < .0001). PROSPECT eligibility was associated with improved DFS (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.61-0.91), overall survival (HR, 0.73; 95% CI, 0.57-0.95), and RFS (HR, 0.68; 95% CI, 0.54-0.86) in univariate analyses. In multivariate analysis, only RFS remained significantly improved for PROSPECT-eligible patients (HR, 0.75; 95% CI, 0.57-1.00, P = .0499). The 3-year DFS and freedom from LR for PROSPECT-eligible patients were 79.1% and 97.4%, respectively, compared to 71.1% and 96.8% for PROSPECT-ineligible patients. Real-world data corroborate the eligibility criteria used in the PROSPECT study; the criteria identify a subgroup of patients in whom risk of recurrence is lower and in whom selective use of chemoradiation should be actively examined. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Clinicopathologic features and outcomes of patients with lung adenocarcinomas harboring BRAF mutations in the Lung Cancer Mutation Consortium

    PubMed Central

    Villaruz, Liza C.; Socinski, Mark A.; Abberbock, Shira; Berry, Lynne D.; Johnson, Bruce E.; Kwiatkowski, David J; Iafrate, A. John; Varella-Garcia, Marileila; Franklin, Wilbur A.; Camidge, D. Ross; Sequist, Lecia V.; Haura, Eric B.; Ladanyi, Mark; Kurland, Brenda F.; Kugler, Kelly; Minna, John D; Bunn, Paul A.; Kris, Mark G.

    2014-01-01

    (1) PURPOSE The advent of effective targeted therapy in BRAFV600E mutant lung adenocarcinomas necessitates further exploration of the unique clinical features and behavior of advanced stage BRAF mutant lung adenocarcinomas. (2) PATIENTS AND METHODS We reviewed data from patients with advanced lung adenocarcinomas enrolled in the Lung Cancer Mutation Consortium whose tumors underwent testing for mutations in EGFR, KRAS, HER2, AKT1, BRAF, MEK1, NRAS, PIK3CA, ALK translocations, and MET amplification. (3) RESULTS Twenty-one BRAF mutations were identified in 951 patients with adenocarcinomas (2.2%: 95% CI 1.4 to 3.4%); 17 (81%: 95% CI 60 to 92%) were BRAFV600E and 4 were non-BRAFV600E mutations. Among the 733 cases tested for all 10 genes, BRAF mutations were more likely to occur in current or former smokers than most other genotypic abnormalities (BRAF versus sensitizing EGFR: 82% versus 36%, mid-P<0.001; versus ALK: 39%, mid-P=0.003; versus other mutations: 49%, mid-P=0.02; versus patients with more than one oncogenic driver (doubleton): 46%, mid-P=0.04.) The double mutation rate among patients with BRAF mutations was 16%, compared with 5% in patients with other genomic abnormalities (mid-P=0.045). Differences were not found in survival between patients with BRAF mutations and those with other genomic abnormalities (P>0.20). (4) CONCLUSIONS We demonstrate BRAF mutations occur in 2.2% of advanced stage lung adenocarcinomas, were most commonly V600E, were associated with distinct clinicopathologic features compared with other genomic subtypes and a high mutation rate in more than one gene, underscoring the importance of comprehensive genomic profiling in assessing patients with advanced lung adenocarcinomas. PMID:25273224

  19. Circulating Folate, Vitamin B6, and Methionine in Relation to Lung Cancer Risk in the Lung Cancer Cohort Consortium (LC3).

    PubMed

    Fanidi, Anouar; Muller, David C; Yuan, Jian-Min; Stevens, Victoria L; Weinstein, Stephanie J; Albanes, Demetrius; Prentice, Ross; Thomsen, Cynthia A; Pettinger, Mary; Cai, Qiuyin; Blot, William J; Wu, Jie; Arslan, Alan A; Zeleniuch-Jacquotte, Anne; McCullough, Marjorie L; Le Marchand, Loic; Wilkens, Lynne R; Haiman, Christopher A; Zhang, Xuehong; Han, Jiali; Stampfer, Meir J; Smith-Warner, Stephanie A; Giovannucci, Edward; Giles, Graham G; Hodge, Allison M; Severi, Gianluca; Johansson, Mikael; Grankvist, Kjell; Langhammer, Arnulf; Krokstad, Steinar; Næss, Marit; Wang, Renwei; Gao, Yu-Tang; Butler, Lesley M; Koh, Woon-Puay; Shu, Xiao-Ou; Xiang, Yong-Bing; Li, Honglan; Zheng, Wei; Lan, Qing; Visvanathan, Kala; Bolton, Judith Hoffman; Ueland, Per Magne; Midttun, Øivind; Ulvik, Arve; Caporaso, Neil E; Purdue, Mark; Ziegler, Regina G; Freedman, Neal D; Buring, Julie E; Lee, I-Min; Sesso, Howard D; Gaziano, J Michael; Manjer, Jonas; Ericson, Ulrika; Relton, Caroline; Brennan, Paul; Johansson, Mattias

    2018-01-01

    Circulating concentrations of B vitamins and factors related to one-carbon metabolism have been found to be strongly inversely associated with lung cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. The extent to which these associations are present in other study populations is unknown. Within 20 prospective cohorts from the National Cancer Institute Cohort Consortium, a nested case-control study was designed including 5364 incident lung cancer case patients and 5364 control subjects who were individually matched to case patients by age, sex, cohort, and smoking status. Centralized biochemical analyses were performed to measure circulating concentrations of vitamin B6, folate, and methionine, as well as cotinine as an indicator of recent tobacco exposure. The association between these biomarkers and lung cancer risk was evaluated using conditional logistic regression models. Participants with higher circulating concentrations of vitamin B6 and folate had a modestly decreased risk of lung cancer risk overall, the odds ratios when comparing the top and bottom fourths (OR 4vs1 ) being 0.88 (95% confidence interval [CI] = 0.78 to 1.00) and 0.86 (95% CI = 0.74 to 0.99), respectively. We found stronger associations among men (vitamin B6: OR 4vs1 = 0.74, 95% CI = 0.62 to 0.89; folate: OR 4vs1 = 0.75, 95% CI = 0.61 to 0.93) and ever smokers (vitamin B6: OR 4vs1 = 0.78, 95% CI = 0.67 to 0.91; folate: OR 4vs1 = 0.87, 95% CI = 0.73 to 1.03). We further noted that the association of folate was restricted to Europe/Australia and Asia, whereas no clear association was observed for the United States. Circulating concentrations of methionine were not associated with lung cancer risk overall or in important subgroups. Although confounding by tobacco exposure or reverse causation cannot be ruled out, these study results are compatible with a small decrease in lung cancer risk in ever smokers who avoid low concentrations

  20. Alcohol and cigarette consumption as predictors of mortality in patients with head and neck cancer: a pooled analysis within the International Head and Neck Cancer Epidemiology (INHANCE) Consortium.

    PubMed

    Giraldi, L; Leoncini, E; Pastorino, R; Wünsch-Filho, V; de Carvalho, M; Lopez, R; Cadoni, G; Arzani, D; Petrelli, L; Matsuo, K; Bosetti, C; La Vecchia, C; Garavello, W; Polesel, J; Serraino, D; Simonato, L; Canova, C; Richiardi, L; Boffetta, P; Hashibe, M; Lee, C A Y; Boccia, S

    2017-08-30

    Our study evaluated whether demographics, pre-diagnosis lifestyle habits and clinical data are associated with the overall survival (OS) and head and neck cancer (HNC)-specific survival in patients with HNC.PATIENTS AND METHODS: We conducted a pooled analysis, including 4,759 HNC patients from five studies within the International Head and Neck Cancer Epidemiology (INHANCE) Consortium. Cox proportional Hazard Ratios (HRs) and the corresponding 95% Confidence Intervals (CIs) were estimated including terms reported significantly associated with the survival in the univariate analysis.RESULTS: Five-years OS was 51.4% for all HNC sites combined: 50.3% for oral cavity, 41.1% for oropharynx, 35.0% for hypopharynx and 63.9% for larynx. When we considered HNC-specific survival, 5-year survival rates were 57.4% for all HNC combined, 54.6% for oral cavity, 45.4% for oropharynx, 37.1% for hypopharynx and 72.3% for larynx. Older ages at diagnosis and advanced tumour staging were unfavourable predictors of OS and HNC-specific survival. In laryngeal cancer, low educational level was an unfavourable prognostic factor for OS (HR = 2.54, 95% CI: 1.01-6.38, for high school or lower vs. college graduate), and status and intensity of alcohol drinking were prognostic factors both of the OS (current drinkers HR = 1.73, CI: 1.16-2.58) and HNC-specific survival (current drinkers HR = 2.11, CI: 1.22-3.66). In oropharyngeal cancer, smoking status was an independent prognostic factors for OS. Smoking intensity (>20 cigarettes/day HR = 1.41, CI: 1.03-1.92) was also an independent prognostic factor for OS in patients with cancer of the oral cavity.CONCLUSIONS: OS and HNC-specific survival differ among HNC sites. Pre-diagnosis cigarette smoking is a prognostic factor of the OS for patients with cancer of the oral cavity and oropharynx, while pre-diagnosis alcohol drinking is a prognostic factor of OS and HNC-specific survival for patients with cancer of the larynx. Low

  1. Medication risk communication with cancer patients in a Middle East cancer care setting

    PubMed Central

    Wilbur, Kerry; Al-Okka, Maha; Jumaat, Ebaa; Eissa, Nesma; Elbashir, Merwa; Al-Yafei, Sumaya M Al Saadi

    2016-01-01

    Purpose Cancer treatments are frequently associated with adverse effects, but there may be a cultural reluctance by care providers to be forthcoming with patients regarding these risks for fear of promoting nonadherence. Conversely, research in a number of countries indicates high levels of patient desire for this information. We sought to explore cancer patient experiences, satisfaction, and preferences for medication risk communication in a Middle East care setting. Methods We developed and administered a ten-item questionnaire (Arabic and English) to a convenience sample of consenting adult patients receiving treatment at the National Center for Cancer Care and Research in Qatar. Results One hundred and forty-three patients were interviewed. Most (88%) stated that the level of side effect information they received was sufficient, with physicians (86%) followed by pharmacists (39%) as the preferred sources. The majority (97%) agreed that knowing about possible side effects would help them recognize and manage the reaction, and 92% agreed that it would help them understand how to minimize or prevent the risks. Eighteen percent indicated that this information would make them not want to take treatment. Two-thirds (65%) had previously experienced intolerance to their cancer treatment regimen. Conclusion Most patients surveyed expressed preference for the details of possible side effects they may encounter in their treatment. However, one in five considered such information a factor for nonadherence, indicating the need for patient-specific approaches when communicating medication risks. PMID:27175061

  2. Folate intake and the risk of oral cavity and pharyngeal cancer: a pooled analysis within the International Head and Neck Cancer Epidemiology Consortium.

    PubMed

    Galeone, Carlotta; Edefonti, Valeria; Parpinel, Maria; Leoncini, Emanuele; Matsuo, Keitaro; Talamini, Renato; Olshan, Andrew F; Zevallos, Jose P; Winn, Deborah M; Jayaprakash, Vijayvel; Moysich, Kirsten; Zhang, Zuo-Feng; Morgenstern, Hal; Levi, Fabio; Bosetti, Cristina; Kelsey, Karl; McClean, Michael; Schantz, Stimson; Yu, Guo-Pei; Boffetta, Paolo; Lee, Yuan-Chin Amy; Hashibe, Mia; La Vecchia, Carlo; Boccia, Stefania

    2015-02-15

    There are suggestions of an inverse association between folate intake and serum folate levels and the risk of oral cavity and pharyngeal cancers (OPCs), but most studies are limited in sample size, with only few reporting information on the source of dietary folate. Our study aims to investigate the association between folate intake and the risk of OPC within the International Head and Neck Cancer Epidemiology (INHANCE) Consortium. We analyzed pooled individual-level data from ten case-control studies participating in the INHANCE consortium, including 5,127 cases and 13,249 controls. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were estimated for the associations between total folate intake (natural, fortification and supplementation) and natural folate only, and OPC risk. We found an inverse association between total folate intake and overall OPC risk (the adjusted OR for the highest vs. the lowest quintile was 0.65, 95% CI: 0.43-0.99), with a stronger association for oral cavity (OR = 0.57, 95% CI: 0.43-0.75). A similar inverse association, though somewhat weaker, was observed for folate intake from natural sources only in oral cavity cancer (OR = 0.64, 95% CI: 0.45-0.91). The highest OPC risk was observed in heavy alcohol drinkers with low folate intake as compared to never/light drinkers with high folate (OR = 4.05, 95% CI: 3.43-4.79); the attributable proportion (AP) owing to interaction was 11.1% (95% CI: 1.4-20.8%). Lastly, we reported an OR of 2.73 (95% CI:2.34-3.19) for those ever tobacco users with low folate intake, compared with nevere tobacco users and high folate intake (AP of interaction =10.6%, 95% CI: 0.41-20.8%). Our project of a large pool of case-control studies supports a protective effect of total folate intake on OPC risk. © 2014 UICC.

  3. Meta-analysis of mismatch repair polymorphisms within the cogent consortium for colorectal cancer susceptibility.

    PubMed

    Picelli, Simone; Lorenzo Bermejo, Justo; Chang-Claude, Jenny; Hoffmeister, Michael; Fernández-Rozadilla, Ceres; Carracedo, Angel; Castells, Antoni; Castellví-Bel, Sergi; Naccarati, Alessio; Pardini, Barbara; Vodickova, Ludmila; Müller, Heiko; Talseth-Palmer, Bente A; Stibbard, Geoffrey; Peterlongo, Paolo; Nici, Carmela; Veneroni, Silvia; Li, Li; Casey, Graham; Tenesa, Albert; Farrington, Susan M; Tomlinson, Ian; Moreno, Victor; van Wezel, Tom; Wijnen, Juul; Dunlop, Malcolm; Radice, Paolo; Scott, Rodney J; Vodicka, Pavel; Ruiz-Ponte, Clara; Brenner, Hermann; Buch, Stephan; Völzke, Henry; Hampe, Jochen; Schafmayer, Clemens; Lindblom, Annika

    2013-01-01

    In the last four years, Genome-Wide Association Studies (GWAS) have identified sixteen low-penetrance polymorphisms on fourteen different loci associated with colorectal cancer (CRC). Due to the low risks conferred by known common variants, most of the 35% broad-sense heritability estimated by twin studies remains unexplained. Recently our group performed a case-control study for eight Single Nucleotide Polymorphisms (SNPs) in 4 CRC genes. The present investigation is a follow-up of that study. We have genotyped six SNPs that showed a positive association and carried out a meta-analysis based on eight additional studies comprising in total more than 8000 cases and 6000 controls. The estimated recessive odds ratio for one of the SNPs, rs3219489 (MUTYH Q338H), decreased from 1.52 in the original Swedish study, to 1.18 in the Swedish replication, and to 1.08 in the initial meta-analysis. Since the corresponding summary probability value was 0.06, we decided to retrieve additional information for this polymorphism. The incorporation of six further studies resulted in around 13000 cases and 13000 controls. The newly updated OR was 1.03. The results from the present large, multicenter study illustrate the possibility of decreasing effect sizes with increasing samples sizes. Phenotypic heterogeneity, differential environmental exposures, and population specific linkage disequilibrium patterns may explain the observed difference of genetic effects between Sweden and the other investigated cohorts.

  4. Meta-Analysis of Mismatch Repair Polymorphisms within the Cogent Consortium for Colorectal Cancer Susceptibility

    PubMed Central

    Chang-Claude, Jenny; Hoffmeister, Michael; Fernández-Rozadilla, Ceres; Carracedo, Angel; Castells, Antoni; Castellví-Bel, Sergi; Juan, Diego Morillas; Raquel, Muñoz; Marisa, Manzano; Francisco, Colina; Jose, Díaz; Carolina, Ibarrola; Guadalupe, López; Alberto, Ibáñez; Antoni, Castells; Virgínia, Piñol; Sergi, Castellví-Bel; Francesc, Balaguer; Victoria, Gonzalo; Teresa, Ocaña; María Dolores, Giráldez; Maria, Pellisé; Anna, Serradesanferm; Leticia, Moreira; Miriam, Cuatrecasas; Josep, M. Piqué; Ángel, Lanas; Javier, Alcedo; Javier, Ortego; Joaquin, Cubiella; Ma, Soledad Díez; Mercedes, Salgado; Eloy, Sánchez; Mariano, Vega; Montserrat, Andreu; Anna, Abuli; Xavier, Bessa; Mar, Iglesias; Agustín, Seoane; Felipe, Bory; Gemma, Navarro; Beatriz, Bellosillo; Josep, Ma Dedeu; Cristina, Álvarez; Marc, Puigvehí; Luis, Bujanda; Ángel, Cosme; Inés, Gil; Mikel, Larzabal; Carlos, Placer; María, del Mar Ramírez; Elisabeth, Hijona; Jose, M. Enríquez-Navascués; Jose, L. Elosegui; Artemio, Payá; Rodrigo, Jover; Cristina, Alenda; Laura, Sempere; Nuria, Acame; Estefanía, Rojas; Lucía, Pérez-Carbonell; Joaquim, Rigau; Ángel, Serrano; Anna, Giménez; Joan, Saló; Eduard, Batiste-Alentorn; Josefina, Autonell; Ramon, Barniol; Ana, María García; Fernando, Carballo; Antonio, Bienvenido; Eduardo, Sanz; Fernando, González; Jaime, Sánchez; Akiko, Ono; Mercedes, Latorre; Enrique, Medina; Jaime, Cuquerella; Pilar, Canelles; Miguel, Martorell; José, Ángel García; Francisco, Quiles; Elisa, Orti; Juan, Clofent; Jaime, Seoane; Antoni, Tardío; Eugenia, Sanchez; Ma, Luisa de Castro; Antoni, Tardío; Juan, Clofent; Vicent, Hernández; Xavier, Llor; Rosa, M. Xicola; Marta, Piñol; Mercè, Rosinach; Anna, Roca; Elisenda, Pons; José, M. Hernández; Miquel, A. Gassull; Fernando, Fernández-Bañares; Josep, M. Viver; Antonio, Salas; Jorge, Espinós; Montserrat, Forné; Maria, Esteve; Josep, M. Reñé; Carmen, Piñol; Juan, Buenestado; Joan, Viñas; Enrique, Quintero; David, Nicolás; Adolfo, Parra; Antonio, Martín; Lidia, Argüello; Vicente, Pons; Virginia, Pertejo; Teresa, Sala; Dolors, Gonzalez; Eva, Roman; Teresa, Ramon; Maria, Poca; Ma, Mar Concepción; Marta, Martin; Lourdes, Pétriz; Daniel, Martinez; Ángel, Carracedo; Clara, Ruiz-Ponte; Ceres, Fernández-Rozadilla; Ma, Magdalena Castro; Sabino, Riestra; Luis, Rodrigo; Javier, Fernández; Jose, Luis Cabriada; Luis, Carreño; Susana, Oquiñena; Federico, Bolado; Elena, Peña; José, Manuel Blas; Gloria, Ceña; Juan, José Sebastián; Antonio, Naranjo; Naccarati, Alessio; Pardini, Barbara; Vodickova, Ludmila; Müller, Heiko; Talseth-Palmer, Bente A.; Stibbard, Geoffrey; Peterlongo, Paolo; Nici, Carmela; Veneroni, Silvia; Li, Li; Casey, Graham; Tenesa, Albert; Farrington, Susan M.; Tomlinson, Ian; Moreno, Victor; van Wezel, Tom; Wijnen, Juul; Dunlop, Malcolm; Radice, Paolo; Scott, Rodney J.; Vodicka, Pavel; Ruiz-Ponte, Clara; Brenner, Hermann; Buch, Stephan; Völzke, Henry; Hampe, Jochen; Schafmayer, Clemens; Lindblom, Annika

    2013-01-01

    In the last four years, Genome-Wide Association Studies (GWAS) have identified sixteen low-penetrance polymorphisms on fourteen different loci associated with colorectal cancer (CRC). Due to the low risks conferred by known common variants, most of the 35% broad-sense heritability estimated by twin studies remains unexplained. Recently our group performed a case-control study for eight Single Nucleotide Polymorphisms (SNPs) in 4 CRC genes. The present investigation is a follow-up of that study. We have genotyped six SNPs that showed a positive association and carried out a meta-analysis based on eight additional studies comprising in total more than 8000 cases and 6000 controls. The estimated recessive odds ratio for one of the SNPs, rs3219489 (MUTYH Q338H), decreased from 1.52 in the original Swedish study, to 1.18 in the Swedish replication, and to 1.08 in the initial meta-analysis. Since the corresponding summary probability value was 0.06, we decided to retrieve additional information for this polymorphism. The incorporation of six further studies resulted in around 13000 cases and 13000 controls. The newly updated OR was 1.03. The results from the present large, multicenter study illustrate the possibility of decreasing effect sizes with increasing samples sizes. Phenotypic heterogeneity, differential environmental exposures, and population specific linkage disequilibrium patterns may explain the observed difference of genetic effects between Sweden and the other investigated cohorts. PMID:24039736

  5. Cigarette, Cigar, and Pipe Smoking and the Risk of Head and Neck Cancers: Pooled Analysis in the International Head and Neck Cancer Epidemiology Consortium

    PubMed Central

    Wyss, Annah; Hashibe, Mia; Chuang, Shu-Chun; Lee, Yuan-Chin Amy; Zhang, Zuo-Feng; Yu, Guo-Pei; Winn, Deborah M.; Wei, Qingyi; Talamini, Renato; Szeszenia-Dabrowska, Neonila; Sturgis, Erich M.; Smith, Elaine; Shangina, Oxana; Schwartz, Stephen M.; Schantz, Stimson; Rudnai, Peter; Purdue, Mark P.; Eluf-Neto, Jose; Muscat, Joshua; Morgenstern, Hal; Michaluart, Pedro; Menezes, Ana; Matos, Elena; Mates, Ioan Nicolae; Lissowska, Jolanta; Levi, Fabio; Lazarus, Philip; La Vecchia, Carlo; Koifman, Sergio; Herrero, Rolando; Hayes, Richard B.; Franceschi, Silvia; Wünsch-Filho, Victor; Fernandez, Leticia; Fabianova, Eleonora; Daudt, Alexander W.; Dal Maso, Luigino; Curado, Maria Paula; Chen, Chu; Castellsague, Xavier; de Carvalho, Marcos Brasilino; Cadoni, Gabriella; Boccia, Stefania; Brennan, Paul; Boffetta, Paolo; Olshan, Andrew F.

    2013-01-01

    Cigar and pipe smoking are considered risk factors for head and neck cancers, but the magnitude of effect estimates for these products has been imprecisely estimated. By using pooled data from the International Head and Neck Cancer Epidemiology (INHANCE) Consortium (comprising 13,935 cases and 18,691 controls in 19 studies from 1981 to 2007), we applied hierarchical logistic regression to more precisely estimate odds ratios and 95% confidence intervals for cigarette, cigar, and pipe smoking separately, compared with reference groups of those who had never smoked each single product. Odds ratios for cigar and pipe smoking were stratified by ever cigarette smoking. We also considered effect estimates of smoking a single product exclusively versus never having smoked any product (reference group). Among never cigarette smokers, the odds ratio for ever cigar smoking was 2.54 (95% confidence interval (CI): 1.93, 3.34), and the odds ratio for ever pipe smoking was 2.08 (95% CI: 1.55, 2.81). These odds ratios increased with increasing frequency and duration of smoking (Ptrend ≤ 0.0001). Odds ratios for cigar and pipe smoking were not elevated among ever cigarette smokers. Head and neck cancer risk was elevated for those who reported exclusive cigar smoking (odds ratio = 3.49, 95% CI: 2.58, 4.73) or exclusive pipe smoking (odds ratio = 3.71, 95% CI: 2.59, 5.33). These results suggest that cigar and pipe smoking are independently associated with increased risk of head and neck cancers. PMID:23817919

  6. Cigarette, cigar, and pipe smoking and the risk of head and neck cancers: pooled analysis in the International Head and Neck Cancer Epidemiology Consortium.

    PubMed

    Wyss, Annah; Hashibe, Mia; Chuang, Shu-Chun; Lee, Yuan-Chin Amy; Zhang, Zuo-Feng; Yu, Guo-Pei; Winn, Deborah M; Wei, Qingyi; Talamini, Renato; Szeszenia-Dabrowska, Neonila; Sturgis, Erich M; Smith, Elaine; Shangina, Oxana; Schwartz, Stephen M; Schantz, Stimson; Rudnai, Peter; Purdue, Mark P; Eluf-Neto, Jose; Muscat, Joshua; Morgenstern, Hal; Michaluart, Pedro; Menezes, Ana; Matos, Elena; Mates, Ioan Nicolae; Lissowska, Jolanta; Levi, Fabio; Lazarus, Philip; La Vecchia, Carlo; Koifman, Sergio; Herrero, Rolando; Hayes, Richard B; Franceschi, Silvia; Wünsch-Filho, Victor; Fernandez, Leticia; Fabianova, Eleonora; Daudt, Alexander W; Dal Maso, Luigino; Curado, Maria Paula; Chen, Chu; Castellsague, Xavier; de Carvalho, Marcos Brasilino; Cadoni, Gabriella; Boccia, Stefania; Brennan, Paul; Boffetta, Paolo; Olshan, Andrew F

    2013-09-01

    Cigar and pipe smoking are considered risk factors for head and neck cancers, but the magnitude of effect estimates for these products has been imprecisely estimated. By using pooled data from the International Head and Neck Cancer Epidemiology (INHANCE) Consortium (comprising 13,935 cases and 18,691 controls in 19 studies from 1981 to 2007), we applied hierarchical logistic regression to more precisely estimate odds ratios and 95% confidence intervals for cigarette, cigar, and pipe smoking separately, compared with reference groups of those who had never smoked each single product. Odds ratios for cigar and pipe smoking were stratified by ever cigarette smoking. We also considered effect estimates of smoking a single product exclusively versus never having smoked any product (reference group). Among never cigarette smokers, the odds ratio for ever cigar smoking was 2.54 (95% confidence interval (CI): 1.93, 3.34), and the odds ratio for ever pipe smoking was 2.08 (95% CI: 1.55, 2.81). These odds ratios increased with increasing frequency and duration of smoking (Ptrend ≤ 0.0001). Odds ratios for cigar and pipe smoking were not elevated among ever cigarette smokers. Head and neck cancer risk was elevated for those who reported exclusive cigar smoking (odds ratio = 3.49, 95% CI: 2.58, 4.73) or exclusive pipe smoking (odds ratio = 3.71, 95% CI: 2.59, 5.33). These results suggest that cigar and pipe smoking are independently associated with increased risk of head and neck cancers.

  7. Infertility and incident endometrial cancer risk: a pooled analysis from the epidemiology of endometrial cancer consortium (E2C2)

    PubMed Central

    Yang, H P; Cook, L S; Weiderpass, E; Adami, H-O; Anderson, K E; Cai, H; Cerhan, J R; Clendenen, T V; Felix, A S; Friedenreich, C M; Garcia-Closas, M; Goodman, M T; Liang, X; Lissowska, J; Lu, L; Magliocco, A M; McCann, S E; Moysich, K B; Olson, S H; Petruzella, S; Pike, M C; Polidoro, S; Ricceri, F; Risch, H A; Sacerdote, C; Setiawan, V W; Shu, X O; Spurdle, A B; Trabert, B; Webb, P M; Wentzensen, N; Xiang, Y-B; Xu, Y; Yu, H; Zeleniuch-Jacquotte, A; Brinton, L A

    2015-01-01

    Background: Nulliparity is an endometrial cancer risk factor, but whether or not this association is due to infertility is unclear. Although there are many underlying infertility causes, few studies have assessed risk relations by specific causes. Methods: We conducted a pooled analysis of 8153 cases and 11 713 controls from 2 cohort and 12 case-control studies. All studies provided self-reported infertility and its causes, except for one study that relied on data from national registries. Logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI). Results: Nulliparous women had an elevated endometrial cancer risk compared with parous women, even after adjusting for infertility (OR=1.76; 95% CI: 1.59–1.94). Women who reported infertility had an increased risk compared with those without infertility concerns, even after adjusting for nulliparity (OR=1.22; 95% CI: 1.13–1.33). Among women who reported infertility, none of the individual infertility causes were substantially related to endometrial cancer. Conclusions: Based on mainly self-reported infertility data that used study-specific definitions of infertility, nulliparity and infertility appeared to independently contribute to endometrial cancer risk. Understanding residual endometrial cancer risk related to infertility, its causes and its treatments may benefit from large studies involving detailed data on various infertility parameters. PMID:25688738

  8. A Large Study of Androgen Receptor Germline Variants and Their Relation to Sex Hormone Levels and Prostate Cancer Risk. Results from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium

    PubMed Central

    Lindström, Sara; Ma, Jing; Altshuler, David; Giovannucci, Edward; Riboli, Elio; Albanes, Demetrius; Allen, Naomi E.; Berndt, Sonja I.; Boeing, Heiner; Bueno-de-Mesquita, H. Bas; Chanock, Stephen J.; Dunning, Alison M.; Feigelson, Heather Spencer; Gaziano, J. Michael; Haiman, Christopher A.; Hayes, Richard B.; Henderson, Brian E.; Hunter, David J.; Kaaks, Rudolf; Kolonel, Laurence N.; Le Marchand, Loic; Martínez, Carmen; Overvad, Kim; Siddiq, Afshan; Stampfer, Meir; Stattin, Pär; Stram, Daniel O.; Thun, Michael J.; Trichopoulos, Dimitrios; Tumino, Rosario; Virtamo, Jarmo; Weinstein, Stephanie J.; Yeager, Meredith; Kraft, Peter; Freedman, Matthew L.

    2010-01-01

    Background: Androgens are key regulators of prostate gland maintenance and prostate cancer growth, and androgen deprivation therapy has been the mainstay of treatment for advanced prostate cancer for many years. A long-standing hypothesis has been that inherited variation in the androgen receptor (AR) gene plays a role in prostate cancer initiation. However, studies to date have been inconclusive and often suffered from small sample sizes. Objective and Methods: We investigated the association of AR sequence variants with circulating sex hormone levels and prostate cancer risk in 6058 prostate cancer cases and 6725 controls of Caucasian origin within the Breast and Prostate Cancer Cohort Consortium. We genotyped a highly polymorphic CAG microsatellite in exon 1 and six haplotype tagging single nucleotide polymorphisms and tested each genetic variant for association with prostate cancer risk and with sex steroid levels. Results: We observed no association between AR genetic variants and prostate cancer risk. However, there was a strong association between longer CAG repeats and higher levels of testosterone (P = 4.73 × 10−5) and estradiol (P = 0.0002), although the amount of variance explained was small (0.4 and 0.7%, respectively). Conclusions: This study is the largest to date investigating AR sequence variants, sex steroid levels, and prostate cancer risk. Although we observed no association between AR sequence variants and prostate cancer risk, our results support earlier findings of a relation between the number of CAG repeats and circulating levels of testosterone and estradiol. PMID:20534771

  9. FCGR polymorphisms and cetuximab efficacy in chemorefractory metastatic colorectal cancer: an international consortium study.

    PubMed

    Geva, Ravit; Vecchione, Loredana; Kalogeras, Konstantinos T; Jensen, Benny Vittrup; Lenz, Heinz-Josef; Yoshino, Takayuki; Paez, David; Montagut, Clara; Souglakos, John; Cappuzzo, Federico; Cervantes, Andrés; Frattini, Milo; Fountzilas, George; Johansen, Julia S; Høgdall, Estrid Vilma; Zhang, Wu; Yang, Dongyun; Yamazaki, Kentaro; Nishina, Tomohiro; Papamichael, Demetris; Vincenzi, Bruno; Macarulla, Teresa; Loupakis, Fotios; De Schutter, Jef; Spindler, Karen Lise Garm; Pfeiffer, Per; Ciardiello, Fortunato; Piessevaux, Hubert; Tejpar, Sabine

    2015-06-01

    We aimed to better clarify the role of germline variants of the FCG2 receptor, FCGR2A-H131R and FCGR3A-V158F, on the therapeutic efficacy of cetuximab in metastatic colorectal cancer (mCRC). A large cohort with sufficient statistical power was assembled. To show a HR advantage of 0.6 in progression-free survival (PFS) for FCGR2A-HH versus the rest and FCGR3A-VV versus the rest, with an 80% power, 80 Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) wild-type (KRAS-WT) and 52 KRAS-WT patients are required, respectively. This leads to a total sample size of 952 and 619 patients, respectively. Samples were collected from 1123 mCRC patients from 15 European centres treated with cetuximab alone or in combination with chemotherapy. Fc gamma receptor (FCGR) status was centrally genotyped. Two additional externally genotyped series were included. Incidences of FCGR2A-HH and FCGR3A-VV in KRAS-WT patients were 220/660 (33%) and 109/676 (16.1%) respectively. There was no difference in median PFS (mPFS) for KRAS-WT patients with FCGR2A-HH (22.0 weeks; 95% CI18.8 to 25.2) versus non-HH (22.0 weeks; 95% CI 19.4 to 24.6) or for FCGR3A-VV (16.4 weeks; 95% CI 13.0 to 19.8) versus non-VV (23 weeks; 95% CI 21.1 to 24.9) (p=0.06). Median overall survival, response rate and disease control rate assessments showed no benefit for either HH or VV. No differences in mPFS were found between the FCGR polymorphisms HH and the others and VV versus the others in KRAS-WT mCRC patients refractory to irinotecan, oxaliplatin and 5-fluorouracil treated with cetuximab. We cannot confirm the effects of other IgG1 antibodies, which may be weaker than previously suggested. Other markers may be needed to study the actual host antibody response to cetuximab. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  10. An early history of human breast cancer: West meets East.

    PubMed

    Yan, Shou-He

    2013-09-01

    Cancer has been increasingly recognized as a global issue. This is especially true in countries like China, where cancer incidence has increased likely because of changes in environment and lifestyle. However, cancer is not a modern disease; early cases have been recorded in ancient medical books in the West and in China. Here, we provide a brief history of cancer, focusing on cancer of the breast, and review the etymology of ai, the Chinese character for cancer. Notable findings from both Western and Chinese traditional medicine are presented to give an overview of the most important, early contributors to our evolving understanding of human breast cancer. We also discuss the earliest historical documents to record patients with breast cancer.

  11. An early history of human breast cancer: West meets East

    PubMed Central

    Yan, Shou-He

    2013-01-01

    Cancer has been increasingly recognized as a global issue. This is especially true in countries like China, where cancer incidence has increased likely because of changes in environment and lifestyle. However, cancer is not a modern disease; early cases have been recorded in ancient medical books in the West and in China. Here, we provide a brief history of cancer, focusing on cancer of the breast, and review the etymology of ai, the Chinese character for cancer. Notable findings from both Western and Chinese traditional medicine are presented to give an overview of the most important, early contributors to our evolving understanding of human breast cancer. We also discuss the earliest historical documents to record patients with breast cancer. PMID:23958056

  12. The AKT inhibitor perifosine in biochemically recurrent prostate cancer: a phase II California/Pittsburgh cancer consortium trial.

    PubMed

    Chee, Karen G; Longmate, Jeff; Quinn, David I; Chatta, Gurkamal; Pinski, Jacek; Twardowski, Przemyslaw; Pan, Chong-Xian; Cambio, Angelo; Evans, Christopher P; Gandara, David R; Lara, Primo N

    2007-12-01

    Perifosine is an oral alkylphospholipid that inhibits cancer cell growth through decreased Akt phosphorylation. We conducted a phase II trial of perifosine in patients with biochemically recurrent, hormone-sensitive prostate cancer. Eligible patients had histologically confirmed prostate cancer, previous prostatectomy and/or radiation therapy, and rising prostate-specific antigen (PSA) without radiographic evidence of metastasis. Previous androgen deprivation therapy < 9 months in duration (completed >or= 1 year before registration) was allowed. The primary endpoint was PSA response, defined as a decrease by >or= 50% from the pretreatment value. Treatment was composed of a loading dose of perifosine 900 mg orally on day 1, then 100 mg daily starting 24 hours later. Of 25 patients, 24 were evaluable for response. After a median follow-up of 8 months, 5 patients (20%) had a reduction in serum PSA levels, but none met criteria for PSA response. Three patients immediately progressed with no response to therapy. Median progression-free survival was 6.64 months (range, 4.53-12.81 months). No change in the PSA doubling time (7 months) was observed before and after treatment initiation. Dose-limiting toxicities (all grade 3) included hyponatremia, arthritis, hyperuricemia, and photophobia. Although well tolerated, perifosine did not meet prespecified PSA criteria for response as a single agent in biochemically recurrent prostate cancer. However, 20% of patients had evidence of PSA reduction, suggesting modest single-agent clinical activity. The role of perifosine in combination with androgen deprivation or chemotherapy is currently under investigation.

  13. Gene-based analysis of the fibroblast growth factor receptor signaling pathway in relation to breast cancer in African American women: the AMBER consortium.

    PubMed

    Ruiz-Narváez, Edward A; Haddad, Stephen A; Lunetta, Kathryn L; Yao, Song; Bensen, Jeannette T; Sucheston-Campbell, Lara E; Hong, Chi-Chen; Haiman, Christopher A; Olshan, Andrew F; Ambrosone, Christine B; Palmer, Julie R

    2016-01-01

    We conducted gene-based analysis in 26 genes in the FGFR signaling pathway to identify genes carrying genetic variation affecting risk of breast cancer and the specific estrogen receptor (ER) subtypes. Tagging single-nucleotide polymorphisms (SNPs) for each gene were selected and genotyped on a customized Illumina Exome Array. Imputation was carried out using 1000 Genomes haplotypes. The analysis included 3237 SNPs in 3663 breast cancer cases (including 1983 ER-positive, and 1098 ER-negative) and 4687 controls from the African American Breast Cancer Epidemiology and Risk consortium, a collaborative project of four large studies of breast cancer in African American women (Carolina Breast Cancer Study, Black Women's Health Study, Women's Circle of Health Study, and Multiethnic Cohort). We used a multi-locus adaptive joint (AdaJoint) test to determine the association of each gene in the FGFR signaling pathway with overall breast cancer and ER subtypes. The FGF1 gene was significantly associated with risk of ER-negative breast cancer (P = 0.001). The FGFR2 gene was associated with risk of overall breast cancer (P = 0.002) and ER-positive breast cancer (P = 0.002). The FGF1 gene affects risk of ER-negative breast cancer in African American women. We confirmed the association of the FGFR2 gene with risk of overall and ER-positive breast cancer. These results highlight the importance of the FGFR signaling pathway in the pathogenesis of breast cancer, and suggest that different genes in the same pathway may be associated with different ER breast cancer subtypes.

  14. Genetic variation in the insulin, insulin-like growth factor, growth hormone, and leptin pathways in relation to breast cancer in African-American women: the AMBER consortium

    PubMed Central

    Ruiz-Narváez, Edward A; Lunetta, Kathryn L; Hong, Chi-Chen; Haddad, Stephen; Yao, Song; Cheng, Ting-Yuan David; Bensen, Jeannette T; Bandera, Elisa V; Haiman, Christopher A; Troester, Melissa A; Ambrosone, Christine B; Rosenberg, Lynn; Palmer, Julie R

    2016-01-01

    The insulin/insulin-like growth factor (IGF) system and related pathways such as growth hormone, and leptin signaling have a key role in cancer development. It is unclear how germline variation in these pathways affects breast cancer risk. We conducted gene-based analyses of 184 genes in the insulin/IGF, growth hormone, and leptin pathways to identify genetic variation associated with risk of breast cancer overall, and for estrogen receptor (ER) subtypes. Tag single-nucleotide polymorphisms (SNPs) for each gene were selected and genotyped on a customized Illumina SNP array. Imputation was carried out using 1000 Genomes haplotypes. The analysis included 91,627 SNPs genotyped or imputed in 3,663 breast cancer cases, (1,983 ER-positive and 1,098 ER-negative) and 4,687 controls from the African American Breast Cancer Epidemiology and Risk consortium, a collaborative project of four large studies of breast cancer in African-American women (Carolina Breast Cancer Study, Black Women's Health Study, Women's Circle of Health Study, and Multiethnic Cohort). We used a multi-locus adaptive joint test to determine the association of each gene with overall breast cancer and ER subtypes. The most significant gene associations (P ≤ 0.01) were BAIAP2 and CALM2 for overall breast cancer; BAIAP2 and CSNK2A1 for ER+ breast cancer; and BRAF, BAD, and MAPK3 for ER− breast cancer. The association of BAD with ER− breast cancer was explained by a two-SNP risk model; all other associations were best explained by one-SNP risk models. In total, six genes and seven SNPs had suggestive associations with overall breast cancer or ER subtypes in African-American women. PMID:27942580

  15. Gene-based analysis of the fibroblast growth factor receptor signaling pathway in relation to breast cancer in African American women: the AMBER consortium

    PubMed Central

    Ruiz-Narváez, Edward A.; Haddad, Stephen A.; Lunetta, Kathryn L.; Yao, Song; Bensen, Jeannette T.; Sucheston-Campbell, Lara E.; Hong, Chi-Chen; Haiman, Christopher A.; Olshan, Andrew F.; Ambrosone, Christine B.; Palmer, Julie R.

    2016-01-01

    Purpose We conducted gene-based analysis in 26 genes in the FGFR signaling pathway to identify genes carrying genetic variation affecting risk of breast cancer and the specific estrogen receptor (ER) subtypes. Methods Tagging single nucleotide polymorphisms (SNPs) for each gene were selected and genotyped on a customized Illumina Exome Array. Imputation was carried out using 1000 Genomes haplotypes. The analysis included 3,237 SNPs in 3,663 breast cancer cases (including 1,983 ER positive, and 1,098 ER-negative and 4,687 controls from the African American Breast Cancer Epidemiology and Risk consortium, a collaborative project of four large studies of breast cancer in African American women (Carolina Breast Cancer Study, Black Women's Health Study, Women's Circle of Health Study, and Multiethnic Cohort). We used a multi-locus adaptive joint (AdaJoint) test to determine the association of each gene in the FGFR signaling pathway with overall breast cancer and ER subtypes. Results The FGF1 gene was significantly associated with risk of ER negative breast cancer (P = 0.001). The FGFR2 gene was associated with risk of overall breast cancer (P = 0.002) and ER positive breast cancer (P = 0.002). Conclusions The FGF1 gene affects risk of ER negative breast cancer in African American women. We confirmed the association of the FGFR2 gene with risk of overall and ER positive breast cancer. These results highlight the importance of the FGFR signaling pathway in the pathogenesis of breast cancer, and suggest that different genes in the same pathway may be associated with different ER breast cancer subtypes. PMID:26743380

  16. 9q31.2-rs865686 as a Susceptibility Locus for Estrogen Receptor-Positive Breast Cancer: Evidence from the Breast Cancer Association Consortium

    PubMed Central

    Warren, Helen; Dudbridge, Frank; Fletcher, Olivia; Orr, Nick; Johnson, Nichola; Hopper, John L.; Apicella, Carmel; Southey, Melissa C.; Mahmoodi, Maryam; Schmidt, Marjanka K.; Broeks, Annegien; Cornelissen, Sten; Braaf, Linda M.; Muir, Kenneth R.; Lophatananon, Artitaya; Chaiwerawattana, Arkom; Wiangnon, Surapon; Fasching, Peter A.; Beckmann, Matthias W.; Ekici, Arif B.; Schulz-Wendtland, Ruediger; Sawyer, Elinor J.; Tomlinson, Ian; Kerin, Michael; Burwinkel, Barbara; Marme, Frederik; Schneeweiss, Andreas; Sohn, Christof; Guénel, Pascal; Truong, Thérèse; Laurent-Puig, Pierre; Mulot, Claire; Bojesen, Stig E; Nielsen, Sune F.; Flyger, Henrik; Nordestgaard, Børge G; Milne, Roger L.; Benítez, Javier; Arias-Pérez, José-Ignacio; Zamora, M. Pilar; Anton-Culver, Hoda; Ziogas, Argyrios; Bernstein, Leslie; Dur, Christina Clarke; Brenner, Hermann; Müller, Heiko; Arndt, Volker; Langheinz, Anne; Meindl, Alfons; Golatta, Michael; Bartram, Claus R.; Schmutzler, Rita K.; Brauch, Hiltrud; Justenhoven, Christina; Brüning, Thomas; Chang-Claude, Jenny; Wang-Gohrke, Shan; Eilber, Ursula; Dörk, Thilo; Schürmann, Peter; Bremer, Michael; Hillemanns, Peter; Nevanlinna, Heli; Muranen, Taru A.; Aittomäki, Kristiina; Blomqvist, Carl; Bogdanova, Natalia; Antonenkova, Natalia; Rogov, Yuriy; Bermisheva, Marina; Prokofyeva, Darya; Zinnatullina, Guzel; Khusnutdinova, Elza; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kosma, Veli-Matti; Hartikainen, Jaana M.; Kataja, Vesa; Chenevix-Trench, Georgia; Beesley, Jonathan; Chen, Xiaoqing; Lambrechts, Diether; Smeets, Ann; Paridaens, Robert; Weltens, Caroline; Flesch-Janys, Dieter; Buck, Katharina; Behrens, Sabine; Peterlongo, Paolo; Bernard, Loris; Manoukian, Siranoush; Radice, Paolo; Couch, Fergus J.; Vachon, Celine; Wang, Xianshu; Olson, Janet; Giles, Graham; Baglietto, Laura; McLean, Cariona A.; Severi, Gianluca; John, Esther M.; Miron, Alexander; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Andrulis, Irene L.; Knight, Julia A.; Mulligan, Anna Marie; Weerasooriya, Nayana; Devilee, Peter; Tollenaar, Robert A.E.M.; Martens, John W.M.; Seynaeve, Caroline M.; Hooning, Maartje J.; Hollestelle, Antoinette; Jager, Agnes; Tilanus-Linthorst, Madeleine M.A.; Hall, Per; Czene, Kamila; Liu, Jianjun; Li, Jingmei; Cox, Angela; Cross, Simon S.; Brock, Ian W.; Reed, Malcolm W.R.; Pharoah, Paul; Blows, Fiona M.; Dunning, Alison M.; Ghoussaini, Maya; Ashworth, Alan; Swerdlow, Anthony; Jones, Michael; Schoemaker, Minouk; Easton, Douglas F.; Humphreys, Manjeet; Wang, Qin; Peto, Julian; dos-Santos-Silva, Isabel

    2013-01-01

    Background Our recent genome-wide association study identified a novel breast cancer susceptibility locus at 9q31.2 (rs865686). Methods To further investigate the rs865686–breast cancer association, we conducted a replication study within the Breast Cancer Association Consortium, which comprises 37 case–control studies (48,394 cases, 50,836 controls). Results This replication study provides additional strong evidence of an inverse association between rs865686 and breast cancer risk [study-adjusted per G-allele OR, 0.90; 95% confidence interval (CI), 0.88; 0.91, P = 2.01 × 10–29] among women of European ancestry. There were ethnic differences in the estimated minor (G)-allele frequency among controls [0.09, 0.30, and 0.38 among, respectively, Asians, Eastern Europeans, and other Europeans; P for heterogeneity (Phet) = 1.3 × 10–143], but no evidence of ethnic differences in per allele OR (Phet = 0.43). rs865686 was associated with estrogen receptor–positive (ER+) disease (per G-allele OR, 0.89; 95% CI, 0.86–0.91; P = 3.13 × 10–22) but less strongly, if at all, with ER-negative (ER–) disease (OR, 0.98; 95% CI, 0.94–1.02; P = 0.26; Phet = 1.16 × 10–6), with no evidence of independent heterogeneity by progesterone receptor or HER2 status. The strength of the breast cancer association decreased with increasing age at diagnosis, with case-only analysis showing a trend in the number of copies of the G allele with increasing age at diagnosis (P for linear trend = 0.0095), but only among women with ER+ tumors. Conclusions This study is the first to show that rs865686 is a susceptibility marker for ER+ breast cancer. Impact The findings further support the view that genetic susceptibility varies according to tumor subtype. PMID:22859399

  17. Association between body mass index and cardiovascular disease mortality in east Asians and south Asians: pooled analysis of prospective data from the Asia Cohort Consortium

    PubMed Central

    Copeland, Wade K; Vedanthan, Rajesh; Grant, Eric; Lee, Jung Eun; Gu, Dongfeng; Gupta, Prakash C; Ramadas, Kunnambath; Inoue, Manami; Tsugane, Shoichiro; Tamakoshi, Akiko; Gao, Yu-Tang; Yuan, Jian-Min; Shu, Xiao-Ou; Ozasa, Kotaro; Tsuji, Ichiro; Kakizaki, Masako; Tanaka, Hideo; Nishino, Yoshikazu; Wang, Renwei; Yoo, Keun-Young; Ahn, Yoon-Ok; Ahsan, Habibul; Pan, Wen-Harn; Pednekar, Mangesh S; Sauvaget, Catherine; Sasazuki, Shizuka; Yang, Gong; Koh, Woon-Puay; Xiang, Yong-Bing; Ohishi, Waka; Watanabe, Takashi; Sugawara, Yumi; Matsuo, Keitaro; You, San-Lin; Park, Sue K; Kim, Dong-Hyun; Parvez, Faruque; Chuang, Shao-Yuan; Ge, Wenzhen; Rolland, Betsy; McLerran, Dale; Sinha, Rashmi; Thornquist, Mark; Kang, Daehee; Feng, Ziding; Boffetta, Paolo; Zheng, Wei

    2013-01-01

    Objective To evaluate the association between body mass index and mortality from overall cardiovascular disease and specific subtypes of cardiovascular disease in east and south Asians. Design Pooled analyses of 20 prospective cohorts in Asia, including data from 835 082 east Asians and 289 815 south Asians. Cohorts were identified through a systematic search of the literature in early 2008, followed by a survey that was sent to each cohort to assess data availability. Setting General populations in east Asia (China, Taiwan, Singapore, Japan, and Korea) and south Asia (India and Bangladesh). Participants 1 124 897 men and women (mean age 53.4 years at baseline). Main outcome measures Risk of death from overall cardiovascular disease, coronary heart disease, stroke, and (in east Asians only) stroke subtypes. Results 49 184 cardiovascular deaths (40 791 in east Asians and 8393 in south Asians) were identified during a mean follow-up of 9.7 years. East Asians with a body mass index of 25 or above had a raised risk of death from overall cardiovascular disease, compared with the reference range of body mass index (values 22.5-24.9; hazard ratio 1.09 (95% confidence interval 1.03 to 1.15), 1.27 (1.20 to 1.35), 1.59 (1.43 to 1.76), 1.74 (1.47 to 2.06), and 1.97 (1.44 to 2.71) for body mass index ranges 25.0-27.4, 27.5-29.9, 30.0-32.4, 32.5-34.9, and 35.0-50.0, respectively). This association was similar for risk of death from coronary heart disease and ischaemic stroke; for haemorrhagic stroke, the risk of death was higher at body mass index values of 27.5 and above. Elevated risk of death from cardiovascular disease was also observed at lower categories of body mass index (hazard ratio 1.19 (95% confidence interval 1.02 to 1.39) and 2.16 (1.37 to 3.40) for body mass index ranges 15.0-17.4 and <15.0, respectively), compared with the reference range. In south Asians, the association between body mass index and mortality from cardiovascular disease was less

  18. Lung cancer among women in north-east China.

    PubMed

    Wu-Williams, A H; Dai, X D; Blot, W; Xu, Z Y; Sun, X W; Xiao, H P; Stone, B J; Yu, S F; Feng, Y P; Ershow, A G

    1990-12-01

    A case-control study of lung cancer involving interviews with 965 female patients and 959 controls in Shenyang and Harbin, two industrial cities which have among the highest rates of lung cancer in China, revealed that cigarette smoking is the main causal factor and accounted for about 35% of the tumours among women. Although the amount smoked was low (the cases averaged eight cigarettes per day), the percentage of smokers among women over age 50 in these cities was nearly double the national average. Air pollution from coal burning stoves was implicated, as risks of lung cancer increased in proportion to years of exposure to 'Kang' and other heating devices indigenous to the region. In addition, the number of meals cooked by deep frying and the frequency of smokiness during cooking were associated with risk of lung cancer. More cases than controls reported workplace exposures to coal dust and to smoke from burning fuel. Elevated risks were observed for smelter workers and decreased risks for textile workers. Prior chronic bronchitis/emphysema, pneumonia, and recent tuberculosis contributed significantly to lung cancer risk, as did a history of tuberculosis and lung cancer in family members. Higher intake of carotene-rich vegetables was not protective against lung cancer in this population. The findings were qualitatively similar across the major cell types of lung cancer, except that the associations with smoking and previous lung diseases were stronger for squamous/oat cell cancers than for adenocarcinoma of the lung.

  19. Common non-synonymous SNPs associated with breast cancer susceptibility: findings from the Breast Cancer Association Consortium

    PubMed Central

    Milne, Roger L.; Burwinkel, Barbara; Michailidou, Kyriaki; Arias-Perez, Jose-Ignacio; Zamora, M. Pilar; Menéndez-Rodríguez, Primitiva; Hardisson, David; Mendiola, Marta; González-Neira, Anna; Pita, Guillermo; Alonso, M. Rosario; Dennis, Joe; Wang, Qin; Bolla, Manjeet K.; Swerdlow, Anthony; Ashworth, Alan; Orr, Nick; Schoemaker, Minouk; Ko, Yon-Dschun; Brauch, Hiltrud; Hamann, Ute; Andrulis, Irene L.; Knight, Julia A.; Glendon, Gord; Tchatchou, Sandrine; Matsuo, Keitaro; Ito, Hidemi; Iwata, Hiroji; Tajima, Kazuo; Li, Jingmei; Brand, Judith S.; Brenner, Hermann; Dieffenbach, Aida Karina; Arndt, Volker; Stegmaier, Christa; Lambrechts, Diether; Peuteman, Gilian; Christiaens, Marie-Rose; Smeets, Ann; Jakubowska, Anna; Lubinski, Jan; Jaworska-Bieniek, Katarzyna; Durda, Katazyna; Hartman, Mikael; Hui, Miao; Yen Lim, Wei; Wan Chan, Ching; Marme, Federick; Yang, Rongxi; Bugert, Peter; Lindblom, Annika; Margolin, Sara; García-Closas, Montserrat; Chanock, Stephen J.; Lissowska, Jolanta; Figueroa, Jonine D.; Bojesen, Stig E.; Nordestgaard, Børge G.; Flyger, Henrik; Hooning, Maartje J.; Kriege, Mieke; van den Ouweland, Ans M.W.; Koppert, Linetta B.; Fletcher, Olivia; Johnson, Nichola; dos-Santos-Silva, Isabel; Peto, Julian; Zheng, Wei; Deming-Halverson, Sandra; Shrubsole, Martha J.; Long, Jirong; Chang-Claude, Jenny; Rudolph, Anja; Seibold, Petra; Flesch-Janys, Dieter; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Cox, Angela; Cross, Simon S.; Reed, Malcolm W.R.; Schmidt, Marjanka K.; Broeks, Annegien; Cornelissen, Sten; Braaf, Linde; Kang, Daehee; Choi, Ji-Yeob; Park, Sue K.; Noh, Dong-Young; Simard, Jacques; Dumont, Martine; Goldberg, Mark S.; Labrèche, France; Fasching, Peter A.; Hein, Alexander; Ekici, Arif B.; Beckmann, Matthias W.; Radice, Paolo; Peterlongo, Paolo; Azzollini, Jacopo; Barile, Monica; Sawyer, Elinor; Tomlinson, Ian; Kerin, Michael; Miller, Nicola; Hopper, John L.; Schmidt, Daniel F.; Makalic, Enes; Southey, Melissa C.; Hwang Teo, Soo; Har Yip, Cheng; Sivanandan, Kavitta; Tay, Wan-Ting; Shen, Chen-Yang; Hsiung, Chia-Ni; Yu, Jyh-Cherng; Hou, Ming-Feng; Guénel, Pascal; Truong, Therese; Sanchez, Marie; Mulot, Claire; Blot, William; Cai, Qiuyin; Nevanlinna, Heli; Muranen, Taru A.; Aittomäki, Kristiina; Blomqvist, Carl; Wu, Anna H.; Tseng, Chiu-Chen; Van Den Berg, David; Stram, Daniel O.; Bogdanova, Natalia; Dörk, Thilo; Muir, Kenneth; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M.; Shu, Xiao-Ou; Lu, Wei; Gao, Yu-Tang; Zhang, Ben; Couch, Fergus J.; Toland, Amanda E.; Yannoukakos, Drakoulis; Sangrajrang, Suleeporn; McKay, James; Wang, Xianshu; Olson, Janet E.; Vachon, Celine; Purrington, Kristen; Severi, Gianluca; Baglietto, Laura; Haiman, Christopher A.; Henderson, Brian E.; Schumacher, Fredrick; Le Marchand, Loic; Devilee, Peter; Tollenaar, Robert A.E.M.; Seynaeve, Caroline; Czene, Kamila; Eriksson, Mikael; Humphreys, Keith; Darabi, Hatef; Ahmed, Shahana; Shah, Mitul; Pharoah, Paul D.P.; Hall, Per; Giles, Graham G.; Benítez, Javier; Dunning, Alison M.; Chenevix-Trench, Georgia; Easton, Douglas F.; Berchuck, Andrew; Eeles, Rosalind A.; Olama, Ali Amin Al; Kote-Jarai, Zsofia; Benlloch, Sara; Antoniou, Antonis; McGuffog, Lesley; Offit, Ken; Lee, Andrew; Dicks, Ed; Luccarini, Craig; Tessier, Daniel C.; Bacot, Francois; Vincent, Daniel; LaBoissière, Sylvie; Robidoux, Frederic; Nielsen, Sune F.; Cunningham, Julie M.; Windebank, Sharon A.; Hilker, Christopher A.; Meyer, Jeffrey; Angelakos, Maggie; Maskiell, Judi; van der Schoot, Ellen; Rutgers, Emiel; Verhoef, Senno; Hogervorst, Frans; Boonyawongviroj, Prat; Siriwanarungsan, Pornthep; Schrauder, Michael; Rübner, Matthias; Oeser, Sonja; Landrith, Silke; Williams, Eileen; Ryder-Mills, Elaine; Sargus, Kara; McInerney, Niall; Colleran, Gabrielle; Rowan, Andrew; Jones, Angela; Sohn, Christof; Schneeweiß, Andeas; Bugert, Peter; Álvarez, Núria; Lacey, James; Wang, Sophia; Ma, Huiyan; Lu, Yani; Deapen, Dennis; Pinder, Rich; Lee, Eunjung; Schumacher, Fred; Horn-Ross, Pam; Reynolds, Peggy; Nelson, David; Ziegler, Hartwig; Wolf, Sonja; Hermann, Volker; Lo, Wing-Yee; Justenhoven, Christina; Baisch, Christian; Fischer, Hans-Peter; Brüning, Thomas; Pesch, Beate; Rabstein, Sylvia; Lotz, Anne; Harth, Volker; Heikkinen, Tuomas; Erkkilä, Irja; Aaltonen, Kirsimari; von Smitten, Karl; Antonenkova, Natalia; Hillemanns, Peter; Christiansen, Hans; Myöhänen, Eija; Kemiläinen, Helena; Thorne, Heather; Niedermayr, Eveline; Bowtell, D; Chenevix-Trench, G; deFazio, A; Gertig, D; Green, A; Webb, P; Green, A.; Parsons, P.; Hayward, N.; Webb, P.; Whiteman, D.; Fung, Annie; Yashiki, June; Peuteman, Gilian; Smeets, Dominiek; Brussel, Thomas Van; Corthouts, Kathleen; Obi, Nadia; Heinz, Judith; Behrens, Sabine; Eilber, Ursula; Celik, Muhabbet; Olchers, Til; Manoukian, Siranoush; Peissel, Bernard; Scuvera, Giulietta; Zaffaroni, Daniela; Bonanni, Bernardo; Feroce, Irene; Maniscalco, Angela; Rossi, Alessandra; Bernard, Loris; Tranchant, Martine; Valois, Marie-France; Turgeon, Annie; Heguy, Lea; Sze Yee, Phuah; Kang, Peter; Nee, Kang In; Mariapun, Shivaani; Sook-Yee, Yoon; Lee, Daphne; Ching, Teh Yew; Taib, Nur Aishah Mohd; Otsukka, Meeri; Mononen, Kari; Selander, Teresa; Weerasooriya, Nayana; staff, OFBCR; Krol-Warmerdam, E.; Molenaar, J.; Blom, J.; Brinton, Louise; Szeszenia-Dabrowska, Neonila; Peplonska, Beata; Zatonski, Witold; Chao, Pei; Stagner, Michael; Bos, Petra; Blom, Jannet; Crepin, Ellen; Nieuwlaat, Anja; Heemskerk, Annette; Higham, Sue; Cross, Simon; Cramp, Helen; Connley, Dan; Balasubramanian, Sabapathy; Brock, Ian; Luccarini, Craig; Conroy, Don; Baynes, Caroline; Chua, Kimberley

    2014-01-01

    Candidate variant association studies have been largely unsuccessful in identifying common breast cancer susceptibility variants, although most studies have been underpowered to detect associations of a realistic magnitude. We assessed 41 common non-synonymous single-nucleotide polymorphisms (nsSNPs) for which evidence of association with breast cancer risk had been previously reported. Case-control data were combined from 38 studies of white European women (46 450 cases and 42 600 controls) and analyzed using unconditional logistic regression. Strong evidence of association was observed for three nsSNPs: ATXN7-K264R at 3p21 [rs1053338, per allele OR = 1.07, 95% confidence interval (CI) = 1.04–1.10, P = 2.9 × 10−6], AKAP9-M463I at 7q21 (rs6964587, OR = 1.05, 95% CI = 1.03–1.07, P = 1.7 × 10−6) and NEK10-L513S at 3p24 (rs10510592, OR = 1.10, 95% CI = 1.07–1.12, P = 5.1 × 10−17). The first two associations reached genome-wide statistical significance in a combined analysis of available data, including independent data from nine genome-wide association studies (GWASs): for ATXN7-K264R, OR = 1.07 (95% CI = 1.05–1.10, P = 1.0 × 10−8); for AKAP9-M463I, OR = 1.05 (95% CI = 1.04–1.07, P = 2.0 × 10−10). Further analysis of other common variants in these two regions suggested that intronic SNPs nearby are more strongly associated with disease risk. We have thus identified a novel susceptibility locus at 3p21, and confirmed previous suggestive evidence that rs6964587 at 7q21 is associated with risk. The third locus, rs10510592, is located in an established breast cancer susceptibility region; the association was substantially attenuated after adjustment for the known GWAS hit. Thus, each of the associated nsSNPs is likely to be a marker for another, non-coding, variant causally related to breast cancer risk. Further fine-mapping and functional studies are required to identify the underlying risk-modifying variants and the genes through which they act

  20. Common non-synonymous SNPs associated with breast cancer susceptibility: findings from the Breast Cancer Association Consortium.

    PubMed

    Milne, Roger L; Burwinkel, Barbara; Michailidou, Kyriaki; Arias-Perez, Jose-Ignacio; Zamora, M Pilar; Menéndez-Rodríguez, Primitiva; Hardisson, David; Mendiola, Marta; González-Neira, Anna; Pita, Guillermo; Alonso, M Rosario; Dennis, Joe; Wang, Qin; Bolla, Manjeet K; Swerdlow, Anthony; Ashworth, Alan; Orr, Nick; Schoemaker, Minouk; Ko, Yon-Dschun; Brauch, Hiltrud; Hamann, Ute; Andrulis, Irene L; Knight, Julia A; Glendon, Gord; Tchatchou, Sandrine; Matsuo, Keitaro; Ito, Hidemi; Iwata, Hiroji; Tajima, Kazuo; Li, Jingmei; Brand, Judith S; Brenner, Hermann; Dieffenbach, Aida Karina; Arndt, Volker; Stegmaier, Christa; Lambrechts, Diether; Peuteman, Gilian; Christiaens, Marie-Rose; Smeets, Ann; Jakubowska, Anna; Lubinski, Jan; Jaworska-Bieniek, Katarzyna; Durda, Katazyna; Hartman, Mikael; Hui, Miao; Yen Lim, Wei; Wan Chan, Ching; Marme, Federick; Yang, Rongxi; Bugert, Peter; Lindblom, Annika; Margolin, Sara; García-Closas, Montserrat; Chanock, Stephen J; Lissowska, Jolanta; Figueroa, Jonine D; Bojesen, Stig E; Nordestgaard, Børge G; Flyger, Henrik; Hooning, Maartje J; Kriege, Mieke; van den Ouweland, Ans M W; Koppert, Linetta B; Fletcher, Olivia; Johnson, Nichola; dos-Santos-Silva, Isabel; Peto, Julian; Zheng, Wei; Deming-Halverson, Sandra; Shrubsole, Martha J; Long, Jirong; Chang-Claude, Jenny; Rudolph, Anja; Seibold, Petra; Flesch-Janys, Dieter; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Cox, Angela; Cross, Simon S; Reed, Malcolm W R; Schmidt, Marjanka K; Broeks, Annegien; Cornelissen, Sten; Braaf, Linde; Kang, Daehee; Choi, Ji-Yeob; Park, Sue K; Noh, Dong-Young; Simard, Jacques; Dumont, Martine; Goldberg, Mark S; Labrèche, France; Fasching, Peter A; Hein, Alexander; Ekici, Arif B; Beckmann, Matthias W; Radice, Paolo; Peterlongo, Paolo; Azzollini, Jacopo; Barile, Monica; Sawyer, Elinor; Tomlinson, Ian; Kerin, Michael; Miller, Nicola; Hopper, John L; Schmidt, Daniel F; Makalic, Enes; Southey, Melissa C; Hwang Teo, Soo; Har Yip, Cheng; Sivanandan, Kavitta; Tay, Wan-Ting; Shen, Chen-Yang; Hsiung, Chia-Ni; Yu, Jyh-Cherng; Hou, Ming-Feng; Guénel, Pascal; Truong, Therese; Sanchez, Marie; Mulot, Claire; Blot, William; Cai, Qiuyin; Nevanlinna, Heli; Muranen, Taru A; Aittomäki, Kristiina; Blomqvist, Carl; Wu, Anna H; Tseng, Chiu-Chen; Van Den Berg, David; Stram, Daniel O; Bogdanova, Natalia; Dörk, Thilo; Muir, Kenneth; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Shu, Xiao-Ou; Lu, Wei; Gao, Yu-Tang; Zhang, Ben; Couch, Fergus J; Toland, Amanda E; Yannoukakos, Drakoulis; Sangrajrang, Suleeporn; McKay, James; Wang, Xianshu; Olson, Janet E; Vachon, Celine; Purrington, Kristen; Severi, Gianluca; Baglietto, Laura; Haiman, Christopher A; Henderson, Brian E; Schumacher, Fredrick; Le Marchand, Loic; Devilee, Peter; Tollenaar, Robert A E M; Seynaeve, Caroline; Czene, Kamila; Eriksson, Mikael; Humphreys, Keith; Darabi, Hatef; Ahmed, Shahana; Shah, Mitul; Pharoah, Paul D P; Hall, Per; Giles, Graham G; Benítez, Javier; Dunning, Alison M; Chenevix-Trench, Georgia; Easton, Douglas F

    2014-11-15

    Candidate variant association studies have been largely unsuccessful in identifying common breast cancer susceptibility variants, although most studies have been underpowered to detect associations of a realistic magnitude. We assessed 41 common non-synonymous single-nucleotide polymorphisms (nsSNPs) for which evidence of association with breast cancer risk had been previously reported. Case-control data were combined from 38 studies of white European women (46 450 cases and 42 600 controls) and analyzed using unconditional logistic regression. Strong evidence of association was observed for three nsSNPs: ATXN7-K264R at 3p21 [rs1053338, per allele OR = 1.07, 95% confidence interval (CI) = 1.04-1.10, P = 2.9 × 10(-6)], AKAP9-M463I at 7q21 (rs6964587, OR = 1.05, 95% CI = 1.03-1.07, P = 1.7 × 10(-6)) and NEK10-L513S at 3p24 (rs10510592, OR = 1.10, 95% CI = 1.07-1.12, P = 5.1 × 10(-17)). The first two associations reached genome-wide statistical significance in a combined analysis of available data, including independent data from nine genome-wide association studies (GWASs): for ATXN7-K264R, OR = 1.07 (95% CI = 1.05-1.10, P = 1.0 × 10(-8)); for AKAP9-M463I, OR = 1.05 (95% CI = 1.04-1.07, P = 2.0 × 10(-10)). Further analysis of other common variants in these two regions suggested that intronic SNPs nearby are more strongly associated with disease risk. We have thus identified a novel susceptibility locus at 3p21, and confirmed previous suggestive evidence that rs6964587 at 7q21 is associated with risk. The third locus, rs10510592, is located in an established breast cancer susceptibility region; the association was substantially attenuated after adjustment for the known GWAS hit. Thus, each of the associated nsSNPs is likely to be a marker for another, non-coding, variant causally related to breast cancer risk. Further fine-mapping and functional studies are required to identify the underlying risk-modifying variants and the genes through which they act. © The

  1. Genome-wide Analysis Identifies Novel Loci Associated with Ovarian Cancer Outcomes: Findings from the Ovarian Cancer Association Consortium.

    PubMed

    Johnatty, Sharon E; Tyrer, Jonathan P; Kar, Siddhartha; Beesley, Jonathan; Lu, Yi; Gao, Bo; Fasching, Peter A; Hein, Alexander; Ekici, Arif B; Beckmann, Matthias W; Lambrechts, Diether; Van Nieuwenhuysen, Els; Vergote, Ignace; Lambrechts, Sandrina; Rossing, Mary Anne; Doherty, Jennifer A; Chang-Claude, Jenny; Modugno, Francesmary; Ness, Roberta B; Moysich, Kirsten B; Levine, Douglas A; Kiemeney, Lambertus A; Massuger, Leon F A G; Gronwald, Jacek; Lubiński, Jan; Jakubowska, Anna; Cybulski, Cezary; Brinton, Louise; Lissowska, Jolanta; Wentzensen, Nicolas; Song, Honglin; Rhenius, Valerie; Campbell, Ian; Eccles, Diana; Sieh, Weiva; Whittemore, Alice S; McGuire, Valerie; Rothstein, Joseph H; Sutphen, Rebecca; Anton-Culver, Hoda; Ziogas, Argyrios; Gayther, Simon A; Gentry-Maharaj, Aleksandra; Menon, Usha; Ramus, Susan J; Pearce, Celeste L; Pike, Malcolm C; Stram, Daniel O; Wu, Anna H; Kupryjanczyk, Jolanta; Dansonka-Mieszkowska, Agnieszka; Rzepecka, Iwona K; Spiewankiewicz, Beata; Goodman, Marc T; Wilkens, Lynne R; Carney, Michael E; Thompson, Pamela J; Heitz, Florian; du Bois, Andreas; Schwaab, Ira; Harter, Philipp; Pisterer, Jacobus; Hillemanns, Peter; Karlan, Beth Y; Walsh, Christine; Lester, Jenny; Orsulic, Sandra; Winham, Stacey J; Earp, Madalene; Larson, Melissa C; Fogarty, Zachary C; Høgdall, Estrid; Jensen, Allan; Kjaer, Susanne Kruger; Fridley, Brooke L; Cunningham, Julie M; Vierkant, Robert A; Schildkraut, Joellen M; Iversen, Edwin S; Terry, Kathryn L; Cramer, Daniel W; Bandera, Elisa V; Orlow, Irene; Pejovic, Tanja; Bean, Yukie; Høgdall, Claus; Lundvall, Lene; McNeish, Ian; Paul, James; Carty, Karen; Siddiqui, Nadeem; Glasspool, Rosalind; Sellers, Thomas; Kennedy, Catherine; Chiew, Yoke-Eng; Berchuck, Andrew; MacGregor, Stuart; Pharoah, Paul D P; Goode, Ellen L; deFazio, Anna; Webb, Penelope M; Chenevix-Trench, Georgia

    2015-12-01

    Chemotherapy resistance remains a major challenge in the treatment of ovarian cancer. We hypothesize that germline polymorphisms might be associated with clinical outcome. We analyzed approximately 2.8 million genotyped and imputed SNPs from the iCOGS experiment for progression-free survival (PFS) and overall survival (OS) in 2,901 European epithelial ovarian cancer (EOC) patients who underwent first-line treatment of cytoreductive surgery and chemotherapy regardless of regimen, and in a subset of 1,098 patients treated with ≥ 4 cycles of paclitaxel and carboplatin at standard doses. We evaluated the top SNPs in 4,434 EOC patients, including patients from The Cancer Genome Atlas. In addition, we conducted pathway analysis of all intragenic SNPs and tested their association with PFS and OS using gene set enrichment analysis. Five SNPs were significantly associated (P ≤ 1.0 × 10(-5)) with poorer outcomes in at least one of the four analyses, three of which, rs4910232 (11p15.3), rs2549714 (16q23), and rs6674079 (1q22), were located in long noncoding RNAs (lncRNAs) RP11-179A10.1, RP11-314O13.1, and RP11-284F21.8, respectively (P ≤ 7.1 × 10(-6)). ENCODE ChIP-seq data at 1q22 for normal ovary show evidence of histone modification around RP11-284F21.8, and rs6674079 is perfectly correlated with another SNP within the super-enhancer MEF2D, expression levels of which were reportedly associated with prognosis in another solid tumor. YAP1- and WWTR1 (TAZ)-stimulated gene expression and high-density lipoprotein (HDL)-mediated lipid transport pathways were associated with PFS and OS, respectively, in the cohort who had standard chemotherapy (pGSEA ≤ 6 × 10(-3)). We have identified SNPs in three lncRNAs that might be important targets for novel EOC therapies. ©2015 American Association for Cancer Research.

  2. Admixture Mapping of African–American Women in the AMBER Consortium Identifies New Loci for Breast Cancer and Estrogen-Receptor Subtypes

    PubMed Central

    Ruiz-Narváez, Edward A.; Sucheston-Campbell, Lara; Bensen, Jeannette T.; Yao, Song; Haddad, Stephen; Haiman, Christopher A.; Bandera, Elisa V.; John, Esther M.; Bernstein, Leslie; Hu, Jennifer J.; Ziegler, Regina G.; Deming, Sandra L.; Olshan, Andrew F.; Ambrosone, Christine B.; Palmer, Julie R.; Lunetta, Kathryn L.

    2016-01-01

    Recent genetic admixture coupled with striking differences in incidence of estrogen receptor (ER) breast cancer subtypes, as well as severity, between women of African and European ancestry, provides an excellent rationale for performing admixture mapping in African American women with breast cancer risk. We performed the largest breast cancer admixture mapping study with in African American women to identify novel genomic regions associated with the disease. We conducted a genome-wide admixture scan using 2,624 autosomal ancestry informative markers (AIMs) in 3,629 breast cancer cases (including 1,968 ER-positive, 1093 ER-negative, and 601 triple-negative) and 4,658 controls from the African American Breast Cancer Epidemiology and Risk (AMBER) Consortium, a collaborative study of four large geographically different epidemiological studies of breast cancer in African American women. We used an independent case-control study to test for SNP association in regions with genome-wide significant admixture signals. We found two novel genome-wide significant regions of excess African ancestry, 4p16.1 and 17q25.1, associated with ER-positive breast cancer. Two regions known to harbor breast cancer variants, 10q26 and 11q13, were also identified with excess of African ancestry. Fine-mapping of the identified genome-wide significant regions suggests the presence of significant genetic associations with ER-positive breast cancer in 4p16.1 and 11q13. In summary, we identified three novel genomic regions associated with breast cancer risk by ER status, suggesting that additional previously unidentified variants may contribute to the racial differences in breast cancer risk in the African American population. PMID:27708667

  3. Genome-wide analysis identifies novel loci associated with ovarian cancer outcomes: findings from the Ovarian Cancer Association Consortium

    PubMed Central

    Johnatty, Sharon E.; Tyrer, Jonathan P.; Kar, Siddhartha; Beesley, Jonathan; Lu, Yi; Gao, Bo; Fasching, Peter A.; Hein, Alexander; Ekici, Arif B.; Beckmann, Matthias W.; Lambrechts, Diether; Nieuwenhuysen, Els Van; Vergote, Ignace; Lambrechts, Sandrina; Rossing, Mary Anne; Doherty, Jennifer A.; Chang-Claude, Jenny; Modugno, Francesmary; Ness, Roberta B.; Moysich, Kirsten B.; Levine, Douglas A.; Kiemeney, Lambertus A.; Massuger, Leon F.A.G.; Gronwald, Jacek; Lubiński, Jan; Jakubowska, Anna; Cybulski, Cezary; Brinton, Louise; Lissowska, Jolanta; Wentzensen, Nicolas; Song, Honglin; Rhenius, Valerie; Campbell, Ian; Eccles, Diana; Sieh, Weiva; Whittemore, Alice S.; McGuire, Valerie; Rothstein, Joseph H.; Sutphen, Rebecca; Anton-Culver, Hoda; Ziogas, Argyrios; Gayther, Simon A.; Gentry-Maharaj, Aleksandra; Menon, Usha; Ramus, Susan J.; Pearce, Celeste L; Pike, Malcolm C; Stram, Daniel O.; Wu, Anna H.; Kupryjanczyk, Jolanta; Dansonka-Mieszkowska, Agnieszka; Rzepecka, Iwona K.; Spiewankiewicz, Beata; Goodman, Marc T.; Wilkens, Lynne R.; Carney, Michael E.; Thompson, Pamela J; Heitz, Florian; du Bois, Andreas; Schwaab, Ira; Harter, Philipp; Pisterer, Jacobus; Hillemanns, Peter; Karlan, Beth Y.; Walsh, Christine; Lester, Jenny; Orsulic, Sandra; Winham, Stacey J; Earp, Madalene; Larson, Melissa C.; Fogarty, Zachary C.; Høgdall, Estrid; Jensen, Allan; Kjaer, Susanne Kruger; Fridley, Brooke L.; Cunningham, Julie M.; Vierkant, Robert A.; Schildkraut, Joellen M.; Iversen, Edwin S.; Terry, Kathryn L.; Cramer, Daniel W.; Bandera, Elisa V.; Orlow, Irene; Pejovic, Tanja; Bean, Yukie; Høgdall, Claus; Lundvall, Lene; McNeish, Ian; Paul, James; Carty, Karen; Siddiqui, Nadeem; Glasspool, Rosalind; Sellers, Thomas; Kennedy, Catherine; Chiew, Yoke-Eng; Berchuck, Andrew; MacGregor, Stuart; deFazio, Anna; Pharoah, Paul D.P.; Goode, Ellen L.; deFazio, Anna; Webb, Penelope M.; Chenevix-Trench, Georgia

    2015-01-01

    Purpose Chemotherapy resistance remains a major challenge in the treatment of ovarian cancer. We hypothesize that germline polymorphisms might be associated with clinical outcome. Experimental Design We analyzed ~2.8 million genotyped and imputed SNPs from the iCOGS experiment for progression-free survival (PFS) and overall survival (OS) in 2,901 European epithelial ovarian cancer (EOC) patients who underwent firstline treatment of cytoreductive surgery and chemotherapy regardless of regimen, and in a subset of 1,098 patients treated with ≥4 cycles of paclitaxel and carboplatin at standard doses. We evaluated the top SNPs in 4,434 EOC patients including patients from The Cancer Genome Atlas. Additionally we conducted pathway analysis of all intragenic SNPs and tested their association with PFS and OS using gene set enrichment analysis. Results Five SNPs were significantly associated (p≤1.0x10−5) with poorer outcomes in at least one of the four analyses, three of which, rs4910232 (11p15.3), rs2549714 (16q23) and rs6674079 (1q22) were located in long non-coding RNAs (lncRNAs) RP11–179A10.1, RP11–314O13.1 and RP11–284F21.8 respectively (p≤7.1x10−6). ENCODE ChIP-seq data at 1q22 for normal ovary shows evidence of histone modification around RP11–284F21.8, and rs6674079 is perfectly correlated with another SNP within the super-enhancer MEF2D, expression levels of which were reportedly associated with prognosis in another solid tumor. YAP1- and WWTR1 (TAZ)-stimulated gene expression, and HDL-mediated lipid transport pathways were associated with PFS and OS, respectively, in the cohort who had standard chemotherapy (pGSEA≤6x10−3). Conclusion We have identified SNPs in three lncRNAs that might be important targets for novel EOC therapies. PMID:26152742

  4. Comparison of 6q25 breast cancer hits from Asian and European Genome Wide Association Studies in the Breast Cancer Association Consortium (BCAC).

    PubMed

    Hein, Rebecca; Maranian, Melanie; Hopper, John L; Kapuscinski, Miroslaw K; Southey, Melissa C; Park, Daniel J; Schmidt, Marjanka K; Broeks, Annegien; Hogervorst, Frans B L; Bueno-de-Mesquita, H Bas; Bueno-de-Mesquit, H Bas; Muir, Kenneth R; Lophatananon, Artitaya; Rattanamongkongul, Suthee; Puttawibul, Puttisak; Fasching, Peter A; Hein, Alexander; Ekici, Arif B; Beckmann, Matthias W; Fletcher, Olivia; Johnson, Nichola; dos Santos Silva, Isabel; Peto, Julian; Sawyer, Elinor; Tomlinson, Ian; Kerin, Michael; Miller, Nicola; Marmee, Frederick; Schneeweiss, Andreas; Sohn, Christof; Burwinkel, Barbara; Guénel, Pascal; Cordina-Duverger, Emilie; Menegaux, Florence; Truong, Thérèse; Bojesen, Stig E; Nordestgaard, Børge G; Flyger, Henrik; Milne, Roger L; Perez, Jose Ignacio Arias; Zamora, M Pilar; Benítez, Javier; Anton-Culver, Hoda; Ziogas, Argyrios; Bernstein, Leslie; Clarke, Christina A; Brenner, Hermann; Müller, Heiko; Arndt, Volker; Stegmaier, Christa; Rahman, Nazneen; Seal, Sheila; Turnbull, Clare; Renwick, Anthony; Meindl, Alfons; Schott, Sarah; Bartram, Claus R; Schmutzler, Rita K; Brauch, Hiltrud; Hamann, Ute; Ko, Yon-Dschun; Wang-Gohrke, Shan; Dörk, Thilo; Schürmann, Peter; Karstens, Johann H; Hillemanns, Peter; Nevanlinna, Heli; Heikkinen, Tuomas; Aittomäki, Kristiina; Blomqvist, Carl; Bogdanova, Natalia V; Zalutsky, Iosif V; Antonenkova, Natalia N; Bermisheva, Marina; Prokovieva, Darya; Farahtdinova, Albina; Khusnutdinova, Elza; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana; Chen, Xiaoqing; Beesley, Jonathan; Lambrechts, Diether; Zhao, Hui; Neven, Patrick; Wildiers, Hans; Nickels, Stefan; Flesch-Janys, Dieter; Radice, Paolo; Peterlongo, Paolo; Manoukian, Siranoush; Barile, Monica; Couch, Fergus J; Olson, Janet E; Wang, Xianshu; Fredericksen, Zachary; Giles, Graham G; Baglietto, Laura; McLean, Catriona A; Severi, Gianluca; Offit, Kenneth; Robson, Mark; Gaudet, Mia M; Vijai, Joseph; Alnæs, Grethe Grenaker; Kristensen, Vessela; Børresen-Dale, Anne-Lise; John, Esther M; Miron, Alexander; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Andrulis, Irene L; Knight, Julia A; Glendon, Gord; Mulligan, Anna Marie; Figueroa, Jonine D; García-Closas, Montserrat; Lissowska, Jolanta; Sherman, Mark E; Hooning, Maartje; Martens, John W M; Seynaeve, Caroline; Collée, Margriet; Hall, Per; Humpreys, Keith; Czene, Kamila; Liu, Jianjun; Cox, Angela; Brock, Ian W; Cross, Simon S; Reed, Malcolm W R; Ahmed, Shahana; Ghoussaini, Maya; Pharoah, Paul D P; Kang, Daehee; Yoo, Keun-Young; Noh, Dong-Young; Jakubowska, Anna; Jaworska, Katarzyna; Durda, Katarzyna; Złowocka, Elżbieta; Sangrajrang, Suleeporn; Gaborieau, Valerie; Brennan, Paul; McKay, James; Shen, Chen-Yang; Yu, Jyh-Cherng; Hsu, Huan-Ming; Hou, Ming-Feng; Orr, Nick; Schoemaker, Minouk; Ashworth, Alan; Swerdlow, Anthony; Trentham-Dietz, Amy; Newcomb, Polly A; Titus, Linda; Egan, Kathleen M; Chenevix-Trench, Georgia; Antoniou, Antonis C; Humphreys, Manjeet K; Morrison, Jonathan; Chang-Claude, Jenny; Easton, Douglas F; Dunning, Alison M

    2012-01-01

    The 6q25.1 locus was first identified via a genome-wide association study (GWAS) in Chinese women and marked by single nucleotide polymorphism (SNP) rs2046210, approximately 180 Kb upstream of ESR1. There have been conflicting reports about the association of this locus with breast cancer in Europeans, and a GWAS in Europeans identified a different SNP, tagged here by rs12662670. We examined the associations of both SNPs in up to 61,689 cases and 58,822 controls from forty-four studies collaborating in the Breast Cancer Association Consortium, of which four studies were of Asian and 39 of European descent. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). Case-only analyses were used to compare SNP effects in Estrogen Receptor positive (ER+) versus negative (ER-) tumours. Models including both SNPs were fitted to investigate whether the SNP effects were independent. Both SNPs are significantly associated with breast cancer risk in both ethnic groups. Per-allele ORs are higher in Asian than in European studies [rs2046210: OR (A/G) = 1.36 (95% CI 1.26-1.48), p = 7.6 × 10(-14) in Asians and 1.09 (95% CI 1.07-1.11), p = 6.8 × 10(-18) in Europeans. rs12662670: OR (G/T) = 1.29 (95% CI 1.19-1.41), p = 1.2 × 10(-9) in Asians and 1.12 (95% CI 1.08-1.17), p = 3.8 × 10(-9) in Europeans]. SNP rs2046210 is associated with a significantly greater risk of ER- than ER+ tumours in Europeans [OR (ER-) = 1.20 (95% CI 1.15-1.25), p = 1.8 × 10(-17) versus OR (ER+) = 1.07 (95% CI 1.04-1.1), p = 1.3 × 10(-7), p(heterogeneity) = 5.1 × 10(-6)]. In these Asian studies, by contrast, there is no clear evidence of a differential association by tumour receptor status. Each SNP is associated with risk after adjustment for the other SNP. These results suggest the presence of two variants at 6q25.1 each independently associated with breast cancer risk in Asians and in Europeans. Of these two, the one tagged by rs2046210 is associated with a greater

  5. Comparison of 6q25 Breast Cancer Hits from Asian and European Genome Wide Association Studies in the Breast Cancer Association Consortium (BCAC)

    PubMed Central

    Hein, Rebecca; Maranian, Melanie; Hopper, John L.; Kapuscinski, Miroslaw K.; Southey, Melissa C.; Park, Daniel J.; Schmidt, Marjanka K.; Broeks, Annegien; Hogervorst, Frans B. L.; Bueno-de-Mesquit, H. Bas; Muir, Kenneth R.; Lophatananon, Artitaya; Rattanamongkongul, Suthee; Puttawibul, Puttisak; Fasching, Peter A.; Hein, Alexander; Ekici, Arif B.; Beckmann, Matthias W.; Fletcher, Olivia; Johnson, Nichola; dos Santos Silva, Isabel; Peto, Julian; Sawyer, Elinor; Tomlinson, Ian; Kerin, Michael; Miller, Nicola; Marmee, Frederick; Schneeweiss, Andreas; Sohn, Christof; Burwinkel, Barbara; Guénel, Pascal; Cordina-Duverger, Emilie; Menegaux, Florence; Truong, Thérèse; Bojesen, Stig E.; Nordestgaard, Børge G.; Flyger, Henrik; Milne, Roger L.; Perez, Jose Ignacio Arias; Zamora, M. Pilar; Benítez, Javier; Anton-Culver, Hoda; Ziogas, Argyrios; Bernstein, Leslie; Clarke, Christina A.; Brenner, Hermann; Müller, Heiko; Arndt, Volker; Stegmaier, Christa; Rahman, Nazneen; Seal, Sheila; Turnbull, Clare; Renwick, Anthony; Meindl, Alfons; Schott, Sarah; Bartram, Claus R.; Schmutzler, Rita K.; Brauch, Hiltrud; Hamann, Ute; Ko, Yon-Dschun; Wang-Gohrke, Shan; Dörk, Thilo; Schürmann, Peter; Karstens, Johann H.; Hillemanns, Peter; Nevanlinna, Heli; Heikkinen, Tuomas; Aittomäki, Kristiina; Blomqvist, Carl; Bogdanova, Natalia V.; Zalutsky, Iosif V.; Antonenkova, Natalia N.; Bermisheva, Marina; Prokovieva, Darya; Farahtdinova, Albina; Khusnutdinova, Elza; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana; Chen, Xiaoqing; Beesley, Jonathan; Investigators, kConFab; Lambrechts, Diether; Zhao, Hui; Neven, Patrick; Wildiers, Hans; Nickels, Stefan; Flesch-Janys, Dieter; Radice, Paolo; Peterlongo, Paolo; Manoukian, Siranoush; Barile, Monica; Couch, Fergus J.; Olson, Janet E.; Wang, Xianshu; Fredericksen, Zachary; Giles, Graham G.; Baglietto, Laura; McLean, Catriona A.; Severi, Gianluca; Offit, Kenneth; Robson, Mark; Gaudet, Mia M.; Vijai, Joseph; Alnæs, Grethe Grenaker; Kristensen, Vessela; Børresen-Dale, Anne-Lise; John, Esther M.; Miron, Alexander; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Andrulis, Irene L.; Knight, Julia A.; Glendon, Gord; Mulligan, Anna Marie; Figueroa, Jonine D.; García-Closas, Montserrat; Lissowska, Jolanta; Sherman, Mark E.; Hooning, Maartje; Martens, John W. M.; Seynaeve, Caroline; Collée, Margriet; Hall, Per; Humpreys, Keith; Czene, Kamila; Liu, Jianjun; Cox, Angela; Brock, Ian W.; Cross, Simon S.; Reed, Malcolm W. R.; Ahmed, Shahana; Ghoussaini, Maya; Pharoah, Paul DP.; Kang, Daehee; Yoo, Keun-Young; Noh, Dong-Young; Jakubowska, Anna; Jaworska, Katarzyna; Durda, Katarzyna; Złowocka, Elżbieta; Sangrajrang, Suleeporn; Gaborieau, Valerie; Brennan, Paul; McKay, James; Shen, Chen-Yang; Yu, Jyh-Cherng; Hsu, Huan-Ming; Hou, Ming-Feng; Orr, Nick; Schoemaker, Minouk; Ashworth, Alan; Swerdlow, Anthony; Trentham-Dietz, Amy; Newcomb, Polly A.; Titus, Linda; Egan, Kathleen M.; Chenevix-Trench, Georgia; Antoniou, Antonis C.; Humphreys, Manjeet K.; Morrison, Jonathan; Chang-Claude, Jenny; Easton, Douglas F.; Dunning, Alison M.

    2012-01-01

    The 6q25.1 locus was first identified via a genome-wide association study (GWAS) in Chinese women and marked by single nucleotide polymorphism (SNP) rs2046210, approximately 180 Kb upstream of ESR1. There have been conflicting reports about the association of this locus with breast cancer in Europeans, and a GWAS in Europeans identified a different SNP, tagged here by rs12662670. We examined the associations of both SNPs in up to 61,689 cases and 58,822 controls from forty-four studies collaborating in the Breast Cancer Association Consortium, of which four studies were of Asian and 39 of European descent. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). Case-only analyses were used to compare SNP effects in Estrogen Receptor positive (ER+) versus negative (ER−) tumours. Models including both SNPs were fitted to investigate whether the SNP effects were independent. Both SNPs are significantly associated with breast cancer risk in both ethnic groups. Per-allele ORs are higher in Asian than in European studies [rs2046210: OR (A/G) = 1.36 (95% CI 1.26–1.48), p = 7.6×10−14 in Asians and 1.09 (95% CI 1.07–1.11), p = 6.8×10−18 in Europeans. rs12662670: OR (G/T) = 1.29 (95% CI 1.19–1.41), p = 1.2×10−9 in Asians and 1.12 (95% CI 1.08–1.17), p = 3.8×10−9 in Europeans]. SNP rs2046210 is associated with a significantly greater risk of ER− than ER+ tumours in Europeans [OR (ER−) = 1.20 (95% CI 1.15–1.25), p = 1.8×10−17 versus OR (ER+) = 1.07 (95% CI 1.04–1.1), p = 1.3×10−7, pheterogeneity = 5.1×10−6]. In these Asian studies, by contrast, there is no clear evidence of a differential association by tumour receptor status. Each SNP is associated with risk after adjustment for the other SNP. These results suggest the presence of two variants at 6q25.1 each independently associated with breast cancer risk in Asians and in Europeans. Of these two, the one

  6. Allergies and risk of pancreatic cancer: a pooled analysis from the Pancreatic Cancer Case-Control Consortium.

    PubMed

    Olson, Sara H; Hsu, Meier; Satagopan, Jaya M; Maisonneuve, Patrick; Silverman, Debra T; Lucenteforte, Ersilia; Anderson, Kristin E; Borgida, Ayelet; Bracci, Paige M; Bueno-de-Mesquita, H Bas; Cotterchio, Michelle; Dai, Qi; Duell, Eric J; Fontham, Elizabeth H; Gallinger, Steven; Holly, Elizabeth A; Ji, Bu-Tian; Kurtz, Robert C; La Vecchia, Carlo; Lowenfels, Albert B; Luckett, Brian; Ludwig, Emmy; Petersen, Gloria M; Polesel, Jerry; Seminara, Daniela; Strayer, Lori; Talamini, Renato

    2013-09-01

    In order to quantify the risk of pancreatic cancer associated with history of any allergy and specific allergies, to investigate differences in the association with risk according to age, gender, smoking status, or body mass index, and to study the influence of age at onset, we pooled data from 10 case-control studies. In total, there were 3,567 cases and 9,145 controls. Study-specific odds ratios and 95% confidence intervals were calculated by using unconditional logistic regression adjusted for age, gender, smoking status, and body mass index. Between-study heterogeneity was assessed by using the Cochran Q statistic. Study-specific odds ratios were pooled by using a random-effects model. The odds ratio for any allergy was 0.79 (95% confidence interval (CI): 0.62, 1.00) with heterogeneity among studies (P < 0.001). Heterogeneity was attributable to one study; with that study excluded, the pooled odds ratio was 0.73 (95% CI: 0.64, 0.84) (Pheterogeneity = 0.23). Hay fever (odds ratio = 0.74, 95% CI: 0.56, 0.96) and allergy to animals (odds ratio = 0.62, 95% CI: 0.41, 0.94) were related to lower risk, while there was no statistically significant association with other allergies or asthma. There were no major differences among subgroups defined by age, gender, smoking status, or body mass index. Older age at onset of allergies was slightly more protective than earlier age.

  7. Meeting report: The 13th Annual Meeting of the Translational Research Cancer Centers Consortium (TrC3); Immune Suppression and the Tumor Microenvironment, Columbus, Ohio; March 1-2, 2010.

    PubMed

    Lesinski, Gregory B; Carson, William E; Repasky, Elizabeth A; Wei, Wei-zen; Kalinski, Pawel; Lotze, Michael T; June, Carl H; Petros, William; Muthusamy, Natarajan; Olencki, Thomas

    2010-09-01

    The Translational Research Cancer Centers Consortium (TrC3) is a cancer immunotherapy network, established to promote biologic therapeutics in the Midwestern and Northeastern regions of The United States. The 13th Annual Meeting of the TrC3 was hosted by The Ohio State University Comprehensive Cancer Center-Arthur G. James Cancer Hospital and Richard J. Solove Research Institute and took place at The Blackwell Hotel and Conference Center in Columbus, OH on March 1-2, 2010 (http://www.osuccc.osu.edu/TrC3/index.htm). This year's theme was "Immune Suppression and the Tumor Microenvironment." The meeting consisted of 21 oral presentations, a roundtable discussion focused on enhancing collaborative relationships within the consortium, and a poster session with 54 abstracts from predoctoral or postdoctoral researchers. This annual meeting brought together more than 170 investigators from 9 regional cancer centers including: Abramson Cancer Center at The University of Pennsylvania, Barbara Ann Karmanos Cancer Institute at Wayne State University, Case Comprehensive Cancer Center, Cleveland Clinic Taussig Cancer Center, James P. Wilmot Cancer Center, Mary Babb Randolph Cancer Center at West Virginia University, The Ohio State University Comprehensive Cancer Center, Penn State Cancer Institute, Roswell Park Cancer Institute, and University of Pittsburgh Cancer Institute. The proceedings of this year's meeting are summarized in this report.

  8. Cancer Care in East and Central Harlem: Community Partnership Needs Assessment

    PubMed Central

    Jandorf, Lina; Freemantle, Hurdley; Sly, Jamilia; Ellison, Jennie; Wong, Carrie R.; Villagra, Cristina; Hong, Joseph; Kaleya, Sara; Poultney, Madrid; Villegas, Carmen; Brenner, Barbara; Bickell, Nina

    2015-01-01

    In the largely African American and Hispanic communities of East and Central Harlem in New York City (NYC), health inequities are glaring. Mortality from cancer is 20–30 % higher than in Manhattan and 30–40 % higher than rates in the general population in NYC. Despite advances in risk assessment, early detection, treatment, and survivorship, individuals in Harlem and similar urban communities are not benefiting equally. Guided by community-based participatory research, this study serves as an important step in understanding cancer care needs and the range of factors that impact the disparate rates of cancer in East and Central Harlem. Forty individual interviews were conducted with community leaders and residents. Major themes included: need for appropriate supportive services; health care access and financial challenges; beliefs related to stigma, trust, and accountability; and the impact of the physical environment on health. Education was seen as a critical area of need and intervention. PMID:23108854

  9. Risk Analysis of Prostate Cancer in PRACTICAL, a Multinational Consortium, Using 25 Known Prostate Cancer Susceptibility Loci

    PubMed Central

    Amin Al Olama, Ali; Benlloch, Sara; Antoniou, Antonis C.; Zeigler-Johnson, Charnita; Stephenson, Robert; Cox, Angela; Southey, Melissa C.; Spurdle, Amanda B.; FitzGerald, Liesel; Leongamornlert, Daniel; Saunders, Edward; Tymrakiewicz, Malgorzata; Guy, Michelle; Dadaev, Tokhir; Little, Sarah J.; Govindasami, Koveela; Sawyer, Emma; Wilkinson, Rosemary; Herkommer, Kathleen; Hopper, John L.; Lophatonanon, Aritaya; Rinckleb, Antje E.; Kote-Jarai, Zsofia; Eeles, Rosalind A.; Easton, Douglas F.

    2015-01-01

    Background Genome-wide association studies have identified multiple genetic variants associated with prostate cancer (PrCa) risk which explain a substantial proportion of familial relative risk. These variants can be used to stratify individuals by their risk of PrCa. Methods We genotyped 25 PrCa susceptibility loci in 40,414 individuals and derived a polygenic risk score (PRS). We estimated empirical Odds Ratios for PrCa associated with different risk strata defined by PRS and derived age-specific absolute risks of developing PrCa by PRS stratum and family history. Results The PrCa risk for men in the top 1% of the PRS distribution was 30.6 (95% CI 16.4-57.3) fold compared with men in the bottom 1%, and 4.2 (95% CI 3.2-5.5) fold compared with the median risk. The absolute risk of PrCa by age 85 was 65.8% for a man with family history in the top 1% of the PRS distribution, compared with 3.7% for a man in the bottom 1%. The PRS was only weakly correlated with serum PSA level (correlation=0.09). Conclusions Risk profiling can identify men at substantially increased or reduced risk of PrCa. The effect size, measured by OR per unit PRS, was higher in men at younger ages and in men with family history of PrCa. Incorporating additional newly identified loci into a PRS should improve the predictive value of risk profiles. Impact We demonstrate that the risk profiling based on SNPs can identify men at substantially increased or reduced risk that could have useful implications for targeted prevention and screening programs. PMID:25837820

  10. A Phase II Trial of Vorinostat (Suberoylanilide Hydroxamic Acid, -SAHA) in Metastatic Breast Cancer: A California Cancer Consortium Study

    PubMed Central

    Luu, Thehang H; Morgan, Robert J; Leong, Lucille; Lim, Dean; McNamara, Mark; Portnow, Jana; Frankel, Paul; Smith, David D.; Doroshow, James H.; Gandara, David R; Aparicio, Ana; Somlo, George

    2011-01-01

    Purpose The primary goal of this trial was to determine the response rate of single-agent vorinostat in patients with metastatic breast cancer. The secondary goals included assessment of time to progression, evaluation of toxicities, and overall survival. Experimental Design From June 2005 to March 2006, fourteen patients received vorinostat, 200 mg orally, twice daily for 14 days of each 21 day cycle. Response and progression were evaluated using RECIST criteria. Results The median age for all patients was 60.5 years (range: 37–88). Eight patients were ER and/or PR positive, four were Her-2 positive. Sites of metastatic disease included brain, liver, lungs, bones, pelvis, pleura, chest wall, and distant lymph nodes. Patients received a median of 1.5 prior (range: 0–2) chemotherapeutic regimens for metastatic disease. Fatigue, nausea, diarrhea, and lymphopenia were the most frequent clinically significant adverse effects. The median number of cycles delivered was two (range: 1–20). There were no complete or partial responses and the study was terminated after the first stage, however 4 patients were observed with stable disease with time to progression of 4,8,9 and 14 months. The median number of months that patients received treatment on this study was 1.7 (range: 0.5–14). Conclusion While not meeting the RECIST response criteria for adequate single-agent activity, the observed tolerable toxicities and the potential for clinical benefit in terms of stable disease suggest that further assessment of vorinostat as a part of combination therapy with either chemotherapeutic or targeted agents in metastatic breast might be undertaken. PMID:18981013

  11. Allergies and Risk of Pancreatic Cancer: A Pooled Analysis From the Pancreatic Cancer Case-Control Consortium

    PubMed Central

    Olson, Sara H.; Hsu, Meier; Satagopan, Jaya M.; Maisonneuve, Patrick; Silverman, Debra T.; Lucenteforte, Ersilia; Anderson, Kristin E.; Borgida, Ayelet; Bracci, Paige M.; Bueno-de-Mesquita, H. Bas; Cotterchio, Michelle; Dai, Qi; Duell, Eric J.; Fontham, Elizabeth H.; Gallinger, Steven; Holly, Elizabeth A.; Ji, Bu-Tian; Kurtz, Robert C.; La Vecchia, Carlo; Lowenfels, Albert B.; Luckett, Brian; Ludwig, Emmy; Petersen, Gloria M.; Polesel, Jerry; Seminara, Daniela; Strayer, Lori; Talamini, Renato

    2013-01-01

    In order to quantify the risk of pancreatic cancer associated with history of any allergy and specific allergies, to investigate differences in the association with risk according to age, gender, smoking status, or body mass index, and to study the influence of age at onset, we pooled data from 10 case-control studies. In total, there were 3,567 cases and 9,145 controls. Study-specific odds ratios and 95% confidence intervals were calculated by using unconditional logistic regression adjusted for age, gender, smoking status, and body mass index. Between-study heterogeneity was assessed by using the Cochran Q statistic. Study-specific odds ratios were pooled by using a random-effects model. The odds ratio for any allergy was 0.79 (95% confidence interval (CI): 0.62, 1.00) with heterogeneity among studies (P < 0.001). Heterogeneity was attributable to one study; with that study excluded, the pooled odds ratio was 0.73 (95% CI: 0.64, 0.84) (Pheterogeneity = 0.23). Hay fever (odds ratio = 0.74, 95% CI: 0.56, 0.96) and allergy to animals (odds ratio = 0.62, 95% CI: 0.41, 0.94) were related to lower risk, while there was no statistically significant association with other allergies or asthma. There were no major differences among subgroups defined by age, gender, smoking status, or body mass index. Older age at onset of allergies was slightly more protective than earlier age. PMID:23820785

  12. Trends in breast biopsy pathology diagnoses among women undergoing mammography in the United States: a report from the Breast Cancer Surveillance Consortium.

    PubMed

    Allison, Kimberly H; Abraham, Linn A; Weaver, Donald L; Tosteson, Anna N A; Nelson, Heidi D; Onega, Tracy; Geller, Berta M; Kerlikowske, Karla; Carney, Patricia A; Ichikawa, Laura E; Buist, Diana S M; Elmore, Joann G

    2015-05-01

    Current data on the pathologic diagnoses of breast biopsy after mammography can inform patients, clinicians, and researchers about important population trends. Breast Cancer Surveillance Consortium data on 4,020,140 mammograms between 1996 and 2008 were linked to 76,567 pathology specimens. Trends in diagnoses in biopsies by time and risk factors (patient age, breast density, and family history of breast cancer) were examined for screening and diagnostic mammography (performed for a breast symptom or short-interval follow-up). Of the total mammograms, 88.5% were screening and 11.5% diagnostic; 1.2% of screening and 6.8% of diagnostic mammograms were followed by biopsies. The frequency of biopsies over time was stable after screening mammograms, but increased after diagnostic mammograms. For biopsies obtained after screening, frequencies of invasive carcinoma increased over time for women ages 40-49 and 60-69, Ductal carcinoma in situ (DCIS) increased for those ages 40-69, whereas benign diagnoses decreased for all ages. No trends in pathology diagnoses were found following diagnostic mammograms. Dense breast tissue was associated with high-risk lesions and DCIS relative to nondense breast tissue. Family history of breast cancer was associated with DCIS and invasive cancer. Although the frequency of breast biopsy after screening mammography has not changed over time, the percentages of biopsies with DCIS and invasive cancer diagnoses have increased. Among biopsies following mammography, women with dense breasts or family history of breast cancer were more likely to have high-risk lesions or invasive cancer. These findings are relevant to breast cancer screening and diagnostic practices. © 2015 American Cancer Society.

  13. Phase II trial of bryostatin-1 in combination with cisplatin in patients with recurrent or persistent epithelial ovarian cancer: a California cancer consortium study

    PubMed Central

    Leong, Lucille; Chow, Warren; Gandara, David; Frankel, Paul; Garcia, Agustin; Lenz, Heinz-Josef; Doroshow, James H.

    2013-01-01

    Summary Background The California Cancer Consortium has performed a Phase II trial of infusional bryostatin, a protein kinase C inhibitor isolated from the marine invertebrate bryozoan, Bugula Neritina, a member of the phylum Ectoprocta, in combination with cisplatin, in patients (pts) with recurrent platinum-sensitive or resistant ovarian cancer (OC). Methods Pts received bryostatin 45 mcg/m2 as a 72 h continuous infusion followed by cisplatin 50 mg/m2. Cycles were repeated every 3 weeks. Dosages were chosen based on phase I data obtained by the CCC in a population of pts with mixed tumor types. Results Eight pts with recurrent or persistent epithelial OC received 23 cycles of treatment. All pts had received previous platinum-based chemotherapy; two pts had received one prior course, five had received two prior courses, and one had received three prior courses of chemotherapy. The median age was 64 (range 32–72), and Karnofsky performance status 90 (range 80–100). A median of 3 cycles of chemotherapy were delivered (range: 1–5). The median progression-free and overall survivals were 3 and 8.2 months respectively. Best responses included two partial responses (one in a platinum-resistant pt), three pts with stable disease, and three progressions. All pts experienced Grade 3 or 4 toxicities including severe myalgias/pain/fatigue/asthenia in six pts, and severe nausea/ vomiting/constipation in two other pts. One pt experienced a seizure and liver function tests were elevated in one other. Conclusions A modest response rate is observed in pts with recurrent or persistent ovarian cancer treated with the combination of bryostatin and cisplatin. The toxicity profile, however, observed in this pt population (primarily severe myalgias), precludes tolerability and prevents this combination from further investigation at this dose and schedule. It is possible that platinum pre-exposure in OC patients exacerbates observed toxicity. Phase II dosages of investigational

  14. Phase II trial of bryostatin-1 in combination with cisplatin in patients with recurrent or persistent epithelial ovarian cancer: a California cancer consortium study.

    PubMed

    Morgan, Robert J; Leong, Lucille; Chow, Warren; Gandara, David; Frankel, Paul; Garcia, Agustin; Lenz, Heinz-Josef; Doroshow, James H

    2012-04-01

    The California Cancer Consortium has performed a Phase II trial of infusional bryostatin, a protein kinase C inhibitor isolated from the marine invertebrate bryozoan, Bugula Neritina, a member of the phylum Ectoprocta, in combination with cisplatin, in patients (pts) with recurrent platinum-sensitive or resistant ovarian cancer (OC). Pts received bryostatin 45 mcg/m(2) as a 72 h continuous infusion followed by cisplatin 50 mg/m(2). Cycles were repeated every 3 weeks. Dosages were chosen based on phase I data obtained by the CCC in a population of pts with mixed tumor types. Eight pts with recurrent or persistent epithelial OC received 23 cycles of treatment. All pts had received previous platinum-based chemotherapy; two pts had received one prior course, five had received two prior courses, and one had received three prior courses of chemotherapy. The median age was 64 (range 32-72), and Karnofsky performance status 90 (range 80-100). A median of 3 cycles of chemotherapy were delivered (range: 1-5). The median progression-free and overall survivals were 3 and 8.2 months respectively. Best responses included two partial responses (one in a platinum-resistant pt), three pts with stable disease, and three progressions. All pts experienced Grade 3 or 4 toxicities including severe myalgias/pain/fatigue/asthenia in six pts, and severe nausea/vomiting/constipation in two other pts. One pt experienced a seizure and liver function tests were elevated in one other. A modest response rate is observed in pts with recurrent or persistent ovarian cancer treated with the combination of bryostatin and cisplatin. The toxicity profile, however, observed in this pt population (primarily severe myalgias), precludes tolerability and prevents this combination from further investigation at this dose and schedule. It is possible that platinum pre-exposure in OC patients exacerbates observed toxicity. Phase II dosages of investigational agents in OC pts that are determined by phase I

  15. Interactions Between Genome-wide Significant Genetic Variants and Circulating Concentrations of Insulin-like Growth Factor 1, Sex Hormones, and Binding Proteins in Relation to Prostate Cancer Risk in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium

    PubMed Central

    Tsilidis, Konstantinos K.; Travis, Ruth C.; Appleby, Paul N.; Allen, Naomi E.; Lindstrom, Sara; Schumacher, Fredrick R.; Cox, David; Hsing, Ann W.; Ma, Jing; Severi, Gianluca; Albanes, Demetrius; Virtamo, Jarmo; Boeing, Heiner; Bueno-de-Mesquita, H. Bas; Johansson, Mattias; Quirós, J. Ramón; Riboli, Elio; Siddiq, Afshan; Tjønneland, Anne; Trichopoulos, Dimitrios; Tumino, Rosario; Gaziano, J. Michael; Giovannucci, Edward; Hunter, David J.; Kraft, Peter; Stampfer, Meir J.; Giles, Graham G.; Andriole, Gerald L.; Berndt, Sonja I.; Chanock, Stephen J.; Hayes, Richard B.; Key, Timothy J.

    2012-01-01

    Genome-wide association studies (GWAS) have identified many single nucleotide polymorphisms (SNPs) associated with prostate cancer risk. There is limited information on the mechanistic basis of these associations, particularly about whether they interact with circulating concentrations of growth factors and sex hormones, which may be important in prostate cancer etiology. Using conditional logistic regression, the authors compared per-allele odds ratios for prostate cancer for 39 GWAS-identified SNPs across thirds (tertile groups) of circulating concentrations of insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein 3 (IGFBP-3), testosterone, androstenedione, androstanediol glucuronide, estradiol, and sex hormone-binding globulin (SHBG) for 3,043 cases and 3,478 controls in the Breast and Prostate Cancer Cohort Consortium. After allowing for multiple testing, none of the SNPs examined were significantly associated with growth factor or hormone concentrations, and the SNP-prostate cancer associations did not differ by these concentrations, although 4 interactions were marginally significant (MSMB-rs10993994 with androstenedione (uncorrected P = 0.008); CTBP2-rs4962416 with IGFBP-3 (uncorrected P = 0.003); 11q13.2-rs12418451 with IGF-1 (uncorrected P = 0.006); and 11q13.2-rs10896449 with SHBG (uncorrected P = 0.005)). The authors found no strong evidence that associations between GWAS-identified SNPs and prostate cancer are modified by circulating concentrations of IGF-1, sex hormones, or their major binding proteins. PMID:22459122

  16. How much do cancer-related symptoms contribute to health-related quality of life in lung and colorectal cancer patients? A report from the Cancer Care Outcomes Research and Surveillance (CanCORS) Consortium.

    PubMed

    Kenzik, Kelly M; Ganz, Patricia A; Martin, Michelle Y; Petersen, Laura; Hays, Ron D; Arora, Neeraj; Pisu, Maria

    2015-08-15

    The objective of this study was to examine associations of symptoms with physical and mental health-related quality of life (HRQOL) in patients with colorectal cancer (CRC) and in patients with lung cancer. Patients with newly diagnosed CRC (n = 3040) or lung cancer (n = 2297) who were participating in the Cancer Care Outcomes Research and Surveillance Consortium study completed surveys on general HRQOL and symptoms. HRQOL was measured by using physical component summary (PCS) and mental component summary (MCS) scores on the Medical Outcomes Study 12-item short-form heath survey. Nonspecific cancer symptoms were measured using items from the European Organization for Research and Treatment of Cancer core quality-of-life questionnaire. Cancer type-specific modules developed by the European Organization for Research and Treatment of Cancer were used to assess CRC-specific and lung cancer-specific symptoms. For both cancer types, linear regression models that were controlled for demographic and clinical information were used to examine correlations of nonspecific and cancer-specific symptoms with PCS and MCS scores. PCS scores for patients with CRC and lung cancer were below the general population norm of 50 (43 and 37, respectively), and MCS scores were at the population norm. For the CRC sample, in the model that included both symptom indices, an increase in nonspecific symptoms was more strongly associated with lower PCS and MCS scores than an increase in CRC-specific symptoms (PCS, standardized coefficient [β] = -0.41 vs -0.09; MCS, β = -0.38 vs -0.08). In a similar model for lung cancer, increases in lung cancer-specific symptoms were more strongly associated with lower PCS scores (β = -0.34 vs -0.20), whereas nonspecific symptoms were more strongly associated with lower MCS scores (β = -0.34 vs -0.14). Symptoms were associated with HRQOL impairments in recently diagnosed patients. Additional supportive care implemented early in cancer care

  17. Development and utilization of complementary communication channels for treatment decision making and survivorship issues among cancer patients: The CIS Research Consortium Experience.

    PubMed

    Fleisher, Linda; Wen, Kuang Yi; Miller, Suzanne M; Diefenbach, Michael; Stanton, Annette L; Ropka, Mary; Morra, Marion; Raich, Peter C

    2015-11-01

    Cancer patients and survivors are assuming active roles in decision-making and digital patient support tools are widely used to facilitate patient engagement. As part of Cancer Information Service Research Consortium's randomized controlled trials focused on the efficacy of eHealth interventions to promote informed treatment decision-making for newly diagnosed prostate and breast cancer patients, and post-treatment breast cancer, we conducted a rigorous process evaluation to examine the actual use of and perceived benefits of two complementary communication channels -- print and eHealth interventions. The three Virtual Cancer Information Service (V-CIS) interventions were developed through a rigorous developmental process, guided by self-regulatory theory, informed decision-making frameworks, and health communications best practices. Control arm participants received NCI print materials; experimental arm participants received the additional V-CIS patient support tool. Actual usage data from the web-based V-CIS was also obtained and reported. Print materials were highly used by all groups. About 60% of the experimental group reported using the V-CIS. Those who did use the V-CIS rated it highly on improvements in knowledge, patient-provider communication and decision-making. The findings show that how patients actually use eHealth interventions either singularly or within the context of other communication channels is complex. Integrating rigorous best practices and theoretical foundations is essential and multiple communication approaches should be considered to support patient preferences.

  18. International Arid Lands Consortium: A synopsis of accomplishments

    Treesearch

    Peter F. Ffolliott; Jeffrey O. Dawson; James T. Fisher; Itshack Moshe; Timothy E. Fulbright; W. Carter Johnson; Paul Verburg; Muhammad Shatanawi; Jim P. M. Chamie

    2003-01-01

    The International Arid Lands Consortium (IALC) was established in 1990 to promote research, education, and training activities related to the development, management, and reclamation of arid and semiarid lands in the Southwestern United States, the Middle East, and elsewhere in the world. The Consortium supports the ecological sustainability and environmentally sound...

  19. Trends in Breast Tissue Sampling and Pathology Diagnoses among Women Undergoing Mammography in the U.S.: A Report from the Breast Cancer Surveillance Consortium

    PubMed Central

    Allison, Kimberly H.; Abraham, Linn A.; Weaver, Donald L.; Tosteson, Anna NA; Nelson, Heidi D.; Onega, Tracy; Geller, Berta M; Kerlikowske, Karla; Carney, Patricia A.; Ichikawa, Laura E.; Buist, Diana S.M.; Elmore, Joann G.

    2015-01-01

    Background Current data on the pathologic diagnoses of breast biopsy after mammography can inform patients, clinicians, and researchers about important population trends. Methods Breast Cancer Surveillance Consortium data on 4,020,140 mammograms between 1996 and 2008 were linked to 76,567 pathology specimens. Trends in diagnoses in biopsies by time and risk factors (patient age, breast density, and family history of breast cancer) were examined for screening and diagnostic mammography (performed for a breast symptom or short interval follow-up). Results Of the total mammograms, 88.5% were screening and 11.5% diagnostic; 1.2% of screening and 6.8% of diagnostic mammograms were followed by biopsies. The frequency of biopsies over time was stable after screening mammograms, but increased after diagnostic mammograms. For biopsies obtained after screening, frequencies of invasive carcinoma increased over time for women aged 40–49 and 60–69, DCIS increased for 40–69, while benign diagnoses decreased for all ages. No trends in pathology diagnoses were found following diagnostic mammograms. Dense breast tissue was associated with high-risk lesions and DCIS relative to non-dense breast tissue. Family history of breast cancer was associated with DCIS and invasive cancer. Conclusions While the frequency of breast biopsy after screening mammography has not changed over time, the percentages of biopsies with DCIS and invasive cancer diagnoses have increased. Among biopsies following mammography, women with dense breasts or family history of breast cancer were more likely to have high-risk lesions or invasive cancer. These findings are relevant to breast cancer screening and diagnostic practices. PMID:25603785

  20. Cervical cancer prevention training in South East Asian LMICs.

    PubMed

    Ng, Joseph Soon-Yau; Ismail-Pratt, Ida

    2017-02-01

    The Association of Southeast Asian Nations (ASEAN) is a confederation of 10 sovereign states occupying approximately 1.7 million square miles of Southeast Asia with an estimated population of just under 630 million. Southeast Asia continues to have one of the world's highest rates of cervical cancer-related death. Organised training in cervical cancer screening is essential but lacking in low to middle income countries (LMICs). Systematic training of local doctors is an essential part of an effective screening program and an effective strategy to reduce cervical cancer-related mortality. Singapore is a first-world economy with a healthcare system that can support this mode of training and is geographically proximate to Southeast Asian LMICs that need this training. This makes it possible for model of tiered training with trainers on site in the LMICs and more advanced training where trainees receive training in Singapore. We present a case study where this tiered system of training is applied to Cambodia and demonstrate that this model of training is not only effective but also sustainable.

  1. ABO blood groups and pancreatic cancer risk and survival: results from the PANcreatic Disease ReseArch (PANDoRA) consortium.

    PubMed

    Rizzato, Cosmeri; Campa, Daniele; Pezzilli, Raffaele; Soucek, Pavel; Greenhalf, William; Capurso, Gabriele; Talar-Wojnarowska, Renata; Heller, Anette; Jamroziak, Krzysztof; Khaw, Kay-Tee; Key, Tim J; Bambi, Franco; Landi, Stefano; Mohelnikova-Duchonova, Beatrice; Vodickova, Ludmila; Büchler, Markus W; Bugert, Peter; Vodicka, Pavel; Neoptolemos, John P; Werner, Jens; Hoheisel, Jörg D; Bauer, Andrea S; Giese, Nathalia; Canzian, Federico

    2013-04-01

    There is strong epidemiologic evidence indicating that common genetic variability could be implicated in pancreatic cancer risk and, to date, various loci have been proposed. In particular, there is increasing evidence of the involvement of ABO gene variability and pancreatic cancer risk. In a large multicentric study of 1,028 pancreatic ductal adenocarcinoma cases and 2,257 controls in the context of the PANcreatic Disease ReseArch (PANDoRA) consortium, we investigated the suggested association with increased risk for carriers of single nucleotide polymorphisms (SNPs) determining the A or B allele in comparison with the O allele, which encodes for a non-functional enzyme. Since glycosyltransferase activity, encoded by ABO, is higher for the A1 variant compared with the A2 variant, we investigated the hypothesis that A1 carriers were at an increased risk of pancreatic cancer. In our analysis, carriers of the A1 were indeed at greater risk of developing the disease. In addition, we investigated the possible influence that genetic variability at the ABO locus may have in pancreatic cancer survival, but we observed no effect in our population.

  2. International Lymphoma Epidemiology Consortium

    Cancer.gov

    The InterLymph Consortium, or formally the International Consortium of Investigators Working on Non-Hodgkin's Lymphoma Epidemiologic Studies, is an open scientific forum for epidemiologic research in non-Hodgkin's lymphoma.

  3. Mortality from all cancers of asbestos factory workers in east London 1933-80

    PubMed Central

    Berry, G; Newhouse, M; Wagner, J

    2000-01-01

    OBJECTIVE—To give the observed and expected deaths due to cancer at all separate sites in asbestos workers in east London, and to analyse these for overall effect and exposure-response trend.
METHODS—The mortality experience of a cohort of over 5000 men and women followed up for over 30 years since first exposure to asbestos has been extracted.
RESULTS—There was a large excess of deaths due to cancer (537 observed, 222 expected). Most of these were due to cancer of the lung (232 observed, 77 expected) and pleural (52) and peritoneal (48) mesothelioma. The exposure-response trend for all these three causes was highly significant. There was also an excess of cancer of the colon (27 observed, 15 expected) which was significantly related to exposure. There were significant excesses of cancer of the ovary, of the liver, and of the oesophagus but with no consistent relation to exposure.
CONCLUSIONS—The excess risk of cancer after exposure to asbestos was mainly due to cancer of the lung and mesothelioma. An exposure related excess of cancer of the colon was also detected but the possibility that some of these deaths may have been peritoneal mesotheliomas could not be excluded. There was no consistent evidence of exposure related excesses at any other site.


Keywords: asbestos; cancer; exposure-response PMID:11024203

  4. New Breast Cancer Risk Variant Discovered at 10q25 in East Asian Women

    PubMed Central

    Shi, Jiajun; Sung, Hyuna; Zhang, Ben; Lu, Wei; Choi, Ji-Yeob; Xiang, Yong-Bing; Kim, Mi Kyung; Iwasaki, Motoki; Long, Jirong; Ji, Bu-Tian; Park, Sue K.; Zheng, Ying; Tsugane, Shoichiro; Yoo, Keun-Young; Wang, Wenjing; Noh, Dong-Young; Han, Wonshik; Kim, Sung-Won; Lee, Min Hyuk; Lee, Jong Won; Lee, Jong-Young; Shen, Chen-Yang; Matsuo, Keitaro; Ahn, Sei-Hyun; Gao, Yu-Tang; Shu, Xiao Ou; Cai, Qiuyin; Kang, Daehee; Zheng, Wei

    2013-01-01

    Background Recently, 41 new genetic susceptibility loci for breast cancer risk were identified in a genome-wide association study conducted in European descendants. Most of these risk variants have not been directly replicated in Asian populations. Methods We evaluated nine of those non-replication loci in East Asians in order to identify new risk variants for breast cancer in these regions. First, we analyzed single nucleotide polymorphisms (SNPs) in these regions using data from two GWAS conducted among Chinese and Korean women, including 5,083 cases and 4,376 controls (Stage 1). In each region we selected a SNP showing the strongest association with breast cancer risk for replication in an independent set of 7,294 cases and 9,404 controls of East Asian descents (Stage 2). Logistic regression models were used to calculate adjusted odds ratios (OR) and 95% confidence intervals (CI) as a measure of the association of breast cancer risk and genetic variants. Results Two SNPs were replicated in Stage 2 at P < 0.05: rs1419026 at 6q14 (per allele OR = 1.07, 95% CI: 1.03-1.12, P = 3.0×10−4) and rs941827 at 10q25 (OR = 0.92, 95% CI: 0.89-0.96, P = 5.3×10−5). The association with rs941827 remained highly statistically significant after adjusting for the risk variant identified initially in women of European ancestry (OR = 0.88, 95% CI: 0.82-0.97, P = 5.3×10−5). Conclusion We identified a new breast cancer risk variant at 10q25 in East Asian women. Impact Results from this study improve the understanding of the genetic basis for breast cancer. PMID:23677579

  5. Prediction of breast cancer risk based on common genetic variants in women of East Asian ancestry.

    PubMed

    Wen, Wanqing; Shu, Xiao-Ou; Guo, Xingyi; Cai, Qiuyin; Long, Jirong; Bolla, Manjeet K; Michailidou, Kyriaki; Dennis, Joe; Wang, Qin; Gao, Yu-Tang; Zheng, Ying; Dunning, Alison M; García-Closas, Montserrat; Brennan, Paul; Chen, Shou-Tung; Choi, Ji-Yeob; Hartman, Mikael; Ito, Hidemi; Lophatananon, Artitaya; Matsuo, Keitaro; Miao, Hui; Muir, Kenneth; Sangrajrang, Suleeporn; Shen, Chen-Yang; Teo, Soo H; Tseng, Chiu-Chen; Wu, Anna H; Yip, Cheng Har; Simard, Jacques; Pharoah, Paul D P; Hall, Per; Kang, Daehee; Xiang, Yongbing; Easton, Douglas F; Zheng, Wei

    2016-12-08

    Approximately 100 common breast cancer susceptibility alleles have been identified in genome-wide association studies (GWAS). The utility of these variants in breast cancer risk prediction models has not been evaluated adequately in women of Asian ancestry. We evaluated 88 breast cancer risk variants that were identified previously by GWAS in 11,760 cases and 11,612 controls of Asian ancestry. SNPs confirmed to be associated with breast cancer risk in Asian women were used to construct a polygenic risk score (PRS). The relative and absolute risks of breast cancer by the PRS percentiles were estimated based on the PRS distribution, and were used to stratify women into different levels of breast cancer risk. We confirmed significant associations with breast cancer risk for SNPs in 44 of the 78 previously reported loci at P < 0.05. Compared with women in the middle quintile of the PRS, women in the top 1% group had a 2.70-fold elevated risk of breast cancer (95% CI: 2.15-3.40). The risk prediction model with the PRS had an area under the receiver operating characteristic curve of 0.606. The lifetime risk of breast cancer for Shanghai Chinese women in the lowest and highest 1% of the PRS was 1.35% and 10.06%, respectively. Approximately one-half of GWAS-identified breast cancer risk variants can be directly replicated in East Asian women. Collectively, common genetic variants are important predictors for breast cancer risk. Using common genetic variants for breast cancer could help identify women at high risk of breast cancer.

  6. An epidemiological study of oral and pharyngeal cancer in Central and South-East Asia

    PubMed Central

    Hirayama, Takeshi

    1966-01-01

    The author has investigated the epidemiology of oral and pharyngeal cancer in several different countries and localities in Central and South-East Asia. From comparisons of the various countries and areas and from detailed case studies among oral-cancer groups and control groups, the author has obtained strong supportive evidence for the association of the disease with the habit of chewing tobacco. He has also found a less marked association with smoking, the drinking of alcohol, and vegetarian dietary customs. PMID:5295564

  7. Cancer epidemiology and control in north-East Asia - past, present and future.

    PubMed

    Long, Ne; Moore, Malcolm A; Chen, Wanqing; Gao, Chao-Ming; Lai, Mei-Shu; Mizoue, Tetsuya; Oyunchimeg, Dondov; Park, Sohee; Shin, Hai-Rim; Tajima, Kazuo; Yoo, Keun-Young; Sobue, Tomotaka

    2010-01-01

    China, Mongolia, Korea and Japan constitute North-East Asia. For reasons of largely shared ethnicity and culture, with various degress of mixed Chinese and Altaic elements, as well as geographical contiguity, they can be usefully grouped together for studies of chronic disease prevalence and particularly cancer. The fact of problems shared in common, with increasing disease rates, underlines the necessity for a coordinated approach to research and development of control measures. To provide a knowledge base, the present review of cancer registration and epidemiology data was conducted. The most frequent cancers in males of North-East Asia are in the lung, liver and stomach, with considerable geographical and temporal variation in their respective prevalences. However, colorectal cancer is also of increasing importance. In females the breast, together with the lung in China, the liver in Mongolia and the stomach in Korea and Japan, are most frequent. Variation in risk factors depends to a large extent on the local level of economic development but overall the countries of the region face similar challenges in achieving effective cancer control.

  8. Breast cancer screening using tomosynthesis in combination with digital mammography compared to digital mammography alone: a cohort study within the PROSPR consortium.

    PubMed

    Conant, Emily F; Beaber, Elisabeth F; Sprague, Brian L; Herschorn, Sally D; Weaver, Donald L; Onega, Tracy; Tosteson, Anna N A; McCarthy, Anne Marie; Poplack, Steven P; Haas, Jennifer S; Armstrong, Katrina; Schnall, Mitchell D; Barlow, William E

    2016-02-01

    Digital breast tomosynthesis (DBT) is emerging as the new standard of care for breast cancer screening based on improved cancer detection coupled with reductions in recall compared to screening with digital mammography (DM) alone. However, many prior studies lack follow-up data to assess false negatives examinations. The purpose of this study is to assess if DBT is associated with improved screening outcomes based on follow-up data from tumor registries or pathology. Retrospective analysis of prospective cohort data from three research centers performing DBT screening in the PROSPR consortium from 2011 to 2014 was performed. Recall and biopsy rates were assessed from 198,881 women age 40-74 years undergoing screening (142,883 DM and 55,998 DBT examinations). Cancer, cancer detection, and false negative rates and positive predictive values were assessed on examinations with one year of follow-up. Logistic regression was used to compare DBT to DM adjusting for research center, age, prior breast imaging, and breast density. There was a reduction in recall with DBT compared to DM (8.7 vs. 10.4 %, p < 0.0001), with adjusted OR = 0.68 (95 % CI = 0.65-0.71). DBT demonstrated a statistically significant increase in cancer detection over DM (5.9 vs. 4.4/1000 screened, adjusted OR = 1.45, 95 % CI = 1.12-1.88), an improvement in PPV1 (6.4 % for DBT vs. 4.1 % for DM, adjusted OR = 2.02, 95 % CI = 1.54-2.65), and no significant difference in false negative rates for DBT compared to DM (0.46 vs. 0.60/1000 screened, p = 0.347). Our data support implementation of DBT screening based on increased cancer detection, reduced recall, and no difference in false negative screening examinations.

  9. Tobacco smoking as a risk factor of bronchioloalveolar carcinoma of the lung: pooled analysis of seven case-control studies in the International Lung Cancer Consortium (ILCCO).

    PubMed

    Boffetta, Paolo; Jayaprakash, Vijayvel; Yang, Ping; Asomaning, Kofi; Muscat, Joshua E; Schwartz, Ann G; Zhang, Zuo-Feng; Le Marchand, Loic; Cote, Michele L; Stoddard, Shawn M; Morgenstern, Hal; Hung, Rayjean J; Christiani, David C

    2011-01-01

    The International Lung Cancer Consortium (ILCCO) was established in 2004, based on the collaboration of research groups leading large molecular epidemiology studies of lung cancer that are ongoing or have been recently completed. This framework offered the opportunity to investigate the role of tobacco smoking in the development of bronchioloalveolar carcinoma (BAC), a rare form of lung cancer. Our pooled data comprised seven case-control studies from the United States, with detailed information on tobacco smoking and histology, which contributed 799 cases of BAC and 15,859 controls. We estimated the odds ratio of BAC for tobacco smoking, using never smokers as a referent category, after adjustment for age, sex, race, and study center. The odds ratio of BAC for ever smoking was 2.47 (95% confidence interval [CI] 2.08, 2.93); the risk increased linearly with duration, amount, and cumulative cigarette smoking and persisted long after smoking cessation. The proportion of BAC cases attributable to smoking was 0.47 (95% CI 0.39, 0.54). This analysis provides a precise estimate of the risk of BAC for tobacco smoking.

  10. Multilayer-omics analyses of human cancers: exploration of biomarkers and drug targets based on the activities of the International Human Epigenome Consortium.

    PubMed

    Kanai, Yae; Arai, Eri

    2014-01-01

    Epigenetic alterations consisting mainly of DNA methylation alterations and histone modification alterations are frequently observed in cancers associated with chronic inflammation and/or persistent infection with viruses or other pathogenic microorganisms, or with cigarette smoking. Accumulating evidence suggests that alterations of DNA methylation are involved even in the early and precancerous stages. On the other hand, in patients with cancers, aberrant DNA methylation is frequently associated with tumor aggressiveness and poor patient outcome. Recently, epigenome alterations have been attracting a great deal of attention from researchers who are focusing on not only cancers but also neuronal, immune and metabolic disorders. In order to accurately identify disease-specific epigenome profiles that could be potentially applicable for disease prevention, diagnosis and therapy, strict comparison with standard epigenome profiles of normal tissues is indispensable. However, epigenome mechanisms show heterogeneity among tissues and cell lineages. Therefore, it is not easy to obtain a comprehensive picture of standard epigenome profiles of normal tissues. In 2010, the International Human Epigenome Consortium (IHEC) was established to coordinate the production of reference maps of human epigenomes for key cellular states. In order to gain substantial coverage of the human epigenome, the IHEC has set an ambitious goal to decipher at least 1000 epigenomes within the next 7-10 years. We consider that pathway analysis using genes showing multilayer-omics abnormalities, including genome, epigenome, transcriptome, proteome and metabolome abnormalities, may be useful for elucidating the molecular background of pathogenesis and for exploring possible therapeutic targets for each disease.

  11. Helicobacter pylori and gastric cancer in the Middle East: A new enigma?

    PubMed Central

    Hussein, Nawfal R

    2010-01-01

    The Middle East is the home of ethnic groups from three main backgrounds: Semitic (Arabs and Jews), Indo-European (Persians and Kurdish) and Turkic (Turkish and Turkmens). Its geographic location, which has been under continuous influences from Asia, Europe and Africa, has made it an ideal site for epidemiological studies on Helicobacter pylori (H. pylori) infection and genotyping. The gastric cancer rate differs in this region from very high in Iran (26.1/105) to low in Israel (12.5/105) and very low in Egypt (3.4/105). Epidemiological studies showed that the prevalence of H. pylori is almost similar in those countries with a high level of infection in childhood. Importantly, the frequency of vacA s1 and m1 regions and cagA+ genotypes were higher in non Semitic populations who inhabit the North than Semitic populations, the inhabitants of Southern parts of the Middle East. H. pylori infection prevalence, distribution pattern of virulence factors, diet and smoking could not have explained the difference in cancer rate. This reflects the multifactorial aetiology of gastric cancer and suggests that H. pylori infection does not always directly correlate with the risk for gastrointestinal disease, such as gastric cancer. Further detailed investigations and international comparative studies of each risk factor need to be performed to investigate whether this represents a true enigma. PMID:20614477

  12. Patient survival and tumor characteristics associated with CHEK2:p.I157T - findings from the Breast Cancer Association Consortium.

    PubMed

    Muranen, Taru A; Blomqvist, Carl; Dörk, Thilo; Jakubowska, Anna; Heikkilä, Päivi; Fagerholm, Rainer; Greco, Dario; Aittomäki, Kristiina; Bojesen, Stig E; Shah, Mitul; Dunning, Alison M; Rhenius, Valerie; Hall, Per; Czene, Kamila; Brand, Judith S; Darabi, Hatef; Chang-Claude, Jenny; Rudolph, Anja; Nordestgaard, Børge G; Couch, Fergus J; Hart, Steven N; Figueroa, Jonine; García-Closas, Montserrat; Fasching, Peter A; Beckmann, Matthias W; Li, Jingmei; Liu, Jianjun; Andrulis, Irene L; Winqvist, Robert; Pylkäs, Katri; Mannermaa, Arto; Kataja, Vesa; Lindblom, Annika; Margolin, Sara; Lubinski, Jan; Dubrowinskaja, Natalia; Bolla, Manjeet K; Dennis, Joe; Michailidou, Kyriaki; Wang, Qin; Easton, Douglas F; Pharoah, Paul D P; Schmidt, Marjanka K; Nevanlinna, Heli

    2016-10-03

    P.I157T is a CHEK2 missense mutation associated with a modest increase in breast cancer risk. Previously, another CHEK2 mutation, the protein truncating c.1100delC has been associated with poor prognosis of breast cancer patients. Here, we have investigated patient survival and characteristics of breast tumors of germ line p.I157T carriers. We included in the analyses 26,801 European female breast cancer patients from 15 studies participating in the Breast Cancer Association Consortium. We analyzed the association between p.I157T and the clinico-pathological breast cancer characteristics by comparing the p.I157T carrier tumors to non-carrier and c.1100delC carrier tumors. Similarly, we investigated the p.I157T associated risk of early death, breast cancer-associated death, distant metastasis, locoregional relapse and second breast cancer using Cox proportional hazards models. Additionally, we explored the p.I157T-associated genomic gene expression profile using data from breast tumors of 183 Finnish female breast cancer patients (ten p.I157T carriers) (GEO: GSE24450). Differential gene expression analysis was performed using a moderated t test. Functional enrichment was investigated using the DAVID functional annotation tool and gene set enrichment analysis (GSEA). The tumors were classified into molecular subtypes according to the St Gallen 2013 criteria and the PAM50 gene expression signature. P.I157T was not associated with increased risk of early death, breast cancer-associated death or distant metastasis relapse, and there was a significant difference in prognosis associated with the two CHEK2 mutations, p.I157T and c.1100delC. Furthermore, p.I157T was associated with lobular histological type and clinico-pathological markers of good prognosis, such as ER and PR expression, low TP53 expression and low grade. Gene expression analysis suggested luminal A to be the most common subtype for p.I157T carriers and CDH1 (cadherin 1) target genes to be significantly

  13. Approaches for the Evaluation of the National Cancer Institute's Summer Curriculum in Cancer Prevention: lessons from the all-Ireland NCI cancer consortium.

    PubMed

    Otero, Isabel V; Williams, Makeda; Harford, Joe B

    2012-06-01

    The NCI Summer Curriculum in Cancer Prevention (SCCP) has provided interdisciplinary training in cancer prevention and control to cancer health-care professionals, including nurses, physicians, and scientists, since 1986. It has trained over 1,200 participants, 256 of them from Ireland and Northern Ireland through two summer courses: a 4-week course on Principles and Practice of Cancer Prevention and Control (PP) and 1-week on Molecular Prevention (MP). This report is our attempt to measure achievements and level of satisfaction among alumni from the island of Ireland upon return to their home institution. A questionnaire was developed to assess this. Our analysis found statistically significant differences in the types of accomplishments reported among respondents of the MP and PP courses as well as statistically significant differences in their level of satisfaction. More data are needed to better explain the differences observed as well as level of resources available to alumni upon their return home.

  14. Situation analysis for cervical cancer diagnosis and treatment in east, central and southern African countries.

    PubMed Central

    Chirenje, Z. M.; Rusakaniko, S.; Kirumbi, L.; Ngwalle, E. W.; Makuta-Tlebere, P.; Kaggwa, S.; Mpanju-Shumbusho, W.; Makoae, L.

    2001-01-01

    OBJECTIVE: To determine the factors influencing cervical cancer diagnosis and treatment in countries of East, Central and Southern Africa (ECSA). METHODS: Data were collected from randomly selected primary health care centres, district and provincial hospitals, and tertiary hospitals in each participating country. Health care workers were interviewed, using a questionnaire; the facilities for screening, diagnosing, and treating cervical cancer in each institution were recorded, using a previously designed checklist. FINDINGS: Although 95% of institutions at all health care levels in ECSA countries had the basic infrastructure to carry out cervical cytology screening, only a small percentage of women were actually screened. Lack of policy guidelines, infrequent supply of basic materials, and a lack of suitable qualified staff were the most common reasons reported. CONCLUSIONS: This study demonstrates that there is an urgent need for more investment in the diagnosis and treatment of cervical cancer in ECSA countries. In these, and other countries with low resources, suitable screening programmes should be established. PMID:11242819

  15. Prostate pathology of genetically engineered mice: definitions and classification. The consensus report from the Bar Harbor meeting of the Mouse Models of Human Cancer Consortium Prostate Pathology Committee.

    PubMed

    Shappell, Scott B; Thomas, George V; Roberts, Richard L; Herbert, Ron; Ittmann, Michael M; Rubin, Mark A; Humphrey, Peter A; Sundberg, John P; Rozengurt, Nora; Barrios, Roberto; Ward, Jerrold M; Cardiff, Robert D

    2004-03-15

    The Pathological Classification of Prostate Lesions in Genetically Engineered Mice (GEM) is the result of a directive from the National Cancer Institute Mouse Models of Human Cancer Consortium Prostate Steering Committee to provide a hierarchical taxonomy of disorders of the mouse prostate to facilitate classification of existing and newly created mouse models and the translation to human prostate pathology. The proposed Bar Harbor Classification system is the culmination of three meetings and workshops attended by various members of the Prostate Pathology Committee of the Mouse Models of Human Cancer Consortium. A 2-day Pathology Workshop was held at The Jackson Laboratory in Bar Harbor, Maine, in October 2001, in which study sets of 93 slides from 22 GEM models were provided to individual panel members. The comparison of mouse and human prostate anatomy and disease demonstrates significant differences and considerable similarities that bear on the interpretation of the origin and natural history of their diseases. The recommended classification of mouse prostate pathology is hierarchical, and includes developmental, inflammatory, benign proliferative, and neoplastic disorders. Among the neoplastic disorders, preinvasive, microinvasive, and poorly differentiated neoplasms received the most attention. Specific criteria were recommended and will be discussed. Transitions between neoplastic states were of particular concern. Preinvasive neoplasias of the mouse prostate were recognized as focal, atypical, and progressive lesions. These lesions were designated as mouse prostatic intraepithelial neoplasia (mPIN). Some atypical lesions were identified in mouse models without evidence of progression to malignancy. The panel recommended that mPIN lesions not be given histological grades, but that mPIN be further classified as to the absence or presence of documented associated progression to invasive carcinoma. Criteria for recognizing microinvasion, for classification of

  16. A Standard Set of Value-Based Patient-Centered Outcomes for Breast Cancer: The International Consortium for Health Outcomes Measurement (ICHOM) Initiative.

    PubMed

    Ong, Wee Loon; Schouwenburg, Maartje G; van Bommel, Annelotte C M; Stowell, Caleb; Allison, Kim H; Benn, Karen E; Browne, John P; Cooter, Rodney D; Delaney, Geoff P; Duhoux, Francois P; Ganz, Patricia A; Hancock, Patricia; Jagsi, Reshma; Knaul, Felicia M; Knip, Anne M; Koppert, Linetta B; Kuerer, Henry M; McLaughin, Sarah; Mureau, Marc A M; Partridge, Ann H; Reid, Dereesa Purtell; Sheeran, Lisa; Smith, Thomas J; Stoutjesdijk, Mark J; Vrancken Peeters, Marie Jeanne T F D; Wengström, Yvonne; Yip, Cheng-Har; Saunders, Christobel

    2016-12-29

    A major challenge in value-based health care is the lack of standardized health outcomes measurements, hindering optimal monitoring and comparison of the quality of health care across different settings globally. The International Consortium for Health Outcomes Measurement (ICHOM) assembled a multidisciplinary international working group, comprised of 26 health care providers and patient advocates, to develop a standard set of value-based patient-centered outcomes for breast cancer (BC). The working group convened via 8 teleconferences and completed a follow-up survey after each meeting. A modified 2-round Delphi method was used to achieve consensus on the outcomes and case-mix variables to be included. Patient focus group meetings (8 early or metastatic BC patients) and online anonymized surveys of 1225 multinational BC patients and survivors were also conducted to obtain patients' input. The standard set encompasses survival and cancer control, and disutility of care (eg, acute treatment complications) outcomes, to be collected through administrative data and/or clinical records. A combination of multiple patient-reported outcomes measurement (PROM) tools is recommended to capture long-term degree of health outcomes. Selected case-mix factors were recommended to be collected at baseline. The ICHOM will endeavor to achieve wide buy-in of this set and facilitate its implementation in routine clinical practice in various settings and institutions worldwide.

  17. Prostate cancer risk related to foods, food groups, macronutrients and micronutrients derived from the UK Dietary Cohort Consortium food diaries

    PubMed Central

    Lane, J A; Oliver, S E; Appleby, P N; Lentjes, M A H; Emmett, P; Kuh, D; Stephen, A; Brunner, E J; Shipley, M J; Hamdy, F C; Neal, D E; Donovan, J L; Khaw, K-T; Key, T J

    2017-01-01

    Background/Objectives: The influence of dietary factors remains controversial for screen-detected prostate cancer and inconclusive for clinically detected disease. We aimed to examine these associations using prospectively collected food diaries. Subjects/Methods: A total of 1,717 prostate cancer cases in middle-aged and older UK men were pooled from four prospective cohorts with clinically detected disease (n=663), with routine data follow-up (means 6.6–13.3 years) and a case-control study with screen-detected disease (n=1054), nested in a randomised trial of prostate cancer treatments (ISCTRN 20141297). Multiple-day food diaries (records) completed by men prior to diagnosis were used to estimate intakes of 37 selected nutrients, food groups and items, including carbohydrate, fat, protein, dairy products, fish, meat, fruit and vegetables, energy, fibre, alcohol, lycopene and selenium. Cases were matched on age and diary date to at least one control within study (n=3528). Prostate cancer risk was calculated, using conditional logistic regression (adjusted for baseline covariates) and expressed as odds ratios in each quintile of intake (±95% confidence intervals). Prostate cancer risk was also investigated by localised or advanced stage and by cancer detection method. Results: There were no strong associations between prostate cancer risk and 37 dietary factors. Conclusions: Prostate cancer risk, including by disease stage, was not strongly associated with dietary factors measured by food diaries in middle-aged and older UK men. PMID:27677361

  18. Knowledge of cervical cancer and screening among women in east-central England.

    PubMed

    Philips, Z; Avis, M; Whynes, D K

    2005-01-01

    This study assesses the extent and accuracy of women's knowledge of cervical cancer, risk factors, and the efficacy of the national screening program. Data were obtained from a questionnaire survey of randomly selected women eligible for screening, drawn from a population in east-central England. The majority of women in the sample overestimated the current incidence of cervical cancer, both absolutely and relative to other cancers. Perceiving incidence to be high was associated with reporting worries about the disease. With respect to the screening process, 78.3% believe that the smear abnormality rate is higher than it actually is, and only 7.6% correctly appreciate that the abnormality rate is highest at younger ages. With respect to performance, 16.3% believed the smear test to be completely accurate, and more than half overestimated the likely number of cancer cases prevented by screening. While certain cervical cancer risk factors were correctly assigned by the majority of women, undue emphasis was placed on genetic influence, while the risks posed by human papillomavirus infection were unfamiliar to almost half of the sample. We conclude that women typically possess only a partial picture of risk factors and overestimate both the incidence of cervical cancer and the efficacy of screening.

  19. Dietary patterns derived with multiple methods from food diaries and breast cancer risk in the UK Dietary Cohort Consortium

    PubMed Central

    Pot, Gerda K; Stephen, Alison M; Dahm, Christina C; Key, Timothy J; Cairns, Benjamin J; Burley, Victoria J; Cade, Janet E; Greenwood, Darren C; Keogh, Ruth H; Bhaniani, Amit; McTaggart, Alison; Lentjes, Marleen AH; Mishra, Gita; Brunner, Eric J; Khaw, Kay Tee

    2015-01-01

    Background/ Objectives In spite of several studies relating dietary patterns to breast cancer risk, evidence so far remains inconsistent. This study aimed to investigate associations of dietary patterns derived with three different methods with breast cancer risk. Subjects/ Methods The Mediterranean Diet Score (MDS), principal components analyses (PCA) and reduced rank regression (RRR) were used to derive dietary patterns in a case-control study of 610 breast cancer cases and 1891 matched controls within 4 UK cohort studies. Dietary intakes were collected prospectively using 4-to 7-day food diaries and resulting food consumption data were grouped into 42 food groups. Conditional logistic regression models were used to estimate odds ratios (ORs) for associations between pattern scores and breast cancer risk adjusting for relevant covariates. A separate model was fitted for post-menopausal women only. Results The MDS was not associated with breast cancer risk (OR comparing 1st tertile with 3rd 1.20 (95% CI 0.92; 1.56)), nor the first PCA-derived dietary pattern, explaining 2.7% of variation of diet and characterized by cheese, crisps and savoury snacks, legumes, nuts and seeds (OR 1.18 (95% CI 0.91; 1.53)). The first RRR-derived pattern, a ‘high-alcohol’ pattern, was associated with a higher risk of breast cancer (OR 1.27; 95% CI 1.00; 1.62), which was most pronounced in post-menopausal women (OR 1.46 (95% CI 1.08; 1.98). Conclusions A ‘high-alcohol’ dietary pattern derived with RRR was associated with an increased breast cancer risk; no evidence of associations of other dietary patterns with breast cancer risk was observed in this study. PMID:25052230

  20. NCI's Clinical Proteomic Tumor Analysis Consortium 1st Annual Scientific Symposium | Office of Cancer Clinical Proteomics Research

    Cancer.gov

    On behalf of the National Cancer Institute and the Office of Cancer Clinical Proteomics Research, you are invited to the First Annual CPTAC Scientific Symposium on Wednesday, November 13, 2013. The purpose of this symposium, which consists of plenary and poster sessions, is for investigators from CPTAC community and beyond to share and discuss novel biological discoveries, analytical methods, and translational approaches using CPTAC data.

  1. Intercenter validation of a knowledge based model for automated planning of volumetric modulated arc therapy for prostate cancer. The experience of the German RapidPlan Consortium.

    PubMed

    Schubert, Carolin; Waletzko, Oliver; Weiss, Christian; Voelzke, Dirk; Toperim, Sevda; Roeser, Arnd; Puccini, Silvia; Piroth, Marc; Mehrens, Christian; Kueter, Jan-Dirk; Hierholz, Kirsten; Gerull, Karsten; Fogliata, Antonella; Block, Andreas; Cozzi, Luca

    2017-01-01

    To evaluate the performance of a model-based optimisation process for volumetric modulated arc therapy applied to prostate cancer in a multicentric cooperative group. The RapidPlan (RP) knowledge-based engine was tested for the planning of Volumetric modulated arc therapy with RapidArc on prostate cancer patients. The study was conducted in the frame of the German RapidPlan Consortium (GRC). 43 patients from one institute of the GRC were used to build and train a RP model. This was further shared with all members of the GRC plus an external site from a different country to increase the heterogeneity of the patient's sampling. An in silico multicentric validation of the model was performed at planning level by comparing RP against reference plans optimized according to institutional procedures. A total of 60 patients from 7 institutes were used. On average, the automated RP based plans resulted fully consistent with the manually optimised set with a modest tendency to improvement in the medium-to-high dose region. A per-site stratification allowed to identify different patterns of performance of the model with some organs at risk resulting better spared with the manual or with the automated approach but in all cases the RP data fulfilled the clinical acceptability requirements. Discrepancies in the performance were due to different contouring protocols or to different emphasis put in the optimization of the manual cases. The multicentric validation demonstrated that it was possible to satisfactorily optimize with the knowledge based model patients from all participating centres. In the presence of possibly significant differences in the contouring protocols, the automated plans, though acceptable and fulfilling the benchmark goals, might benefit from further fine tuning of the constraints. The study demonstrates that, at least for the case of prostate cancer patients, it is possibile to share models among different clinical institutes in a cooperative framework.

  2. Intercenter validation of a knowledge based model for automated planning of volumetric modulated arc therapy for prostate cancer. The experience of the German RapidPlan Consortium

    PubMed Central

    Schubert, Carolin; Waletzko, Oliver; Weiss, Christian; Voelzke, Dirk; Toperim, Sevda; Roeser, Arnd; Puccini, Silvia; Piroth, Marc; Mehrens, Christian; Kueter, Jan-Dirk; Hierholz, Kirsten; Gerull, Karsten; Fogliata, Antonella; Block, Andreas

    2017-01-01

    Purpose To evaluate the performance of a model-based optimisation process for volumetric modulated arc therapy applied to prostate cancer in a multicentric cooperative group. The RapidPlan (RP) knowledge-based engine was tested for the planning of Volumetric modulated arc therapy with RapidArc on prostate cancer patients. The study was conducted in the frame of the German RapidPlan Consortium (GRC). Methods and materials 43 patients from one institute of the GRC were used to build and train a RP model. This was further shared with all members of the GRC plus an external site from a different country to increase the heterogeneity of the patient’s sampling. An in silico multicentric validation of the model was performed at planning level by comparing RP against reference plans optimized according to institutional procedures. A total of 60 patients from 7 institutes were used. Results On average, the automated RP based plans resulted fully consistent with the manually optimised set with a modest tendency to improvement in the medium-to-high dose region. A per-site stratification allowed to identify different patterns of performance of the model with some organs at risk resulting better spared with the manual or with the automated approach but in all cases the RP data fulfilled the clinical acceptability requirements. Discrepancies in the performance were due to different contouring protocols or to different emphasis put in the optimization of the manual cases. Conclusions The multicentric validation demonstrated that it was possible to satisfactorily optimize with the knowledge based model patients from all participating centres. In the presence of possibly significant differences in the contouring protocols, the automated plans, though acceptable and fulfilling the benchmark goals, might benefit from further fine tuning of the constraints. The study demonstrates that, at least for the case of prostate cancer patients, it is possibile to share models among different

  3. Genome-wide association analyses in East Asians identify new susceptibility loci for colorectal cancer

    PubMed Central

    Jia, Wei-Hua; Zhang, Ben; Matsuo, Keitaro; Shin, Aesun; Xiang, Yong-Bing; Jee, Sun Ha; Kim, Dong-Hyun; Ren, Zefang; Cai, Qiuyin; Long, Jirong; Shi, Jiajun; Wen, Wanqing; Yang, Gong; Delahanty, Ryan J.; Ji, Bu-Tian; Pan, Zhi-Zhong; Matsuda, Fumihiko; Gao, Yu-Tang; Oh, Jae Hwan; Ahn, Yoon-Ok; Park, Eun Jung; Li, Hong-Lan; Park, Ji Won; Jo, Jaeseong; Jeong, Jin-Young; Hosono, Satoyo; Casey, Graham; Peters, Ulrike; Shu, Xiao-Ou; Zeng, Yi-Xin; Zheng, Wei

    2013-01-01

    To identify novel genetic factors for colorectal cancer (CRC), we conducted a genome-wide association study in East Asians. By analyzing genome-wide data in 2,098 cases and 5,749 controls, we selected 64 promising SNPs for replication in an independent set of samples including up to 5,358 cases and 5,922 controls. We identified four SNPs with a P-value of 8.58 × 10−7 to 3.77 × 10−10 in the combined analysis of all East Asian samples. Three of the four SNPs were replicated in a study conducted among 26,060 European descendants with a combined P-value of 1.22 × 10−10 for rs647161 (5q31.1), 6.64 × 10−9 for rs2423279 (20p12.3), and 3.06 × 10−8 for rs10774214 (12p13.32 near the CCND2 gene), respectively, derived from the meta-analysis of data from both East Asian and European populations. This study identified three new CRC susceptibility loci and provides additional insight into the genetics and biology of CRC. PMID:23263487

  4. High Prevalence of the BIM Deletion Polymorphism in Young Female Breast Cancer in an East Asian Country

    PubMed Central

    Lin, Ching-Hung; Shen, Chen-Yang; Lee, Jih-Hsiang; Huang, Chiun-Sheng; Yang, Chih-Hsin; Kuo, Wen-Hung; Chang, Dwan-Ying; Hsiung, Chia-Ni; Kuo, Kuan-Ting; Chen, Wei-Wu; Chen, I-Chun; Wu, Pei-Fang; Kuo, Sung-Hsin; Chen, Chien-Jen

    2015-01-01

    Background A rapid surge of female breast cancer has been observed in young women in several East Asian countries. The BIM deletion polymorphism, which confers cell resistance to apoptosis, was recently found exclusively in East Asian people with prevalence rate of 12%. We aimed to evaluate the possible role of this genetic alteration in carcinogenesis of breast cancer in East Asians. Method Female healthy volunteers (n = 307), patients in one consecutive stage I-III breast cancer cohort (n = 692) and one metastatic breast cancer cohort (n = 189) were evaluated. BIM wild-type and deletion alleles were separately genotyped in genomic DNAs. Results Both cancer cohorts consistently showed inverse associations between the BIM deletion polymorphism and patient age (≤35 y vs. 36-50 y vs. >50 y: 29% vs. 22% vs. 15%, P = 0.006 in the consecutive cohort, and 40% vs. 23% vs. 13%, P = 0.023 in the metastatic cohort). In healthy volunteers, the frequencies of the BIM deletion polymorphism were similar (13%-14%) in all age groups. Further analyses indicated that the BIM deletion polymorphism was not associated with specific clinicopathologic features, but it was associated with poor overall survival (adjusted hazard ratio 1.71) in the consecutive cohort. Conclusions BIM deletion polymorphism may be involved in the tumorigenesis of the early-onset breast cancer among East Asians. PMID:25909194

  5. A case-control analysis of smoking and breast cancer in African American women: findings from the AMBER Consortium.

    PubMed

    Park, Song-Yi; Palmer, Julie R; Rosenberg, Lynn; Haiman, Christopher A; Bandera, Elisa V; Bethea, Traci N; Troester, Melissa A; Viscidi, Emma; Kolonel, Laurence N; Olshan, Andrew F; Ambrosone, Christine B

    2016-06-01

    Recent population studies suggest a role of smoking in the etiology of breast cancer, but few have been conducted among African American women. In a collaborative project of four large studies, we examined associations between smoking measures and breast cancer risk by menopause and hormone receptor status [estrogen receptor-positive (ER+), ER-negative (ER-) and triple-negative (ER-, PR-, HER2-)]. The study included 5791 African American women with breast cancer and 17376 African American controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated in multivariable logistic regression analysis with adjustment for study and risk factors. Results differed by menopausal status. Among postmenopausal women, positive associations were observed for long duration and greater pack-years of smoking: relative to never smoking, fully adjusted ORs were 1.14 (95% CI: 1.03-1.26) for duration ≥20 years and 1.16 (95% CI: 1.01-1.33) for ≥20 pack-years. By contrast, inverse associations were observed among premenopausal women, with ORs of 0.80 (95% CI: 0.68-95) for current smoking and 0.81 (95% CI: 0.69-0.96) for former smoking, without trends by duration. Associations among postmenopausal women were somewhat stronger for ER+ breast cancer. The findings suggest that the relation of cigarette smoking to breast cancer risk in African American women may vary by menopausal status and breast cancer subtype. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  6. Epidemiological and pathological aspects of skin cancer in North East of Romania.

    PubMed

    Andrese, Elena; Solovăstru, Laura Gheucă; Taranu, Tatiana; Iancu, Luminiţa Smaranda

    2014-01-01

    In the last years skin cancer has become the most frequent cancer in humans, with the majority made up of two tumors: malignant melanoma (MM) and non-melanoma skin cancer (NMSC). To provide for the first time in the North East region of Romania, descriptive epidemiological data of melanoma and non-melanoma skin cancers. We undertook a retrospective study over a five year period on the most frequent forms of skin cancer, basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and MM, which included a total number of 1231 patients, hospitalized and treated in the Plastic Surgery Department of "St. Spiridon" Emergency Clinical Hospital, Iaşi from 2008 until 2012. Results: BCC was diagnosed in a total of 675 patients, representing 54.9%. SCC was found in 217 patients, representing 17.6% and melanoma was diagnosed in 119 cases, a percent of 9.7% of the total number. The predominance of cutaneous malignancies waried with age, major site distribution was face and neck for BCC and SCC and the trunk for MM. This article describes the most common forms of skin cancer in our region, BCC (almost 55%), SCC (17.6%), and less in number MM (near to 10%); these results are similar to those published abroad in the last years. Future more elaborate interventional studies are necessary to identify the main risk factors in order to design the best preventive methods and, according to the skin cancer trend to specify the needs for dermatology network in our country.

  7. Consortium Proves Adage.

    ERIC Educational Resources Information Center

    Seidel, Kim

    1997-01-01

    Describes the Minnesota Preparatory Schools, a secondary-level consortium formed by Cotter High School, Saint Mary's University, the Minnesota Academy of Mathematics and Science, De La Salle Language Institute, and the Minnesota Conservatory for the Arts. Indicates that the consortium provides students with flexible schedules geared toward their…

  8. Consortium Directory, 1986.

    ERIC Educational Resources Information Center

    Baus, Frederick, Comp.; LaRocco, Teresa, Comp.

    Information on 133 higher education consortia is presented in this directory. Each consortium meets the following criteria: voluntary, formal organization; includes at least two member institutions; undertakes more than a single program; is administered by a professional director; and receives continuing membership support. For each consortium,…

  9. Quantitative trait loci predicting circulating sex steroid hormones in men from the NCI-Breast and Prostate Cancer Cohort Consortium (BPC3)

    PubMed Central

    Ahn, Jiyoung; Schumacher, Fredrick R.; Berndt, Sonja I.; Pfeiffer, Ruth; Albanes, Demetrius; Andriole, Gerald L.; Ardanaz, Eva; Boeing, Heiner; Bueno-de-Mesquita, Bas; Chanock, Stephen J.; Clavel-Chapelon, Françoise; Diver, W. Ryan; Feigelson, Heather Spencer; Gaziano, J. Michael; Giovannucci, Edward; Haiman, Christopher A.; Henderson, Brian E.; Hoover, Robert N.; Kolonel, Laurence N.; Kraft, Peter; Ma, Jing; Le Marchand, Loïc; Overvad, Kim; Palli, Domenico; Stattin, Pär; Stampfer, Meir; Stram, Daniel O.; Thomas, Gilles; Thun, Michael J.; Travis, Ruth C.; Trichopoulos, Dimitrios; Virtamo, Jarmo; Weinstein, Stephanie J.; Yeager, Meredith; Kaaks, Rudolf; Hunter, David J.; Hayes, Richard B.

    2009-01-01

    Twin studies suggest a heritable component to circulating sex steroid hormones and sex hormone-binding globulin (SHBG). In the NCI-Breast and Prostate Cancer Cohort Consortium, 874 SNPs in 37 candidate genes in the sex steroid hormone pathway were examined in relation to circulating levels of SHBG (N = 4720), testosterone (N = 4678), 3α-androstanediol-glucuronide (N = 4767) and 17β-estradiol (N = 2014) in Caucasian men. rs1799941 in SHBG is highly significantly associated with circulating levels of SHBG (P = 4.52 × 10−21), consistent with previous studies, and testosterone (P = 7.54 × 10−15), with mean difference of 26.9 and 14.3%, respectively, comparing wild-type to homozygous variant carriers. Further noteworthy novel findings were observed between SNPs in ESR1 with testosterone levels (rs722208, mean difference = 8.8%, P = 7.37 × 10−6) and SRD5A2 with 3α-androstanediol-glucuronide (rs2208532, mean difference = 11.8%, P = 1.82 × 10−6). Genetic variation in genes in the sex steroid hormone pathway is associated with differences in circulating SHBG and sex steroid hormones. PMID:19574343

  10. Stereotactic body radiotherapy in patients with stage I non-small-cell lung cancer aged 75 years and older: retrospective results from a multicenter consortium.

    PubMed

    Samuels, Michael A; Kandula, Shravan; Koru-Sengul, Tulay; Bogart, Jeffrey A; Salama, Joseph K; Aridgides, Paul D; Gajra, Ajeet; Lilenbaum, Rogerio C

    2013-07-01

    This study was a retrospective analysis of elderly patients treated with stereotactic body radiotherapy (SBRT) in the setting of a multi-institutional consortium. Three institutions pooled data on patients aged ≥ 75 years who received SBRT for stage I non-small-cell lung cancer (NSCLC). Forty-seven tumors in 46 patients were analyzed in patients aged 75 to 92 years (median, 82 years). Treatment was delivered during 2007 to 2009, with a median follow-up of 12.4 months. All patients underwent staging positron emission tomography-computed tomography (PET-CT), and 87% of tumors were confirmed by biopsy results. Total doses were 35 to 60 Gy, mainly in 3 to 5 fractions. All tumors were treated using a linear accelerator, with 96% of patients receiving 3-dimensional (3D) conformal RT and 4% undergoing intensity modulated RT (IMRT). At the time of analysis, the local failure rate was 2% (1 of 47). The regional failure rate was 9% (4 of 47). The distant failure rate was 6% (3 of 47). The combined failure rate was 15% (7 of 47) because 1 patient experienced both regional and distant failure. Among 20 tumors with any acute toxicity, there were no ≥ grade 3 toxicities. Pneumonitis (n = 10) grades 1 (n = 3) and 2 (n = 2) was seen in 15% and 10% of patients, respectively; these data were missing for 25% of patients. SBRT in patients aged ≥ 75 years with stage I NSCLC proved tolerable, with toxicity rates comparable to those in younger patients. Excellent rates of local, regional, and distant control were achieved at a median follow-up of 12.4 months. This patient population represents a rapidly growing segment of the early lung cancer population, and SBRT appears to be a safe and effective treatment option for patients who are not optimal candidates for surgery. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Impact of Socioeconomic Status on Timing of Relapse and Overall Survival for Children Treated on Dana-Farber Cancer Institute ALL Consortium Protocols (2000-2010).

    PubMed

    Bona, Kira; Blonquist, Traci M; Neuberg, Donna S; Silverman, Lewis B; Wolfe, Joanne

    2016-06-01

    Population-based evidence suggests that lower socioeconomic status (SES) negatively impacts the overall survival (OS) of children with leukemia; however, the relationships between SES and treatment-related mortality, relapse, and timing of relapse remain unclear. We examined OS, event-free survival (EFS) and cumulative incidence (CI) and timing of relapse by community-level poverty for 575 children aged 1-18 years with newly diagnosed acute lymphoblastic leukemia (ALL) treated on consecutive phase III multicenter Dana-Farber Cancer Institute ALL Consortium Protocols between 2000 and 2010. Children were categorized into high- and low-poverty areas for the analysis using aggregate U.S. Census data linked to zip code. Children living in high-poverty areas experienced a 5-year OS of 85% as compared with 92% for those in low-poverty areas (P = 0.02); poverty remained marginally significant (P = 0.07) after adjustment for immunophenotype, age, and white blood cell count. There were no differences detected in EFS or CI relapse by poverty area. However, 92% of the relapses observed in children from high-poverty areas occurred <36 months from complete remission, compared to 48% of those in children from low-poverty areas (P = 0.008). U.S. children with ALL living in high-poverty areas have a higher risk of early relapse when compared with those living in low-poverty areas despite uniform treatment. This may in part explain decreased OS observed in these children. This finding highlights disparities in childhood cancer outcomes by SES despite uniform treatment. Further investigations of the mechanistic pathways underlying this finding are needed. © 2016 Wiley Periodicals, Inc.

  12. Genetic variation in the immunosuppression pathway genes and breast cancer susceptibility: a pooled analysis of 42,510 cases and 40,577 controls from the Breast Cancer Association Consortium.

    PubMed

    Lei, Jieping; Rudolph, Anja; Moysich, Kirsten B; Behrens, Sabine; Goode, Ellen L; Bolla, Manjeet K; Dennis, Joe; Dunning, Alison M; Easton, Douglas F; Wang, Qin; Benitez, Javier; Hopper, John L; Southey, Melissa C; Schmidt, Marjanka K; Broeks, Annegien; Fasching, Peter A; Haeberle, Lothar; Peto, Julian; Dos-Santos-Silva, Isabel; Sawyer, Elinor J; Tomlinson, Ian; Burwinkel, Barbara; Marmé, Frederik; Guénel, Pascal; Truong, Thérèse; Bojesen, Stig E; Flyger, Henrik; Nielsen, Sune F; Nordestgaard, Børge G; González-Neira, Anna; Menéndez, Primitiva; Anton-Culver, Hoda; Neuhausen, Susan L; Brenner, Hermann; Arndt, Volker; Meindl, Alfons; Schmutzler, Rita K; Brauch, Hiltrud; Hamann, Ute; Nevanlinna, Heli; Fagerholm, Rainer; Dörk, Thilo; Bogdanova, Natalia V; Mannermaa, Arto; Hartikainen, Jaana M; Van Dijck, Laurien; Smeets, Ann; Flesch-Janys, Dieter; Eilber, Ursula; Radice, Paolo; Peterlongo, Paolo; Couch, Fergus J; Hallberg, Emily; Giles, Graham G; Milne, Roger L; Haiman, Christopher A; Schumacher, Fredrick; Simard, Jacques; Goldberg, Mark S; Kristensen, Vessela; Borresen-Dale, Anne-Lise; Zheng, Wei; Beeghly-Fadiel, Alicia; Winqvist, Robert; Grip, Mervi; Andrulis, Irene L; Glendon, Gord; García-Closas, Montserrat; Figueroa, Jonine; Czene, Kamila; Brand, Judith S; Darabi, Hatef; Eriksson, Mikael; Hall, Per; Li, Jingmei; Cox, Angela; Cross, Simon S; Pharoah, Paul D P; Shah, Mitul; Kabisch, Maria; Torres, Diana; Jakubowska, Anna; Lubinski, Jan; Ademuyiwa, Foluso; Ambrosone, Christine B; Swerdlow, Anthony; Jones, Michael; Chang-Claude, Jenny

    2016-01-01

    Immunosuppression plays a pivotal role in assisting tumors to evade immune destruction and promoting tumor development. We hypothesized that genetic variation in the immunosuppression pathway genes may be implicated in breast cancer tumorigenesis. We included 42,510 female breast cancer cases and 40,577 controls of European ancestry from 37 studies in the Breast Cancer Association Consortium (2015) with available genotype data for 3595 single nucleotide polymorphisms (SNPs) in 133 candidate genes. Associations between genotyped SNPs and overall breast cancer risk, and secondarily according to estrogen receptor (ER) status, were assessed using multiple logistic regression models. Gene-level associations were assessed based on principal component analysis. Gene expression analyses were conducted using RNA sequencing level 3 data from The Cancer Genome Atlas for 989 breast tumor samples and 113 matched normal tissue samples. SNP rs1905339 (A>G) in the STAT3 region was associated with an increased breast cancer risk (per allele odds ratio 1.05, 95 % confidence interval 1.03-1.08; p value = 1.4 × 10(-6)). The association did not differ significantly by ER status. On the gene level, in addition to TGFBR2 and CCND1, IL5 and GM-CSF showed the strongest associations with overall breast cancer risk (p value = 1.0 × 10(-3) and 7.0 × 10(-3), respectively). Furthermore, STAT3 and IL5 but not GM-CSF were differentially expressed between breast tumor tissue and normal tissue (p value = 2.5 × 10(-3), 4.5 × 10(-4) and 0.63, respectively). Our data provide evidence that the immunosuppression pathway genes STAT3, IL5, and GM-CSF may be novel susceptibility loci for breast cancer in women of European ancestry.

  13. Efficacy of pazopanib in progressive, radioiodine-refractory, metastatic differentiated thyroid cancers: results of a phase 2 consortium study

    PubMed Central

    Bible, Keith C; Suman, Vera J; Molina, Julian R; Smallridge, Robert C; Maples, William J; Menefee, Michael E; Rubin, Joseph; Sideras, Kostandinos; Morris, John C; McIver, Bryan; Burton, Jill K; Webster, Kevin P; Bieber, Carolyn; Traynor, Anne M; Flynn, Patrick J; Goh, Boon Cher; Tang, Hui; Ivy, Susan Percy; Erlichman, Charles

    2011-01-01

    Summary Background Chemotherapy has historically proven ineffective in advanced differentiated thyroid cancers, but the realisation that various tyrosine kinases are activated in the disease suggested a potential therapeutic role for tyrosine-kinase inhibitors. We investigated the safety and efficacy of pazopanib. Methods This phase 2 trial was done from Feb 22, 2008, to Jan 31, 2009, in patients with metastatic, rapidly progressive, radioiodine-refractory differentiated thyroid cancers. Each patient received 800 mg continuous pazopanib daily in 4-week cycles until disease progression, drug intolerance, or both occurred. Up to two previous therapies were allowed, and measurable disease with radiographic progression in the 6-month period before enrolment was a requirement for inclusion. The primary endpoint was any tumour response, according to the Response Evaluation Criteria in Solid Tumors 1.0. This study is registered with ClinicalTrials.gov, number NCT00625846. Findings 39 patients were enrolled. One patient had received no previous radioiodine therapy and another withdrew consent before treatment. Clinical outcomes could, therefore, be assessed in 37 patients (19 [51%] men, median age 63 years). The study is closed to accrual of new patients, but several enrolled patients are still being treated. Patients received a median of 12 cycles (range 1 to >23, total >383). Confirmed partial responses were recorded in 18 patients (response rate 49%, 95% CI 35–68), with likelihood of response lasting longer than 1 year calculated to be 66%. Maximum concentration of pazopanib in plasma during cycle one was significantly correlated with radiographic response (r=−0·40, p=0·021). 16 (43%) patients required dose reductions owing to adverse events, the most frequent of which (any grade) were fatigue (29 patients), skin and hair hypopigmentation (28), diarrhoea (27), and nausea (27). Two patients who died during treatment had pre-existing contributory disorders

  14. Saracatinib as a metastasis inhibitor in metastatic castration-resistant prostate cancer: A University of Chicago Phase 2 Consortium and DOD/PCF Prostate Cancer Clinical Trials Consortium Study.

    PubMed

    Posadas, Edwin M; Ahmed, Rafi S; Karrison, Theodore; Szmulewitz, Russell Z; O'Donnell, Peter H; Wade, James L; Shen, James; Gururajan, Murali; Sievert, Margarit; Stadler, Walter M

    2016-02-15

    Fyn is a kinase that is upregulated in a subset of metastatic castration-resistant prostate cancer. Saracatinib potently inhibits Fyn activation. We have noted a relationship between Fyn expression and directional motility, a cellular process related to metastasis. As such we hypothesized that treatment with saracatinib would increase the time required to develop new metastatic lesions. Patients with metastatic castration-resistant prostate cancer that had progressed after docetaxel were eligible for enrollment. This study was executed as a randomized discontinuation trial. During a lead-in phase of two 28-Day cycles, all patients received saracatinib. Afterward, patients with radiographically stable disease were randomized to either saracatinib or placebo. Patients continued treatment until evidence of new metastasis. Thirty-one patients were treated. Only 26% of patients had stable disease after 8 weeks and thus proceeded to randomization. This required early termination of the study for futility. The 70% of patients who progressed after the lead-in phase exhibited expansion of existing lesions or decompensation due to clinical progression without new metastatic lesions. Fatigue was reported in more than 25% of patients (all grades) with only two patients experiencing grade 3 toxicity. Other grade 3 adverse events included dehydration, thrombocytopenia, and weakness. This study was unable to determine if saracatinib had potential as metastasis inhibitor. Metastasis inhibition by saracatinib may still be viable in an earlier time in the disease history. © 2015 Wiley Periodicals, Inc.

  15. Serum Cadmium Levels in Pancreatic Cancer Patients from the East Nile Delta Region of Egypt

    PubMed Central

    Kriegel, Alison M.; Soliman, Amr S.; Zhang, Qing; El-Ghawalby, Nabih; Ezzat, Farouk; Soultan, Ahmed; Abdel-Wahab, Mohamed; Fathy, Omar; Ebidi, Gamal; Bassiouni, Nadia; Hamilton, Stanley R.; Abbruzzese, James L.; Lacey, Michelle R.; Blake, Diane A.

    2006-01-01

    The northeast Nile Delta region exhibits a high incidence of early-onset pancreatic cancer. It is well documented that this region has one of the highest levels of pollution in Egypt. Epidemiologic studies have suggested that cadmium, a prevalent pollutant in the northeast Nile Delta region, plays a role in the development of pancreatic cancer. Objective: We aimed to assess serum cadmium levels as markers of exposure in pancreatic cancer patients and noncancer comparison subjects from the same region in Egypt. Design and Participants: We assessed serum cadmium levels of 31 newly diagnosed pancreatic cancer patients and 52 hospital comparison subjects from Mansoura, Egypt. Evaluation/Measurements: Serum cadmium levels were measured using a novel immunoassay procedure. Results: We found a significant difference between the mean serum cadmium levels in patients versus comparison subjects (mean ± SD, 11.1 ± 7.7 ng/mL vs. 7.1 ± 5.0 ng/mL, respectively; p = 0.012) but not in age, sex, residence, occupation, or smoking status. The odds ratio (OR) for pancreatic cancer risk was significant for serum cadmium level [OR = 1.12; 95% confidence interval (CI), 1.04–1.23; p = 0.0089] and farming (OR = 3.25; 95% CI, 1.03–11.64; p = 0.0475) but not for age, sex, residence, or smoking status. Conclusions: The results from this pilot study suggest that pancreatic cancer in the East Nile Delta region is significantly associated with high levels of serum cadmium and farming. Relevance to Clinical Practice/Public Health: Future studies should further investigate the etiologic relationship between cadmium exposure and pancreatic carcinogenesis in cadmium-exposed populations. PMID:16393667

  16. International Robotic Radical Cystectomy Consortium: A way forward.

    PubMed

    Raza, Syed Johar; Field, Erinn; Kibel, Adam S; Mottrie, Alex; Weizer, Alon Z; Wagner, Andrew; Hemal, Ashok K; Scherr, Douglas S; Schanne, Francis; Gaboardi, Franco; Wu, Guan; Peabody, James O; Koauk, Jihad; Redorta, Joan Palou; Pattaras, John G; Rha, Koon-Ho; Richstone, Lee; Balbay, M Derya; Menon, Mani; Hayn, Mathew; Stoeckle, Micheal; Wiklund, Peter; Dasgupta, Prokar; Pruthi, Raj; Ghavamian, Reza; Khan, Shamim; Siemer, Stephan; Maatman, Thomas; Wilson, Timothy; Poulakis, Vassilis; Wilding, Greg; Guru, Khurshid A

    2014-07-01

    Robot-assisted radical cystectomy (RARC) is an emerging operative alternative to open surgery for the management of invasive bladder cancer. Studies from single institutions provide limited data due to the small number of patients. In order to better understand the related outcomes, a world-wide consortium was established in 2006 of patients undergoing RARC, called the International Robotic Cystectomy Consortium (IRCC). Thus far, the IRCC has reported its findings on various areas of operative interest and continues to expand its capacity to include other operative modalities and transform it into the International Radical Cystectomy Consortium. This article summarizes the findings of the IRCC and highlights the future direction of the consortium.

  17. Risk factors for head and neck cancer in young adults: a pooled analysis in the INHANCE consortium

    PubMed Central

    Toporcov, Tatiana Natasha; Znaor, Ariana; Zhang, Zuo-Feng; Yu, Guo-Pei; Winn, Deborah M; Wei, Qingyi; Vilensky, Marta; Vaughan, Thomas; Thomson, Peter; Talamini, Renato; Szeszenia-Dabrowska, Neonila; Sturgis, Erich M; Smith, Elaine; Shangina, Oxana; Schwartz, Stephen M; Schantz, Stimson; Rudnai, Peter; Richiardi, Lorenzo; Ramroth, Heribert; Purdue, Mark P; Olshan, Andrew F; Eluf-Neto, José; Muscat, Joshua; Moyses, Raquel Ajub; Morgenstern, Hal; Menezes, Ana; McClean, Michael; Matsuo, Keitaro; Mates, Dana; Macfarlane, Tatiana V; Lissowska, Jolanta; Levi, Fabio; Lazarus, Philip; Vecchia, Carlo La; Lagiou, Pagona; Koifman, Sergio; Kjaerheim, Kristina; Kelsey, Karl; Holcatova, Ivana; Herrero, Rolando; Healy, Claire; Hayes, Richard B; Franceschi, Silvia; Fernandez, Leticia; Fabianova, Eleonora; Daudt, Alexander W; Curioni, Otávio Alberto; Maso, Luigino Dal; Curado, Maria Paula; Conway, David I; Chen, Chu; Castellsague, Xavier; Canova, Cristina; Cadoni, Gabriella; Brennan, Paul; Boccia, Stefania; Antunes, José Leopoldo Ferreira; Ahrens, Wolfgang; Agudo, Antonio; Boffetta, Paolo; Hashibe, Mia; Lee, Yuan-Chin Amy; Filho, Victor Wünsch

    2015-01-01

    Background: Increasing incidence of head and neck cancer (HNC) in young adults has been reported. We aimed to compare the role of major risk factors and family history of cancer in HNC in young adults and older patients. Methods: We pooled data from 25 case-control studies and conducted separate analyses for adults ≤45 years old (‘young adults’, 2010 cases and 4042 controls) and >45 years old (‘older adults’, 17 700 cases and 22 704 controls). Using logistic regression with studies treated as random effects, we estimated adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Results: The young group of cases had a higher proportion of oral tongue cancer (16.0% in women; 11.0% in men) and unspecified oral cavity / oropharynx cancer (16.2%; 11.1%) and a lower proportion of larynx cancer (12.1%; 16.6%) than older adult cases. The proportions of never smokers or never drinkers among female cases were higher than among male cases in both age groups. Positive associations with HNC and duration or pack-years of smoking and drinking were similar across age groups. However, the attributable fractions (AFs) for smoking and drinking were lower in young when compared with older adults (AFs for smoking in young women, older women, young men and older men, respectively, = 19.9% (95% CI = 9.8%, 27.9%), 48.9% (46.6%, 50.8%), 46.2% (38.5%, 52.5%), 64.3% (62.2%, 66.4%); AFs for drinking = 5.3% (−11.2%, 18.0%), 20.0% (14.5%, 25.0%), 21.5% (5.0%, 34.9%) and 50.4% (46.1%, 54.3%). A family history of early-onset cancer was associated with HNC risk in the young [OR = 2.27 (95% CI = 1.26, 4.10)], but not in the older adults [OR = 1.10 (0.91, 1.31)]. The attributable fraction for family history of early-onset cancer was 23.2% (8.60% to 31.4%) in young compared with 2.20% (−2.41%, 5.80%) in older adults. Conclusions: Differences in HNC aetiology according to age group may exist. The lower AF of cigarette smoking and alcohol drinking in young

  18. Low frequency of cigarette smoking and the risk of head and neck cancer in the INHANCE consortium pooled analysis.

    PubMed

    Berthiller, Julien; Straif, Kurt; Agudo, Antonio; Ahrens, Wolfgang; Bezerra Dos Santos, Alexandre; Boccia, Stefania; Cadoni, Gabriella; Canova, Cristina; Castellsague, Xavier; Chen, Chu; Conway, David; Curado, Maria Paula; Dal Maso, Luigino; Daudt, Alexander W; Fabianova, Eleonora; Fernandez, Leticia; Franceschi, Silvia; Fukuyama, Erica E; Hayes, Richard B; Healy, Claire; Herrero, Rolando; Holcatova, Ivana; Kelsey, Karl; Kjaerheim, Kristina; Koifman, Sergio; Lagiou, Pagona; La Vecchia, Carlo; Lazarus, Philip; Levi, Fabio; Lissowska, Jolanta; Macfarlane, Tatiana; Mates, Dana; McClean, Michael; Menezes, Ana; Merletti, Franco; Morgenstern, Hal; Muscat, Joshua; Olshan, Andrew F; Purdue, Mark; Ramroth, Heribert; Rudnai, Peter; Schwartz, Stephen M; Serraino, Diego; Shangina, Oxana; Smith, Elaine; Sturgis, Erich M; Szeszenia-Dabrowska, Neonila; Thomson, Peter; Vaughan, Thomas L; Vilensky, Marta; Wei, Qingyi; Winn, Deborah M; Wünsch-Filho, Victor; Zhang, Zuo-Feng; Znaor, Ariana; Ferro, Gilles; Brennan, Paul; Boffetta, Paolo; Hashibe, Mia; Lee, Yuan-Chin Amy

    2016-06-01

    Cigarette smoking is a major risk factor for head and neck cancer (HNC). To our knowledge, low cigarette smoking (<10 cigarettes per day) has not been extensively investigated in fine categories or among never alcohol drinkers. We conducted a pooled analysis of individual participant data from 23 independent case-control studies including 19 660 HNC cases and 25 566 controls. After exclusion of subjects using other tobacco products including cigars, pipes, snuffed or chewed tobacco and straw cigarettes (tobacco product used in Brazil), as well as subjects smoking more than 10 cigarettes per day, 4093 HNC cases and 13 416 controls were included in the analysis. The lifetime average frequency of cigarette consumption was categorized as follows: never cigarette users, >0-3, >3-5, >5-10 cigarettes per day. Smoking >0-3 cigarettes per day was associated with a 50% increased risk of HNC in the study population [odds ratio (OR) = 1.52, 95% confidence interval (CI): (1.21, 1.90). Smoking >3-5 cigarettes per day was associated in each subgroup from OR = 2.01 (95% CI: 1.22, 3.31) among never alcohol drinkers to OR = 2.74 (95% CI: 2.01, 3.74) among women and in each cancer site, particularly laryngeal cancer (OR = 3.48, 95% CI: 2.40, 5.05). However, the observed increased risk of HNC for low smoking frequency was not found among smokers with smoking duration shorter than 20 years. Our results suggest a public health message that low frequency of cigarette consumption contributes to the development of HNC. However, smoking duration seems to play at least an equal or a stronger role in the development of HNC. © The Author 2015; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.

  19. Palliative care in the community for children with cancer in South East England.

    PubMed

    Spencer, L; Battye, L

    2001-09-01

    In-depth interviews and discussions were held with 40 different professionals in South East England involved in managing palliative care for children with cancer in the community. Participants included paediatric oncologists and outreach nurse specialists in tertiary centres, paediatricians in shared care units, children's community nurses, general practitioners, social workers and child psychologists. The research examined palliative care services available in the region, exploring attitudes to both current provision and possible service improvements. Providing palliative care in the community involves multi-agency collaboration and the study highlighted a range of different approaches to case management with the diversity of resources available. Key improvements proposed by health-care professionals included: better communication and liaison between all the professionals involved; clearer allocation of roles and responsibilities; 24-hour availability of specialist advice on palliative care for children with cancer; faster access to social work and psychology services at the community level; continuity of nursing and respite care. The provision of specialist local palliative care services for children with cancer was generally rejected. The participants favoured improving community palliative care for all children with life-limiting or life-threatening conditions with community nursing teams providing continuity of care and outreach nurses providing specialist advice and support.

  20. Measurement and evaluation of digital cervicography programs in two cervical cancer screening camps in East Africa

    NASA Astrophysics Data System (ADS)

    Peterson, Curtis W.; Mink, Jonah; Levitz, David

    2017-03-01

    Cervical cancer disproportionately affects women living in low- and middle-income countries. To address this global crisis, many governments and NGOs have implemented community-based screening and treatment programs at outreach camps. Here, high volumes of patients are able to access care: screening and diagnosis followed by immediate treatment of precancerous lesions onsite. However, monitoring and evaluation (M&E) of these efforts presents challenges, since each event typically relies on a different health workforce, and refers patients to different facilities for follow up and advanced care. To address these challenges, a digital imaging intervention was deployed at several screening camps in East Africa. Trained nurses screened women using a connected low-cost mobile colposcope built around a smartphone. A decision support job aid was integrated into the app controlling the device, guiding nurses and recording their diagnosis and treatment decisions. Aggregating the data from the job aid allowed M&E of the screening camp in real-time. In this paper, the M&E data from 2 different screening camps in East Africa are compared. Additionally, screening camps are compared to stationary clinics. Differences in the patient screening times, treatment rates, and individual nurse statistics were all documented through the job aid allowing for much improved epidemiological information following outreach events thus enabling targeted program improvements and provider training. Reporting data from screening camps were also shared online via public web pages, facilitating broader dissemination of health needs in specific East African communities, and sparking conversations with regional stakeholders about local disease burden.

  1. Assessing a Consortium's Effectiveness.

    ERIC Educational Resources Information Center

    Peterson, Lorna M.

    2002-01-01

    Using the example of the Five Colleges consortium, explores the measuring of benefits and costs involved in intercollegiate cooperation. Discusses how the benefits are often other than cost-savings, which is ostensibly why many institutions join such consortia. (EV)

  2. NCI Cohort Consortium Membership

    Cancer.gov

    The NCI Cohort Consortium membership is international and includes investigators responsible for more than 40 high-quality cohorts who are studying large and diverse populations in more than 15 different countries.

  3. A survey of industries and colorectal cancer screening of employees in the East Midlands of England.

    PubMed Central

    Hart, A R; Wicks, A C; Mayberry, J F

    1993-01-01

    The number of industries in the East Midlands of England who were prepared to enroll their employees in a scheme to detect colorectal cancer by faecal occult blood testing was investigated. Company directors were asked if they would supply a list of their employees over the age of 40 years and allow a research team to give a 15 min talk at the workplace. Forty-nine per cent of firms responded to the questionnaire and 27% of businesses were prepared to enroll. There was no difference in mean total employees between firms willing and unwilling to participate (unpaired t-test, P > 0.05). The commonest reason given by managers rejecting the scheme was that they did not believe the workforce would be interested. PMID:8230058

  4. Men of African Descent and Carcinoma of the Prostate Consortium

    Cancer.gov

    The Men of African Descent and Carcinoma of the Prostate Consortium collaborates on epidemiologic studies to address the high burden of prostate cancer and to understand the causes of etiology and outcomes among men of African ancestry.

  5. Results and harmonization guidelines from two large-scale international Elispot proficiency panels conducted by the Cancer Vaccine Consortium (CVC/SVI)

    PubMed Central

    Panageas, Katherine S.; Ben-Porat, Leah; Boyer, Jean; Britten, Cedrik M.; Clay, Timothy M.; Kalos, Michael; Maecker, Holden T.; Romero, Pedro; Yuan, Jianda; Martin Kast, W.; Hoos, Axel

    2007-01-01

    The Cancer Vaccine Consortium of the Sabin Vaccine Institute (CVC/SVI) is conducting an ongoing large-scale immune monitoring harmonization program through its members and affiliated associations. This effort was brought to life as an external validation program by conducting an international Elispot proficiency panel with 36 laboratories in 2005, and was followed by a second panel with 29 participating laboratories in 2006 allowing for application of learnings from the first panel. Critical protocol choices, as well as standardization and validation practices among laboratories were assessed through detailed surveys. Although panel participants had to follow general guidelines in order to allow comparison of results, each laboratory was able to use its own protocols, materials and reagents. The second panel recorded an overall significantly improved performance, as measured by the ability to detect all predefined responses correctly. Protocol choices and laboratory practices, which can have a dramatic effect on the overall assay outcome, were identified and lead to the following recommendations: (A) Establish a laboratory SOP for Elispot testing procedures including (A1) a counting method for apoptotic cells for determining adequate cell dilution for plating, and (A2) overnight rest of cells prior to plating and incubation, (B) Use only pre-tested serum optimized for low background: high signal ratio, (C) Establish a laboratory SOP for plate reading including (C1) human auditing during the reading process and (C2) adequate adjustments for technical artifacts, and (D) Only allow trained personnel, which is certified per laboratory SOPs to conduct assays. Recommendations described under (A) were found to make a statistically significant difference in assay performance, while the remaining recommendations are based on practical experiences confirmed by the panel results, which could not be statistically tested. These results provide initial harmonization guidelines

  6. Results and harmonization guidelines from two large-scale international Elispot proficiency panels conducted by the Cancer Vaccine Consortium (CVC/SVI).

    PubMed

    Janetzki, Sylvia; Panageas, Katherine S; Ben-Porat, Leah; Boyer, Jean; Britten, Cedrik M; Clay, Timothy M; Kalos, Michael; Maecker, Holden T; Romero, Pedro; Yuan, Jianda; Kast, W Martin; Hoos, Axel

    2008-03-01

    The Cancer Vaccine Consortium of the Sabin Vaccine Institute (CVC/SVI) is conducting an ongoing large-scale immune monitoring harmonization program through its members and affiliated associations. This effort was brought to life as an external validation program by conducting an international Elispot proficiency panel with 36 laboratories in 2005, and was followed by a second panel with 29 participating laboratories in 2006 allowing for application of learnings from the first panel. Critical protocol choices, as well as standardization and validation practices among laboratories were assessed through detailed surveys. Although panel participants had to follow general guidelines in order to allow comparison of results, each laboratory was able to use its own protocols, materials and reagents. The second panel recorded an overall significantly improved performance, as measured by the ability to detect all predefined responses correctly. Protocol choices and laboratory practices, which can have a dramatic effect on the overall assay outcome, were identified and lead to the following recommendations: (A) Establish a laboratory SOP for Elispot testing procedures including (A1) a counting method for apoptotic cells for determining adequate cell dilution for plating, and (A2) overnight rest of cells prior to plating and incubation, (B) Use only pre-tested serum optimized for low background: high signal ratio, (C) Establish a laboratory SOP for plate reading including (C1) human auditing during the reading process and (C2) adequate adjustments for technical artifacts, and (D) Only allow trained personnel, which is certified per laboratory SOPs to conduct assays. Recommendations described under (A) were found to make a statistically significant difference in assay performance, while the remaining recommendations are based on practical experiences confirmed by the panel results, which could not be statistically tested. These results provide initial harmonization guidelines

  7. Long-term results of Dana-Farber Cancer Institute ALL Consortium protocols for children with newly diagnosed acute lymphoblastic leukemia (1985-2000).

    PubMed

    Silverman, L B; Stevenson, K E; O'Brien, J E; Asselin, B L; Barr, R D; Clavell, L; Cole, P D; Kelly, K M; Laverdiere, C; Michon, B; Schorin, M A; Schwartz, C L; O'Holleran, E W; Neuberg, D S; Cohen, H J; Sallan, S E

    2010-02-01

    The Dana-Farber Cancer Institute (DFCI) acute lymphoblastic leukemia (ALL) Consortium has been conducting multi-institutional clinical trials in childhood ALL since 1981. The treatment backbone has included 20-30 consecutive weeks of asparaginase during intensification and frequent vincristine/corticosteroid pulses during the continuation phase. Between 1985 and 2000, 1457 children aged 0-18 years were treated on four consecutive protocols: 85-01 (1985-1987), 87-01 (1987-1991), 91-01 (1991-1955) and 95-01 (1996-2000). The 10-year event-free survival (EFS)+/-s.e. by protocol was 77.9+/-2.8% (85-01), 74.2+/-2.3% (87-01), 80.8+/-2.1% (91-01) and 80.5+/-1.8% (95-01). Approximately 82% of patients treated in the 1980s and 88% treated in the 1990s were long-term survivors. Both EFS and overall survival (OS) rates were significantly higher for patients treated in the 1990s compared with the 1980s (P=0.05 and 0.01, respectively). On the two protocols conducted in the 1990s, EFS was 79-85% for T-cell ALL patients and 75-78% for adolescents (age 10-18 years). Results of randomized studies revealed that dexrazoxane prevented acute cardiac injury without adversely affecting EFS or OS in high-risk (HR) patients, and frequently dosed intrathecal chemotherapy was an effective substitute for cranial radiation in standard-risk (SR) patients. Current studies continue to focus on improving efficacy while minimizing acute and late toxicities.

  8. Vitamin D-associated genetic variation and risk of breast cancer in the breast and prostate cancer cohort consortium (BPC3).

    PubMed

    Mondul, Alison M; Shui, Irene M; Yu, Kai; Weinstein, Stephanie J; Tsilidis, Konstantinos K; Joshi, Amit D; Agudo, Antonio; Berg, Christine D; Black, Amanda; Buring, Julie E; Chasman, Daniel I; Gaudet, Mia M; Haiman, Christopher; Hankinson, Susan E; Henderson, Brian E; Hoover, Robert N; Hunter, David J; Khaw, Kay-Tee; Kühn, Tilman; Kvaskoff, Marina; Le Marchand, Loic; Lindström, Sara; McCullough, Marjorie L; Overvad, Kim; Peeters, Petra H; Riboli, Elio; Ridker, Paul M; Stram, Daniel O; Sund, Malin; Trichopoulos, Dimitrios; Tumino, Rosario; Weiderpass, Elisabete; Willett, Walter; Kraft, Peter; Ziegler, Regina G; Albanes, Demetrius

    2015-03-01

    Two recent genome-wide association studies (GWAS) identified SNPs in or near four genes related to circulating 25-hydroxyvitamin D [25(OH)D] concentration. To examine the hypothesized inverse relationship between vitamin D status and breast cancer, we studied the associations between SNPs in these genes and breast cancer risk in a large pooled study of 9,456 cases and 10,816 controls from six cohorts. SNP markers localized to each of four genes (GC, CYP24A1, CYP2R1, and DHCR7) previously associated with 25(OH)D were genotyped and examined both individually and as a 4-SNP polygenic score. Logistic regression was used to estimate the associations between the genetic variants and risk of breast cancer. We found no association between any of the four SNPs or their polygenic score and breast cancer risk. Our findings do not support an association between vitamin D status, as reflected by 25(OH)D-related genotypes, and breast cancer risk. These findings may contribute to future meta-analyses and scientific review articles, and provide new data about the association between vitamin D-related genes and breast cancer. Cancer Epidemiol Biomarkers Prev; 24(3); 627-30. ©2014 AACR. ©2014 American Association for Cancer Research.

  9. Community Palliative Care in Turkey: A Collaborative Promoter to a New Concept in the Middle East.

    PubMed

    Hacıkamiloglu, Ezgi; Utku, Ezgi Simsek; Cukurova, Zafer; Keskinkilic, Bekir; Topcu, Ibrahim; Gultekin, Murat; Silbermann, Michael

    2016-01-01

    The Middle East has been struggling with basic issues of cancer care, and in specific, palliative care, at the primary health care level in the communities. The Middle East Cancer Consortium designated this issue as the highest priority of its activities in the region. Following basic and advanced courses and national and international workshops, local governments recognized the essentiality of developing palliative care services in their respective countries. As the result of these training activities, in 2010, the Ministry of Health in Turkey initiated a novel program whereby population-based and home-based palliative care teams were developed throughout the country, including peripheral regions in the countries where appropriate care was not available. This initiative led to a dramatic increase in the number of cancer patients receiving palliative care at their homes. The Turkish initiative can serve as a model to other countries in the Middle East and beyond it.

  10. Enhanced statistical tests for GWAS in admixed populations: assessment using African Americans from CARe and a Breast Cancer Consortium.

    PubMed

    Pasaniuc, Bogdan; Zaitlen, Noah; Lettre, Guillaume; Chen, Gary K; Tandon, Arti; Kao, W H Linda; Ruczinski, Ingo; Fornage, Myriam; Siscovick, David S; Zhu, Xiaofeng; Larkin, Emma; Lange, Leslie A; Cupples, L Adrienne; Yang, Qiong; Akylbekova, Ermeg L; Musani, Solomon K; Divers, Jasmin; Mychaleckyj, Joe; Li, Mingyao; Papanicolaou, George J; Millikan, Robert C; Ambrosone, Christine B; John, Esther M; Bernstein, Leslie; Zheng, Wei; Hu, Jennifer J; Ziegler, Regina G; Nyante, Sarah J; Bandera, Elisa V; Ingles, Sue A; Press, Michael F; Chanock, Stephen J; Deming, Sandra L; Rodriguez-Gil, Jorge L; Palmer, Cameron D; Buxbaum, Sarah; Ekunwe, Lynette; Hirschhorn, Joel N; Henderson, Brian E; Myers, Simon; Haiman, Christopher A; Reich, David; Patterson, Nick; Wilson, James G; Price, Alkes L

    2011-04-01

    While genome-wide association studies (GWAS) have primarily examined populations of European ancestry, more recent studies often involve additional populations, including admixed populations such as African Americans and Latinos. In admixed populations, linkage disequilibrium (LD) exists both at a fine scale in ancestral populations and at a coarse scale (admixture-LD) due to chromosomal segments of distinct ancestry. Disease association statistics in admixed populations have previously considered SNP association (LD mapping) or admixture association (mapping by admixture-LD), but not both. Here, we introduce a new statistical framework for combining SNP and admixture association in case-control studies, as well as methods for local ancestry-aware imputation. We illustrate the gain in statistical power achieved by these methods by analyzing data of 6,209 unrelated African Americans from the CARe project genotyped on the Affymetrix 6.0 chip, in conjunction with both simulated and real phenotypes, as well as by analyzing the FGFR2 locus using breast cancer GWAS data from 5,761 African-American women. We show that, at typed SNPs, our method yields an 8% increase in statistical power for finding disease risk loci compared to the power achieved by standard methods in case-control studies. At imputed SNPs, we observe an 11% increase in statistical power for mapping disease loci when our local ancestry-aware imputation framework and the new scoring statistic are jointly employed. Finally, we show that our method increases statistical power in regions harboring the causal SNP in the case when the causal SNP is untyped and cannot be imputed. Our methods and our publicly available software are broadly applicable to GWAS in admixed populations.

  11. Enhanced Statistical Tests for GWAS in Admixed Populations: Assessment using African Americans from CARe and a Breast Cancer Consortium

    PubMed Central

    Pasaniuc, Bogdan; Zaitlen, Noah; Lettre, Guillaume; Chen, Gary K.; Tandon, Arti; Kao, W. H. Linda; Ruczinski, Ingo; Fornage, Myriam; Siscovick, David S.; Zhu, Xiaofeng; Larkin, Emma; Lange, Leslie A.; Cupples, L. Adrienne; Yang, Qiong; Akylbekova, Ermeg L.; Musani, Solomon K.; Divers, Jasmin; Mychaleckyj, Joe; Li, Mingyao; Papanicolaou, George J.; Millikan, Robert C.; Ambrosone, Christine B.; John, Esther M.; Bernstein, Leslie; Zheng, Wei; Hu, Jennifer J.; Ziegler, Regina G.; Nyante, Sarah J.; Bandera, Elisa V.; Ingles, Sue A.; Press, Michael F.; Chanock, Stephen J.; Deming, Sandra L.; Rodriguez-Gil, Jorge L.; Palmer, Cameron D.; Buxbaum, Sarah; Ekunwe, Lynette; Hirschhorn, Joel N.; Henderson, Brian E.; Myers, Simon; Haiman, Christopher A.; Reich, David; Patterson, Nick; Wilson, James G.; Price, Alkes L.

    2011-01-01

    While genome-wide association studies (GWAS) have primarily examined populations of European ancestry, more recent studies often involve additional populations, including admixed populations such as African Americans and Latinos. In admixed populations, linkage disequilibrium (LD) exists both at a fine scale in ancestral populations and at a coarse scale (admixture-LD) due to chromosomal segments of distinct ancestry. Disease association statistics in admixed populations have previously considered SNP association (LD mapping) or admixture association (mapping by admixture-LD), but not both. Here, we introduce a new statistical framework for combining SNP and admixture association in case-control studies, as well as methods for local ancestry-aware imputation. We illustrate the gain in statistical power achieved by these methods by analyzing data of 6,209 unrelated African Americans from the CARe project genotyped on the Affymetrix 6.0 chip, in conjunction with both simulated and real phenotypes, as well as by analyzing the FGFR2 locus using breast cancer GWAS data from 5,761 African-American women. We show that, at typed SNPs, our method yields an 8% increase in statistical power for finding disease risk loci compared to the power achieved by standard methods in case-control studies. At imputed SNPs, we observe an 11% increase in statistical power for mapping disease loci when our local ancestry-aware imputation framework and the new scoring statistic are jointly employed. Finally, we show that our method increases statistical power in regions harboring the causal SNP in the case when the causal SNP is untyped and cannot be imputed. Our methods and our publicly available software are broadly applicable to GWAS in admixed populations. PMID:21541012

  12. Pharmcodynamics (PD) and Pharmacokinetics (PK) of E7389 (Eribulin, Halichondrin B Analog) During a Phase I Trial in Patients with Advanced Solid Tumors: A California Cancer Consortium Trial

    PubMed Central

    Morgan, Robert J.; Synold, Timothy W.; Longmate, Jeffrey A.; Quinn, David I; Gandara, David; Lenz, Heinz-Josef; Ruel, Christopher; Xi, Bixin; Lewis, Michael D.; Colevas, A. Dimitrios; Doroshow, James; Newman, Edward M.

    2015-01-01

    Background The California Cancer Consortium completed a Phase I trial of E7389 (eribulin mesylate), an analog of the marine natural product halichondrin B. This trial was to determine the pharmacodynamics, pharmacokinetics, and MTD of E7389 administered by bolus injection weekly for three weeks out of four. Methods This trial included a rapid titration design. Real-time pharmacokinetics were utilized to guide dose escalation. Initially, single patient cohorts were enrolled with intra- and inter-patient dose-doubling. The second phase was a standard 3 + 3 dose escalation schedule. At the MTD, a cohort of patients was enrolled for target validation studies (separate manuscript). The starting dose was 0.125 mg/m2, and doses were doubled within and between patients in the first phase. Blood and urine sampling for E7389 pharmacokinetics was performed on doses 1 and 3 of cycle 1. Levels were determined using a LC/MS/MS assay. Results 40 patients were entered. Thirty-eight were evaluable for toxicity, thirty-five for response. The rapid escalation ended with a grade 3 elevation of alkaline phosphatase at 0.5 mg/m2/wk. The second phase ended at 2.0 mg/m2/wk with dose-limiting toxicities of grade 3 and 4 febrile neutropenia. Other toxicities included hypoglycemia, hypophosphatemia, and fatigue. The MTD was 1.4 mg/m2/wk. Responses included 4 partial responses, (lung cancer [2], urothelial [1], and melanoma [1]). Conclusions E7389 was well-tolerated in this trial with the major toxicity being myelosuppression. PD shows that E7389 induces significant morphologic changes (bundle formation) in the microtubules of peripheral blood mononuclear cells and tumor cells in vivo. The data suggest that lower intra-tumoral levels of β-tubulin III or higher intra-tumoral levels of MAP4 may correlate with response to E7389, while lower intra-tumoral levels of stathmin may be associated with progression. PK data reveals that E7389 exhibits a tri-exponential elimination from the plasma of

  13. Assessing interactions between the associations of common genetic susceptibility variants, reproductive history and body mass index with breast cancer risk in the breast cancer association consortium: a combined case-control study.

    PubMed

    Milne, Roger L; Gaudet, Mia M; Spurdle, Amanda B; Fasching, Peter A; Couch, Fergus J; Benítez, Javier; Arias Pérez, José Ignacio; Zamora, M Pilar; Malats, Núria; Dos Santos Silva, Isabel; Gibson, Lorna J; Fletcher, Olivia; Johnson, Nichola; Anton-Culver, Hoda; Ziogas, Argyrios; Figueroa, Jonine; Brinton, Louise; Sherman, Mark E; Lissowska, Jolanta; Hopper, John L; Dite, Gillian S; Apicella, Carmel; Southey, Melissa C; Sigurdson, Alice J; Linet, Martha S; Schonfeld, Sara J; Freedman, D Michal; Mannermaa, Arto; Kosma, Veli-Matti; Kataja, Vesa; Auvinen, Päivi; Andrulis, Irene L; Glendon, Gord; Knight, Julia A; Weerasooriya, Nayana; Cox, Angela; Reed, Malcolm Wr; Cross, Simon S; Dunning, Alison M; Ahmed, Shahana; Shah, Mitul; Brauch, Hiltrud; Ko, Yon-Dschun; Brüning, Thomas; Lambrechts, Diether; Reumers, Joke; Smeets, Ann; Wang-Gohrke, Shan; Hall, Per; Czene, Kamila; Liu, Jianjun; Irwanto, Astrid K; Chenevix-Trench, Georgia; Holland, Helene; Giles, Graham G; Baglietto, Laura; Severi, Gianluca; Bojensen, Stig E; Nordestgaard, Børge G; Flyger, Henrik; John, Esther M; West, Dee W; Whittemore, Alice S; Vachon, Celine; Olson, Janet E; Fredericksen, Zachary; Kosel, Matthew; Hein, Rebecca; Vrieling, Alina; Flesch-Janys, Dieter; Heinz, Judith; Beckmann, Matthias W; Heusinger, Katharina; Ekici, Arif B; Haeberle, Lothar; Humphreys, Manjeet K; Morrison, Jonathan; Easton, Doug F; Pharoah, Paul D; García-Closas, Montserrat; Goode, Ellen L; Chang-Claude, Jenny

    2010-01-01

    Several common breast cancer genetic susceptibility variants have recently been identified. We aimed to determine how these variants combine with a subset of other known risk factors to influence breast cancer risk in white women of European ancestry using case-control studies participating in the Breast Cancer Association Consortium. We evaluated two-way interactions between each of age at menarche, ever having had a live birth, number of live births, age at first birth and body mass index (BMI) and each of 12 single nucleotide polymorphisms (SNPs) (10q26-rs2981582 (FGFR2), 8q24-rs13281615, 11p15-rs3817198 (LSP1), 5q11-rs889312 (MAP3K1), 16q12-rs3803662 (TOX3), 2q35-rs13387042, 5p12-rs10941679 (MRPS30), 17q23-rs6504950 (COX11), 3p24-rs4973768 (SLC4A7), CASP8-rs17468277, TGFB1-rs1982073 and ESR1-rs3020314). Interactions were tested for by fitting logistic regression models including per-allele and linear trend main effects for SNPs and risk factors, respectively, and single-parameter interaction terms for linear departure from independent multiplicative effects. These analyses were applied to data for up to 26,349 invasive breast cancer cases and up to 32,208 controls from 21 case-control studies. No statistical evidence of interaction was observed beyond that expected by chance. Analyses were repeated using data from 11 population-based studies, and results were very similar. The relative risks for breast cancer associated with the common susceptibility variants identified to date do not appear to vary across women with different reproductive histories or body mass index (BMI). The assumption of multiplicative combined effects for these established genetic and other risk factors in risk prediction models appears justified.

  14. Assessing interactions between the associations of common genetic susceptibility variants, reproductive history and body mass index with breast cancer risk in the breast cancer association consortium: a combined case-control study

    PubMed Central

    2010-01-01

    Introduction Several common breast cancer genetic susceptibility variants have recently been identified. We aimed to determine how these variants combine with a subset of other known risk factors to influence breast cancer risk in white women of European ancestry using case-control studies participating in the Breast Cancer Association Consortium. Methods We evaluated two-way interactions between each of age at menarche, ever having had a live birth, number of live births, age at first birth and body mass index (BMI) and each of 12 single nucleotide polymorphisms (SNPs) (10q26-rs2981582 (FGFR2), 8q24-rs13281615, 11p15-rs3817198 (LSP1), 5q11-rs889312 (MAP3K1), 16q12-rs3803662 (TOX3), 2q35-rs13387042, 5p12-rs10941679 (MRPS30), 17q23-rs6504950 (COX11), 3p24-rs4973768 (SLC4A7), CASP8-rs17468277, TGFB1-rs1982073 and ESR1-rs3020314). Interactions were tested for by fitting logistic regression models including per-allele and linear trend main effects for SNPs and risk factors, respectively, and single-parameter interaction terms for linear departure from independent multiplicative effects. Results These analyses were applied to data for up to 26,349 invasive breast cancer cases and up to 32,208 controls from 21 case-control studies. No statistical evidence of interaction was observed beyond that expected by chance. Analyses were repeated using data from 11 population-based studies, and results were very similar. Conclusions The relative risks for breast cancer associated with the common susceptibility variants identified to date do not appear to vary across women with different reproductive histories or body mass index (BMI). The assumption of multiplicative combined effects for these established genetic and other risk factors in risk prediction models appears justified. PMID:21194473

  15. Associations of common variants at 1p11.2 and 14q24.1 (RAD51L1) with breast cancer risk and heterogeneity by tumor subtype: findings from the Breast Cancer Association Consortium.

    PubMed

    Figueroa, Jonine D; Garcia-Closas, Montserrat; Humphreys, Manjeet; Platte, Radka; Hopper, John L; Southey, Melissa C; Apicella, Carmel; Hammet, Fleur; Schmidt, Marjanka K; Broeks, Annegien; Tollenaar, Rob A E M; Van't Veer, Laura J; Fasching, Peter A; Beckmann, Matthias W; Ekici, Arif B; Strick, Reiner; Peto, Julian; dos Santos Silva, Isabel; Fletcher, Olivia; Johnson, Nichola; Sawyer, Elinor; Tomlinson, Ian; Kerin, Michael; Burwinkel, Barbara; Marme, Federik; Schneeweiss, Andreas; Sohn, Christof; Bojesen, Stig; Flyger, Henrik; Nordestgaard, Børge G; Benítez, Javier; Milne, Roger L; Ignacio Arias, Jose; Zamora, M Pilar; Brenner, Hermann; Müller, Heiko; Arndt, Volker; Rahman, Nazneen; Turnbull, Clare; Seal, Sheila; Renwick, Anthony; Brauch, Hiltrud; Justenhoven, Christina; Brüning, Thomas; Chang-Claude, Jenny; Hein, Rebecca; Wang-Gohrke, Shan; Dörk, Thilo; Schürmann, Peter; Bremer, Michael; Hillemanns, Peter; Nevanlinna, Heli; Heikkinen, Tuomas; Aittomäki, Kristiina; Blomqvist, Carl; Bogdanova, Natalia; Antonenkova, Natalia; Rogov, Yuri I; Karstens, Johann Hinrich; Bermisheva, Marina; Prokofieva, Darya; Gantcev, Shamil Hanafievich; Khusnutdinova, Elza; Lindblom, Annika; Margolin, Sara; Chenevix-Trench, Georgia; Beesley, Jonathan; Chen, Xiaoqing; Mannermaa, Arto; Kosma, Veli-Matti; Soini, Ylermi; Kataja, Vesa; Lambrechts, Diether; Yesilyurt, Betül T; Chrisiaens, Marie-Rose; Peeters, Stephanie; Radice, Paolo; Peterlongo, Paolo; Manoukian, Siranoush; Barile, Monica; Couch, Fergus; Lee, Adam M; Diasio, Robert; Wang, Xianshu; Giles, Graham G; Severi, Gianluca; Baglietto, Laura; Maclean, Catriona; Offit, Ken; Robson, Mark; Joseph, Vijai; Gaudet, Mia; John, Esther M; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Andrulis, Irene; Knight, Julia A; Mulligan, Anna Marie; O'Malley, Frances P; Brinton, Louise A; Sherman, Mark E; Lissowska, Jolanta; Chanock, Stephen J; Hooning, Maartje; Martens, John W M; van den Ouweland, Ans M W; Collée, J Margriet; Hall, Per; Czene, Kamila; Cox, Angela; Brock, Ian W; Reed, Malcolm W R; Cross, Simon S; Pharoah, Paul; Dunning, Alison M; Kang, Daehee; Yoo, Keun-Young; Noh, Dong-Young; Ahn, Sei-Hyun; Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna; Sangrajrang, Suleeporn; Gaborieau, Valerie; Brennan, Paul; McKay, James; Shen, Chen-Yang; Ding, Shian-ling; Hsu, Huan-Ming; Yu, Jyh-Cherng; Anton-Culver, Hoda; Ziogas, Argyrios; Ashworth, Alan; Swerdlow, Anthony; Jones, Michael; Orr, Nick; Trentham-Dietz, Amy; Egan, Kathleen; Newcomb, Polly; Titus-Ernstoff, Linda; Easton, Doug; Spurdle, Amanda B

    2011-12-01

    A genome-wide association study (GWAS) identified single-nucleotide polymorphisms (SNPs) at 1p11.2 and 14q24.1 (RAD51L1) as breast cancer susceptibility loci. The initial GWAS suggested stronger effects for both loci for estrogen receptor (ER)-positive tumors. Using data from the Breast Cancer Association Consortium (BCAC), we sought to determine whether risks differ by ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), grade, node status, tumor size, and ductal or lobular morphology. We genotyped rs11249433 at 1p.11.2, and two highly correlated SNPs rs999737 and rs10483813 (r(2)= 0.98) at 14q24.1 (RAD51L1), for up to 46 036 invasive breast cancer cases and 46 930 controls from 39 studies. Analyses by tumor characteristics focused on subjects reporting to be white women of European ancestry and were based on 25 458 cases, of which 87% had ER data. The SNP at 1p11.2 showed significantly stronger associations with ER-positive tumors [per-allele odds ratio (OR) for ER-positive tumors was 1.13, 95% CI = 1.10-1.16 and, for ER-negative tumors, OR was 1.03, 95% CI = 0.98-1.07, case-only P-heterogeneity = 7.6 × 10(-5)]. The association with ER-positive tumors was stronger for tumors of lower grade (case-only P= 6.7 × 10(-3)) and lobular histology (case-only P= 0.01). SNPs at 14q24.1 were associated with risk for most tumor subtypes evaluated, including triple-negative breast cancers, which has not been described previously. Our results underscore the need for large pooling efforts with tumor pathology data to help refine risk estimates for SNP associations with susceptibility to different subtypes of breast cancer.

  16. Aspirin, Nonaspirin Nonsteroidal Anti-inflammatory Drug, and Acetaminophen Use and Risk of Invasive Epithelial Ovarian Cancer: A Pooled Analysis in the Ovarian Cancer Association Consortium

    PubMed Central

    2014-01-01

    Background Regular aspirin use is associated with reduced risk of several malignancies. Epidemiologic studies analyzing aspirin, nonaspirin nonsteroidal anti-inflammatory drug (NSAID), and acetaminophen use and ovarian cancer risk have been inconclusive. Methods We analyzed pooled data from 12 population-based case–control studies of ovarian cancer, including 7776 case patients and 11843 control subjects accrued between 1992 and 2007. Odds ratios (ORs) for associations of medication use with invasive epithelial ovarian cancer were estimated in individual studies using logistic regression and combined using random effects meta-analysis. Associations between frequency, dose, and duration of analgesic use and risk of ovarian cancer were also assessed. All statistical tests were two-sided. Results Aspirin use was associated with a reduced risk of ovarian cancer (OR = 0.91; 95% confidence interval [CI] = 0.84 to 0.99). Results were similar but not statistically significant for nonaspirin NSAIDs, and there was no association with acetaminophen. In seven studies with frequency data, the reduced risk was strongest among daily aspirin users (OR = 0.80; 95% CI = 0.67 to 0.96). In three studies with dose information, the reduced risk was strongest among users of low dose (<100mg) aspirin (OR = 0.66; 95% CI = 0.53 to 0.83), whereas for nonaspirin NSAIDs, the reduced risk was strongest for high dose (≥500mg) usage (OR = 0.76; 95% CI = 0.64 to 0.91). Conclusions Aspirin use was associated with a reduced risk of ovarian cancer, especially among daily users of low-dose aspirin. These findings suggest that the same aspirin regimen proven to protect against cardiovascular events and several cancers could reduce the risk of ovarian cancer 20% to 34% depending on frequency and dose of use. PMID:24503200

  17. Vitamin-D associated genetic variation and risk of breast cancer in the Breast and Prostate Cancer Cohort Consortium (BPC3)

    PubMed Central

    Mondul, Alison M.; Shui, Irene M.; Yu, Kai; Weinstein, Stephanie J.; Tsilidis, Konstantinos K.; Joshi, Amit D.; Agudo, Antonio; Berg, Christine D.; Black, Amanda; Buring, Julie E.; Chasman, Daniel I.; Gaudet, Mia M.; Haiman, Christopher; Hankinson, Susan E.; Henderson, Brian E.; Hoover, Robert N.; Hunter, David J.; Khaw, Kay-Tee; Kühn, Tilman; Kvaskoff, Marina; Le Marchand, Loic; Lindström, Sara; McCullough, Marjorie L.; Overvad, Kim; Peeters, Petra H.; Riboli, Elio; Ridker, Paul M; Stram, Daniel O.; Sund, Malin; Trichopoulos, Dimitrios; Tumino, Rosario; Weiderpass, Elisabete; Willett, Walter; Kraft, Peter; Ziegler, Regina G.; Albanes, Demetrius

    2015-01-01

    Background Two recent genome-wide association studies (GWAS) identified SNPs related to circulating 25-hydroxyvitamin D [25(OH)D] concentration in or near four genes. To examine the hypothesized inverse relationship between vitamin D status and breast cancer, we studied the associations between SNPs in these genes and breast cancer risk in a large pooled study of 9,456 cases and 10,816 controls from six cohorts. Methods SNP markers localized to each of four genes (GC, CYP24A1, CYP2R1, and DHCR7) previously associated with 25(OH)D were genotyped and examined both individually and as a 4-SNP polygenic score. Logistic regression was used to estimate the associations between the genetic variants and risk of breast cancer. Results We found no association between any of the four SNPs or their polygenic score and breast cancer risk. Conclusions Our findings do not support an association between vitamin D status, as reflected by 25(OH)D-related genotypes, and breast cancer risk. Impact These findings may contribute to future meta-analyses and scientific review articles, and provide new data about the association between vitamin D-related genes and breast cancer. PMID:25542828

  18. [Oral cavity and pharynx cancer in the region of Siberia and Far East].

    PubMed

    Choinzonov, E L; Pisareva, L F; Odintsova, I N; Zhuikova, L D

    2015-01-01

    The objective of the present work was to study the prevalence of malignant oral cavity and pharynx neoplasms among the population of the region of Siberia and Far East. These neoplasms are the ninth most frequent conditions in the structure of malignant tumours among the male population and rank the eighteenth among the women. On the whole, the morbidity rate of oral cavity and pharyngeal cancer (3.8‱ and 2.0‱ respectively) was consistent with the mean morbidity levels in Russia. The risk of the development of these conditions among the men is significantly higher than among the women. The highest morbidity is recorded among the subjects at the age of 65-69 years. It increases in the subjects of either sex at a rate that is 3.4 times higher in the women than in the men. The study revealed the territories characterized ether by the enhanced or by the reduced risk of oral cavity and pharyngeal cancer development. The prevalence of this pathology was estimated at 28.4 per 100,000 population, with the overall active detectability being 11.8%, that of stage 1 an 2 disease 7.8% and 19.3% respectively. One-year lethality was 35.6%. The radical treatment was completed in 41.1% of the patients; 45.8% of them were followed up during 5 years. It is concluded that the increasing oral cavity and pharyngeal cancer morbidity and the insufficient volume of preventive measures taken together suggest the necessity of closer cooperation of general practitioners and dental surgeons with oncologists.

  19. A large-scale assessment of two-way SNP interactions in breast cancer susceptibility using 46 450 cases and 42 461 controls from the breast cancer association consortium

    PubMed Central

    Milne, Roger L.; Herranz, Jesús; Michailidou, Kyriaki; Dennis, Joe; Tyrer, Jonathan P.; Zamora, M. Pilar; Arias-Perez, José Ignacio; González-Neira, Anna; Pita, Guillermo; Alonso, M. Rosario; Wang, Qin; Bolla, Manjeet K.; Czene, Kamila; Eriksson, Mikael; Humphreys, Keith; Darabi, Hatef; Li, Jingmei; Anton-Culver, Hoda; Neuhausen, Susan L.; Ziogas, Argyrios; Clarke, Christina A.; Hopper, John L.; Dite, Gillian S.; Apicella, Carmel; Southey, Melissa C.; Chenevix-Trench, Georgia; Swerdlow, Anthony; Ashworth, Alan; Orr, Nicholas; Schoemaker, Minouk; Jakubowska, Anna; Lubinski, Jan; Jaworska-Bieniek, Katarzyna; Durda, Katarzyna; Andrulis, Irene L.; Knight, Julia A.; Glendon, Gord; Mulligan, Anna Marie; Bojesen, Stig E.; Nordestgaard, Børge G.; Flyger, Henrik; Nevanlinna, Heli; Muranen, Taru A.; Aittomäki, Kristiina; Blomqvist, Carl; Chang-Claude, Jenny; Rudolph, Anja; Seibold, Petra; Flesch-Janys, Dieter; Wang, Xianshu; Olson, Janet E.; Vachon, Celine; Purrington, Kristen; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Dunning, Alison M.; Shah, Mitul; Guénel, Pascal; Truong, Thérèse; Sanchez, Marie; Mulot, Claire; Brenner, Hermann; Dieffenbach, Aida Karina; Arndt, Volker; Stegmaier, Christa; Lindblom, Annika; Margolin, Sara; Hooning, Maartje J.; Hollestelle, Antoinette; Collée, J. Margriet; Jager, Agnes; Cox, Angela; Brock, Ian W.; Reed, Malcolm W.R.; Devilee, Peter; Tollenaar, Robert A.E.M.; Seynaeve, Caroline; Haiman, Christopher A.; Henderson, Brian E.; Schumacher, Fredrick; Le Marchand, Loic; Simard, Jacques; Dumont, Martine; Soucy, Penny; Dörk, Thilo; Bogdanova, Natalia V.; Hamann, Ute; Försti, Asta; Rüdiger, Thomas; Ulmer, Hans-Ulrich; Fasching, Peter A.; Häberle, Lothar; Ekici, Arif B.; Beckmann, Matthias W.; Fletcher, Olivia; Johnson, Nichola; dos Santos Silva, Isabel; Peto, Julian; Radice, Paolo; Peterlongo, Paolo; Peissel, Bernard; Mariani, Paolo; Giles, Graham G.; Severi, Gianluca; Baglietto, Laura; Sawyer, Elinor; Tomlinson, Ian; Kerin, Michael; Miller, Nicola; Marme, Federik; Burwinkel, Barbara; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M.; Lambrechts, Diether; Yesilyurt, Betul T.; Floris, Giuseppe; Leunen, Karin; Alnæs, Grethe Grenaker; Kristensen, Vessela; Børresen-Dale, Anne-Lise; García-Closas, Montserrat; Chanock, Stephen J.; Lissowska, Jolanta; Figueroa, Jonine D.; Schmidt, Marjanka K.; Broeks, Annegien; Verhoef, Senno; Rutgers, Emiel J.; Brauch, Hiltrud; Brüning, Thomas; Ko, Yon-Dschun; Couch, Fergus J.; Toland, Amanda E.; Yannoukakos, Drakoulis; Pharoah, Paul D.P.; Hall, Per; Benítez, Javier; Malats, Núria; Easton, Douglas F.

    2014-01-01

    Part of the substantial unexplained familial aggregation of breast cancer may be due to interactions between common variants, but few studies have had adequate statistical power to detect interactions of realistic magnitude. We aimed to assess all two-way interactions in breast cancer susceptibility between 70 917 single nucleotide polymorphisms (SNPs) selected primarily based on prior evidence of a marginal effect. Thirty-eight international studies contributed data for 46 450 breast cancer cases and 42 461 controls of European origin as part of a multi-consortium project (COGS). First, SNPs were preselected based on evidence (P < 0.01) of a per-allele main effect, and all two-way combinations of those were evaluated by a per-allele (1 d.f.) test for interaction using logistic regression. Second, all 2.5 billion possible two-SNP combinations were evaluated using Boolean operation-based screening and testing, and SNP pairs with the strongest evidence of interaction (P < 10−4) were selected for more careful assessment by logistic regression. Under the first approach, 3277 SNPs were preselected, but an evaluation of all possible two-SNP combinations (1 d.f.) identified no interactions at P < 10−8. Results from the second analytic approach were consistent with those from the first (P > 10−10). In summary, we observed little evidence of two-way SNP interactions in breast cancer susceptibility, despite the large number of SNPs with potential marginal effects considered and the very large sample size. This finding may have important implications for risk prediction, simplifying the modelling required. Further comprehensive, large-scale genome-wide interaction studies may identify novel interacting loci if the inherent logistic and computational challenges can be overcome. PMID:24242184

  20. Pre-diagnosis insulin-like growth factor-I and risk of epithelial invasive ovarian cancer by histological subtypes: A collaborative re-analysis from the Ovarian Cancer Cohort Consortium.

    PubMed

    Ose, Jennifer; Schock, Helena; Poole, Elizabeth M; Lehtinen, Matti; Visvanathan, Kala; Helzlsouer, Kathy; Buring, Julie E; Lee, I-Min; Tjønneland, Anne; Boutron-Ruault, Marie-Christine; Trichopoulou, Antonia; Mattiello, Amalia; Onland-Moret, N Charlotte; Weiderpass, Elisabete; Sánchez, María-José; Idahl, Annika; Travis, Ruth C; Rinaldi, Sabina; Merritt, Melissa A; Wentzensen, Nicolas; Tworoger, Shelley S; Kaaks, Rudolf; Fortner, Renée T

    2017-05-01

    Biologic evidence suggests that the Insulin-like growth factor (IGF)-family may be involved in the etiology of epithelial invasive ovarian cancer (EOC). However, prospective studies investigating the role of IGF-I in ovarian carcinogenesis have yielded conflicting results. We pooled and harmonized data from 6 case-control studies nested within the Ovarian Cancer Cohort Consortium to investigate the association between pre-diagnosis IGF-I concentrations and subsequent risk of EOC. We evaluated IGF-I concentrations and risk of EOC overall and by tumor subtype (defined by histology, grade, stage) in 1,270 cases and 2,907 matched controls. Multivariable conditional logistic regression models were used to calculate odds ratios (OR) and 95% confidence intervals (CI). Doubling of IGF-I concentration was associated with significantly lower risk of overall EOC [ORlog2 = 0.82; CI 0.72-0.93]. We observed no heterogeneity by tumor characteristics (e.g., histology, p het = 0.62), menopausal status at blood collection (p het = 0.79), or age at diagnosis (p het = 0.60). These results suggest that IGF-I concentrations are inversely associated with EOC risk, independent of histological phenotype. Future prospective research should consider potential mechanisms for this association, including, considering other members of the IGF-family to better characterize the role of IGF-signaling in the etiology of EOC.

  1. COFFEE AND TEA INTAKE AND RISK OF HEAD AND NECK CANCER: POOLED ANALYSIS IN THE INTERNATIONAL HEAD AND NECK CANCER EPIDEMIOLOGY CONSORTIUM

    PubMed Central

    Galeone, Carlotta; Tavani, Alessandra; Pelucchi, Claudio; Turati, Federica; Winn, Deborah M.; Levi, Fabio; Yu, Guo-Pei; Morgenstern, Hal; Kelsey, Karl; Maso, Luigino Dal; Purdue, Mark P.; McClean, Michael; Talamini, Renato; Hayes, Richard B.; Franceschi, Silvia; Schantz, Stimson; Zhang, Zuo-Feng; Ferro, Gilles; Chuang, Shu-Chun; Boffetta, Paolo; La Vecchia, Carlo; Hashibe, Mia

    2011-01-01

    Background Only a few studies have explored the relation between coffee and tea intake and head and neck (HN) cancers, with inconsistent results. Methods We pooled individual-level data from nine case-control studies of HN cancers, including 5139 cases and 9028 controls. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) adjusting for potential confounders. Results Caffeinated coffee intake was inversely related with the risk of cancer of the oral cavity and pharynx (OP): the ORs were 0.96 (95% CI 0.94–0.98) for an increment of one cup per day and 0.61 (95% CI 0.47–0.80) in drinkers of >4 cups per day vs. non-drinkers. This latter estimate was consistent for different anatomical sites (ORs were 0.46, 95%CI 0.30–0.71 for oral cavity, 0.58, 95% CI 0.41–0.82 for oropharyngeal/hypopharyngeal and 0.61, 95% CI 0.37–1.01 for OP not otherwise specified), and across strata of selected covariates. No association of caffeinated coffee drinking was found with laryngeal cancer (OR=0.96, 95% CI 0.64–1.45 in drinkers of >4 cups per day vs. non-drinkers). Data on decaffeinated coffee were too sparse for detailed analysis, but indicated no increased risk. Tea intake was not associated with HN cancer risk (OR=0.99, 95% CI 0.89–1.11 for drinkers vs. non-drinkers). Conclusions This pooled-analysis of case-control studies support the hypothesis of an inverse association between caffeinated coffee drinking and OP cancer risk. Impact Given widespread use of coffee and the relatively high incidence and low survival of HN cancers, the observed inverse association may have appreciable public health relevance. PMID:20570908

  2. Trends in mortality from cancers of the breast, colon, prostate, esophagus, and stomach in East Asia: role of nutrition transition.

    PubMed

    Zhang, Jianjun; Dhakal, Ishwori B; Zhao, Zijin; Li, Lang

    2012-09-01

    Although substantial nutrition transition, characterized by an increased intake of energy, animal fat, and red meats, has occurred during the last several decades in East Asia, few studies have systematically evaluated temporal trends in cancer incidence or mortality among populations in this area. Therefore, we sought to investigate this question with tremendous public health implications. Data on mortality rates of cancers of the breast, colon, prostate, esophagus, and stomach for China (1988-2000), Hong Kong (1960-2006), Japan (1950-2006), Korea (1985-2006), and Singapore (1963-2006) were obtained from WHO. Joinpoint regression was used to investigate trends in mortality of these cancers. A remarkable increase in mortality rates of breast, colon, and prostate cancers and a precipitous decrease in those of esophageal and stomach cancers have been observed in selected countries (except breast cancer in Hong Kong) during the study periods. For example, the annual percentage increase in breast cancer mortality was 5.5% (95% confidence interval: 3.8, 7.3%) for the period 1985-1993 in Korea, and mortality rates for prostate cancer significantly increased by 3.2% (95% confidence interval: 3.0, 3.3%) per year from 1958 to 1993 in Japan. These changes in cancer mortality lagged ∼ 10 years behind the inception of the nutrition transition toward a westernized diet in selected countries or regions. There have been striking changes in mortality rates of breast, colon, prostate, esophageal, and stomach cancers in East Asia during the last several decades, which may be at least in part attributable to the concurrent nutrition transition.

  3. A phase II trial of the Src-kinase inhibitor AZD0530 in patients with advanced castration-resistant prostate cancer: a California Cancer Consortium study.

    PubMed

    Lara, Primo N; Longmate, Jeff; Evans, Christopher P; Quinn, David I; Twardowski, Przemyslaw; Chatta, Gurkamal; Posadas, Edwin; Stadler, Walter; Gandara, David R

    2009-03-01

    Prostate cancer cells undergo neuroendocrine differentiation during androgen deprivation and secrete neuropeptides, hence activating androgen receptor-regulated genes. Src-family protein kinases are involved in neuropeptide-induced prostate cancer growth and migration. A phase II trial of AZD0530, an oral Src-family kinase inhibitor, in patients with advanced castration resistant prostate cancer was conducted. The primary endpoint was prostate cancer-specific antigen (PSA) response rate, defined as a 30% or greater decrease. A two-stage Simon design was used. Eligibility criteria included documentation of castration resistance (including antiandrogen withdrawal), adequate end-organ function, and performance status, and not more than one prior taxane-based chemotherapy regimen. AZD0530 was given at 175 mg orally once daily continuously. Rapid accrual led to 28 patients registering in the first stage. Median age was 67 years. Sixteen patients had performance status (PS) 0, eight patients had PS 1, and four patients had PS 2. Nine patients (32%) had prior docetaxel-based chemotherapy. Five patients had transient PSA reductions not meeting PSA response criteria. Median progression-free survival time was 8 weeks. Treatment was generally well tolerated. AZD0530, a potent oral Src kinase inhibitor, is feasible and tolerable in this pretreated patient population but possessed little clinical efficacy as monotherapy. Strong preclinical evidence warrants further investigation of AZD0530 in earlier-stage prostate cancer or as combination therapy.

  4. Screening mammography. A missed clinical opportunity Results of the NCI (National Cancer Institute) Breast Cancer Screening Consortium and national health interview survey studies

    SciTech Connect

    Not Available

    1990-07-04

    Data from seven studies sponsored by the National Cancer Institute (NCI) were used to determine current rates of breast cancer screening and to identify the characteristics of and reasons for women not being screened. All seven studies were population-based surveys of women aged 50 to 74 years without breast cancer. While over 90% of non-Hispanic white respondents had regular sources of medical care, 46% to 76% had a clinical breast examination within the previous year, and only 25% to 41% had a mammogram. Less educated and poorer women had fewer mammograms. The two most common reasons women gave for never having had a mammogram were that they did not known they needed it and that their physician had not recommended it. Many physicians may have overlooked the opportunity to recommend mammography for older women when performing a clinical breast examination and to educate their patients about the benefit of screening mammography.

  5. The Nebraska Instrument Sharing Consortium.

    ERIC Educational Resources Information Center

    Smith, David H.

    1986-01-01

    The Nebraska Instrument Sharing Consortium (NISC) is a group of small colleges that have banded together to provide modern instrumentation to their students at an affordable price. Consortium activities are described, including how the instruments are moved between campuses. (JN)

  6. Recent progress in carcinogenesis, progression and therapy of lung cancer: the 19th Hiroshima Cancer Seminar: the 3rd Three Universities' Consortium International Symposium, November 2009.

    PubMed

    Tahara, Eiichi; Yasui, Wataru; Ito, Hisao; Harris, Curtis C

    2010-07-01

    This symposium presented recent progress of the pathogenesis and treatment of lung cancer. Aberrantly increased expression of miR-21 plays a significant role in lung carcinogenesis and is a potential therapeutic target in both epidermal growth factor receptor-mutant and wild-type cases. miR-34 may be necessary for the radiation-induced DNA damage response. Detailed expression profiling analyses of transcriptome have potential to provide increased understanding of the molecular biology of lung cancer. An embryonic signature is present in lung adenocarcinoma only, associated with a worse clinical outcome. Cytoplasmic expression of caveolin and membranous expression of CD26 are specific to mesothelioma. Nectin-4 is a new candidate for serum and tissue biomarker as well as a therapeutic target for lung cancer. Clinical presentations have provided us a great deal information on epidermal growth factor receptor mutations for personalized therapy, combination therapy with inhibitors of the tyrosine kinase activity of epidermal growth factor receptor and cytotoxic agents, antibody-dependent cellular cytotoxicity activity, and current management of lung cancer depending on both the extent of the disease and the treatment approach.

  7. Combustion Byproducts Recycling Consortium

    SciTech Connect

    Paul Ziemkiewicz; Tamara Vandivort; Debra Pflughoeft-Hassett; Y. Paul Chugh; James Hower

    2008-08-31

    The Combustion Byproducts Recycling Consortium (CBRC) program was developed as a focused program to remove and/or minimize the barriers for effective management of over 123 million tons of coal combustion byproducts (CCBs) annually generated in the USA. At the time of launching the CBRC in 1998, about 25% of CCBs were beneficially utilized while the remaining was disposed in on-site or off-site landfills. During the ten (10) year tenure of CBRC (1998-2008), after a critical review, 52 projects were funded nationwide. By region, the East, Midwest, and West had 21, 18, and 13 projects funded, respectively. Almost all projects were cooperative projects involving industry, government, and academia. The CBRC projects, to a large extent, successfully addressed the problems of large-scale utilization of CCBs. A few projects, such as the two Eastern Region projects that addressed the use of fly ash in foundry applications, might be thought of as a somewhat smaller application in comparison to construction and agricultural uses, but as a novel niche use, they set the stage to draw interest that fly ash substitution for Portland cement might not attract. With consideration of the large increase in flue gas desulfurization (FGD) gypsum in response to EPA regulations, agricultural uses of FGD gypsum hold promise for large-scale uses of a product currently directed to the (currently stagnant) home construction market. Outstanding achievements of the program are: (1) The CBRC successfully enhanced professional expertise in the area of CCBs throughout the nation. The enhanced capacity continues to provide technology and information transfer expertise to industry and regulatory agencies. (2) Several technologies were developed that can be used immediately. These include: (a) Use of CCBs for road base and sub-base applications; (b) full-depth, in situ stabilization of gravel roads or highway/pavement construction recycled materials; and (c) fired bricks containing up to 30%-40% F

  8. The Global Opioid Policy Initiative (GOPI) project to evaluate the availability and accessibility of opioids for the management of cancer pain in Africa, Asia, Latin America and the Caribbean, and the Middle East: introduction and methodology.

    PubMed

    Cherny, N I; Cleary, J; Scholten, W; Radbruch, L; Torode, J

    2013-12-01

    Opioid analgesics are critical to the effective relief of cancer pain. Effective treatment is predicated on sound assessments, individually tailored analgesic therapy, and the availability and accessibility of the required medications. In some countries, pain relief is hampered by the lack of availability or barriers to the accessibility of opioid analgesics. As the follow-up to a successful project to evaluate the availability and accessibility of opioids and regulatory barriers in Europe, the European Society for Medical Oncology (ESMO) and the European Association for Palliative Care (EAPC) undertook to expand their research to those parts of the world where data were lacking regarding these aspects of care, in particular Africa, Asia, the Middle East, Latin America and the Caribbean, and the states of India. This project has been undertaken in collaboration with the Union for International Cancer Control (UICC), the Pain and Policy Studies Group (PPSG) of the University of Wisconsin, and the World Health Organization (WHO), together with a consortium of 17 international oncology and palliative care societies. This article describes the study methodology.

  9. Attitudes, beliefs and perceptions regarding truth disclosure of cancer-related information in the Middle East: a review.

    PubMed

    Bou Khalil, Rami

    2013-02-01

    The aim of this review is to evaluate the current status concerning attitudes, beliefs and/or practices of patients, family members, health professionals and/or caregivers regarding truth disclosure about a cancer diagnosis in the Greater Middle East countries. A search was done via MedLine for all publications related to this review objective. 55 publications were included emanating from Egypt, Iran, Israel, Jordan, Kuwait, Lebanon, Palestine Pakistan, Saudi Arabia, Turkey, and United Arab Emirates. In the Greater Middle East region, a diagnosis of cancer is still mixed with social stigma and misperceptions related to incurability. Physicians conserve a truth disclosure policy in which from one side they respect some of the historical and cultural misperceptions about cancer and accordingly, tell the truth about cancer to one of the family members and from another side acknowledge the patients' right to know the truth and tend to disclose it for him(or her) when possible. Family members and caregivers' attitudes, perceptions and beliefs about telling the truth to the patient seem to be in favor of concealment. Discrepant results concerning physicians' and patients' evaluation of the quality of truth disclosure exist in the literature. Education programs in breaking bad news are lacking in many countries. Finally, the most important and common problem affecting truth disclosure to a patient suffering from cancer is the lack of codes and legislations concerning the patients' rights in an informed consent. Studies, legislations and training programs are needed in this domain in Middle Eastern societies.

  10. Performance of automated scoring of ER, PR, HER2, CK5/6 and EGFR in breast cancer tissue microarrays in the Breast Cancer Association Consortium

    PubMed Central

    Howat, William J; Blows, Fiona M; Provenzano, Elena; Brook, Mark N; Morris, Lorna; Gazinska, Patrycja; Johnson, Nicola; McDuffus, Leigh‐Anne; Miller, Jodi; Sawyer, Elinor J; Pinder, Sarah; van Deurzen, Carolien H M; Jones, Louise; Sironen, Reijo; Visscher, Daniel; Caldas, Carlos; Daley, Frances; Coulson, Penny; Broeks, Annegien; Sanders, Joyce; Wesseling, Jelle; Nevanlinna, Heli; Fagerholm, Rainer; Blomqvist, Carl; Heikkilä, Päivi; Ali, H Raza; Dawson, Sarah‐Jane; Figueroa, Jonine; Lissowska, Jolanta; Brinton, Louise; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli‐Matti; Cox, Angela; Brock, Ian W; Cross, Simon S; Reed, Malcolm W; Couch, Fergus J; Olson, Janet E; Devillee, Peter; Mesker, Wilma E; Seyaneve, Caroline M; Hollestelle, Antoinette; Benitez, Javier; Perez, Jose Ignacio Arias; Menéndez, Primitiva; Bolla, Manjeet K; Easton, Douglas F; Schmidt, Marjanka K; Pharoah, Paul D; Sherman, Mark E

    2014-01-01

    Abstract Breast cancer risk factors and clinical outcomes vary by tumour marker expression. However, individual studies often lack the power required to assess these relationships, and large‐scale analyses are limited by the need for high throughput, standardized scoring methods. To address these limitations, we assessed whether automated image analysis of immunohistochemically stained tissue microarrays can permit rapid, standardized scoring of tumour markers from multiple studies. Tissue microarray sections prepared in nine studies containing 20 263 cores from 8267 breast cancers stained for two nuclear (oestrogen receptor, progesterone receptor), two membranous (human epidermal growth factor receptor 2 and epidermal growth factor receptor) and one cytoplasmic (cytokeratin 5/6) marker were scanned as digital images. Automated algorithms were used to score markers in tumour cells using the Ariol system. We compared automated scores against visual reads, and their associations with breast cancer survival. Approximately 65–70% of tissue microarray cores were satisfactory for scoring. Among satisfactory cores, agreement between dichotomous automated and visual scores was highest for oestrogen receptor (Kappa = 0.76), followed by human epidermal growth factor receptor 2 (Kappa = 0.69) and progesterone receptor (Kappa = 0.67). Automated quantitative scores for these markers were associated with hazard ratios for breast cancer mortality in a dose‐response manner. Considering visual scores of epidermal growth factor receptor or cytokeratin 5/6 as the reference, automated scoring achieved excellent negative predictive value (96–98%), but yielded many false positives (positive predictive value = 30–32%). For all markers, we observed substantial heterogeneity in automated scoring performance across tissue microarrays. Automated analysis is a potentially useful tool for large‐scale, quantitative scoring of immunohistochemically stained tissue

  11. Nutrient intake and nutritional status of newly diagnosed patients with cancer from the East Coast of Peninsular Malaysia.

    PubMed

    Menon, Kavitha; Razak, Shariza Abdul; Ismail, Karami A; Krishna, Bhavaraju Venkata Murali

    2014-09-30

    Cancer therapy in Malaysia primarily focuses on the clinical management of patients with cancer and malnutrition continues to be one of the major causes of death in these patients. There is a dearth of information on the nutrient intake and status of newly diagnosed patients with cancer prior to the initiation of treatment. The present study aims to assess the nutrient intake and status of newly diagnosed patients with cancer from the East Coast of Peninsular Malaysia. A cross-sectional study was conducted using a convenient sample of newly diagnosed adult patients with cancer (n = 70) attending the Oncology clinic, Hospital Universiti Sains Malaysia in the East Coast of Peninsular Malaysia. Information on socio-demographic characteristics, clinical status, anthropometry, dietary intake and biochemical data including blood samples was obtained. The mean (SD) age, triceps skin fold (TSF), mid upper arm circumference (MUAC) and body mass index (BMI) of participants was 21.1(3.9) years, 17.6(7.9) mm, 24.1(5.5) cm, and 21.1(3.9) Kg/m(2), respectively; 39% participants had BMI <18.5 Kg/m(2). One-third of newly diagnosed patients with cancer were undernourished (i.e. women: MUAC <220 mm; men: <230 mm). The proportion (%) of participants with low haemoglobin (<120 g/L) and serum albumin (<38 g/dL) were 62% and 26%, respectively. The older women had significantly lower macro and micro nutrient intakes compared to men in the same age group (P <0.05). At the time of diagnosis, greater than one-third of patients with cancer from the East Coast of Peninsular Malaysia were underweight and undernourished. The majority of patients with cancer had poor micronutrient intakes; the older women had a poor macro and micronutrient intakes. Before the initiation of rigorous clinical management of patients with cancer, screening for nutritional status, subsequent nutrition counseling, and interventions are essential to improve their nutritional status; consequently, response to cancer

  12. p16 hypermethylation: a biomarker for increased esophageal cancer susceptibility in high incidence region of North East India.

    PubMed

    Das, Mandakini; Saikia, Bhaskar Jyoti; Sharma, Santanu Kumar; Sekhon, Gaganpreet Singh; Mahanta, Jagadish; Phukan, Rup Kumar

    2015-03-01

    Esophageal cancer is one of the most common cancers in North East India. The molecular mechanisms of esophageal cancer susceptibility in North East India have not been fully understood. There is a need for identification of biomarkers to identify people at risk of esophageal cancer. p16 is an essential G1 cell cycle regulatory gene whose loss of function is associated with carcinogenesis. Therefore, we conducted this study to determine the prevalence of p16 gene methylation in patients with esophageal cancer to assess the feasibility of using gene methylation as a biomarker. A total of 100 newly diagnosed esophageal cancer cases along with equal number of age, sex, and ethnicity-matched controls were included in this study. Methylation-specific PCR was used to determine the p16 methylation status. Aberrant promoter methylation of the p16 gene was detected in 81 of 100 (81%) esophageal cancer cases. Hypermethylation of p16 gene was found to be influenced by lifestyle factors. Betel quid and tobacco chewing habit synergistically with p16 methylation elevated the risk for esophageal cancer development (adjusted odds ratio (OR) = 6.88, 95% confidence interval (CI) = 1.64-28.81, p = 0.003 for betel quid chewing and adjusted OR = 7.02, 95% CI = 1.87-26.38, p = 0.001 for tobacco chewing). Further, intake of green leafy vegetables and fruits lowered the risk of esophageal cancer (adjusted OR = 0.16, 95 % CI = 0.04-0.58, p = 0.05 for green leafy vegetables and adjusted OR = 0.15, 95% CI = 0.04-0.64, p = 0.01 for fruits). Thus, p16 hypermethylation may aid as a biomarker in identifying habitués at greater risk for esophageal cancer susceptibility in high incidence region of North East India.

  13. Disparities in Perceived Unmet Need for Supportive Services Among Patients With Lung Cancer in the Cancer Care Outcomes Research and Surveillance Consortium

    PubMed Central

    John, Dolly A.; Kawachi, Ichiro; Lathan, Christopher S.; Ayanian, John Z.

    2015-01-01

    BACKGROUND The authors investigated the prevalence, determinants of, and disparities in any perceived unmet need for 8 supportive services (home nurse, support group, psychological services, social worker, physical/occupational rehabilitation, pain management, spiritual counseling, and smoking cessation) by race/ethnicity and nativity and how it is associated with perceived quality of care among US patients with lung cancer. METHODS Data from a multiregional, multihealth system representative cohort of 4334 newly diagnosed patients were analyzed. Binomial logistic regression models adjusted for patient clustering. RESULTS Patients with any perceived unmet need (9% overall) included 7% of white–US-born (USB), 9% of white–foreign-born (FB), 13% of black-USB, 8% of Latino-USB, 24% of Latino-FB, 4% of Asian/Pacific Islander (API)-USB, 14% of API-FB, and 11% of “other” patients (P <.001). Even after controlling for demographic and socioeconomic factors, health system and health care access, and need, black-USB, Latino-FB, and Asian-FB patients were more likely to perceive an unmet need than white-USB patients by 5.1, 10.9, and 5.6 percentage points, respectively (all P<.05). Being younger, female, never married, uninsured, a current smoker, or under surrogate care or having comorbidity, anxiety/depression, or a cost/insurance barrier to getting tests/treatments were associated with any unmet need. Patients with any unmet need were more likely to rate care as less-than-“excellent” by 13 percentage points than patients with no unmet need (P<.001). CONCLUSIONS Significant disparities in unmet supportive service need by race/ethnicity and nativity highlight immigrants with lung cancer as being particularly underserved. Eliminating disparities in access to needed supportive services is essential for delivering patient-centered, equitable cancer care. PMID:24985538

  14. Predictors of Long-Term Quality of Life for Survivors of Stage II/III Rectal Cancer in the Cancer Care Outcomes Research and Surveillance Consortium

    PubMed Central

    Charlton, Mary E.; Stitzenberg, Karyn B.; Lin, Chi; Schlichting, Jennifer A.; Halfdanarson, Thorvardur R.; Juarez, Grelda Yazmin; Pendergast, Jane F.; Chrischilles, Elizabeth A.; Wallace, Robert B.

    2015-01-01

    Purpose: Many patients do not receive guideline-recommended neoadjuvant chemoradiotherapy for resectable rectal cancer. Little is known regarding long-term quality of life (QOL) associated with various treatment approaches. Our objective was to determine patient characteristics and subsequent QOL associated with treatment approach. Methods: Our study was a geographically diverse population- and health system–based cohort study that included adults age 21 years or older with newly diagnosed stage II/III rectal cancer who were recruited from 2003 to 2005. Eligible patients were contacted 1 to 4 months after diagnosis and asked to participate in a telephone survey and to consent to medical record review, with separate follow-up QOL surveys conducted 1 and 7 years after diagnosis. Results: Two hundred thirty-nine patients with stage II/III rectal cancer were included in this analysis. Younger age (< 65 v ≥ 65 years: odds ratio, 2.49; 95% CI, 1.33 to 4.65) was significantly associated with increased odds of receiving neoadjuvant or adjuvant chemoradiotherapy. The adjuvant chemoradiotherapy group had significantly worse mean EuroQol-5D (range, 0 to 1) and Short Form-12 physical health component scores (standardized mean, 50) at 1-year follow-up than the neoadjuvant chemoradiotherapy group (0.75 v 0.85; P = .002; 37.2 v 43.3; P = .01, respectively) and the group that received only one or neither form of treatment (0.75 v 0.85; P = .02; 37.2 v 45.1; P = .008, respectively). Conclusion: Neoadjuvant treatment may result in better QOL and functional status 1 year after diagnosis. Further evaluation of patient and provider reasons for not pursuing neoadjuvant therapy is necessary to determine how and where to target process improvement and/or education efforts to ensure that patients have access to recommended treatment options. PMID:26080831

  15. Validation of self-reported comorbidity status of breast cancer patients with medical records: the California Breast Cancer Survivorship Consortium (CBCSC).

    PubMed

    Vigen, Cheryl; Kwan, Marilyn L; John, Esther M; Gomez, Scarlett Lin; Keegan, Theresa H M; Lu, Yani; Shariff-Marco, Salma; Monroe, Kristine R; Kurian, Allison W; Cheng, Iona; Caan, Bette J; Lee, Valerie S; Roh, Janise M; Bernstein, Leslie; Sposto, Richard; Wu, Anna H

    2016-03-01

    To compare information from self-report and electronic medical records for four common comorbidities (diabetes, hypertension, myocardial infarction, and other heart diseases). We pooled data from two multiethnic studies (one case-control and one survivor cohort) enrolling 1,936 women diagnosed with breast cancer, who were members of Kaiser Permanente Northern California. Concordance varied by comorbidity; kappa values ranged from 0.50 for other heart diseases to 0.87 for diabetes. Sensitivities for comorbidities from self-report versus medical record were similar for racial/ethnic minorities and non-Hispanic Whites, and did not vary by age, neighborhood socioeconomic status, or education. Women with a longer history of comorbidity or who took medications for the comorbidity were more likely to report the condition. Hazard ratios for all-cause mortality were not consistently affected by source of comorbidity information; the hazard ratio was lower for diabetes, but higher for the other comorbidities when medical record versus self-report was used. Model fit was better when the medical record versus self-reported data were used. Comorbidities are increasingly recognized to influence the survival of patients with breast or other cancers. Potential effects of misclassification of comorbidity status should be considered in the interpretation of research results.

  16. Cancer of the cervix: knowledge, beliefs and screening behaviours of health workers in Mudzi District in Mashonaland East Province, Zimbabwe.

    PubMed

    Tarwireyi, F; Chirenje, Z M; Rusakaniko, S

    2003-01-01

    To assess the knowledge, beliefs and screening behaviours on cervical cancer among health workers in Mudzi District. Cross sectional survey. Mudzi District Hospital and all the 20 rural health centres in Mudzi District of Mashonaland East. Sixty health workers in Mudzi District. Knowledge of cervical cancer risk factors, screening methods and treatment options. Beliefs and screening behaviours. The knowledge levels were lower for many of the predisposing factors of cervical cancer except for the use of vaginal herbs or chemicals, which 85% of the health workers knew. Though 50% of the respondents knew of the Pap smear as a screening method for cervical cancer, 86.6% did not know the human papiloma virus screening and 90% did not know of the visual inspection of the cervix using acetic acid. There were also very low knowledge levels for most of the treatment options for pre-cancer with all health workers not knowing the leep and the Laser options. The majority 73.3% believed that they where not at risk of developing cervical cancer. Most of the respondents, 81.7%, had not undergone any form of cervical cancer screening. However, the main reason for non screening was that there were no cervical cancer screening facilities in Mudzi District. The study revealed low knowledge levels, negative beliefs about the risk of developing cervical cancer and poor screening behaviours among health workers in Mudzi District. Training in cervical cancer is, therefore, recommended for the health workers. However, the training should be combined with setting up facilities for cervical cancer screening.

  17. Translational Breast Cancer Research Consortium (TBCRC) 022: A Phase II Trial of Neratinib for Patients With Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer and Brain Metastases.

    PubMed

    Freedman, Rachel A; Gelman, Rebecca S; Wefel, Jeffrey S; Melisko, Michelle E; Hess, Kenneth R; Connolly, Roisin M; Van Poznak, Catherine H; Niravath, Polly A; Puhalla, Shannon L; Ibrahim, Nuhad; Blackwell, Kimberly L; Moy, Beverly; Herold, Christina; Liu, Minetta C; Lowe, Alarice; Agar, Nathalie Y R; Ryabin, Nicole; Farooq, Sarah; Lawler, Elizabeth; Rimawi, Mothaffar F; Krop, Ian E; Wolff, Antonio C; Winer, Eric P; Lin, Nancy U

    2016-03-20

    Evidence-based treatments for metastatic, human epidermal growth factor receptor 2 (HER2)-positive breast cancer in the CNS are limited. Neratinib is an irreversible inhibitor of erbB1, HER2, and erbB4, with promising activity in HER2-positive breast cancer; however, its activity in the CNS is unknown. We evaluated the efficacy of treatment with neratinib in patients with HER2-positive breast cancer brain metastases in a multicenter, phase II open-label trial. Eligible patients were those with HER2-positive brain metastases (≥ 1 cm in longest dimension) who experienced progression in the CNS after one or more line of CNS-directed therapy, such as whole-brain radiotherapy, stereotactic radiosurgery, and/or surgical resection. Patients received neratinib 240 mg orally once per day, and tumors were assessed every two cycles. The primary endpoint was composite CNS objective response rate (ORR), requiring all of the following: ≥ 50% reduction in volumetric sum of target CNS lesions and no progression of non-target lesions, new lesions, escalating corticosteroids, progressive neurologic signs/symptoms, or non-CNS progression--the threshold for success was five of 40 responders. Forty patients were enrolled between February 2012 and June 2013; 78% of patients had previous whole-brain radiotherapy. Three women achieved a partial response (CNS objective response rate, 8%; 95% CI, 2% to 22%). The median number of cycles received was two (range, one to seven cycles), with a median progression-free survival of 1.9 months. Five women received six or more cycles. The most common grade ≥ 3 event was diarrhea (occurring in 21% of patients taking prespecified loperamide prophylaxis and 28% of those without prophylaxis). Patients in the study experienced a decreased quality of life over time. Although neratinib had low activity and did not meet our threshold for success, 12.5% of patients received six or more cycles. Studies combining neratinib with chemotherapy in patients

  18. Kansas Wind Energy Consortium

    SciTech Connect

    Gruenbacher, Don

    2015-12-31

    This project addresses both fundamental and applied research problems that will help with problems defined by the DOE “20% Wind by 2030 Report”. In particular, this work focuses on increasing the capacity of small or community wind generation capabilities that would be operated in a distributed generation approach. A consortium (KWEC – Kansas Wind Energy Consortium) of researchers from Kansas State University and Wichita State University aims to dramatically increase the penetration of wind energy via distributed wind power generation. We believe distributed generation through wind power will play a critical role in the ability to reach and extend the renewable energy production targets set by the Department of Energy. KWEC aims to find technical and economic solutions to enable widespread implementation of distributed renewable energy resources that would apply to wind.

  19. Advanced Separation Consortium

    SciTech Connect

    2006-01-01

    The Center for Advanced Separation Technologies (CAST) was formed in 2001 under the sponsorship of the US Department of Energy to conduct fundamental research in advanced separation and to develop technologies that can be used to produce coal and minerals in an efficient and environmentally acceptable manner. The CAST consortium consists of seven universities - Virginia Tech, West Virginia University, University of Kentucky, Montana Tech, University of Utah, University of Nevada-Reno, and New Mexico Tech. The consortium brings together a broad range of expertise to solve problems facing the US coal industry and the mining sector in general. At present, a total of 60 research projects are under way. The article outlines some of these, on topics including innovative dewatering technologies, removal of mercury and other impurities, and modelling of the flotation process. 1 photo.

  20. Evaluation of a candidate breast cancer associated SNP in ERCC4 as a risk modifier in BRCA1 and BRCA2 mutation carriers. Results from the Consortium of Investigators of Modifiers of BRCA1/BRCA2 (CIMBA)

    PubMed Central

    Osorio, A; Milne, R L; Pita, G; Peterlongo, P; Heikkinen, T; Simard, J; Chenevix-Trench, G; Spurdle, A B; Beesley, J; Chen, X; Healey, S; Neuhausen, S L; Ding, Y C; Couch, F J; Wang, X; Lindor, N; Manoukian, S; Barile, M; Viel, A; Tizzoni, L; Szabo, C I; Foretova, L; Zikan, M; Claes, K; Greene, M H; Mai, P; Rennert, G; Lejbkowicz, F; Barnett-Griness, O; Andrulis, I L; Ozcelik, H; Weerasooriya, N; Gerdes, A-M; Thomassen, M; Cruger, D G; Caligo, M A; Friedman, E; Kaufman, B; Laitman, Y; Cohen, S; Kontorovich, T; Gershoni-Baruch, R; Dagan, E; Jernström, H; Askmalm, M S; Arver, B; Malmer, B; Domchek, S M; Nathanson, K L; Brunet, J; Ramón y Cajal, T; Yannoukakos, D; Hamann, U; Hogervorst, F B L; Verhoef, S; García, EB Gómez; Wijnen, J T; van den Ouweland, A; Easton, D F; Peock, S; Cook, M; Oliver, C T; Frost, D; Luccarini, C; Evans, D G; Lalloo, F; Eeles, R; Pichert, G; Cook, J; Hodgson, S; Morrison, P J; Douglas, F; Godwin, A K; Sinilnikova, O M; Barjhoux, L; Stoppa-Lyonnet, D; Moncoutier, V; Giraud, S; Cassini, C; Olivier-Faivre, L; Révillion, F; Peyrat, J-P; Muller, D; Fricker, J-P; Lynch, H T; John, E M; Buys, S; Daly, M; Hopper, J L; Terry, M B; Miron, A; Yassin, Y; Goldgar, D; Singer, C F; Gschwantler-Kaulich, D; Pfeiler, G; Spiess, A-C; Hansen, Thomas v O; Johannsson, O T; Kirchhoff, T; Offit, K; Kosarin, K; Piedmonte, M; Rodriguez, G C; Wakeley, K; Boggess, J F; Basil, J; Schwartz, P E; Blank, S V; Toland, A E; Montagna, M; Casella, C; Imyanitov, E N; Allavena, A; Schmutzler, R K; Versmold, B; Engel, C; Meindl, A; Ditsch, N; Arnold, N; Niederacher, D; Deißler, H; Fiebig, B; Varon-Mateeva, R; Schaefer, D; Froster, U G; Caldes, T; de la Hoya, M; McGuffog, L; Antoniou, A C; Nevanlinna, H; Radice, P; Benítez, J

    2009-01-01

    Background: In this study we aimed to evaluate the role of a SNP in intron 1 of the ERCC4 gene (rs744154), previously reported to be associated with a reduced risk of breast cancer in the general population, as a breast cancer risk modifier in BRCA1 and BRCA2 mutation carriers. Methods: We have genotyped rs744154 in 9408 BRCA1 and 5632 BRCA2 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) and assessed its association with breast cancer risk using a retrospective weighted cohort approach. Results: We found no evidence of association with breast cancer risk for BRCA1 (per-allele HR: 0.98, 95% CI: 0.93–1.04, P=0.5) or BRCA2 (per-allele HR: 0.97, 95% CI: 0.89–1.06, P=0.5) mutation carriers. Conclusion: This SNP is not a significant modifier of breast cancer risk for mutation carriers, though weak associations cannot be ruled out. PMID:19920816

  1. Evaluation of a candidate breast cancer associated SNP in ERCC4 as a risk modifier in BRCA1 and BRCA2 mutation carriers. Results from the Consortium of Investigators of Modifiers of BRCA1/BRCA2 (CIMBA).

    PubMed

    Osorio, A; Milne, R L; Pita, G; Peterlongo, P; Heikkinen, T; Simard, J; Chenevix-Trench, G; Spurdle, A B; Beesley, J; Chen, X; Healey, S; Neuhausen, S L; Ding, Y C; Couch, F J; Wang, X; Lindor, N; Manoukian, S; Barile, M; Viel, A; Tizzoni, L; Szabo, C I; Foretova, L; Zikan, M; Claes, K; Greene, M H; Mai, P; Rennert, G; Lejbkowicz, F; Barnett-Griness, O; Andrulis, I L; Ozcelik, H; Weerasooriya, N; Gerdes, A-M; Thomassen, M; Cruger, D G; Caligo, M A; Friedman, E; Kaufman, B; Laitman, Y; Cohen, S; Kontorovich, T; Gershoni-Baruch, R; Dagan, E; Jernström, H; Askmalm, M S; Arver, B; Malmer, B; Domchek, S M; Nathanson, K L; Brunet, J; Ramón Y Cajal, T; Yannoukakos, D; Hamann, U; Hogervorst, F B L; Verhoef, S; Gómez García, E B; Wijnen, J T; van den Ouweland, A; Easton, D F; Peock, S; Cook, M; Oliver, C T; Frost, D; Luccarini, C; Evans, D G; Lalloo, F; Eeles, R; Pichert, G; Cook, J; Hodgson, S; Morrison, P J; Douglas, F; Godwin, A K; Sinilnikova, O M; Barjhoux, L; Stoppa-Lyonnet, D; Moncoutier, V; Giraud, S; Cassini, C; Olivier-Faivre, L; Révillion, F; Peyrat, J-P; Muller, D; Fricker, J-P; Lynch, H T; John, E M; Buys, S; Daly, M; Hopper, J L; Terry, M B; Miron, A; Yassin, Y; Goldgar, D; Singer, C F; Gschwantler-Kaulich, D; Pfeiler, G; Spiess, A-C; Hansen, Thomas V O; Johannsson, O T; Kirchhoff, T; Offit, K; Kosarin, K; Piedmonte, M; Rodriguez, G C; Wakeley, K; Boggess, J F; Basil, J; Schwartz, P E; Blank, S V; Toland, A E; Montagna, M; Casella, C; Imyanitov, E N; Allavena, A; Schmutzler, R K; Versmold, B; Engel, C; Meindl, A; Ditsch, N; Arnold, N; Niederacher, D; Deissler, H; Fiebig, B; Varon-Mateeva, R; Schaefer, D; Froster, U G; Caldes, T; de la Hoya, M; McGuffog, L; Antoniou, A C; Nevanlinna, H; Radice, P; Benítez, J

    2009-12-15

    In this study we aimed to evaluate the role of a SNP in intron 1 of the ERCC4 gene (rs744154), previously reported to be associated with a reduced risk of breast cancer in the general population, as a breast cancer risk modifier in BRCA1 and BRCA2 mutation carriers. We have genotyped rs744154 in 9408 BRCA1 and 5632 BRCA2 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) and assessed its association with breast cancer risk using a retrospective weighted cohort approach. We found no evidence of association with breast cancer risk for BRCA1 (per-allele HR: 0.98, 95% CI: 0.93-1.04, P = 0.5) or BRCA2 (per-allele HR: 0.97, 95% CI: 0.89-1.06, P = 0.5) mutation carriers. This SNP is not a significant modifier of breast cancer risk for mutation carriers, though weak associations cannot be ruled out.

  2. A phase II study of medroxyprogesterone acetate in patients with hormone receptor negative metastatic breast cancer: translational breast cancer research consortium trial 007.

    PubMed

    Miller, Kathy D; Althouse, Sandra K; Nabell, Lisle; Rugo, Hope; Carey, Lisa; Kimmick, Gretchen; Jones, David R; Merino, Maria J; Steeg, Patricia S

    2014-11-01

    Preclinical data suggest that medroxyprogesterone acetate (MPA) has both anti-metastatic and anti-angiogenic activity in the absence of hormone receptors (HR). This phase II trial assessed the activity of MPA alone or in combination with low-dose chemotherapy in patients with metastatic HR-negative breast cancer. Postmenopausal women with HR-negative disease were eligible if they had not received more than 3 chemotherapy regimens for metastatic disease. All patients were treated with MPA 1,000-1,500 mg/day orally; patients in cohort two also received low-dose oral cyclophosphamide and methotrexate (ldCM, 50 mg/day and 2.5 mg twice daily on Days 1 and 2 each week). Tissue and circulating biomarkers were assessed serially. The primary endpoint was clinical benefit response defined as objective response or stable disease >6 months. Thirty patients were enrolled (14 MPA monotherapy; 16 MPA + ldCM); median age was 55 (35-80); nearly all had visceral involvement. Despite dose escalation in 90 % of patients, only 17 (57 %) patients ever achieved MPA trough concentrations >50 ng/ml. One patient developed grade 4 renal failure in the setting of rapid disease progression and dehydration. There were no objective responses. One patient in each cohort (~7 %) had stable disease for > 6 months. Skin Nm23 expression increased after 4 weeks of MPA + ldCM, but there were no significant changes in TSP-1, PAI-1 antigen, or PAI-1 activity. MPA had limited activity and does not warrant further development in patients with HR-negative advanced breast cancer. Poor bioavailability limited exposure despite dose escalation.

  3. The BADER Consortium

    DTIC Science & Technology

    2014-10-01

    will study individuals with upper extremity amputations, a subgroup of injured service people who have been underrepresented in research in the past...external auditing purposes.  Two charges from the BADER Consortium were randomly selected for audit under the annual University of Delaware audit...use at Navy sites.  Fully executed two CRADAs for new research projects. Institution Date of distribution Date of completed agreement

  4. Military Suicide Research Consortium

    DTIC Science & Technology

    2014-10-01

    Reduction in self- esteem may impact this relationship such that if self-esteem is not reduced as a result of bullying , psychological distress and sui...resources of the military, impact unit morale, and take a large emotional toll on the involved friends, family, and commanders. There is significant...practice that will have a direct impact on suicide-related and other mental health outcomes for military personnel. 3. Disseminate Consortium

  5. Evaluation of Breast Cancer Cases Diagnosed In the Breast Cancer Screening Program In the Near East University Hospital of North Cyprus

    PubMed Central

    Durdiyeva, Muhabbet Koralp; Besim, Hasan; Arslan, Kalbim; Özkayalar, Hanife; Yılmaz, Güliz; Mocan, Gamze Kuzey; Bulakbaşı, Nail

    2015-01-01

    Objective This study is about determination and eveluation of the breast cancer cases which were diagnosed during the early diagnosis and screening programs covering a three years of digital mammography images at the Near East University Hospital. Materials and Methods This study covers 2136 women patients who applied to the early diagnosis and screening program of the Near East University Hospital between July 2010 and July 2013. The mamographic images were re evaluated retrospectively according to ACR’s (The American College of Radiology) BİRADS (Breast Imaging Reporting and Data System). The mamographic results as required were correlated with breast ultrasound (US) and compared with the pathologic results of materials obtained by surgery or biopsy. The results were analyzed statistically in comparison with the literature data. Results The women who were screened aged between 34–73 years with a median of 53.5 (SD = 27.5). Suspected malignancy were evaluated in 54 patients, which 42 of them were diagnosed BIRADS 4 and 12 patients BIRADS 5 and 21 patients were correleted breast cancer based on histopathologic examination. 17 patients had the breast-conserving surgery and 4 patients were treated with mastectomy. Conclusion Breast cancers that are detected at early stages by breast cancer screening tests are more likely to be smaller and still confined to the breast resulting in more simple operations and more succesfull treatment. Promoting the breast cancer screening and registration programs in our country will help to control the desease at our region.

  6. Evaluation of Breast Cancer Cases Diagnosed In the Breast Cancer Screening Program In the Near East University Hospital of North Cyprus.

    PubMed

    Durdiyeva, Muhabbet Koralp; Besim, Hasan; Arslan, Kalbim; Özkayalar, Hanife; Yılmaz, Güliz; Mocan, Gamze Kuzey; Bulakbaşı, Nail

    2015-01-01

    This study is about determination and eveluation of the breast cancer cases which were diagnosed during the early diagnosis and screening programs covering a three years of digital mammography images at the Near East University Hospital. This study covers 2136 women patients who applied to the early diagnosis and screening program of the Near East University Hospital between July 2010 and July 2013. The mamographic images were re evaluated retrospectively according to ACR's (The American College of Radiology) BİRADS (Breast Imaging Reporting and Data System). The mamographic results as required were correlated with breast ultrasound (US) and compared with the pathologic results of materials obtained by surgery or biopsy. The results were analyzed statistically in comparison with the literature data. The women who were screened aged between 34-73 years with a median of 53.5 (SD = 27.5). Suspected malignancy were evaluated in 54 patients, which 42 of them were diagnosed BIRADS 4 and 12 patients BIRADS 5 and 21 patients were correleted breast cancer based on histopathologic examination. 17 patients had the breast-conserving surgery and 4 patients were treated with mastectomy. Breast cancers that are detected at early stages by breast cancer screening tests are more likely to be smaller and still confined to the breast resulting in more simple operations and more succesfull treatment. Promoting the breast cancer screening and registration programs in our country will help to control the desease at our region.

  7. The Stroke Belt Consortium.

    PubMed

    Alberts, M J

    1996-01-01

    The "Stroke Belt" describes a region of the southeastern United States with a high incidence of stroke and mortality due to stroke. In an effort to address the problem of stroke in this region, we have formed the Stroke Belt Consortium (SBC). This report describes the formation and functions of the SBC. The SBC is a unique organization with representatives from many areas, including health care, government, nonprofit organizations, the pharmaceutical industry, minority groups, educational groups, and managed care. The goals of the consortium are to advance public and professional education about stroke in the Stroke Belt, with a special emphasis on the populations in that region. The first meeting of the consortium was held in November 1994. Many helpful and innovative ideas and initiatives were generated at the first SBC meeting. These included improved techniques for professional education, the development of a mass media campaign for public education, screening of college students for stroke risk factors, and using fast-food restaurants and sporting events as venues to promote stroke education. This type of organized effort may produce cost-effective programs and initiatives, particularly for largescale educational efforts, that will enhance the prevention and treatment of stroke patients. If successful in the Stroke Belt, similar organizations can be formed in other regions of the nation to address specific issues related to stroke prevention, education, and treatment.

  8. Breast cancer in South East Asia: comparison of presentation and outcome between a middle income and a high income country.

    PubMed

    Saxena, Nakul; Hartman, Mikael; Bhoo-Pathy, Nirmala; Lim, Jennifer N W; Aw, Tar-Ching; Iau, Philip; Taib, Nur Aishah; Lee, Soo-Chin; Yip, Cheng-Har; Verkooijen, Helena M

    2012-12-01

    There are large differences in socio-economic growth within the region of South East Asia, leading to sharp contrasts in health-systems development between countries. This study compares breast cancer presentation and outcome between patients from a high income country (Singapore) and a middle income country (Malaysia) in South East Asia. Within the Singapore Malaysia Breast Cancer Registry we identified all consecutive patients diagnosed with breast cancer between 1993 and 2007 at the National University Hospital in Singapore (high income country, n=2,141) and the University of Malaya Medical Center in Kuala Lumpur, Malaysia (middle income country, n=3,320). We compared demographics, tumor characteristics, treatment patterns, and survival between patients from both countries. In Malaysia, patients were less often diagnosed with in situ breast cancer (adjusted odds ratio [ORadj] 0.2; 95% confidence interval [95% CI] 0.1-0.3), more likely to be diagnosed with late stage (III and IV) disease (ORadj for stage III 1.6; 95% CI 1.3-2.0; ORadj for stage IV 1.2; 95% CI 1.1-1.4) as compared to patients from Singapore. Univariate analysis showed that Malaysian patients were at a 72% increased risk of death as compared to Singaporeans. After adjusting for other prognostic factors, the risk decreased by only 5% (ORadj 1.67, 95% CI 1.44-1.92). Differences in way of presentation (except stage and tumor size) and treatment of breast cancer patients from the two countries are small. The overall survival of breast cancer patients from Malaysia is much lower than that of Singaporean patients.

  9. GAS STORAGE TECHNOLGOY CONSORTIUM

    SciTech Connect

    Robert W. Watson

    2004-04-23

    Gas storage is a critical element in the natural gas industry. Producers, transmission and distribution companies, marketers, and end users all benefit directly from the load balancing function of storage. The unbundling process has fundamentally changed the way storage is used and valued. As an unbundled service, the value of storage is being recovered at rates that reflect its value. Moreover, the marketplace has differentiated between various types of storage services, and has increasingly rewarded flexibility, safety, and reliability. The size of the natural gas market has increased and is projected to continue to increase towards 30 trillion cubic feet (TCF) over the next 10 to 15 years. Much of this increase is projected to come from electric generation, particularly peaking units. Gas storage, particularly the flexible services that are most suited to electric loads, is critical in meeting the needs of these new markets. In order to address the gas storage needs of the natural gas industry, an industry-driven consortium was created--the Gas Storage Technology Consortium (GSTC). The objective of the GSTC is to provide a means to accomplish industry-driven research and development designed to enhance operational flexibility and deliverability of the Nation's gas storage system, and provide a cost effective, safe, and reliable supply of natural gas to meet domestic demand. To accomplish this objective, the project is divided into three phases that are managed and directed by the GSTC Coordinator. Base funding for the consortium is provided by the U.S. Department of Energy (DOE). In addition, funding is anticipated from the Gas Technology Institute (GTI). The first phase, Phase 1A, was initiated on September 30, 2003, and is scheduled for completion on March 31, 2004. Phase 1A of the project includes the creation of the GSTC structure, development of constitution (by-laws) for the consortium, and development and refinement of a technical approach (work plan) for

  10. GAS STORAGE TECHNOLOGY CONSORTIUM

    SciTech Connect

    Robert W. Watson

    2004-04-17

    Gas storage is a critical element in the natural gas industry. Producers, transmission and distribution companies, marketers, and end users all benefit directly from the load balancing function of storage. The unbundling process has fundamentally changed the way storage is used and valued. As an unbundled service, the value of storage is being recovered at rates that reflect its value. Moreover, the marketplace has differentiated between various types of storage services, and has increasingly rewarded flexibility, safety, and reliability. The size of the natural gas market has increased and is projected to continue to increase towards 30 trillion cubic feet (TCF) over the next 10 to 15 years. Much of this increase is projected to come from electric generation, particularly peaking units. Gas storage, particularly the flexible services that are most suited to electric loads, is critical in meeting the needs of these new markets. In order to address the gas storage needs of the natural gas industry, an industry-driven consortium was created--the Gas Storage Technology Consortium (GSTC). The objective of the GSTC is to provide a means to accomplish industry-driven research and development designed to enhance operational flexibility and deliverability of the Nation's gas storage system, and provide a cost effective, safe, and reliable supply of natural gas to meet domestic demand. To accomplish this objective, the project is divided into three phases that are managed and directed by the GSTC Coordinator. Base funding for the consortium is provided by the U.S. Department of Energy (DOE). In addition, funding is anticipated from the Gas Technology Institute (GTI). The first phase, Phase 1A, was initiated on September 30, 2003, and is scheduled for completion on March 31, 2004. Phase 1A of the project includes the creation of the GSTC structure, development of constitution (by-laws) for the consortium, and development and refinement of a technical approach (work plan) for

  11. Phase II trial of the farnesyltransferase inhibitor tipifarnib plus fulvestrant in hormone receptor-positive metastatic breast cancer: New York Cancer Consortium Trial P6205

    PubMed Central

    Li, T.; Christos, P. J.; Sparano, J. A.; Hershman, D. L.; Hoschander, S.; O'Brien, K.; Wright, J. J.; Vahdat, L. T.

    2009-01-01

    Background: Fulvestrant produces a clinical benefit rate (CBR) of ∼45% in tamoxifen-resistant, hormone receptor (HR)-positive metastatic breast cancer (MBC) and 32% in aromatase inhibitor (AI)-resistant disease. The farnesyltransferase inhibitor tipifarnib inhibits Ras signaling and has preclinical and clinical activity in endocrine therapy-resistant disease. The objective of this study was to determine the efficacy and safety of tipifarnib–fulvestrant combination in HR-positive MBC. Patients and methods: Postmenopausal women with no prior chemotherapy for metastatic disease received i.m. fulvestrant 250 mg on day 1 plus oral tipifarnib 300 mg twice daily on days 1–21 every 28 days. The primary end point was CBR. Results: The CBR was 51.6% [95% confidence interval (CI) 34.0% to 69.2%] in 31 eligible patients and 47.6% (95% CI 26.3% to 69.0%) in 21 patients with AI-resistant disease. A futility analysis indicated that it was unlikely to achieve the prespecified 70% CBR. Tipifarnib dose modification was required in 8 of 33 treated patients (24%). Conclusions: The target CBR of 70% for the tipifarnib–fulvestrant combination in HR-positive MBC was set too high and was not achieved. The 48% CBR in AI-resistant disease compares favorably with the 32% CBR observed with fulvestrant alone in prior studies and merit further clinical and translational evaluation. PMID:19153124

  12. Combination epigenetic therapy in metastatic colorectal cancer (mCRC) with subcutaneous 5-azacitidine and entinostat: a phase 2 consortium/stand Up 2 cancer study

    PubMed Central

    Azad, Nilofer S.; el-Khoueiry, Anthony; Yin, Jun; Oberg, Ann L.; Flynn, Patrick; Adkins, Douglas; Sharma, Anup; Weisenberger, Daniel J.; Brown, Thomas; Medvari, Prakriti; Jones, Peter A.; Easwaran, Hariharan; Kamel, Ihab; Bahary, Nathan; Kim, George; Picus, Joel; Pitot, Henry C.; Erlichman, Charles; Donehower, Ross; Shen, Hui; Laird, Peter W.; Piekarz, Richard; Baylin, Stephen; Ahuja, Nita

    2017-01-01

    Purpose Therapy with demethylating agent 5-azacitidine and histone deacetylase inhibitor entinostat shows synergistic re-expression of tumor-suppressor genes and growth inhibition in colorectal (CRC) cell lines and in vivo studies. Experimental Design We conducted a phase II, multi-institutional study of the combination in metastatic CRC patients. Subcutaneous azacitidine was administered at 40 mg/m2 days 1-5 and 8-10 and entinostat was given 7 mg orally on days 3 and 10. An interim analysis indicated toxicity crossed the pre-specified safety boundary but was secondary to disease. A 2nd cohort with added eligibility restrictions was accrued: prior therapies were limited to no more than 2 or 3 (KRAS-mutated and KRAS-wildtype cancers, respectively) and <30% of liver involvement. The primary endpoint was RECIST response. Serial biopsies were performed at baseline and after 2 cycles of therapy. Results Forty-seven patients were enrolled (24:Cohort 1, 23:Cohort 2). Patients were heavily pre-treated (median prior therapies 4: Cohort 1 and 2.5: cohort 2). No responses were observed. Median progression-free survival was 1.9 months; overall survival was 5.6 and 8.3 months in Cohorts 1 and 2, respectively. Toxicity was tolerable and as expected. Unsupervised cluster analysis of serial tumor biopsies suggested greater DNA demethylation in patients with PFS above the median. Conclusion In this first trial of CRC patients with combination epigenetic therapy, we show tolerable therapy without significant clinical activity as determined by RECIST responses. Reversal of hypermethylation was seen in a subset of patients and correlated with improved PFS. PMID:28186961

  13. Combination epigenetic therapy in metastatic colorectal cancer (mCRC) with subcutaneous 5-azacitidine and entinostat: a phase 2 consortium/stand up 2 cancer study.

    PubMed

    Azad, Nilofer S; El-Khoueiry, Anthony; Yin, Jun; Oberg, Ann L; Flynn, Patrick; Adkins, Douglas; Sharma, Anup; Weisenberger, Daniel J; Brown, Thomas; Medvari, Prakriti; Jones, Peter A; Easwaran, Hariharan; Kamel, Ihab; Bahary, Nathan; Kim, George; Picus, Joel; Pitot, Henry C; Erlichman, Charles; Donehower, Ross; Shen, Hui; Laird, Peter W; Piekarz, Richard; Baylin, Stephen; Ahuja, Nita

    2017-05-23

    Therapy with demethylating agent 5-azacitidine and histone deacetylase inhibitor entinostat shows synergistic re-expression of tumor-suppressor genes and growth inhibition in colorectal (CRC) cell lines and in vivo studies. We conducted a phase II, multi-institutional study of the combination in metastatic CRC patients. Subcutaneous azacitidine was administered at 40 mg/m2 days 1-5 and 8-10 and entinostat was given 7 mg orally on days 3 and 10. An interim analysis indicated toxicity crossed the pre-specified safety boundary but was secondary to disease. A 2nd cohort with added eligibility restrictions was accrued: prior therapies were limited to no more than 2 or 3 (KRAS-mutated and KRAS-wildtype cancers, respectively) and <30% of liver involvement. The primary endpoint was RECIST response. Serial biopsies were performed at baseline and after 2 cycles of therapy. Forty-seven patients were enrolled (24:Cohort 1, 23:Cohort 2). Patients were heavily pre-treated (median prior therapies 4: Cohort 1 and 2.5: cohort 2). No responses were observed. Median progression-free survival was 1.9 months; overall survival was 5.6 and 8.3 months in Cohorts 1 and 2, respectively. Toxicity was tolerable and as expected. Unsupervised cluster analysis of serial tumor biopsies suggested greater DNA demethylation in patients with PFS above the median. In this first trial of CRC patients with combination epigenetic therapy, we show tolerable therapy without significant clinical activity as determined by RECIST responses. Reversal of hypermethylation was seen in a subset of patients and correlated with improved PFS.

  14. Breast cancer clinicopathological presentation, gravity and challenges in Eritrea, East Africa: management practice in a resource-poor setting.

    PubMed

    Tesfamariam, Asmerom; Gebremichael, Andemariam; Mufunda, Jacob

    2013-06-05

    In Africa, breast cancer closely compares with cervical cancer as the most common malignancy affecting women and the incidence rates appear to be rising. Early detection of breast cancer is a key strategy for a good treatment outcome. However, there is no established protocol or guideline for management of breast cancer in Eritrea, East Africa. To assess the clinicopathological presentation, gravity and management challenges presented in breast cancer treatment in Eritrea. Methods. Our investigation was a retrospective, descriptive study to assess the clinical features and severity of breast cancer at time of presentation. We reviewed the medical records of all patients who presented with breast malignancies over the 2-year period from 1 January 2007 to 31 December 2008. Eighty-two patients ranging in age from 26 - 80 years (mean 48 years) were included in the study. Of these 51% were premenopausal women; 61% of the patients presented with breast mass only and the remainder with manifestations of local (mass plus discharge, breast pain or breast ulceration) or distant metastatic disease. More than 60% of the patients presented after >2 years following onset of symptoms. Two-thirds of patients had late stage (III or IV) disease. All except one case was managed surgically. Most cases presented at younger age and advanced stage. These findings call for strengthening health education to promote early health-seeking behaviour and advocacy for the introduction of national screening, implementation of a management protocol and establishment of a radio-chemotherapy centre.

  15. A questionnaire-based survey on screening for gastric and colorectal cancer by physicians in East Asian countries in 2010.

    PubMed

    Naito, Yuji; Uchiyama, Kazuhiko; Kinoshita, Yoshikazu; Fukudo, Shin; Joh, Takashi; Suzuki, Hidekazu; Takahashi, Shin'ichi; Ueno, Fumiaki; Fujiwara, Yasuhiro; Arakawa, Tetsuo; Matsumoto, Takayuki; Hahm, Ki-Baik; Kachintorn, Udom; Syam, Ari Fahrial; Rani, Abdul Aziz; Sollano, Jose D; Zhu, Qi

    2012-01-01

    The incidence of gastric cancer (GC) is high, and colorectal cancer (CRC) has significantly increased in Asian countries. To examine the current screening for GC and CRC within East Asia by means of a questionnaire survey. Representative members of the Committee of the International Gastrointestinal Consensus Symposium provided a questionnaire to physicians in six East Asian countries. A total of 449 physicians participated in this survey. In all countries, more than 70% of physicians started GC screening between 40 and 59 years. The most popular method to screen for GC was endoscopy (92.7%), but combination methods such as Helicobacter pylori (HP) antibody, barium X-ray, and tumor marker with endoscopy differed by country. For HP-positive individuals, most physicians screened every year by endoscopy, and for individuals post-HP eradication, about half of physicians (56.3%) thought there was a need to follow-up with GC screening. Among all physicians, the most common age to start CRC screening was in the 40s (39.8%) and 50s (40.9%). Based on the American Cancer Society Recommendations, a fecal occult blood test every year was the most popular method for CRC screening overall. However, among each country, this test was most popular in only Japan (76.9%) and Indonesia. In other countries, sigmoidoscopy every 5 years and total colonoscopy every 10 years were the most popular methods. There are similarities and differences in the screening of GC and CRC among East Asian countries. Copyright © 2012 S. Karger AG, Basel.

  16. Genomic standards consortium projects.

    PubMed

    Field, Dawn; Sterk, Peter; Kottmann, Renzo; De Smet, J Wim; Amaral-Zettler, Linda; Cochrane, Guy; Cole, James R; Davies, Neil; Dawyndt, Peter; Garrity, George M; Gilbert, Jack A; Glöckner, Frank Oliver; Hirschman, Lynette; Klenk, Hans-Peter; Knight, Rob; Kyrpides, Nikos; Meyer, Folker; Karsch-Mizrachi, Ilene; Morrison, Norman; Robbins, Robert; San Gil, Inigo; Sansone, Susanna; Schriml, Lynn; Tatusova, Tatiana; Ussery, Dave; Yilmaz, Pelin; White, Owen; Wooley, John; Caporaso, Gregory

    2014-06-15

    The Genomic Standards Consortium (GSC) is an open-membership community that was founded in 2005 to work towards the development, implementation and harmonization of standards in the field of genomics. Starting with the defined task of establishing a minimal set of descriptions the GSC has evolved into an active standards-setting body that currently has 18 ongoing projects, with additional projects regularly proposed from within and outside the GSC. Here we describe our recently enacted policy for proposing new activities that are intended to be taken on by the GSC, along with the template for proposing such new activities.

  17. Federal consortium visit

    NASA Image and Video Library

    2011-02-10

    Members of the Southeast U.S. Federal Laboratory Consortium for Technology Transfer gather at the base of the B-1/B-2 Test Stand during a Feb. 10 visit to John C. Stennis Space Center. The group visited Stennis to tour facilities and receive briefings on work at the rocket engine test site. They also visited the INFINITY at NASA Stennis Space Center site and received a briefing on construction of the new science center. The FLC is a nationwide network of federal laboratories to facilitate technology transfers between federal agencies and commercial companies.

  18. Immune factors and viral interactions in brain cancer etiology and outcomes, The 2016 Brain Tumor Epidemiology Consortium Meeting report

    PubMed Central

    Johnson, Kimberly J.; Hainfellner, Johannes A.; Lau, Ching C.; Scheurer, Michael E.; Woehrer, Adelheid; Wiemels, Joseph

    2016-01-01

    The Brain Tumor Epidemiology Consortium (BTEC) is an international consortium that aims to advance development of multicenter and interdisciplinary collaborations that focus on research related to the etiology, outcomes, and prevention of brain tumors. The 17th annual BTEC meeting was held in Barcelona, Spain on June 21 – 23, 2016. The meeting focused on immune and viral factors that influence brain tumor development. Fundamentals of innate and adaptive immunity were reviewed, the role of immune checkpoint inhibitors in primary and secondary brain tumors was addressed, vaccination strategies for glioma treatment were presented, and the potential contribution of immune dysfunction and viruses tropic for glial cells in gliomagenesis was discussed. Further contributions addressed the risk of non-ionizing radiation, molecular and birth characteristics on brain tumor induction/outcomes, and patterns of care and effects of different treatments on brain tumor survival in the real world setting. The next BTEC meeting will be held in June 2017 in Banff, Canada, and will focus on brain tumor epidemiology in the era of precision medicine. PMID:27546018

  19. Portrait of a Consortium: ANKOS (Anatolian University Libraries Consortium)

    ERIC Educational Resources Information Center

    Erdogan, Phyllis; Karasozen, Bulent

    2009-01-01

    The Anatolian University Libraries Consortium (ANKOS) was created in 2001 with only a few members subscribed to nine e-journal collections and bibliographic databases. This Turkish library consortium had developed from one state and three private universities joining together for the purchase of two databases in 1999. Over time, the numbers of…

  20. Portrait of a Consortium: ANKOS (Anatolian University Libraries Consortium)

    ERIC Educational Resources Information Center

    Erdogan, Phyllis; Karasozen, Bulent

    2009-01-01

    The Anatolian University Libraries Consortium (ANKOS) was created in 2001 with only a few members subscribed to nine e-journal collections and bibliographic databases. This Turkish library consortium had developed from one state and three private universities joining together for the purchase of two databases in 1999. Over time, the numbers of…

  1. The Structural Genomics Consortium

    PubMed Central

    Jones, Molly Morgan; Castle-Clarke, Sophie; Brooker, Daniel; Nason, Edward; Huzair, Farah; Chataway, Joanna

    2014-01-01

    Abstract The Structural Genomics Consortium (SGC) supports drug discovery efforts through a unique, open access model of public-private collaboration. This study presents the results of an independent evaluation of the Structural Genomics Consortium, conducted by RAND Europe with the Institute on Governance. The evaluation aimed to establish the role of the SGC within the wider drug discovery and PPP landscape, assessing the merits of the SGC open access model relative to alternative models of funding R&D in this space, as well as the key trends and opportunities in the external environment that may impact on the future of the SGC. It also established the incentives and disincentives for investment, strengths and weaknesses of the SGC's model, and the opportunities and threats the SGC will face in the future. This enabled us to assess the most convincing arguments for funding the SGC at present; important trade-offs or limitations that should be addressed in moving towards the next funding phase; and whether funders are anticipating changes either to the SGC or the wider PPP landscape. Finally, we undertook a quantitative analysis to ascertain what judgements can be made about the SGC's past and current performance track record, before unpacking the role of the external environment and particular actors within the SGC in developing scenarios for the future. PMID:28560088

  2. Physical activity and risk of prostate and bladder cancer in China: The South and East China case-control study on prostate and bladder cancer

    PubMed Central

    de Vogel, Stefan; Zhong, Weide; Zhong, Zhaohui; Xie, Li-Ping; Hu, Zhiquan; Deng, Yilan; Yang, Kai; Liang, Yuxiang; Zeng, Xing; Wong, Yong Chuan; Tam, Po-Chor; Hemelt, Marjolein; Zeegers, Maurice P.

    2017-01-01

    Background Recent meta-analyses have suggested a modest protective effect of high levels of physical activity on developing both prostate and bladder cancer, but significant heterogeneity between studies included in these meta-analyses existed. To our knowledge, few Chinese studies investigated the association between physical activity and prostate cancer and none between physical activity and bladder cancer. Given the inconsistencies between previous studies and because studies on the relation between physical activity and prostate and bladder cancer in China are scarce, it remains elusive whether there is a relationship between physical activity and prostate and bladder cancer within the Chinese population. Methods We investigated the association between physical activity and risk of developing prostate and bladder cancer within a hospital-based case-control study in the East and South of China among 260 and 438 incident prostate and bladder cancer cases, respectively, and 427 controls. A questionnaire was administered to measure physical activity as metabolic equivalents (METs). Random effects logistic regression was used to calculate odds ratios (ORs) of prostate and bladder cancer for different levels of physical activity and for the specific activities of walking and cycling. Results Increasing overall physical activity was associated with a significant reduction in prostate cancer risk (Ptrend = 0.04) with the highest activity tertile level showing a nearly 50% reduction in prostate cancer risk (OR = 0.53, 95%CI: 0.28–0.98). Overall physical activity was not significantly associated with risk of bladder cancer (Ptrend = 0.61), neither were vigorous (Ptrend = 0.60) or moderate levels of physical activity (Ptrend = 0.21). Walking and cycling were not significantly associated with e