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Sample records for cancer pooled analysis

  1. A pooled analysis of alcohol intake and colorectal cancer

    PubMed Central

    Wang, Yue; Duan, Hong; Yang, Helen; Lin, Jie

    2015-01-01

    Object: In order to provide an updated quantification of the association between alcohol intake and colorectal cancer, we conducted a meta-analysis of published observational studies. Method: Two cohort and 22 case-control studies presenting results for at least three categories of alcohol intake were identified from a PubMed search of articles published before July 2014. Data were extracted independently by two reviewers. Random effects meta-analyses, subgroup analyses, and meta regression were performed for modeling the dose-response relation. Result: The pooled relative risk (RR) for any alcohol intake compared with non/occasional drinking was 1.13 [95% confidence interval (CI), 1.09-1.17]. The RRs were 1.07 (95% CI, 1.02-1.13), 1.23 (95% CI, 1.15-1.32) and 1.37 (95% CI, 1.26-1.49) for light (≤12.5 g/day), moderate (12.6 to 49.9 g/day) and heavy drinking (≥50 g/day), respectively. The risks were consistent in the subgroup analyses of sex and tumor site. Conclusion: This meta-analysis provides strong evidence for an association between alcohol intake and colorectal cancer risk. PMID:26221225

  2. Previous Lung Diseases and Lung Cancer Risk: A Pooled Analysis From the International Lung Cancer Consortium

    PubMed Central

    Brenner, Darren R.; Boffetta, Paolo; Duell, Eric J.; Bickeböller, Heike; Rosenberger, Albert; McCormack, Valerie; Muscat, Joshua E.; Yang, Ping; Wichmann, H.-Erich; Brueske-Hohlfeld, Irene; Schwartz, Ann G.; Cote, Michele L.; Tjønneland, Anne; Friis, Søren; Le Marchand, Loic; Zhang, Zuo-Feng; Morgenstern, Hal; Szeszenia-Dabrowska, Neonila; Lissowska, Jolanta; Zaridze, David; Rudnai, Peter; Fabianova, Eleonora; Foretova, Lenka; Janout, Vladimir; Bencko, Vladimir; Schejbalova, Miriam; Brennan, Paul; Mates, Ioan N.; Lazarus, Philip; Field, John K.; Raji, Olaide; McLaughlin, John R.; Liu, Geoffrey; Wiencke, John; Neri, Monica; Ugolini, Donatella; Andrew, Angeline S.; Lan, Qing; Hu, Wei; Orlow, Irene; Park, Bernard J.; Hung, Rayjean J.

    2012-01-01

    To clarify the role of previous lung diseases (chronic bronchitis, emphysema, pneumonia, and tuberculosis) in the development of lung cancer, the authors conducted a pooled analysis of studies in the International Lung Cancer Consortium. Seventeen studies including 24,607 cases and 81,829 controls (noncases), mainly conducted in Europe and North America, were included (1984–2011). Using self-reported data on previous diagnoses of lung diseases, the authors derived study-specific effect estimates by means of logistic regression models or Cox proportional hazards models adjusted for age, sex, and cumulative tobacco smoking. Estimates were pooled using random-effects models. Analyses stratified by smoking status and histology were also conducted. A history of emphysema conferred a 2.44-fold increased risk of lung cancer (95% confidence interval (CI): 1.64, 3.62 (16 studies)). A history of chronic bronchitis conferred a relative risk of 1.47 (95% CI: 1.29, 1.68 (13 studies)). Tuberculosis (relative risk = 1.48, 95% CI: 1.17, 1.87 (16 studies)) and pneumonia (relative risk = 1.57, 95% CI: 1.22, 2.01 (12 studies)) were also associated with lung cancer risk. Among never smokers, elevated risks were observed for emphysema, pneumonia, and tuberculosis. These results suggest that previous lung diseases influence lung cancer risk independently of tobacco use and that these diseases are important for assessing individual risk. PMID:22986146

  3. Alcohol intake and ovarian cancer risk: a pooled analysis of 10 cohort studies.

    PubMed

    Genkinger, J M; Hunter, D J; Spiegelman, D; Anderson, K E; Buring, J E; Freudenheim, J L; Goldbohm, R A; Harnack, L; Hankinson, S E; Larsson, S C; Leitzmann, M; McCullough, M L; Marshall, J; Miller, A B; Rodriguez, C; Rohan, T E; Schatzkin, A; Schouten, L J; Wolk, A; Zhang, S M; Smith-Warner, S A

    2006-03-13

    Alcohol has been hypothesized to promote ovarian carcinogenesis by its potential to increase circulating levels of estrogen and other hormones; through its oxidation byproduct, acetaldehyde, which may act as a cocarcinogen; and by depletion of folate and other nutrients. Case-control and cohort studies have reported conflicting results relating alcohol intake to ovarian cancer risk. We conducted a pooled analysis of the primary data from ten prospective cohort studies. The analysis included 529 638 women among whom 2001 incident epithelial ovarian cases were documented. After study-specific relative risks (RR) and 95% confidence intervals (CI) were calculated by Cox proportional hazards models, and then were pooled using a random effects model; no associations were observed for intakes of total alcohol (pooled multivariate RR=1.12, 95% CI 0.86-1.44 comparing > or =30 to 0 g day(-1) of alcohol) or alcohol from wine, beer or spirits and ovarian cancer risk. The association with alcohol consumption was not modified by oral contraceptive use, hormone replacement therapy, parity, menopausal status, folate intake, body mass index, or smoking. Associations for endometrioid, mucinous, and serous ovarian cancer were similar to the overall findings. This pooled analysis does not support an association between moderate alcohol intake and ovarian cancer risk. PMID:16495916

  4. 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. PMID:24947688

  5. 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

  6. Dairy products and pancreatic cancer risk: a pooled analysis of 14 cohort studies.

    PubMed

    Genkinger, J M; Wang, M; Li, R; Albanes, D; Anderson, K E; Bernstein, L; van den Brandt, P A; English, D R; Freudenheim, J L; Fuchs, C S; Gapstur, S M; Giles, G G; Goldbohm, R A; Håkansson, N; Horn-Ross, P L; Koushik, A; Marshall, J R; McCullough, M L; Miller, A B; Robien, K; Rohan, T E; Schairer, C; Silverman, D T; Stolzenberg-Solomon, R Z; Virtamo, J; Willett, W C; Wolk, A; Ziegler, R G; Smith-Warner, S A

    2014-06-01

    Pancreatic cancer has few early symptoms, is usually diagnosed at late stages, and has a high case-fatality rate. Identifying modifiable risk factors is crucial to reducing pancreatic cancer morbidity and mortality. Prior studies have suggested that specific foods and nutrients, such as dairy products and constituents, may play a role in pancreatic carcinogenesis. In this pooled analysis of the primary data from 14 prospective cohort studies, 2212 incident pancreatic cancer cases were identified during follow-up among 862 680 individuals. Adjusting for smoking habits, personal history of diabetes, alcohol intake, body mass index (BMI), and energy intake, multivariable study-specific hazard ratios (MVHR) and 95% confidence intervals (CIs) were calculated using the Cox proportional hazards models and then pooled using a random effects model. There was no association between total milk intake and pancreatic cancer risk (MVHR = 0.98, 95% CI = 0.82-1.18 comparing ≥500 with 1-69.9 g/day). Similarly, intakes of low-fat milk, whole milk, cheese, cottage cheese, yogurt, and ice-cream were not associated with pancreatic cancer risk. No statistically significant association was observed between dietary (MVHR = 0.96, 95% CI = 0.77-1.19) and total calcium (MVHR = 0.89, 95% CI = 0.71-1.12) intake and pancreatic cancer risk overall when comparing intakes ≥1300 with <500 mg/day. In addition, null associations were observed for dietary and total vitamin D intake and pancreatic cancer risk. Findings were consistent within sex, smoking status, and BMI strata or when the case definition was limited to pancreatic adenocarcinoma. Overall, these findings do not support the hypothesis that consumption of dairy foods, calcium, or vitamin D during adulthood is associated with pancreatic cancer risk. PMID:24631943

  7. A pooled analysis of smoking and colorectal cancer: timing of exposure and interactions with environmental factors

    PubMed Central

    Gong, Jian; Hutter, Carolyn; Baron, John A.; Berndt, Sonja; Caan, Bette; Campbell, Peter T; Casey, Graham; Chan, Andrew T.; Cotterchio, Michelle; Fuchs, Charles S.; Gallinger, Steven; Giovannucci, Edward; Harrison, Tabitha; Hayes, Richard; Hsu, Li; Jiao, Shuo; Lin, Yi; Lindor, Noralane M.; Newcomb, Polly; Pflugeisen, Bethann; Phipps, Amanda I.; Rohan, Thomas; Schoen, Robert; Seminara, Daniela; Slattery, Martha; Stelling, Deanna; Thomas, Fridtjof; Warnick, Greg; White, Emily; Potter, John; Peters, Ulrike

    2012-01-01

    Background Considerable evidence suggests that cigarette smoking is associated with a higher risk of colorectal cancer. What is unclear, however, is the impact of quitting smoking on risk attenuation and whether other risk factors for colorectal cancer modify this association. Methods We performed a pooled analysis of 8 studies, including 6,796 colorectal cancer cases and 7,770 controls to evaluate the association between cigarette smoking history and colorectal cancer risk, and to investigate potential effect modification by other risk factors. Results Current smokers (OR=1.26, 95% CI=1.11–1.43) and former smokers (OR=1.18, 95% CI=1.09–1.27), relative to never smokers, showed higher risks of colorectal cancer. Former smokers remained at higher colorectal cancer risk, relative to never smokers, for up to about 25 years after quitting. The impact of time since quitting varied by cancer subsite: the excess risk due to smoking decreased immediately after quitting for proximal colon and rectal cancer, but not until about 20 years post-quitting for distal colon cancer. Further, we observed borderline statistically significant additive interactions between smoking status and BMI (relative excess risk due to interaction [RERI]=0.15, 95% CI:−0.01–0.31, P=0.06) and significant additive interaction between smoking status and fruit consumption (RERI=0.16, 95% CI: 0.01–0.30, P=0.04). Conclusion Colorectal cancer risk remained increased for about 25 years after quitting smoking, and the pattern of decline in risk varied by cancer subsite. BMI and fruit intake modified the risk associated with smoking. Impact These results contribute to a better understanding of the mechanisms through which smoking impacts colorectal cancer etiology. PMID:23001243

  8. HPV type distribution in invasive cervical cancers in Italy: pooled analysis of three large studies

    PubMed Central

    2012-01-01

    Objective The aim of this study is to describe the prevalence of HPV types in invasive cervical cancers in Italy from 1996 to 2008. Methods A pooled analysis of the three largest case series typed to date was performed. HPV typing was performed on paraffin-embedded slices. Molecular analyses were performed in four laboratories. Multivariate analyses were performed to test the associations between calendar time, age, and geographical area and the proportion of types 16/18. Results Out of 574 cancers, 24 (4.2%) were HPV negative. HPV 16 and 18 were responsible for 74.4% (378/508) and 80.3% (49/61) of the squamous cancers and adenocarcinomas, respectively. Other frequent types were 31 (9.5%), 45 (6.4%), and 58 (3.3%) for squamous cancers and 45 (13.3%), 31, 35, and 58 (5.0%) for adenocarcinomas. The proportion of HPV 16 and/or 18 decreased with age (p-value for trend <0.03), while it increased in cancers diagnosed in more recent years (p-value for trend < 0.005). Conclusions The impact of HPV 16/18 vaccine on cervical cancer will be greater for early onset cancers. In vaccinated women, screening could be started at an older age without reducing protection. PMID:23110797

  9. FAMILY HISTORY OF CANCER: POOLED ANALYSIS IN THE INTERNATIONAL HEAD AND NECK CANCER EPIDEMIOLOGY (INHANCE) CONSORTIUM

    PubMed Central

    Negri, Eva; Boffetta, Paolo; Berthiller, Julien; Castellsague, Xavier; Curado, Maria Paula; Maso, Luigino Dal; Daudt, Alexander W.; Fabianova, Eleonora; Fernandez, Leticia; Wünsch-Filho, Victor; Franceschi, Silvia; Hayes, Richard B.; Herrero, Rolando; Koifman, Sergio; Lazarus, Philip; Lence, Juan J.; Levi, Fabio; Mates, Dana; Matos, Elena; Menezes, Ana; Muscat, Joshua; Eluf-Neto, Jose; Olshan, Andrew F.; Rudnai, Peter; Shangina, Oxana; Sturgis, Erich M.; Szeszenia-Dabrowska, Neonilia; Talamini, Renato; Wei, Qingyi; Winn, Deborah M.; Zaridze, David; Lissowska, Jolanta; Zhang, Zuo-Feng; Ferro, Gilles; Brennan, Paul; Vecchia, Carlo La; Hashibe, Mia

    2013-01-01

    Alcohol and tobacco consumption are well recognized risk factors for head and neck cancer (HNC). Evidence suggests that genetic predisposition may also play a role. Only a few epidemiologic studies, however, have considered the relation between HNC risk and family history of HNC and other cancers. We pooled individual- level data across 12 case-control studies including 8,967 HNC cases and 13,627 controls. We obtained pooled odds ratios (OR) using fixed and random effect models, and adjusting for potential confounding factors. All statistical tests were two-sided. A family history of HNC in first-degree relatives increased the risk of HNC (OR=1.7, 95% confidence interval, CI, 1.2-2.3). The risk was higher when the affected relative was a sibling (OR=2.2, 95% CI 1.6-3.1) rather than a parent (OR=1.5, 95% CI 1.1-1.8), and for more distal HNC anatomic sites (hypopharynx and larynx). The risk was also higher, or limited to, subjects exposed to tobacco. The OR rose to 7.2 (95% CI 5.5-9.5) among subjects with family history, who were alcohol and tobacco users. A weak but significant association (OR=1.1, 95% CI 1.0-1.2) emerged for family history of other tobacco-related neoplasms, particularly with laryngeal cancer (OR=1.3, 95% CI 1.1-1.5). No association was observed for family history of non-tobacco related neoplasms and the risk of HNC (OR=1.0, 95% CI 0.9-1.1). Familial factors play a role in the etiology of HNC. In both subjects with and without family history of HNC, avoidance of tobacco and alcohol exposure may be the best way to avoid HNC. PMID:18814262

  10. Cigarette smoking and risk of ovarian cancer: a pooled analysis of 21 case–control studies

    PubMed Central

    Faber, Mette T.; Kjær, Susanne K.; Dehlendorff, Christian; Chang-Claude, Jenny; Andersen, Klaus K.; Høgdall, Estrid; Webb, Penelope M.; Jordan, Susan J.; Rossing, Mary Anne; Doherty, Jennifer A.; Lurie, Galina; Thompson, Pamela J.; Carney, Michael E.; Goodman, Marc T.; Ness, Roberta B.; Modugnos, Francesmary; Edwards, Robert P.; Bunker, Clareann H.; Goode, Ellen L.; Fridley, Brooke L.; Vierkant, Robert A.; Larson, Melissa C.; Schildkraut, Joellen; Cramer, Daniel W.; Terry, Kathryn L.; Vitonis, Allison F.; Bandera, Elisa V.; Olson, Sara H.; King, Melony; Chandran, Urmila; Kiemeney, Lambertus A.; Massuger, Leon F. A. G.; van Altena, Anne M.; Vermeulen, Sita H.; Brinton, Louise; Wentzensen, Nicolas; Lissowska, Jolanta; Yang, Hannah P.; Moysich, Kirsten B.; Odunsi, Kunle; Kasza, Karin; Odunsi-Akanji, Oluwatosin; Song, Honglin; Pharaoh, Paul; Shah, Mitul; Whittemore, Alice S.; McGuire, Valerie; Sieh, Weiva; Sutphen, Rebecca; Menon, Usha; Gayther, Simon A.; Ramus, Susan J.; Gentry-Maharaj, Aleksandra; Pearce, Celeste Leigh; Wu, Anna H.; Pike, Malcolm C.; Risch, Harvey A.

    2013-01-01

    Purpose The majority of previous studies have observed an increased risk of mucinous ovarian tumors associated with cigarette smoking, but the association with other histological types is unclear. In a large pooled analysis, we examined the risk of epithelial ovarian cancer associated with multiple measures of cigarette smoking with a focus on characterizing risks according to tumor behavior and histology. Methods We used data from 21 case–control studies of ovarian cancer (19,066 controls, 11,972 invasive and 2,752 borderline cases). Study-specific odds ratios (OR) and 95 % confidence intervals (CI) were obtained from logistic regression models and combined into a pooled odds ratio using a random effects model. Results Current cigarette smoking increased the risk of invasive mucinous (OR = 1.31; 95 % CI: 1.03–1.65) and borderline mucinous ovarian tumors (OR = 1.83; 95 % CI: 1.39–2.41), while former smoking increased the risk of borderline serous ovarian tumors (OR = 1.30; 95 % CI: 1.12–1.50). For these histological types, consistent dose– response associations were observed. No convincing associations between smoking and risk of invasive serous and endometrioid ovarian cancer were observed, while our results provided some evidence of a decreased risk of invasive clear cell ovarian cancer. Conclusions Our results revealed marked differences in the risk profiles of histological types of ovarian cancer with regard to cigarette smoking, although the magnitude of the observed associations was modest. Our findings, which may reflect different etiologies of the histological types, add to the fact that ovarian cancer is a heterogeneous disease. PMID:23456270

  11. Polycyclic Aromatic Hydrocarbon–DNA Adducts and Breast Cancer: A Pooled Analysis

    PubMed Central

    GAMMON, MARILIE D.; SAGIV, SHARON K.; ENG, SYBIL M.; SHANTAKUMAR, SUMITRA; GAUDET, MIA M.; TEITELBAUM, SUSAN L.; BRITTON, JULIE A.; TERRY, MARY BETH; WANG, LIAN WEN; WANG, QIAO; STELLMAN, STEVE D.; BEYEA, JAN; HATCH, MAUREEN; KABAT, GEOFFREY C.; WOLFF, MARY S.; LEVIN, BRUCE; NEUGUT, ALFRED I.; SANTELLA, REGINA M.

    2007-01-01

    Polycyclic aromatic hydrocarbon (PAH)-DNA adducts have been associated with breast cancer in several small studies. The authors’ pooled analysis included 873 cases and 941 controls from a population-based case-control study. Competitive enzyme-linked immunosorbent assay in peripheral mononuclear cells was conducted in 2 rounds, and results were pooled on the basis of round-specific quantiles. The odds ratio for breast cancer was elevated in relation to detectable PAH-DNA adducts (1.29 as compared with non-detectable adduct levels; 95% confidence interval = 1.05, 1.58), but there was no apparent dose-response relationship with increasing quantiles. No consistent pattern emerged when the results were stratified by PAH sources (e.g., active cigarette smoking or PAH-containing foods), or when the cases were categorized by stage of disease or hormone receptor status. These data provide only modest support for an association between PAH-DNA adducts and breast cancer development. PMID:16789472

  12. Association of marijuana smoking with oropharyngeal and oral tongue cancers: Pooled analysis from the INHANCE Consortium

    PubMed Central

    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

    2013-01-01

    Background The incidence of oropharyngeal and oral tongue cancers have increased over the last twenty years which parallels increased use of marijuana among individuals born after 1950. Methods Pooled analysis of individual-level data from nine case-control studies from the U.S. 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. Results Compared with never marijuana smokers, ever marijuana smokers had an elevated risk of oropharyngeal (adjusted odds ratio [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 decreased with increasing frequency (ptrend=0.005), duration (ptrend=0.002), and joint-years of marijuana use (ptrend=0.004), and was reduced among never users tobacco and alcohol users. 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. Conclusions These results suggest that the association of marijuana use with Head and Neck Carcinoma may differ by tumor site. Impact The associations of marijuana use with oropharyngeal and oral tongue cancer are consistent with both possible pro- and anti-carcinogenic 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. PMID:24351902

  13. Infertility, fertility drugs, and ovarian cancer: a pooled analysis of case-control studies.

    PubMed

    Ness, Roberta B; Cramer, Daniel W; Goodman, Marc T; Kjaer, Susanne Krûger; Mallin, Kathy; Mosgaard, Berit Jul; Purdie, David M; Risch, Harvey A; Vergona, Ronald; Wu, Anna H

    2002-02-01

    Controversy surrounds the relations among infertility, fertility drug use, and the risk of ovarian cancer. The authors pooled interview data on infertility and fertility drug use from eight case-control studies conducted between 1989 and 1999 in the United States, Denmark, Canada, and Australia. Odds ratios and 95% confidence intervals were calculated, adjusting for age, race, family history of ovarian cancer, duration of oral contraception use, tubal ligation, gravidity, education, and site. Included in the analysis were 5,207 cases and 7,705 controls. Among nulligravid women, attempts for more than 5 years to become pregnant compared with attempts for less than 1 year increased the risk of ovarian cancer 2.67-fold (95% confidence interval (CI): 1.91, 3.74). Among nulliparous, subfertile women, neither any fertility drug use (odds ratio (OR) = 1.60, 95% CI: 0.90, 2.87) nor more than 12 months of use (OR = 1.54, 95% CI: 0.45, 5.27) was associated with ovarian cancer. Fertility drug use in nulligravid women was associated with borderline serous tumors (OR = 2.43, 95% CI: 1.01, 5.88) but not with any invasive histologic subtypes. Endometriosis (OR = 1.73, 95% CI: 1.10, 2.71) and unknown cause of infertility (OR = 1.19, 95% CI: 1.00, 1.40) increased cancer risk. These data suggest a role for specific biologic causes of infertility, but not for fertility drugs in overall risk for ovarian cancer. PMID:11821246

  14. Determinants of Epstein-Barr virus-positive gastric cancer: an international pooled analysis

    PubMed Central

    Camargo, M C; Murphy, G; Koriyama, C; Pfeiffer, R M; Kim, W H; Herrera-Goepfert, R; Corvalan, A H; Carrascal, E; Abdirad, A; Anwar, M; Hao, Z; Kattoor, J; Yoshiwara-Wakabayashi, E; Eizuru, Y; Rabkin, C S; Akiba, S

    2011-01-01

    Background: Meta-analyses of the published literature indicate that about 9% of gastric cancers contain Epstein-Barr virus (EBV), with consistent and significant differences by sex and anatomic subsite. This study aimed to identify additional determinants of EBV positivity and their joint effects. Methods: From 15 international populations with consistent laboratory testing for EBV, we pooled individual-level data for 5081 gastric cancer cases including information on age, sex, subsite, histologic type, diagnostic stage, geographic region, and period of diagnosis. First, we combined population-specific EBV prevalence estimates using random effects meta-analysis. We then aggregated individual-level data to estimate odds ratios of EBV positivity in relation to all variables, accounting for within-population clustering. Results: In unadjusted analyses, EBV positivity was significantly higher in males, young subjects, non-antral subsites, diffuse-type histology, and in studies from the Americas. Multivariable analyses confirmed significant associations with histology and region. Sex interacted with age (P=0.003) and subsite (P=0.002) such that male predominance decreased with age for both subsites. The positivity of EBV was not significantly associated with either stage or time period. Conclusion: Aggregating individual-level data provides additional information over meta-analyses. Distinguishing histologic and geographic features as well as interactions among age, sex, and subsite further support classification of EBV-associated gastric cancer as a distinct aetiologic entity. PMID:21654677

  15. Lung cancer risk among bricklayers in a pooled analysis of case–control studies

    PubMed Central

    Consonni, Dario; Matteis, Sara De; Pesatori, Angela C; Bertazzi, Pier Alberto; Olsson, Ann C; Kromhout, Hans; Peters, Susan; Vermeulen, Roel CH; Pesch, Beate; Brüning, Thomas; Kendzia, Benjamin; Behrens, Thomas; Stücker, Isabelle; Guida, Florence; Wichmann, Heinz-Erich; Brüske, Irene; Landi, Maria Teresa; Caporaso, Neil E; Gustavsson, Per; Plato, Nils; Tse, Lap Ah; Yu, Ignatius Tak-sun; Jöckel, Karl-Heinz; Ahrens, Wolfgang; Pohlabeln, Hermann; Merletti, Franco; Richiardi, Lorenzo; Simonato, Lorenzo; Forastiere, Francesco; Siemiatycki, Jack; Parent, Marie-Élise; Tardón, Adonina; Boffetta, Paolo; Zaridze, David; Chen, Ying; Field, John K; 't Mannetje, Andrea; Pearce, Neil; McLaughlin, John; Demers, Paul; Lissowska, Jolanta; Szeszenia-Dabrowska, Neonila; Bencko, Vladimir; Foretova, Lenka; Janout, Vladimir; Rudnai, Peter; Fabiánová, Eleonóra; Stanescu Dumitru, Rodica; Bueno-de-Mesquita, H B(as); Schüz, Joachim; Straif, Kurt

    2015-01-01

    Bricklayers may be exposed to several lung carcinogens, including crystalline silica and asbestos. Previous studies that analyzed lung cancer risk among these workers had several study design limitations. We examined lung cancer risk among bricklayers within SYNERGY, a large international pooled analysis of case–control studies on lung cancer and the joint effects of occupational carcinogens. For men ever employed as bricklayers we estimated odds ratios (OR) and 95% confidence intervals (CI) adjusted for study center, age, lifetime smoking history and employment in occupations with exposures to known or suspected lung carcinogens. Among 15,608 cases and 18,531 controls, there were 695 cases and 469 controls who had ever worked as bricklayers (OR: 1.47; 95% CI: 1.28–1.68). In studies using population controls the OR was 1.55 (95% CI: 1.32–1.81, 540/349 cases/controls), while it was 1.24 (95% CI: 0.93–1.64, 155/120 cases/controls) in hospital-based studies. There was a clear positive trend with length of employment (p < 0.001). The relative risk was higher for squamous (OR: 1.68, 95% CI: 1.42–1.98, 309 cases) and small cell carcinomas (OR: 1.78, 95% CI: 1.44–2.20, 140 cases), than for adenocarcinoma (OR: 1.17, 95% CI: 0.95–1.43, 150 cases) (p-homogeneity: 0.0007). ORs were still elevated after additional adjustment for education and in analyses using blue collar workers as referents. This study provided robust evidence of increased lung cancer risk in bricklayers. Although non-causal explanations cannot be completely ruled out, the association is plausible in view of the potential for exposure to several carcinogens, notably crystalline silica and to a lesser extent asbestos. What's new? In their work, bricklayers can be exposed to various airborne carcinogens, including crystalline silica and asbestos. Previous studies of cancer risk have not accounted for full employment history or smoking status, and failed to establish a firm relationship between bricklaying and lung cancer. In this study, the authors used data from the largest collection of case-control studies on lung cancer with complete occupational and smoking history existing today, the SYNERGY project. They found clear evidence that lung cancer risk increases in proportion to the length of time spent working as a bricklayer, paving the way for better protection and compensation for those in this occupation. PMID:24861979

  16. 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. PMID:25930054

  17. Lung cancer risk among bricklayers in a pooled analysis of case-control studies.

    PubMed

    Consonni, Dario; De Matteis, Sara; Pesatori, Angela C; Bertazzi, Pier Alberto; Olsson, Ann C; Kromhout, Hans; Peters, Susan; Vermeulen, Roel C H; Pesch, Beate; Brüning, Thomas; Kendzia, Benjamin; Behrens, Thomas; Stücker, Isabelle; Guida, Florence; Wichmann, Heinz-Erich; Brüske, Irene; Landi, Maria Teresa; Caporaso, Neil E; Gustavsson, Per; Plato, Nils; Tse, Lap Ah; Yu, Ignatius Tak-Sun; Jöckel, Karl-Heinz; Ahrens, Wolfgang; Pohlabeln, Hermann; Merletti, Franco; Richiardi, Lorenzo; Simonato, Lorenzo; Forastiere, Francesco; Siemiatycki, Jack; Parent, Marie-Élise; Tardón, Adonina; Boffetta, Paolo; Zaridze, David; Chen, Ying; Field, John K; 't Mannetje, Andrea; Pearce, Neil; McLaughlin, John; Demers, Paul; Lissowska, Jolanta; Szeszenia-Dabrowska, Neonila; Bencko, Vladimir; Foretova, Lenka; Janout, Vladimir; Rudnai, Peter; Fabiánová, Eleonóra; Stanescu Dumitru, Rodica; Bueno-de-Mesquita, H Bas; Schüz, Joachim; Straif, Kurt

    2015-01-15

    Bricklayers may be exposed to several lung carcinogens, including crystalline silica and asbestos. Previous studies that analyzed lung cancer risk among these workers had several study design limitations. We examined lung cancer risk among bricklayers within SYNERGY, a large international pooled analysis of case-control studies on lung cancer and the joint effects of occupational carcinogens. For men ever employed as bricklayers we estimated odds ratios (OR) and 95% confidence intervals (CI) adjusted for study center, age, lifetime smoking history and employment in occupations with exposures to known or suspected lung carcinogens. Among 15,608 cases and 18,531 controls, there were 695 cases and 469 controls who had ever worked as bricklayers (OR: 1.47; 95% CI: 1.28-1.68). In studies using population controls the OR was 1.55 (95% CI: 1.32-1.81, 540/349 cases/controls), while it was 1.24 (95% CI: 0.93-1.64, 155/120 cases/controls) in hospital-based studies. There was a clear positive trend with length of employment (p < 0.001). The relative risk was higher for squamous (OR: 1.68, 95% CI: 1.42-1.98, 309 cases) and small cell carcinomas (OR: 1.78, 95% CI: 1.44-2.20, 140 cases), than for adenocarcinoma (OR: 1.17, 95% CI: 0.95-1.43, 150 cases) (p-homogeneity: 0.0007). ORs were still elevated after additional adjustment for education and in analyses using blue collar workers as referents. This study provided robust evidence of increased lung cancer risk in bricklayers. Although non-causal explanations cannot be completely ruled out, the association is plausible in view of the potential for exposure to several carcinogens, notably crystalline silica and to a lesser extent asbestos. PMID:24861979

  18. Circulating Carotenoids and Risk of Breast Cancer: Pooled Analysis of Eight Prospective Studies

    PubMed Central

    2012-01-01

    Background Carotenoids, micronutrients in fruits and vegetables, may reduce breast cancer risk. Most, but not all, past studies of circulating carotenoids and breast cancer have found an inverse association with at least one carotenoid, although the specific carotenoid has varied across studies. Methods We conducted a pooled analysis of eight cohort studies comprising more than 80% of the world’s published prospective data on plasma or serum carotenoids and breast cancer, including 3055 case subjects and 3956 matched control subjects. To account for laboratory differences and examine population differences across studies, we recalibrated participant carotenoid levels to a common standard by reassaying 20 plasma or serum samples from each cohort together at the same laboratory. Using conditional logistic regression, adjusting for several breast cancer risk factors, we calculated relative risks (RRs) and 95% confidence intervals (CIs) using quintiles defined among the control subjects from all studies. All P values are two-sided. Results Statistically significant inverse associations with breast cancer were observed for α-carotene (top vs bottom quintile RR = 0.87, 95% CI = 0.71 to 1.05, Ptrend = .04), β-carotene (RR = 0.83, 95% CI = 0.70 to 0.98, Ptrend = .02), lutein+zeaxanthin (RR = 0.84, 95% CI = 0.70 to 1.01, Ptrend = .05), lycopene (RR = 0.78, 95% CI = 0.62 to 0.99, Ptrend = .02), and total carotenoids (RR = 0.81, 95% CI = 0.68 to 0.96, Ptrend = .01). β-Cryptoxanthin was not statistically significantly associated with risk. Tests for heterogeneity across studies were not statistically significant. For several carotenoids, associations appeared stronger for estrogen receptor negative (ER−) than for ER+ tumors (eg, β-carotene: ER−: top vs bottom quintile RR = 0.52, 95% CI = 0.36 to 0.77, Ptrend = .001; ER+: RR = 0.83, 95% CI = 0.66 to 1.04, Ptrend = .06; Pheterogeneity = .01). Conclusions This comprehensive prospective analysis suggests women with higher circulating levels of α-carotene, β-carotene, lutein+zeaxanthin, lycopene, and total carotenoids may be at reduced risk of breast cancer. PMID:23221879

  19. Intake of Fruits and Vegetables and Risk of Pancreatic Cancer in a Pooled Analysis of 14 Cohort Studies

    PubMed Central

    Koushik, Anita; Spiegelman, Donna; Albanes, Demetrius; Anderson, Kristin E.; Bernstein, Leslie; van den Brandt, Piet A.; Bergkvist, Leif; English, Dallas R.; Freudenheim, Jo L.; Fuchs, Charles S.; Genkinger, Jeanine M.; Giles, Graham G.; Goldbohm, R. Alexandra; Horn-Ross, Pamela L.; Männistö, Satu; McCullough, Marjorie L.; Millen, Amy E.; Miller, Anthony B.; Robien, Kim; Rohan, Thomas E.; Schatzkin, Arthur; Shikany, James M.; Stolzenberg-Solomon, Rachael Z.; Willett, Walter C.; Wolk, Alicja; Ziegler, Regina G.; Smith-Warner, Stephanie A.

    2012-01-01

    Fruit and vegetable intake may protect against pancreatic cancer, since fruits and vegetables are rich in potentially cancer-preventive nutrients. Most case-control studies have found inverse associations between fruit and vegetable intake and pancreatic cancer risk, although bias due to reporting error cannot be ruled out. In most prospective studies, inverse associations have been weaker and imprecise because of small numbers of cases. The authors examined fruit and vegetable intake in relation to pancreatic cancer risk in a pooled analysis of 14 prospective studies from North America, Europe, and Australia (study periods between 1980 and 2005). Relative risks and 2-sided 95% confidence intervals were estimated separately for the 14 studies using the Cox proportional hazards model and were then pooled using a random-effects model. Of 862,584 men and women followed for 7−20 years, 2,212 developed pancreatic cancer. The pooled multivariate relative risks of pancreatic cancer per 100-g/day increase in intake were 1.01 (95% confidence interval (CI): 0.99, 1.03) for total fruits and vegetables, 1.01 (95% CI: 0.99, 1.03) for total fruits, and 1.02 (95% CI: 0.99, 1.06) for total vegetables. Associations were similar for men and women separately and across studies. These results suggest that fruit and vegetable intake during adulthood is not associated with a reduced pancreatic cancer risk. PMID:22875754

  20. Thyroid Cancer after Childhood Exposure to External Radiation: An Updated Pooled Analysis of 12 Studies.

    PubMed

    Veiga, Lene H S; Holmberg, Erik; Anderson, Harald; Pottern, Linda; Sadetzki, Siegal; Adams, M Jacob; Sakata, Ritsu; Schneider, Arthur B; Inskip, Peter; Bhatti, Parveen; Johansson, Robert; Neta, Gila; Shore, Roy; de Vathaire, Florent; Damber, Lena; Kleinerman, Ruth; Hawkins, Michael M; Tucker, Margaret; Lundell, Marie; Lubin, Jay H

    2016-05-01

    Studies have causally linked external thyroid radiation exposure in childhood with thyroid cancer. In 1995, investigators conducted relative risk analyses of pooled data from seven epidemiologic studies. Doses were mostly <10 Gy, although childhood cancer therapies can result in thyroid doses >50 Gy. We pooled data from 12 studies of thyroid cancer patients who were exposed to radiation in childhood (ages <20 years), more than doubling the data, including 1,070 (927 exposed) thyroid cancers and 5.3 million (3.4 million exposed) person-years. Relative risks increased supralinearly through 2-4 Gy, leveled off between 10-30 Gy and declined thereafter, remaining significantly elevated above 50 Gy. There was a significant relative risk trend for doses <0.10 Gy (P < 0.01), with no departure from linearity (P = 0.36). We observed radiogenic effects for both papillary and nonpapillary tumors. Estimates of excess relative risk per Gy (ERR/Gy) were homogeneous by sex (P = 0.35) and number of radiation treatments (P = 0.84) and increased with decreasing age at the time of exposure. The ERR/Gy estimate was significant within ten years of radiation exposure, 2.76 (95% CI, 0.94-4.98), based on 42 exposed cases, and remained elevated 50 years and more after exposure. Finally, exposure to chemotherapy was significantly associated with thyroid cancer, with results supporting a nonsynergistic (additive) association with radiation. PMID:27128740

  1. Intakes of coffee, tea, milk, soda and juice and renal cell cancer in a pooled analysis of 13 prospective studies.

    PubMed

    Lee, Jung Eun; Hunter, David J; Spiegelman, Donna; Adami, Hans-Olov; Bernstein, Leslie; van den Brandt, Piet A; Buring, Julie E; Cho, Eunyoung; English, Dallas; Folsom, Aaron R; Freudenheim, Jo L; Gile, Graham G; Giovannucci, Edward; Horn-Ross, Pamela L; Leitzmann, Michael; Marshall, James R; Mnnist, Satu; McCullough, Marjorie L; Miller, Anthony B; Parker, Alexander S; Pietinen, Pirjo; Rodriguez, Carmen; Rohan, Thomas E; Schatzkin, Arthur; Schouten, Leo J; Willett, Walter C; Wolk, Alicja; Zhang, Shumin M; Smith-Warner, Stephanie A

    2007-11-15

    Specific beverage intake may be associated with the risk of renal cell cancer through a diluting effect of carcinogens, alterations of hormone levels, or other changes in the renal tubular environment, but few prospective studies have examined these associations. We evaluated the associations between coffee, tea, milk, soda and fruit and vegetable juice intakes and renal cell cancer risk in a pooled analysis of 13 prospective studies (530,469 women and 244,483 men). Participants completed a validated food-frequency questionnaire at baseline. Using the primary data, the study-specific relative risks (RRs) were calculated and then pooled using a random effects model. A total of 1,478 incident renal cell cancer cases were identified during a follow-up of 7-20 years across studies. Coffee consumption was associated with a modestly lower risk of renal cell cancer (pooled multivariate RR for 3 or more 8 oz (237 ml) cups/day versus less than one 8 oz (237 ml) cup/day = 0.84; 95% CI = 0.67-1.05; p value, test for trend = 0.22). Tea consumption was also inversely associated with renal cell cancer risk (pooled multivariate RR for 1 or more 8 oz (237 ml) cups/day versus nondrinkers = 0.85; 95% CI = 0.71-1.02; pvalue, test for trend = 0.04). No clear associations were observed for milk, soda or juice. Our findings provide strong evidence that neither coffee nor tea consumption increases renal cell cancer risk. Instead, greater consumption of coffee and tea may be associated with a lower risk of renal cell cancer. (c) 2007 Wiley-Liss, Inc. PMID:17583573

  2. Tubal ligation and risk of ovarian cancer subtypes: a pooled analysis of case-control studies

    PubMed Central

    Sieh, Weiva; Salvador, Shannon; McGuire, Valerie; Weber, Rachel Palmieri; Terry, Kathryn L; Rossing, Mary Anne; Risch, Harvey; Wu, Anna H; Webb, Penelope M; Moysich, Kirsten; Doherty, Jennifer A; Felberg, Anna; Miller, Dianne; Jordan, Susan J; Goodman, Marc T; Lurie, Galina; Chang-Claude, Jenny; Rudolph, Anja; Kjær, Susanne Krüger; Jensen, Allan; Høgdall, Estrid; Bandera, Elisa V; Olson, Sara H; King, Melony G; Rodriguez-Rodriguez, Lorna; Kiemeney, Lambertus A; Marees, Tamara; Massuger, Leon F; van Altena, Anne M; Ness, Roberta B; Cramer, Daniel W; Pike, Malcolm C; Pearce, Celeste Leigh; Berchuck, Andrew; Schildkraut, Joellen M; Whittemore, Alice S

    2013-01-01

    Background Tubal ligation is a protective factor for ovarian cancer, but it is unknown whether this protection extends to all invasive histological subtypes or borderline tumors. We undertook an international collaborative study to examine the association between tubal ligation and ovarian cancer subtypes. Methods We pooled primary data from 13 population-based case-control studies, including 10 157 patients with ovarian cancer (7942 invasive; 2215 borderline) and 13 904 control women. Invasive cases were analysed by histological type, grade and stage, and borderline cases were analysed by histological type. Pooled odds ratios were estimated using conditional logistic regression to match on site, race/ethnicity and age categories, and to adjust for age, oral contraceptive use duration and number of full-term births. Results Tubal ligation was associated with significantly reduced risks of invasive serous (OR, 0.81; 95% CI, 0.74-0.89; P < 0.001), endometrioid (OR, 0.48; 95% CI, 0.40-0.59; P < 0.001), clear cell (OR, 0.52; 95% CI, 0.40-0.67; P < 0.001) and mucinous (OR, 0.68; 95% CI, 0.52-0.89; P = 0.005) cancers. The magnitude of risk reduction was significantly greater for invasive endometrioid (P < 0.0001) and clear cell (P = 0.0018) than for serous cancer. No significant associations were found with borderline serous or mucinous tumours. Conclusions We found that the protective effects of tubal ligation on ovarian cancer risk were subtype-specific. These findings provide insights into distinct aetiologies of ovarian cancer subtypes and mechanisms underlying the protective effects of tubal ligation. PMID:23569193

  3. The association between polymorphisms in the leptin receptor gene and risk of breast cancer: a systematic review and pooled analysis.

    PubMed

    Wang, Li-qiang; Shen, Wei; Xu, Lan; Chen, Min-Bin; Gong, Ting; Lu, Pei-Hua; Tao, Guo-Qing

    2012-11-01

    Many epidemiological studies have found that leptin correlates to body fat extent and breast cancer. Leptin exerts its physiological action through the leptin receptor (LEPR). However, published data on the association between LEPR alleles and breast cancer occurrence have led to in contradictory results. A total of 10 studies were identified to the meta-analysis, including 4,644 cases and 5,485 controls for LEPR rs1137101 polymorphism, 5 studies with 2,759 cases and 4,464 controls for rs1137100 polymorphism, and 2 studies for rs8051542, rs8051542, and rs8051542 polymorphisms. The pooled odds ratios (OR) with 95% confidence intervals (CI) for breast cancer risk associated with LEPR genotypes were estimated. Elevated breast cancer risk was associated with LEPR rs1137101 polymorphism when all studies were pooled in the meta-analysis (allele contrast model: OR=0.71, 95% CI=0.551-0.997). In the stratified analysis by ethnicity, significantly increased risks were also found among Asians for allele contrast model (OR 0.414, 95% CI 0.312-0.550) and dominant model (OR 0.537, 95% CI 0.370-0.781); for Africans, significantly increased risks were also found for allele contrast model (OR 0.716, 95% CI 0.595-0.861), homozygote codominant (OR 0.537, 95% CI 0.370-0.781) and dominant model (OR 1.595, 95% CI 1.207-2.108). And significantly elevated breast cancer risk was associated with LEPR rs1137100 polymorphism for allele contrast (OR=0.666, 95% CI=0.603-0.720) and homozygote codominant models (OR=0.344, 95% CI=0.282-0.421). For LEPR rs8179183, rs4655537, and rs3762274 polymorphisms, no significant associations were detected in all comparison models. This pooled analysis suggested that rs1137101 and rs1137100 polymorphisms were significantly correlated with breast cancer risk and the A allele of LEPR rs1137101 variant and the G allele of LEPR rs1137100 variant were low-penetrant risk factors for developing breast cancer. Further, no significant associations existed between LEPR rs8179183, rs4655537, and rs3762274 polymorphisms and risk of breast cancer. PMID:22983835

  4. 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

  5. Lung Cancer Risk Among Hairdressers: A Pooled Analysis of Case-Control Studies Conducted Between 1985 and 2010

    PubMed Central

    Olsson, Ann C.; Xu, Yiwen; Schüz, Joachim; Vlaanderen, Jelle; Kromhout, Hans; Vermeulen, Roel; Peters, Susan; Stücker, Isabelle; Guida, Florence; Brüske, Irene; Wichmann, Heinz-Erich; Consonni, Dario; Landi, Maria Teresa; Caporaso, Neil; Tse, Lap Ah; Yu, Ignatius Tak-sun; Siemiatycki, Jack; Richardson, Lesley; Mirabelli, Dario; Richiardi, Lorenzo; Simonato, Lorenzo; Gustavsson, Per; Plato, Nils; Jöckel, Karl-Heinz; Ahrens, Wolfgang; Pohlabeln, Hermann; Tardón, Adonina; Zaridze, David; Marcus, Michael W.; ‘t Mannetje, Andrea; Pearce, Neil; McLaughlin, John; Demers, Paul; Szeszenia-Dabrowska, Neonila; Lissowska, Jolanta; Rudnai, Peter; Fabianova, Eleonora; Dumitru, Rodica Stanescu; Bencko, Vladimir; Foretova, Lenka; Janout, Vladimir; Boffetta, Paolo; Fortes, Cristina; Bueno-de-Mesquita, Bas; Kendzia, Benjamin; Behrens, Thomas; Pesch, Beate; Brüning, Thomas; Straif, Kurt

    2013-01-01

    Increased lung cancer risks among hairdressers were observed in large registry-based cohort studies from Scandinavia, but these studies could not adjust for smoking. Our objective was to evaluate the lung cancer risk among hairdressers while adjusting for smoking and other confounders in a pooled database of 16 case-control studies conducted in Europe, Canada, China, and New Zealand between 1985 and 2010 (the Pooled Analysis of Case-Control Studies on the Joint Effects of Occupational Carcinogens in the Development of Lung Cancer). Lifetime occupational and smoking information was collected through interviews with 19,369 cases of lung cancer and 23,674 matched population or hospital controls. Overall, 170 cases and 167 controls had ever worked as hairdresser or barber. The odds ratios for lung cancer in women were 1.65 (95% confidence interval (CI): 1.16, 2.35) without adjustment for smoking and 1.12 (95% CI: 0.75, 1.68) with adjustment for smoking; however, women employed before 1954 also experienced an increased lung cancer risk after adjustment for smoking (odds ratio = 2.66, 95% CI: 1.09, 6.47). The odds ratios in male hairdressers/barbers were generally not elevated, except for an increased odds ratio for adenocarcinoma in long-term barbers (odds ratio = 2.20, 95% CI: 1.02, 4.77). Our results suggest that the increased lung cancer risks among hairdressers are due to their smoking behavior; single elevated risk estimates should be interpreted with caution and need replication in other studies. PMID:24068200

  6. Lung cancer risk among hairdressers: a pooled analysis of case-control studies conducted between 1985 and 2010.

    PubMed

    Olsson, Ann C; Xu, Yiwen; Schüz, Joachim; Vlaanderen, Jelle; Kromhout, Hans; Vermeulen, Roel; Peters, Susan; Stücker, Isabelle; Guida, Florence; Brüske, Irene; Wichmann, Heinz-Erich; Consonni, Dario; Landi, Maria Teresa; Caporaso, Neil; Tse, Lap Ah; Yu, Ignatius Tak-sun; Siemiatycki, Jack; Richardson, Lesley; Mirabelli, Dario; Richiardi, Lorenzo; Simonato, Lorenzo; Gustavsson, Per; Plato, Nils; Jöckel, Karl-Heinz; Ahrens, Wolfgang; Pohlabeln, Hermann; Tardón, Adonina; Zaridze, David; Marcus, Michael W; 't Mannetje, Andrea; Pearce, Neil; McLaughlin, John; Demers, Paul; Szeszenia-Dabrowska, Neonila; Lissowska, Jolanta; Rudnai, Peter; Fabianova, Eleonora; Dumitru, Rodica Stanescu; Bencko, Vladimir; Foretova, Lenka; Janout, Vladimir; Boffetta, Paolo; Fortes, Cristina; Bueno-de-Mesquita, Bas; Kendzia, Benjamin; Behrens, Thomas; Pesch, Beate; Brüning, Thomas; Straif, Kurt

    2013-11-01

    Increased lung cancer risks among hairdressers were observed in large registry-based cohort studies from Scandinavia, but these studies could not adjust for smoking. Our objective was to evaluate the lung cancer risk among hairdressers while adjusting for smoking and other confounders in a pooled database of 16 case-control studies conducted in Europe, Canada, China, and New Zealand between 1985 and 2010 (the Pooled Analysis of Case-Control Studies on the Joint Effects of Occupational Carcinogens in the Development of Lung Cancer). Lifetime occupational and smoking information was collected through interviews with 19,369 cases of lung cancer and 23,674 matched population or hospital controls. Overall, 170 cases and 167 controls had ever worked as hairdresser or barber. The odds ratios for lung cancer in women were 1.65 (95% confidence interval (CI): 1.16, 2.35) without adjustment for smoking and 1.12 (95% CI: 0.75, 1.68) with adjustment for smoking; however, women employed before 1954 also experienced an increased lung cancer risk after adjustment for smoking (odds ratio = 2.66, 95% CI: 1.09, 6.47). The odds ratios in male hairdressers/barbers were generally not elevated, except for an increased odds ratio for adenocarcinoma in long-term barbers (odds ratio = 2.20, 95% CI: 1.02, 4.77). Our results suggest that the increased lung cancer risks among hairdressers are due to their smoking behavior; single elevated risk estimates should be interpreted with caution and need replication in other studies. PMID:24068200

  7. Risk of lung cancer and consumption of vegetables and fruit in Japanese: A pooled analysis of cohort studies in Japan.

    PubMed

    Wakai, Kenji; Sugawara, Yumi; Tsuji, Ichiro; Tamakoshi, Akiko; Shimazu, Taichi; Matsuo, Keitaro; Nagata, Chisato; Mizoue, Tetsuya; Tanaka, Keitaro; Inoue, Manami; Tsugane, Shoichiro; Sasazuki, Shizuka

    2015-08-01

    International reviews have concluded that consumption of fruit and vegetables might decrease the risk of lung cancer. However, the relevant epidemiological evidence still remains insufficient in Japan. Therefore, we performed a pooled analysis of data from four population-based cohort studies in Japan with >200 000 participants and >1700 lung cancer cases. We computed study-specific hazard ratios by quintiles of vegetable and fruit consumption as assessed by food frequency questionnaires. Summary hazard ratios were estimated by pooling the study-specific hazard ratios with a fixed-effect model. In men, we found inverse associations between fruit consumption and the age-adjusted and area-adjusted risk of mortality or incidence of lung cancer. However, the associations were largely attenuated after adjustment for smoking and energy intake. The significant decrease in risk among men remained only for a moderate level of fruit consumption; the lowest summary hazard ratios were found in the third quintile of intake (mortality: 0.71, 95% confidence interval 0.60-0.84; incidence: 0.83, 95% confidence interval 0.70-0.98). This decrease in risk was mainly detected in ever smokers. Conversely, vegetable intake was positively correlated with the risk of incidence of lung cancer after adjustment for smoking and energy intake in men (trend P, 0.024); the summary hazard ratio for the highest quintile was 1.26 (95% confidence interval 1.05-1.50). However, a similar association was not detected for mortality from lung cancer. In conclusion, a moderate level of fruit consumption is associated with a decreased risk of lung cancer in men among the Japanese population. PMID:26033436

  8. Thyroid cancer after exposure to external radiation: A pooled analysis of seven studies

    SciTech Connect

    Ron, E.; Lubin, J.H.; Pottern, L.M.; Tucker, M.A.; Boice, J.D. Jr.; Shore, R.E.; Mabuchi, Kiyohiko; Modan, B.; Schneider, A.B.

    1995-03-01

    The thyroid gland of children is especially vulnerable to the carcinogenic action of ionizing radiation. To provide insights into various modifying influences on risk, seven major studies with organ doses to individual subjects were evaluated. Five cohort studies (atomic bomb survivors, children treated for tinea capitis, two studies of children irradiated for enlarged tonsils, and infants irradiated for an enlarged thymus gland) and two case-control studies (patients with cervical cancer and childhood cancer) were studied. The combined studies include almost 120,000 people (approximately 58,000 exposed to a wide range of doses and 61,000 nonexposed subjects), nearly 700 thyroid cancers and 3,000,000 person years of follow-up. For persons exposed to radiation before age 15 years, linearity best described the dose response, even down to 0.10 Gy. At the highest doses (>10 Gy), associated with cancer therapy, there appeared to be a decrease or leveling of risk. For childhood exposures, the pooled excess relative risk per Gy (ERR/Gy) was 7.7 (95% CI = 2.1, 28.7) and the excess absolute risk per 10{sup 4} PY Gy (EAR/10{sup 4} PY Gy) was 4.4 (95% CI = 1.9, 10.1). The attributable risk percent (AR%) at 1 Gy was 88%. However, these summary estimates were affected strongly by age at exposure even within this limited age range. The ERR was greater (P = 0.07) for females than males, but the findings from the individual studies were not consistent. The EAR was higher among women, reflecting their higher rate of naturally occurring thyroid cancer. The distribution of ERR over time followed neither a simple multiplicative nor an additive pattern in relation to background occurrence. Only two cases were seen within 5 years of exposure. The ERR began to decline about 30 years after exposure but was still elevated at 40 years. Risk also decreased significantly with increasing age at exposure, with little risk apparent after age 20 years. 56 refs., 5 figs., 8 tabs.

  9. 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. PMID:26275006

  10. 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

  11. 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. PMID:23820785

  12. γ-Glutamyltransferase and Breast Cancer Risk Beyond Alcohol Consumption and Other Life Style Factors – A Pooled Cohort Analysis

    PubMed Central

    Preyer, Oliver; Johansen, Dorthe; Holly, Jessica; Stocks, Tanja; Pompella, Alfonso; Nagel, Gabriele; Concin, Hans; Ulmer, Hanno; Concin, Nicole

    2016-01-01

    Objective Elevated γ-Glutamyltransferase serum levels are associated with increased risk of overall cancer incidence and several site-specific malignancies. In the present prospective study we report on the associations of serum γ-Glutamyltransferase with the risk of breast cancer in a pooled population-based cohort considering established life style risk factors. Methods Two cohorts were included in the present study, i.e. the Vorarlberg (n = 97,268) and the Malmoe cohort (n = 9,790). Cox proportional hazards regression models were fitted to estimate HRs for risk of breast cancer. Results In multivariate analysis adjusted for age, body mass index and smoking status, women with γ-Glutamyltransferase levels in the top quartile were at significantly higher risk for breast cancer compared to women in the lowest quartile (HR 1.21, 95% CI 1.09 to 1.35; p = 0.005). In the subgroup analysis of the Malmoe cohort, γ-Glutamyltransferase remained an independent risk factor for breast cancer when additionally considering alcohol intake. A statistically significant increase in risk was seen in women with γ-Glutamyltransferase-levels in the top versus lowest quartile in a multivariate model adjusted for age, body mass index, smoking status, physical activity, parity, oral contraceptive-use and alcohol consumption (HR 1.37, 95% CI 1.11–1.69, p = 0.006). Conclusion Our findings identified γ-Glutamyltransferase as an independent risk factor for breast cancer beyond the consumption of alcohol and other life style risk factors. PMID:26863311

  13. Association between endometriosis and risk of histological subtypes of ovarian cancer: a pooled analysis of case–control studies

    PubMed Central

    Pearce, Celeste Leigh; Templeman, Claire; Rossing, Mary Anne; Lee, Alice; Near, Aimee M; Webb, Penelope M; Nagle, Christina M; Doherty, Jennifer A; Cushing-Haugen, Kara L; Wicklund, Kristine G; Chang-Claude, Jenny; Hein, Rebecca; Lurie, Galina; Wilkens, Lynne R; Carney, Michael E; Goodman, Marc T; Moysich, Kirsten; Kjaer, Susanne K; Hogdall, Estrid; Jensen, Allan; Goode, Ellen L; Fridley, Brooke L; Larson, Melissa C; Schildkraut, Joellen M; Palmieri, Rachel T; Cramer, Daniel W; Terry, Kathryn L; Vitonis, Allison F; Titus, Linda J; Ziogas, Argyrios; Brewster, Wendy; Anton-Culver, Hoda; Gentry-Maharaj, Alexandra; Ramus, Susan J; Anderson, A Rebecca; Brueggmann, Doerthe; Fasching, Peter A; Gayther, Simon A; Huntsman, David G; Menon, Usha; Ness, Roberta B; Pike, Malcolm C; Risch, Harvey; Wu, Anna H; Berchuck, Andrew

    2012-01-01

    Summary Background Endometriosis is a risk factor for epithelial ovarian cancer; however, whether this risk extends to all invasive histological subtypes or borderline tumours is not clear. We undertook an international collaborative study to assess the association between endometriosis and histological subtypes of ovarian cancer. Methods Data from 13 ovarian cancer case–control studies, which were part of the Ovarian Cancer Association Consortium, were pooled and logistic regression analyses were undertaken to assess the association between self-reported endometriosis and risk of ovarian cancer. Analyses of invasive cases were done with respect to histological subtypes, grade, and stage, and analyses of borderline tumours by histological subtype. Age, ethnic origin, study site, parity, and duration of oral contraceptive use were included in all analytical models. Findings 13 226 controls and 7911 women with invasive ovarian cancer were included in this analysis. 818 and 738, respectively, reported a history of endometriosis. 1907 women with borderline ovarian cancer were also included in the analysis, and 168 of these reported a history of endometriosis. Self-reported endometriosis was associated with a significantly increased risk of clear-cell (136 [20·2%] of 674 cases vs 818 [6·2%] of 13 226 controls, odds ratio 3·05, 95% CI 2·43–3·84, p<0·0001), low-grade serous (31 [9·2%] of 336 cases, 2·11, 1·39–3·20, p<0·0001), and endometrioid invasive ovarian cancers (169 [13·9%] of 1220 cases, 2·04, 1·67–2·48, p<0·0001). No association was noted between endometriosis and risk of mucinous (31 [6·0%] of 516 cases, 1·02, 0·69–1·50, p=0·93) or high-grade serous invasive ovarian cancer (261 [7·1%] of 3659 cases, 1·13, 0·97–1·32, p=0·13), or borderline tumours of either subtype (serous 103 [9·0%] of 1140 cases, 1·20, 0·95–1·52, p=0·12, and mucinous 65 [8·5%] of 767 cases, 1·12, 0·84–1·48, p=0·45). Interpretation Clinicians should be aware of the increased risk of specific subtypes of ovarian cancer in women with endometriosis. Future efforts should focus on understanding the mechanisms that might lead to malignant transformation of endometriosis so as to help identify subsets of women at increased risk of ovarian cancer. Funding Ovarian Cancer Research Fund, National Institutes of Health, California Cancer Research Program, California Department of Health Services, Lon V Smith Foundation, European Community's Seventh Framework Programme, German Federal Ministry of Education and Research of Germany, Programme of Clinical Biomedical Research, German Cancer Research Centre, Eve Appeal, Oak Foundation, UK National Institute of Health Research, National Health and Medical Research Council of Australia, US Army Medical Research and Materiel Command, Cancer Council Tasmania, Cancer Foundation of Western Australia, Mermaid 1, Danish Cancer Society, and Roswell Park Alliance Foundation. PMID:22361336

  14. Anthropometry and head and neck cancer:a pooled analysis of cohort data

    PubMed Central

    Gaudet, Mia M; Kitahara, Cari M; Newton, Christina C; Bernstein, Leslie; Reynolds, Peggy; Weiderpass, Elisabete; Kreimer, Aimée R; Yang, Gong; Adami, Hans-Olov; Alavanja, Michael C; Beane Freeman, Laura E; Boeing, Heiner; Buring, Julie; Chaturvedi, Anil; Chen, Yu; D’Aloisio, Aimee A; Freedman, Michal; Gao, Yu-Tang; Gaziano, J Michael; Giles, Graham G; Håkansson, Niclas; Huang, Wen-Yi; Lee, I-Min; Linet, Martha S; MacInnis, Robert J; Park, Yikyung; Prizment, Anna; Purdue, Mark P; Riboli, Elio; Robien, Kim; Sandler, Dale P; Schairer, Catherine; Sesso, Howard D; Ou Shu, Xiao; White, Emily; Wolk, Alicja; Xiang, Yong-Bing; Zelenuich-Jacquotte, Anne; Zheng, Wei; Patel, Alpa V; Hartge, Patricia; Berrington de González, Amy; Gapstur, Susan M

    2015-01-01

    Background: Associations between anthropometry and head and neck cancer (HNC) risk are inconsistent. We aimed to evaluate these associations while minimizing biases found in previous studies. Methods: We pooled data from 1 941 300 participants, including 3760 cases, in 20 cohort studies and used multivariable-adjusted Cox proportional hazard regression models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association of anthropometric measures with HNC risk overall and stratified by smoking status. Results: Greater waist circumference (per 5 cm: HR = 1.04, 95% CI 1.03–1.05, P-value for trend = <0.0001) and waist-to-hip ratio (per 0.1 unit: HR = 1.07, 95% CI 1.05–1.09, P-value for trend = <0.0001), adjusted for body mass index (BMI), were associated with higher risk and did not vary by smoking status (P-value for heterogeneity = 0.85 and 0.44, respectively). Associations with BMI (P-value for interaction = <0.0001) varied by smoking status. Larger BMI was associated with higher HNC risk in never smokers (per 5 kg/m2: HR = 1.15, 95% CI 1.06–1.24, P-value for trend = 0.0006), but not in former smokers (per 5 kg/m2: HR = 0.99, 95% CI 0.93–1.06, P-value for trend = 0.79) or current smokers (per 5 kg/m2: HR = 0.76, 95% CI 0.71–0.82, P-value for trend = <0.0001). Larger hip circumference was not associated with a higher HNC risk. Greater height (per 5 cm) was associated with higher risk of HNC in never and former smokers, but not in current smokers. Conclusions: Waist circumference and waist-to-hip ratio were associated positively with HNC risk regardless of smoking status, whereas a positive association with BMI was only found in never smokers. PMID:26050257

  15. Pooled Analysis of Performance of Liquid Based Cytology in Population-Based Cervical Cancer Screening Studies in China

    PubMed Central

    Pan, Qin-Jing; Hu, Shang-ying; Zhang, Xun; Ci, Pu-wa; Zhang, Wen-hua; Guo, Hui-qin; Cao, Jian; Zhao, Fang-hui; Lytwyn, Alice; Qiao, You-lin

    2013-01-01

    Background Liquid based cytology (LBC) has been widely used for cervical cancer screening. Despite numerous studies and systematic reviews, few large studies have focused on biopsy-confirmed cervical lesions and controversy remains about its diagnostic accuracy. The aim of our study was to assess LBC for detecting biopsy-confirmed cervical intraepithelial neoplasia (CIN) and cancer. Methods We performed a pooled analysis of LBC using data from 13 population-based, cross-sectional, cervical-cancer screening studies performed in China from 1999 to 2008. Participants (n = 26782) received LBC and HPV testing. Screen-positive women were referred for colposcopy and biopsy. We analyzed the accuracy of LBC for detecting biopsy-confirmed CIN2 or worse lesion (CIN2+) as well as CIN3 or worse lesion (CIN3+). Results Of 25830 women included in the analysis, CIN2+ was found in 107/2612(4.1%) with ASC, 142/923 (15.4%) with LSIL, 512/784 (65.3%) with HSIL, 29/30 (96.7%) with SCC, 4/27(14.8%) with AGC, and 0.4% (85/21454) with normal cytology results. No invasive cancers had ASC, AGC or cytological normal slides. The overall sensitivity, specificity, PPV, NPV and accuracy of LBC for detecting CIN2+ were 81.0%, 95.4%, 38.3%, 99.3 % and 94.9% respectively. Although HC2 was more sensitive than LBC, the specificity, PPV and overall accuracy of LBC were higher than those of HC2, at 85.2%, 18.6% and 85.5%, respectively. Conclusions The results indicate that performance of LBC can effectively predict a risk of existing CIN2+ and may be a good screening tool for cervical cancer prevention in a developing country. PMID:23907807

  16. 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

  17. 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

  18. 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% CI = 0.95 to 1.94, P = .09) or CBP tumors. Conclusions This study shows that reproductive factors and BMI are most clearly associated with hormone receptor–positive tumors and suggest that triple-negative or CBP tumors may have distinct etiology. PMID:21191117

  19. Efficacy of fourth-line chemotherapy in advanced non-small-cell lung cancer: a systematic review and pooled analysis of published studies.

    PubMed

    Petrelli, Fausto; Coinu, Andrea; Cabiddu, Mary; Borgonovo, Karen; Ghilardi, Mara; Lonati, Veronica; Barni, Sandro

    2015-09-01

    There are no agents labelled for use as fourth-line therapy for non-small-cell lung cancer, even though it is currently prescribed in about 5-10% of patients. Here, we provide a pooled analysis of published studies on the efficacy of treatments in patients who have had at least three unsuccessful lines of therapy. The literature search was performed on Pubmed, EMBASE, the Web of Science, SCOPUS, CINAHL, Google Scholar and the Cochrane Library using the terms 'lung cancer' OR NSCLC AND 'fourth line'. The response rates and disease control rates were pooled using a random-effect or a fixed-effect model according to heterogeneity. Median progression-free survival and overall survival data were also collected and aggregated to obtain pooled median values of the included studies. Overall, 14 studies (673 patients), which were almost entirely published by Asian institutions, were eligible for this pooled analysis. Among these were two phase II trials and 12 retrospective cohort series. In general, the pooled overall response rate was 13.6% [95% confidence interval (CI) 10-18.3] and the pooled overall disease control rate was 47.3% (95% CI 38-56.9). The pooled median progression-free survival for these studies was 3.34 months (95% CI 2.42-4.27). The pooled median overall survival for these studies was 10.5 months (95% CI 9.57-11.52). In conclusion, for non-small-cell lung cancer patients who have undergone three or more unsuccessful lines of therapy, fourth-line treatment could be offered in select cases to those with a good performance status. PMID:26020807

  20. Welding and Lung Cancer in a Pooled Analysis of Case-Control Studies

    PubMed Central

    Kendzia, Benjamin; Behrens, Thomas; Jöckel, Karl-Heinz; Siemiatycki, Jack; Kromhout, Hans; Vermeulen, Roel; Peters, Susan; Van Gelder, Rainer; Olsson, Ann; Brüske, Irene; Wichmann, H.-Erich; Stücker, Isabelle; Guida, Florence; Tardón, Adonina; Merletti, Franco; Mirabelli, Dario; Richiardi, Lorenzo; Pohlabeln, Hermann; Ahrens, Wolfgang; Landi, Maria Teresa; Caporaso, Neil; Consonni, Dario; Zaridze, David; Szeszenia-Dabrowska, Neonila; Lissowska, Jolanta; Gustavsson, Per; Marcus, Michael; Fabianova, Eleonora; ‘t Mannetje, Andrea; Pearce, Neil; Tse, Lap Ah; Yu, Ignatius Tak-sun; Rudnai, Peter; Bencko, Vladimir; Janout, Vladimir; Mates, Dana; Foretova, Lenka; Forastiere, Francesco; McLaughlin, John; Demers, Paul; Bueno-de-Mesquita, Bas; Boffetta, Paolo; Schüz, Joachim; Straif, Kurt; Pesch, Beate; Brüning, Thomas

    2013-01-01

    Several epidemiologic studies have indicated an increased risk of lung cancer among welders. We used the SYNERGY project database to assess welding as a risk factor for developing lung cancer. The database includes data on 15,483 male lung cancer cases and 18,388 male controls from 16 studies in Europe, Canada, China, and New Zealand conducted between 1985 and 2010. Odds ratios and 95% confidence intervals between regular or occasional welding and lung cancer were estimated, with adjustment for smoking, age, study center, and employment in other occupations associated with lung cancer risk. Overall, 568 cases and 427 controls had ever worked as welders and had an odds ratio of developing lung cancer of 1.44 (95% confidence interval: 1.25, 1.67) with the odds ratio increasing for longer duration of welding. In never and light smokers, the odds ratio was 1.96 (95% confidence interval: 1.37, 2.79). The odds ratios were somewhat higher for squamous and small cell lung cancers than for adenocarcinoma. Another 1,994 cases and 1,930 controls had ever worked in occupations with occasional welding. Work in any of these occupations was associated with some elevation of risk, though not as much as observed in regular welders. Our findings lend further support to the hypothesis that welding is associated with an increased risk of lung cancer. PMID:24052544

  1. A pooled analysis of the outcome of prospective colonoscopic surveillance for familial colorectal cancer.

    PubMed

    Mesher, David; Dove-Edwin, Isis; Sasieni, Peter; Vasen, Hans; Bernstein, Inge; Royer-Pokora, Brigitte; Holinski-Feder, Elke; Lalloo, Fiona; Evans, D Gareth; Forsberg, Anna; Lindblom, Annika; Thomas, Huw

    2014-02-15

    Surveillance guidelines for the management of familial colorectal cancer (FCC), a dominant family history of colorectal cancer in which the polyposis syndromes and Lynch syndrome have been excluded, are not firmly established. The outcome of colonoscopic surveillance is studied using data from six centers. DNA mismatch repair deficiency was excluded by genetic testing. Families were classified as FCC type X if they fulfilled the original Amsterdam criteria (AC) and late onset (LOFCC) if they fulfilled the AC apart from not having a cancer aged under 50. The most advanced findings on colonoscopy were analyzed. One thousand five hundred eighty-five individuals (median age 47.3, 44% male) from 530 FCC families (349 FCC type X) underwent a total of 4,992 colonoscopies with 7,904 patient-years of follow-up. Results for FCC type X and LOFCC were very similar. At baseline, 22 prevalent asymptomatic colorectal cancers were diagnosed, 120 (7.6%) individuals had high-risk adenomas and 225 (14.2%) simple adenomas. One thousand eighty-eight individuals had a further colonoscopy (median follow-up of 6.2 years). Of nine individuals diagnosed with cancer, eight had a previous history of at least one polyp/adenoma. High-risk adenomas were detected in 92 (8.7%) and multiple adenomas were detected in 20 (1.9%) individuals. Both FCC type X and LOFCC have a high prevalence of colorectal cancers and on follow-up develop high-risk adenomas (including multiple adenomas), but infrequent interval cancers. They should be managed similarly with five-yearly colonoscopies undertaken from between 30 and 40 with more intensive surveillance in individuals developing multiple or high-risk adenomas. PMID:23901040

  2. Secondhand smoke exposure in adulthood and risk of lung cancer among never smokers: a pooled analysis of two large studies.

    PubMed

    Brennan, Paul; Buffler, Patricia A; Reynolds, Peggy; Wu, Anna H; Wichmann, H Erich; Agudo, Antonio; Pershagen, Göran; Jöckel, Karl-Heinz; Benhamou, Simone; Greenberg, Raymond S; Merletti, Franco; Winck, Carlos; Fontham, Elizabeth T H; Kreuzer, Michaela; Darby, Sarah C; Forastiere, Francesco; Simonato, Lorenzo; Boffetta, Paolo

    2004-03-01

    The interpretation of the evidence linking exposure to secondhand smoke with lung cancer is constrained by the imprecision of risk estimates. The objective of the study was to obtain precise and valid estimates of the risk of lung cancer in never smokers following exposure to secondhand smoke, including adjustment for potential confounders and exposure misclassification. Pooled analysis of data from 2 previously reported large case-control studies was used. Subjects included 1263 never smoking lung cancer patients and 2740 population and hospital controls recruited during 1985-1994 from 5 metropolitan areas in the United States, 11 areas in Germany, Italy, Sweden, United Kingdom, France, Spain and Portugal. Odds ratios (ORs) of lung cancer were calculated for ever exposure and duration of exposure to secondhand smoke from spouse, workplace and social sources. The OR for ever exposure to spousal smoking was 1.18 (95% CI = 1.01-1.37) and for long-term exposure was 1.23 (95% CI = 1.01-1.51). After exclusion of proxy interviews, the OR for ever exposure from the workplace was 1.16 (95% CI = 0.99-1.36) and for long-term exposure was 1.27 (95% CI = 1.03-1.57). Similar results were obtained for exposure from social settings and for exposure from combined sources. A dose-response relationship was present with increasing duration of exposure to secondhand smoke for all 3 sources, with an OR of 1.32 (95% CI = 1.10-1.79) for the long-term exposure from all sources. There was no evidence of confounding by employment in high-risk occupations, education or low vegetable intake. Sensitivity analysis for the effects of misclassification (both positive and negative) indicated that the observed risks are likely to underestimate the true risk. Clear dose-response relationships consistent with a causal association were observed between exposure to secondhand smoke from spousal, workplace and social sources and the development of lung cancer among never smokers. PMID:14735478

  3. 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

  4. Higher frequency of certain cancers in LRRK2 G2019S mutation carriers with Parkinson's disease: A pooled analysis

    PubMed Central

    Agalliu, Ilir; Luciano, Marta San; Mirelman, Anat; Giladi, Nir; Waro, Bjorg; Aasly, Jan; Inzelberg, Rivka; Hassin-Baer, Sharon; Friedman, Eitan; Ruiz-Martinez, Javier; Marti-Masso, Jose Felix; Orr-Urtreger, Avi; Bressman, Susan; Saunders-Pullman, Rachel

    2015-01-01

    Importance Parkinson disease (PD) patients who harbor LRRK2 G2019S mutations may have increased risks of non-skin cancers. However, the results have been inconsistent across studies. Objective To analyze pooled data from five centers to further examine the association between LRRK2 G2019S mutation and cancer among PD patients and to explore factors that could explain discrepancies. Design, Setting, and Participants Clinical, demographic, and genotyping data as well as cancer outcomes were pooled from 1,549 PD patients recruited across five movement disorders clinics located in Europe, Israel, and the United States. Associations between LRRK2 G2019S mutation and the outcomes were examined using mixed-effects logistic regression models to estimate odds ratios (ORs) and 95% CIs. Models were adjusted for age and ethnicity (Ashkenazi Jewish vs. others) as fixed effects and study center as a random effect. Main Outcomes and Measures All cancers combined, non-skin cancers, smoking-related cancers, hormone-related cancers, and other types of cancer. Results The overall prevalence of the LRRK2 G2019S mutation was 11.4% among all PD patients. Mutation carriers were younger at PD diagnosis and more likely to be women (53.1%) and of Ashkenazi Jewish descent (76.8%) in comparison with individuals who were not mutation carriers. The LRRK2 G2019S mutation carriers had statistically significant increased risks for non-skin cancers (OR, 1.62; 95%CI 1.042.52), hormone-related cancers (OR, 1.87; 95%CI 1.073.26) and breast cancer (OR, 2.34; 95%CI 1.055.22) in comparison with noncarriers. There were no associations with other cancers. There were no major statistically significant differences in results when the data were stratified by Ashkenazi Jewish ethnicity; however, there was some evidence of heterogeneity across centers. Conclusions and Relevance This multinational study from five centers demonstrates that LRRK2 G2019S mutation carriers have an overall increased risk of cancer, especially for hormone-related cancer and breast cancer in women. Larger prospective cohorts or family-based studies investigating associations between LRRK2 mutations and cancer among PD patients are warranted to better understand the underlying genetic susceptibility between PD and hormone-related cancers. PMID:25401981

  5. Improved survival of gastric cancer with tumour Epstein–Barr virus positivity: an international pooled analysis

    PubMed Central

    Camargo, M Constanza; Kim, Woo-Ho; Chiaravalli, Anna Maria; Kim, Kyoung-Mee; Corvalan, Alejandro H; Matsuo, Keitaro; Yu, Jun; Sung, Joseph J Y; Herrera-Goepfert, Roberto; Meneses-Gonzalez, Fernando; Kijima, Yuko; Natsugoe, Shoji; Liao, Linda M; Lissowska, Jolanta; Kim, Sung; Hu, Nan; Gonzalez, Carlos A; Yatabe, Yashushi; Koriyama, Chihaya; Hewitt, Stephen M; Akiba, Suminori; Gulley, Margaret L; Taylor, Philip R; Rabkin, Charles S

    2015-01-01

    Background and objective About 9% of gastric carcinomas have Epstein–Barr virus (EBV) in the tumour cells, but it is unclear whether viral presence influences clinical progression. We therefore examined a large multicentre case series for the association of tumour EBV status with survival after gastric cancer diagnosis, accounting for surgical stage and other prognostic factors. Methods We combined individual-level data on 4599 gastric cancer patients diagnosed between 1976 and 2010 from 13 studies in Asia (n=8), Europe (n=3), and Latin America (n=2). EBV positivity of tumours was assessed by in situ hybridisation. Mortality HRs for EBV positivity were estimated by Cox regression models stratified by study, adjusted for distributions of sex (71% male), age (mean 58 years), stage (52% tumour-node-metastasis stages III or IV), tumour histology (49% poorly differentiated, 57% Lauren intestinal-type), anatomic subsite (70% non-cardia) and year of diagnosis. Variations by study and continent were assessed using study-specific HRs for EBV positivity. Results During median 3.0 years follow-up, 49% of patients died. Stage was strongly predictive of mortality, with unadjusted HRs (vs stage I) of 3.1 for stage II, 8.1 for stage III and 13.2 for stage IV. Tumour EBV positivity was 8.2% overall and inversely associated with stage (adjusted OR: 0.79 per unit change). Adjusted for stage and other confounders, EBV positivity was associated with lower mortality (HR, 0.72; 95% CI 0.61 to 0.86), with low heterogeneity among the study populations (p=0.2). The association did not significantly vary across patient or tumour characteristics. There was no significant variation among the three continent-specific HRs (p=0.4). Conclusions Our findings suggest that tumour EBV positivity is an additional prognostic indicator in gastric cancer. Further studies are warranted to identify the mechanisms underlying this protective association. PMID:23580779

  6. Meta-analysis of extremely low frequency electromagnetic fields and cancer risk: a pooled analysis of epidemiologic studies.

    PubMed

    Zhang, Yemao; Lai, Jinsheng; Ruan, Guoran; Chen, Chen; Wang, Dao Wen

    2016-03-01

    Studies have suggested that extremely low frequency electromagnetic fields (ELF-EMF) may affect physiological functions in animal models. However, epidemiologic studies investigating the association of ELF-EMF with the susceptibility to cancer yield contradictory results. In this comprehensive analysis, we conducted a search for case-control surveys regarding the associations of ELF-EMF and cancer susceptibility in electronic databases. A total of 42 studies involving 13,259 cases and 100,882 controls were retrieved. Overall, increased susceptibility to cancer was identified in the ELF-EMF exposed population (OR=1.08, 95% CI: 1.01, 1.15, P=0.02). In the stratified analyses, increased risk was found in North America (OR=1.10; 95% CI: 1.02, 1.20, P=0.02), especially the United States (OR=1.10; 95% CI: 1.01, 1.20, P=0.03). However, studies from Europe contradict these results. Moreover, a higher risk was found to be statistically significantly associated with the residential exposed population (OR=1.18; 95% CI: 1.02, 1.37, P=0.03). Furthermore, an increased cancer risk was found in interview-based surveys (OR=1.16; 95% CI: 1.00, 1.35, P=0.04). In device measurement-based studies, a slight increased risk was found only in premenopausal breast cancer (OR=1.23; 95% CI: 1.01, 1.49, P=0.04). Our meta-analysis suggests that ELF-EMFs are associated with cancer risk, mainly in the United States and in residential exposed populations. Methodological challenges might explain the differences among studies. PMID:26703095

  7. 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

  8. HIGH CONSTANT INCIDENCE RATES OF SECOND PRIMARY CANCERS OF THE HEAD AND NECK: A POOLED ANALYSIS OF 13 CANCER REGISTRIES

    PubMed Central

    Bosetti, Cristina; Scelo, Ghislaine; Chuang, Shu-Chun; Tonita, Jon M.; Tamaro, Sharon; Jonasson, Jon G.; Kliewer, Erich V.; Hemminki, Kari; Weiderpass, Elisabete; Pukkala, Eero; Tracey, Elizabeth; Olsen, Jorgen H.; Pompe-Kirn, Vera; Brewster, David H.; Martos, Carmen; Chia, Kee-Seng; Brennan, Paul; Hashibe, Mia; Levi, Fabio; La Vecchia, Carlo; Boffetta, Paolo

    2010-01-01

    Scanty data are available on the incidence (i.e., the absolute risk) of second cancers of the head and neck (HN) and its pattern with age. We investigated this issue using data from a multicentric study of 13 population-based cancer registries from Europe, Canada, Australia and Singapore for the years 1943-2000. A total of 99,257 patients had a first primary HN cancer (15,985 tongue, 22,378 mouth, 20,758 pharyngeal, and 40,190 laryngeal cancer), contributing to 489,855 person-years of follow-up. 1294 of the patients (1.3%) were diagnosed with second HN cancers (342 tongue, 345 mouth, 418 pharynx, and 189 larynx). Male incidence rates of first HN cancer steeply increased from 0.68/100,000 at age 30-34 to 46.2/100,000 at age 70-74, and leveled off at higher age; female incidence increased from 0.50/100,000 at age 30-34 to 16.5/100,000 at age 80-84. However, age-specific incidence of second HN cancers after a first HN cancer in men was around 200-300/100,000 between age 40-44 and age 70-74, and tended to decline at subsequent ages (150/100,000 at age 80-84); in women, incidence of second HN cancers was around 200-300/100,000 between age 45-49 and 80-84. The patterns of age-specific incidence were consistent for different subsites of second HN cancer and sexes; moreover, they were similar for age-specific incidence of first primary HN cancer in patients who subsequently developed a second HN cancer. The incidence of second HN cancers does not increase with age, but remains constant, or if anything, decreases with advancing age. Impact statement While the incidence of first primary cancers of the head and neck increases with advancing age that of second primary cancers is stable between age 40 and 70 and, if anything, declines thereafter. PMID:20824702

  9. Pooled Analysis of a Self-Sampling HPV DNA Test as a Cervical Cancer Primary Screening Method

    PubMed Central

    Zhao, Fang-Hui; Lewkowitz, Adam K.; Chen, Feng; Lin, Margaret J.; Hu, Shang-Ying; Zhang, Xun; Pan, Qin-Jing; Ma, Jun-Fei; Niyazi, Mayineur; Li, Chang-Qing; Li, Shu-Min; Smith, Jennifer S.; Belinson, Jerome L.; Castle, Philip E.

    2012-01-01

    Background Worldwide, one-seventh of cervical cancers occur in China, which lacks a national screening program. By evaluating the diagnostic accuracy of self-collected cervicovaginal specimens tested for human papillomavirus (HPV) DNA (Self-HPV testing) in China, we sought to determine whether Self-HPV testing may serve as a primary cervical cancer screening method in low-resource settings. Methods We compiled individual patient data from five population-based cervical cancer–screening studies in China. Participants (n = 13 140) received Self-HPV testing, physician-collected cervical specimens for HPV testing (Physician-HPV testing), liquid-based cytology (LBC), and visual inspection with acetic acid (VIA). Screen-positive women underwent colposcopy and confirmatory biopsy. We analyzed the accuracies of pooled Self-HPV testing, Physician-HPV testing, VIA, and LBC to detect biopsy-confirmed cervical intraepithelial neoplasia grade 2 or more severe (CIN2+) and CIN3+. All statistical tests were two-sided. Results Of 13 004 women included in the analysis, 507 (3.9%) were diagnosed as CIN2+, 273 (2.1%) as CIN3+, and 37 (0.3%) with cervical cancer. Self-HPV testing had 86.2% sensitivity and 80.7% specificity for detecting CIN2+ and 86.1% sensitivity and 79.5% specificity for detecting CIN3+. VIA had statistically significantly lower sensitivity for detecting CIN2+ (50.3%) and CIN3+ (55.7%) and higher specificity for detecting CIN2+ (87.4%) and CIN3+ (86.9%) (all P values < .001) than Self-HPV testing, LBC had lower sensitivity for detecting CIN2+ (80.7%, P = .015), similar sensitivity for detecting CIN3+ (89.0%, P = .341), and higher specificity for detecting CIN2+ (94.0%, P < .001) and CIN3+ (92.8%, P < .001) than Self-HPV testing. Physician-HPV testing was more sensitive for detecting CIN2+ (97.0%) and CIN3+ (97.8%) but similarly specific for detecting CIN2+ (82.7%) and CIN3+ (81.3%) (all P values <.001) than Self-HPV testing. Conclusions The sensitivity of Self-HPV testing compared favorably with that of LBC and was superior to the sensitivity of VIA. Self-HPV testing may complement current screening programs by increasing population coverage in settings that do not have easy access to comprehensive cytology-based screening. PMID:22271765

  10. Multi-institutional Pooled Analysis on Adjuvant Chemoradiation in Pancreatic Cancer

    SciTech Connect

    Morganti, Alessio G.; Falconi, Massimo; Stiphout, Ruud G.P.M. van; Mattiucci, Gian-Carlo; Alfieri, Sergio; Calvo, Felipe A.; Dubois, Jean-Bernard; Fastner, Gerd; Herman, Joseph M.; Maidment, Bert W.; Miller, Robert C.; Regine, William F.; Reni, Michele; Sharma, Navesh K.; Ippolito, Edy; and others

    2014-11-15

    Purpose: To determine the impact of chemoradiation therapy (CRT) on overall survival (OS) after resection of pancreatic adenocarcinoma. Methods and Materials: A multicenter retrospective review of 955 consecutive patients who underwent complete resection with macroscopically negative margins (R0-1) for invasive carcinoma (T1-4; N0-1; M0) of the pancreas was performed. Exclusion criteria included metastatic or unresectable disease at surgery, macroscopic residual disease (R2), treatment with intraoperative radiation therapy (IORT), and a histological diagnosis of no ductal carcinoma, or postoperative death (within 60 days of surgery). In all, 623 patients received postoperative radiation therapy (RT), 575 patients received concurrent chemotherapy (CT), and 462 patients received adjuvant CT. Results: Median follow-up was 21.0 months. Median OS after adjuvant CRT was 39.9 versus 24.8 months after no adjuvant CRT (P<.001) and 27.8 months after CT alone (P<.001). Five-year OS was 41.2% versus 24.8% with and without postoperative CRT, respectively. The positive impact of CRT was confirmed by multivariate analysis (hazard ratio [HR] = 0.72; confidence interval [CI], 0.60-0.87; P=.001). Adverse prognostic factors identified by multivariate analysis included the following: R1 resection (HR = 1.17; CI = 1.07-1.28; P<.001), higher pT stage (HR = 1.23; CI = 1.11-1.37; P<.001), positive lymph nodes (HR = 1.27; CI = 1.15-1.41; P<.001), and tumor diameter >20 mm (HR = 1.14; CI = 1.05-1.23; P=.002). Multivariate analysis also showed a better prognosis in patients treated in centers with >10 pancreatic resections per year (HR = 0.87; CI = 0.78-0.97; P=.014) Conclusion: This study represents the largest comparative study on adjuvant therapy in patients after resection of carcinoma of the pancreas. Overall survival was better in patients who received adjuvant CRT.

  11. Carotenoid intakes and risk of breast cancer defined by estrogen receptor and progesterone receptor status: a pooled analysis of 18 prospective cohort studies123

    PubMed Central

    Spiegelman, Donna; Baglietto, Laura; Bernstein, Leslie; Boggs, Deborah A; van den Brandt, Piet A; Buring, Julie E; Gapstur, Susan M; Giles, Graham G; Giovannucci, Edward; Goodman, Gary; Hankinson, Susan E; Helzlsouer, Kathy J; Horn-Ross, Pamela L; Inoue, Manami; Jung, Seungyoun; Khudyakov, Polyna; Larsson, Susanna C; Lof, Marie; McCullough, Marjorie L; Miller, Anthony B; Neuhouser, Marian L; Palmer, Julie R; Park, Yikyung; Robien, Kim; Rohan, Thomas E; Ross, Julie A; Schouten, Leo J; Shikany, James M; Tsugane, Shoichiro; Visvanathan, Kala; Weiderpass, Elisabete; Wolk, Alicja; Willett, Walter C; Zhang, Shumin M; Ziegler, Regina G; Smith-Warner, Stephanie A

    2012-01-01

    Background: Epidemiologic studies examining associations between carotenoid intakes and risk of breast cancer by estrogen receptor (ER) and progesterone receptor (PR) status are limited. Objective: We investigated these associations in a pooled analysis of 18 cohort studies. Design: Of 1,028,438 participants followed for a maximum follow-up of 26 y across studies, 33,380 incident invasive breast cancers were identified. Study-specific RRs and 95% CIs were estimated by using Cox proportional hazards regression and then pooled by using a random-effects model. Results: ?-Carotene, ?-carotene, and lutein/zeaxanthin intakes were inversely associated with the risk of ER-negative (ER?) breast cancer (pooled multivariable RRs of the comparison between the highest and lowest quintiles): ?-carotene (0.87; 95% CI: 0.78, 0.97), ?-carotene (0.84; 95% CI: 0.77, 0.93), and lutein/zeaxanthin (0.87; 95% CI: 0.79, 0.95). These variables were not inversely associated with the risk of ER-positive (ER+) breast cancer (pooled multivariable RRs for the same comparison): ?-carotene (1.04; 95% CI: 0.99, 1.09), ?-carotene (1.04; 95% CI: 0.98, 1.10), and lutein/zeaxanthin (1.00; 95% CI: 0.93, 1.07). Although the pooled RRs for quintile 5 for ?-cryptoxanthin were not significant, inverse trends were observed for ER? and ER+ breast cancer (P-trend ? 0.05). Nonsignificant associations were observed for lycopene intake. The associations were largely not appreciably modified by several breast cancer risk factors. Nonsignificant associations were observed for PR-positive and PR-negative breast cancer. Conclusions: Intakes of ?-carotene, ?-carotene, and lutein/zeaxanthin were inversely associated with risk of ER?, but not ER+, breast cancer. However, the results need to be interpreted with caution because it is unclear whether the observed association is real or due to other constituents in the same food sources. PMID:22277553

  12. 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

  13. A pooled analysis of post-diagnosis lifestyle factors in association with late estrogen-receptor-positive breast cancer prognosis.

    PubMed

    Nechuta, Sarah; Chen, Wendy Y; Cai, Hui; Poole, Elizabeth M; Kwan, Marilyn L; Flatt, Shirley W; Patterson, Ruth E; Pierce, John P; Caan, Bette J; Ou Shu, Xiao

    2016-05-01

    Lifestyle factors have been well studied in relation to breast cancer prognosis overall; however, associations of lifestyle and late outcomes (>5 years after diagnosis) have been much less studied, and no studies have focused on estrogen receptor-positive (ER+) breast cancer survivors, who may have high risk of late recurrence and mortality. We utilized a large prospective pooling study to evaluate the associations of lifestyle factors with late recurrence and all-cause mortality among 6,295 5-year ER+ Stage I-III breast cancer survivors. Pooled and harmonized data were available on clinical factors and lifestyle factors (pre- to post-diagnosis weight change, body mass index (BMI) (kg/m(2) ), recreational physical activity, alcohol intake and smoking history), measured on average 2.1 years after diagnosis. Updated information for weight only was available. Study heterogeneity was evaluated by the Q-statistic. Multivariable Cox regression models were stratified by study. Adjusting for clinical factors and potential confounders, ≥10% weight gain and obesity (BMI, 30-34.99 and ≥35) were associated with increased risk of late recurrence (hazard ratios (95% confidence intervals): 1.24 (1.00-1.53), 1.40 (1.05-1.86) and 1.41 (1.02-1.93), respectively). Daily alcohol intake was associated with late recurrence, 1.28 (1.01-1.62). Physical activity was inversely associated with late all-cause mortality (0.81 (0.71-0.93) and 0.71 (0.61-0.82) for 4.9 to <17.4 and ≥17.4 metabolic equivalent-hr/week). A U-shaped association was observed for late all-cause mortality and BMI using updated weight (1.42 (1.15-1.74) and 1.40 (1.09-1.81), <21.5 and ≥35, respectively). Smoking was associated with increased risk of late outcomes. In this large prospective pooling project, modifiable lifestyle factors were associated with late outcomes among long-term ER+ breast cancer survivors. PMID:26606746

  14. Obesity and the Risk of Papillary Thyroid Cancer: A Pooled Analysis of Three Case–Control Studies

    PubMed Central

    Xu, Li; Port, Matthias; Landi, Stefano; Gemignani, Federica; Cipollini, Monica; Elisei, Rossella; Goudeva, Lilia; Müller, Jörg Andreas; Nerlich, Kai; Pellegrini, Giovanni; Reiners, Christoph; Romei, Cristina; Schwab, Robert; Abend, Michael

    2014-01-01

    Background: There is a correlation between temporal trends of obesity prevalence and papillary thyroid cancer (PTC) incidence in the United States. Obesity is a well-recognized risk factor for many cancers, but there are few studies on the association between obesity and PTC risk. We investigated the association between anthropometric measurements and PTC risk using pooled individual data from three case–control populations. Methods: Height and weight information were obtained from three independent case–control studies, including 1917 patients with PTC (1360 women and 557 men) and 2127 cancer-free controls from the United States, Italy, and Germany. Body mass index (BMI), body fat percentage, and body surface area (BSA) were calculated. An unconditional logistic regression model was used to calculate odds ratios (ORs) and confidence intervals (CIs) with respect to risk of PTC, adjusted by age, sex, race/ethnicity, and study site. Results: In the pooled population, for both men and women, an increased risk of PTC was found to be associated with greater weight, BMI, body fat percentage, and BSA, whereas a reduced risk of PTC was associated with greater height, in the pooled population for both men and women. Compared with normal-weight subjects (BMI 18.5–24.9 kg/m2), the ORs for overweight (BMI 25–29.9 kg/m2) and obese (BMI≥30 kg/m2) subjects were 1.72 [CI 1.48–2.00] and 4.17 [CI 3.41–5.10] respectively. Compared with the lowest quartile of body fat percentage, the ORs for the highest quartile were 3.83 [CI 2.85–5.15] in women and 4.05 [CI 2.67–6.15] in men. Conclusion: Anthropometric factors, especially BMI and body fat percentage, were significantly associated with increased risk of PTC. Future studies of anthropometric factors and PTC that incorporate intermediate factors, including adiposity and hormone biomarkers, are essential to help clarify potential mechanisms of the relationship. PMID:24555500

  15. Urine BLCA-4 exerts potential role in detecting patients with bladder cancers: a pooled analysis of individual studies

    PubMed Central

    Cai, Qiliang; Wu, Yudong; Guo, Zhanjun; Gong, Rui; Tang, Yang; Yang, Kuo; Li, Xiaodong; Guo, Xuemei; Niu, Yuanjie; Zhao, Yan

    2015-01-01

    Epidemiological studies have explored the diagnostic effect of urine BLCA-4 in bladder cancer. However, the results remain controversial. Therefore, we conducted this pooled analyses to determine the overall accuracy of urine BLCA-4 in bladder cancer. A comprehensive electronic and hand search was conducted for related literatures though several databases. QUADAS-2 was used to assess the quality of each included studies. Diagnostic parameters were calculated using Meta-Disc (version 1.4) and Stata (version 12.0) software. Nine published articles with 1,119 subjects were included. The summary estimates were: sensitivity 0.93 (95% confidence interval [CI] = 0.90-0.95), specificity 0.97 (95% CI, 0.95-0.98), positive likelihood ratio 48.16 (95% CI, 11.77-197.01), negative likelihood ratio 0.08 (95% CI, 0.06-0.11), diagnostic odds ratio 534.03 (95% CI, 150.15-1899.31), and the AUC was 0.9607. In conclusion, urine BLCA-4 is a promising marker in diagnosing bladder cancer. PMID:26462026

  16. COFFEE, TEA AND SUGAR-SWEETENED CARBONATED SOFT DRINK INTAKE AND PANCREATIC CANCER RISK: A POOLED ANALYSIS OF 14 COHORT STUDIES

    PubMed Central

    Genkinger, Jeanine M.; Li, Ruifeng; Spiegelman, Donna; Anderson, Kristin E.; Albanes, Demetrius; Bergkvist, Leif; Bernstein, Leslie; Black, Amanda; van den Brandt, Piet A.; English, Dallas R.; Freudenheim, Jo L.; Fuchs, Charles S.; Giles, Graham G.; Giovannucci, Edward; Goldbohm, R. Alexandra; Horn-Ross, Pamela L.; Jacobs, Eric J.; Koushik, Anita; Männistö, Satu; Marshall, James R.; Miller, Anthony B.; Patel, Alpa V.; Robien, Kim; z, Thomas E.; Schairer, Catherine; Stolzenberg-Solomon, Rachael; Wolk, Alicja; Ziegler, Regina G.; Smith-Warner, Stephanie A.

    2011-01-01

    BACKGROUND Coffee has been hypothesized to have pro- and anti-carcinogenic properties, while tea may contain anti-carcinogenic compounds. Studies assessing coffee intake and pancreatic cancer risk have yielded mixed results, while findings for tea intake have mostly been null. Sugar-sweetened carbonated soft drink (abbreviated as SSB) intake has been associated with higher circulating levels of insulin, which may promote carcinogenesis. Few prospective studies have examined SSB intake and pancreatic cancer risk; results have been heterogeneous. METHODS In this pooled analysis from 14 prospective cohort studies, 2,185 incident pancreatic cancer cases were identified among 853,894 individuals during follow-up. Multivariate (MV) study-specific relative risks (RR) and 95% confidence intervals (CI) were calculated using Cox proportional hazards models and then pooled using a random effects model. RESULTS No statistically significant associations were observed between pancreatic cancer risk and intake of coffee (MVRR=1.10, 95% CI=0.81-1.48 comparing ≥900 to <0g/day; 237g≈8oz), tea (MVRR=0.96, 95% CI=0.78-1.16 comparing ≥400 to 0g/day; 237g≈8oz) or SSB (MVRR=1.19, 95% CI=0.98-1.46 comparing ≥250 to 0g/day; 355g≈12oz) (p-value, test for between-studies heterogeneity >0.05). These associations were consistent across levels of sex, smoking status and body mass index. When modeled as a continuous variable, a positive association was evident for SSB (MVRR=1.06, 95% CI=1.02-1.12). CONCLUSION AND IMPACT Overall, no associations were observed for intakes of coffee or tea during adulthood and pancreatic cancer risk. Although we were only able to examine modest intake of SSB, there was a suggestive, modest positive association for risk of pancreatic cancer for intakes of SSB. PMID:22194529

  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 adults may be due to the reduced length of exposure due to the lower age. Other characteristics, such as those that are inherited, may play a more important role in HNC in young adults compared with older adults. PMID:25613428

  18. 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. PMID:25627906

  19. Total Exposure and Exposure Rate Effects for Alcohol and Smoking and Risk of Head and Neck Cancer: A Pooled Analysis of Case-Control Studies

    PubMed Central

    Purdue, Mark; Kelsey, Karl; Zhang, Zuo-Feng; Winn, Debbie; Wei, Qingyi; Talamini, Renato; Szeszenia-Dabrowska, Neonilia; Sturgis, Erich M.; Smith, Elaine; Shangina, Oxana; Schwartz, Stephen M.; Rudnai, Peter; Neto, Jose Eluf; Muscat, Joshua; Morgenstern, Hal; Menezes, Ana; Matos, Elena; Mates, Ioan Nicolae; Lissowska, Jolanta; Levi, Fabio; Lazarus, Philip; Vecchia, Carlo La; Koifman, Sergio; Herrero, Rolando; Franceschi, Silvia; Wünsch-Filho, Victor; Fernandez, Leticia; Fabianova, Eleonora; Daudt, Alexander W.; Maso, Luigino Dal; Curado, Maria Paula; Chen, Chu; Castellsague, Xavier; Brennan, Paul; Boffetta, Paolo; Hashibe, Mia; Hayes, Richard B.

    2009-01-01

    Although cigarette smoking and alcohol consumption increase risk for head and neck cancers, there have been few attempts to model risks quantitatively and to formally evaluate cancer site-specific risks. The authors pooled data from 15 case-control studies and modeled the excess odds ratio (EOR) to assess risk by total exposure (pack-years and drink-years) and its modification by exposure rate (cigarettes/day and drinks/day). The smoking analysis included 1,761 laryngeal, 2,453 pharyngeal, and 1,990 oral cavity cancers, and the alcohol analysis included 2,551 laryngeal, 3,693 pharyngeal, and 3,116 oval cavity cancers, with over 8,000 controls. Above 15 cigarettes/day, the EOR/pack-year decreased with increasing cigarettes/day, suggesting that greater cigarettes/day for a shorter duration was less deleterious than fewer cigarettes/day for a longer duration. Estimates of EOR/pack-year were homogeneous across sites, while the effects of cigarettes/day varied, indicating that the greater laryngeal cancer risk derived from differential cigarettes/day effects and not pack-years. EOR/drink-year estimates increased through 10 drinks/day, suggesting that greater drinks/day for a shorter duration was more deleterious than fewer drinks/day for a longer duration. Above 10 drinks/day, data were limited. EOR/drink-year estimates varied by site, while drinks/day effects were homogeneous, indicating that the greater pharyngeal/oral cavity cancer risk with alcohol consumption derived from the differential effects of drink-years and not drinks/day. PMID:19745021

  20. Family history of cancer and risk of pancreatic cancer: a pooled analysis from the Pancreatic Cancer Cohort Consortium (PanScan).

    PubMed

    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

    2010-09-01

    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 5 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 odds ratios (ORs) = 1.76, 95% confidence interval (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

  1. Preferred Roles in Treatment Decision Making Among Patients With Cancer: A Pooled Analysis of Studies Using the Control Preferences Scale

    PubMed Central

    Singh, Jasvinder A.; Sloan, Jeff A.; Atherton, Pamela J.; Smith, Tenbroeck; Hack, Thomas F.; Huschka, Mashele M.; Rummans, Teresa A.; Clark, Matthew M.; Diekmann, Brent; Degner, Lesley F.

    2010-01-01

    Objectives To collect normative data, assess differences between demographic groups, and indirectly compare US and Canadian medical systems relative to patient expectations of involvement in cancer treatment decision making. Study Design Meta-analysis. Methods Individual patient data were compiled across 6 clinical studies among 3491 patients with cancer who completed the 2-item Control Preferences Scale indicating the roles they preferred versus actually experienced in treatment decision making. Results The roles in treatment decision making that patients preferred were 26% active, 49% collaborative, and 25% passive. The roles that patients reported actually experiencing were 30% active, 34% collaborative, and 36% passive. Roughly 61% of patients reported having their preferred role; only 6% experienced extreme discordance between their preferred versus actual roles. More men than women (66% vs 60%, P = .001) and more US patients than Canadian patients (84% vs 54%, P <.001) reported concordance between their preferred versus actual roles. More Canadian patients than US patients preferred and actually experienced (42% vs 18%, P <.001) passive roles. More women than men reported taking a passive role (40% vs 24%, P <.001). Older patients preferred and were more likely than younger patients to assume a passive role. Conclusions Roughly half of the studied patients with cancer indicated that they preferred to have a collaborative relationship with physicians. Although most patients had the decision-making role they preferred, about 40% experienced discordance. This highlights the need for incorporation of individualized patient communication styles into treatment plans. PMID:20873956

  2. Pooled analysis of 3 European case-control studies: I. Reproductive factors and risk of epithelial ovarian cancer.

    PubMed

    Negri, E; Franceschi, S; Tzonou, A; Booth, M; La Vecchia, C; Parazzini, F; Beral, V; Boyle, P; Trichopoulos, D

    1991-08-19

    The role of reproductive factors in the aetiology of epithelial ovarian cancer has been re-assessed in a meta-analysis of 3 hospital-based case-control studies conducted in Europe (i.e. Italy, the United Kingdom and Greece), providing a total dataset of 1,140 cases and 2,724 controls. Multiple logistic regression models were used to obtain relative risk (RR) estimates adjusted for study centre, age, socio-cultural indicators, age at menopause, and oral contraceptive use. The risk decreased with increasing number of births and the trend in risk was significant (chi 2(1) = 7.50, p less than 0.01). In comparison to nulliparous women, those who reported 4 or more births had a 40% reduction in risk of ovarian cancer (RR = 0.6, 95% confidence interval, CI: 0.4-0.8). An RR estimate of 1.4 (95% CI: 1.1-1.7) as found, overall, for age of 35 or more at first birth compared to age of 25 or less at first birth. In each stratum and overall, nulliparous women did not appear to be at increased risk compared to those who delayed birth of their first child until age 35 or more. In each study, as well as in the overall dataset, an inverse association between number of abortions and ovarian cancer risk emerged. Overall, the inverse relationship was highly significant, RR estimates for 1 and 2 or more abortions, as compared to none, being 0.9 (95% CI: 0.8 and 1.1) and 0.7 (95% CI: 0.6-0.9) respectively. The effects of parity, age at first birth and number of abortions emerged consistently in various strata of study centre and age. PMID:1874569

  3. Risk factors for endometrial cancer in black and white women: A pooled analysis from the Epidemiology of Endometrial Cancer Consortium (E2C2)

    PubMed Central

    Cote, Michele L.; Alhajj, Tala; Ruterbusch, Julie J.; Bernstein, Leslie; Brinton, Louise A.; Blot, William J.; Chen, Chu; Gass, Margery; Gaussoin, Sarah; Henderson, Brian; Lee, Eunjung; Horn-Ross, Pamela L.; Kolonel, Laurence N.; Kaunitz, Andrew; Liang, Xiaolin; Nicholson, Wanda K.; Park, Amy B.; Petruzella, Stacey; Rebbeck, Timothy R.; Setiawan, V. Wendy; Signorello, Lisa B.; Simon, Michael S.; Weiss, Noel S.; Wentzensen, Nicolas; Yang, Hannah P.; Zeleniuch-Jacquotte, Anne; Olson, Sara H.

    2015-01-01

    Purpose Endometrial cancer (EC) is the most common gynecologic cancer in the United States. Over the last decade, the incidence rate has been increasing, with a larger increase among blacks. The aim of this study was to compare risk factors for EC in black and white women. Methods Data from 7 cohort and 4 case-control studies were pooled. Unconditional logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals for each risk factor in blacks and whites separately. Results Data were pooled for 2,011 black women (516 cases and 1,495 controls) and 19,297 white women (5,693 cases and 13,604 controls). BMI ? 30 was associated with an approximate 3-fold increase in risk of EC in both black and white women (ORblack=2.93, 95% CI: 2.11, 4.07 and ORwhite=2.99, 95% CI: 2.74, 3.26). Diabetes was associated with a 3040% increase in risk among both groups. Increasing parity was associated with decreasing risk of EC in blacks and whites (p-value=0.02 and <0.001, respectively). Current and former smoking was associated with decreased risk of EC among all women. Both black and white women who used oral contraceptives for 10+ years were also at reduced risk of EC (OR=0.49, 95% CI: 0.27, 0.88 and OR=0.69, 95% CI: 0.58, 0.83, respectively). Previous history of hypertension was not associated with EC risk in either group. Conclusions The major known risk factors for EC exert similar effects on black and white women. Differences in the incidence rates between the two populations may be due to differences in the prevalence of risk factors. PMID:25534916

  4. Comparison of anthropometric measures as predictors of cancer incidence: A pooled collaborative analysis of 11 Australian cohorts.

    PubMed

    Harding, Jessica L; Shaw, Jonathan E; Anstey, Kaarin J; Adams, Robert; Balkau, Beverley; Brennan-Olsen, Sharon L; Briffa, Tom; Davis, Timothy M E; Davis, Wendy A; Dobson, Annette; Flicker, Leon; Giles, Graham; Grant, Janet; Huxley, Rachel; Knuiman, Matthew; Luszcz, Mary; MacInnis, Robert J; Mitchell, Paul; Pasco, Julie A; Reid, Christopher; Simmons, David; Simons, Leon; Tonkin, Andrew; Woodward, Mark; Peeters, Anna; Magliano, Dianna J

    2015-10-01

    Obesity is a risk factor for cancer. However, it is not known if general adiposity, as measured by body mass index (BMI) or central adiposity [e.g., waist circumference (WC)] have stronger associations with cancer, or which anthropometric measure best predicts cancer risk. We included 79,458 men and women from the Australian and New Zealand Diabetes and Cancer Collaboration with complete data on anthropometry [BMI, WC, Hip Circumference (HC), WHR, waist to height ratio (WtHR), A Body Shape Index (ABSI)], linked to the Australian Cancer Database. Cox proportional hazards models assessed the association between each anthropometric marker, per standard deviation and the risk of overall, colorectal, post-menopausal (PM) breast, prostate and obesity-related cancers. We assessed the discriminative ability of models using Harrell's c-statistic. All anthropometric markers were associated with overall, colorectal and obesity-related cancers. BMI, WC and HC were associated with PM breast cancer and no significant associations were seen for prostate cancer. Strongest associations were observed for WC across all outcomes, excluding PM breast cancer for which HC was strongest. WC had greater discrimination compared to BMI for overall and colorectal cancer in men and women with c-statistics ranging from 0.70 to 0.71. We show all anthropometric measures are associated with the overall, colorectal, PM breast and obesity-related cancer in men and women, but not prostate cancer. WC discriminated marginally better than BMI. However, all anthropometric measures were similarly moderately predictive of cancer risk. We do not recommend one anthropometric marker over another for assessing an individuals' risk of cancer. PMID:25810218

  5. Angiogenesis inhibitors rechallenge in patients with advanced non-small-cell lung cancer: a pooled analysis of randomized controlled trials

    PubMed Central

    Zhao, Lingdi; Li, Wei; Zhang, Huiying; Hou, Nan; Guo, Lanwei; Gao, Quanli

    2015-01-01

    Purpose Data on the role of angiogenesis inhibitors (AIs) rechallenge in the treatment of advanced non-small-cell lung cancer (NSCLC) patients who previously received bevacizumab remain limited. We aim to investigate the efficacy of AIs in the treatment of advanced NSCLC in this setting. Methods Studies from PubMed, Web of Science, and abstracts presented at American Society of Clinical Oncology meeting up to December 1, 2014 were searched to identify relevant studies. Eligible studies included prospective randomized controlled trials evaluating AIs in advanced NSCLC, with survival data on patients who previously received bevacizumab. The end points were overall survival and progression-free survival. Statistical analyses were conducted by using either random effects or fixed effect models according to the heterogeneity of included studies. Results A total of 452 patients with advanced NSCLC who previously received bevacizumab were identified for analysis. The meta-analysis results demonstrated that AI rechallenge significantly improved progression-free survival (hazard ratio: 0.72, 95% confidence interval: 0.58–0.89, P=0.002) when compared to non-AI containing regimens. Additionally, a nonsignificant improvement in overall survival was also observed in advanced NSCLC in this setting (hazard ratio: 0.82, 95% confidence interval: 0.65–1.03, P=0.087). Similar results were also observed in subgroup analysis according to treatment regimens. Conclusion The findings of this study suggest that NSCLC patients who relapsed after a first-line bevacizumab-containing chemotherapy obtain improved clinical benefits from AI rechallenge. Prospective clinical trials investigating the role of AI rechallenge in this setting are recommended. PMID:26491352

  6. The RTK/ERK pathway is associated with prostate cancer risk on the SNP level: a pooled analysis of 41 sets of data from case-control studies.

    PubMed

    Chen, Yang; Li, Tianyu; Yu, Xiaoqiang; Xu, Jianfeng; Li, Jianling; Luo, Dexiang; Mo, Zengnan; Hu, Yanling

    2014-01-25

    Prostate cancer (PCa) is a malignant disease influencing numerous men worldwide every year. However, the exact pathogenesis and the genes, environment, and other factors involved have not been explained clearly. Some studies have proposed that cell signaling pathways might play a key role in the development and progression of PCa. According to our previous study, the RTK/ERK pathway containing nearly 40 genes was associated with PCa risk. On the basis of these genes, we conducted a meta-analysis with our own Chinese Consortium for Prostate Cancer Genetics (ChinaPCa) study and available studies in the databases to describe the association between the pathway and PCa on the SNP level. The results suggested that rs4764695/IGF1 (recessive model: pooled OR=0.92, 95%CI=0.852-0.994, P=0.034; I(2)=0%, P=0.042; allele analysis: pooled OR=0.915, 95%CI=0.874-0.958, P=0; I(2)=0%, P=0.424; codominant model: OR=0.835, 95%CI=0.762-0.916, P=0; I(2)=0%, P=0.684) and rs1570360/VEGF (recessive model: OR=0.596, 95%CI=0.421-0.843, P=0.003; I(2)=23.9%, P=0.269; codominant model: OR=0.576, 95%CI=0.404-0.820, P=0.002; I(2)=49.1%, P=0.140) were significantly associated with PCa. In subgroup analysis, the relationship was also found in Caucasians for IGF1 (dominant model: OR=0.834, 95%CI=0.769-0.904, P=0; allele analysis: OR=0.908, 95%CI=0.863-0.955, P=0; AA vs CC: OR=0.829, 95%CI=0.750-0.916, P=0; AC vs CC: OR=0.837, 95%CI=0.768-0.912, P=0). In addition, in Asians (allele analysis: OR=0.21, 95%CI=0.168-0.262, P=0) and Caucasians (recessive model: OR=0.453, 95%CI: 0.240-0.855, P=0.015; codominant model: OR=0.464, 95%CI=0.240-0.898, P=0.023) for VEGF, the association was significant. The results indicated that rs4764695/IGF1 and rs1570360/VEGF might play a key role in the development and progression of PCa. On the SNP level, we suggest that the study gives us a new view of gene-pathway analysis and targeted therapy for PCa. PMID:24177231

  7. Analysis of deoxyribonucleotide pools in human cancer cell lines using a liquid chromatography coupled with tandem mass spectrometry technique

    PubMed Central

    Zhang, Wei; Tan, Shenglan; Paintsil, Elijah; Dutschman, Ginger E.; Gullen, Elizabeth A.; Chu, Edward; Cheng, Yung-Chi

    2011-01-01

    Endogenous ribonucleotides and deoxyribonucleotides play a critical role in cell function, and determination of their levels is of fundamental importance in understanding key cellular processes involved in energy metabolism and molecular and biochemical signaling pathways. In this study, we determined the respective ribonucleotide and deoxyribonucleotide pool sizes in different human cell lines using a simple sample preparation method and LC/MS/MS. This assay was used to determine alterations in deoxyribonucleotide pools in human pancreatic PANC-1 cells in response to hypoxia and to treatment with either hydroxyurea or aphidicolin. The levels of all deoxyribonucleotide metabolites decreased with hypoxia treatment, except for dUMP, which increased by two-fold. This LC/MS/MS assay is simple, fast, and sensitive, and it represents a significant advance over previously published methodologies. PMID:21620803

  8. Improving Selection Criteria for ALK Inhibitor Therapy in Non-Small Cell Lung Cancer: A Pooled-Data Analysis on Diagnostic Operating Characteristics of Immunohistochemistry.

    PubMed

    Jiang, Long; Yang, Haihong; He, Ping; Liang, Wenhua; Zhang, Jianrong; Li, Jingpei; Liu, Yang; He, Jianxing

    2016-05-01

    Lung cancer is often diagnosed by molecular markers for prediction and treatment. To date, the golden standard for detection of anaplastic lymphoma kinase (ALK) rearrangements is fluorescence in situ hybridization (FISH). We performed a pooled-data analysis on the diagnostic operating characteristics of immunohistochemistry (IHC) assay on non-small cell lung cancer (NSCLC). We searched Embase, Pubmed, and Springer databases. The results of IHC were evaluated using a modified H-score. We used a 2-level bivariate meta-analysis following a random effect model to summarize sensitivity and specificity and fit hierarchical summary receiver-operating characteristic curves. We also performed sensitivity analysis using different antibodies to investigate potential heterogeneity. Twelve studies consisting of a total of 3754 NSCLC specimens were analyzed. When we defined 1+/2+/3+, 2+/3+, and 3+ as ALK positive, we found the sensitivities to be 99% (95% confidence interval [CI], 97%-100%), 86% (95% CI, 73%-93%), and 56% (95% CI, 36%-74%) and the specificities to be 98% (95% CI, 95%-99%), 99% (95% CI, 99%-100%), and 100% (95% CI, 100%-100%), respectively. We demonstrated that when defining 3+ as positive and 0 as negative the sensitivity was 99% and specificity was 100%. In our sensitivity analysis, we found the sensitivity of D5F3 and 5A4 antibodies to be much higher than that of ALK1. We concluded that IHC scores 0 and 3+ were nearly 100% concordant with FISH-negative and FISH-positive status, respectively. However, IHC scores 1+ and 2+ might require further confirmatory testing by FISH assay. IHC assay using D5F3 and 5A4 antibodies reliably detected NSCLC with ALK rearrangement and may be useful as a screening method to identify these tumors. PMID:26825369

  9. Complete response to preoperative chemoradiation and survival in esophageal cancer: a pooled analysis of three single-institution phase II trials.

    PubMed

    Orditura, M; Galizia, G; Morgillo, F; Martinelli, E; Lieto, E; Vitiello, F; Di Martino, N; Pacelli, R; Renda, A; Ciardiello, F; De Vita, F

    2012-02-01

    This pooled analysis was performed using individual patient data from three phase II trials that included on the whole 113 esophageal cancer treated preoperatively with chemoradiotherapy (CRT), in order to analyze the efficacy and survival outcomes according to the achievement of the pathologic complete response (pCR). Thirty-nine patients were treated with 5-fluorouracil/cisplatin and RT (40 Gy), 33 patients received paclitaxel/cisplatin weekly during weeks 1-6 with and RT (46 Gy), 41 patients were treated with induction bio-chemotherapy with cetuximab and FOLFOX-4 followed by concomitant cetuximab and RT of 50.4 Gy. One hundred and two out of 113 resected patients were included in the survival analysis. The median overall survival (OS) time for the whole population was 21.5 months. The 12, 24, and 36 months OS rates were 85.4, 45.2, and 33%, respectively. The difference in survival probability between patients with pCR and patients with partial response or stable disease after treatment was significant (P= 0.0002, hazard ratios = 0.21, 95% CI 0.18-0.60). On multivariate analysis, the pathologic response and histology were the only covariates independently associated with OS (P= 0.0157 and P= 0.0212, respectively). In our series, complete responder patients had a significant longer survival probability after treatment when compared to patients with partial response or stable disease. PMID:21762278

  10. The association between polymorphisms in the MDR1 gene and risk of cancer: a systematic review and pooled analysis of 52 case–control studies

    PubMed Central

    2013-01-01

    Background The multidrug resistance (MDR) 1 gene encodes a 170-kDa membrane transporter called P-glycoprotein, which plays an important role in protecting cells against lipophilic xenobiotics by the way of an ATP-dependent cellular efflux mechanism. Three polymorphisms of MDR1, 3435C > T located in exon 26, 1236C > T in exon 12 and 2677G > T/A in exon 21 were the most extensively studied and were identified functionally important and ethnically diverse mapping to the gene region. Considering the potential influence of altering MDR1 activity, it is plausible that MDR1 polymorphisms might play a role in the development of cancer. Although the effects of MDR1 polymorphisms on susceptibility to human cancer have been investigated in many studies, the results still remain conflicting. Methods To resolve these conflicts, we performed a quantitative synthesis of the association between these three polymorphisms and cancer risk, including 52 studies (15789 cases and 20274 controls) for 3435C > T polymorphism, 10 studies (2101 cases and 2842 controls) for 1236C > T polymorphism and 18 studies (3585 cases and 4351 controls) for 2677G > T/A polymorphism. Results The stratified analyses for 3435C > T polymorphism, individuals with T-allele in 3435C > T had significantly higher ALL risks (TT versus CC: OR =1.286, 95% CI =1.123-1.474); significantly elevated risks were observed among Caucasian populations (TT versus CC: OR =1.276, 95% CI =1.112-1.464). When restricting the analysis to the source of controls, we found that HB (hospital-based) genetic models had higher risks (TT versus CC: OR =1.307, 95% CI =1.046-1.632), as well as in PB (population-based) genetic models (TT versus CC: OR =1.294, 95% CI =1.079-1.55). The T/A-allele frequency of 2677G > T/A polymorphism was associated with higher risk of cancer (TT + TA + AA vs. GG: OR =1.348, 95% CI =1.031-1.762), significantly elevated risks were observed among Asian populations (TT + TA + AA vs. GG: OR =1.642, 95% CI =1.340-2.012), and elevated risks could be associated with PB models (TT + TA + AA vs. GG: OR =1.641, 95% CI =1.018-2.646). Conclusions Our meta-analysis suggested that 3435C > T polymorphism and 2677G > T/A polymorphism were associated with cancer risk when all studies were pooled together, while 1236C > T polymorphism not. PMID:23687985

  11. Communicating advanced cancer patients’ symptoms via the Internet: A pooled analysis of two randomized trials examining caregiver preparedness, physical burden and negative mood

    PubMed Central

    Chih, Ming-Yuan; DuBenske, Lori L; Hawkins, Robert P; Brown, Roger L; Dinauer, Susan K; Cleary, James F; Gustafson, David H

    2013-01-01

    Background Using available communication technologies, clinicians may offer timely support to family caregivers in managing symptoms in patients with advanced cancer at home. Aim To assess the effects of an online symptom reporting system on caregiver preparedness, physical burden, and negative mood. Design A pooled analysis of two randomized trials (NCT00214162 and NCT00365963) was conducted to compare caregiver outcomes at 6 and 12 months after intervention between two randomized, unblinded groups using General Linear Mixed Modeling. Caregivers in one group (Comprehensive Health Enhancement Support System-Only) were given access to an interactive cancer communication system, the Comprehensive Health Enhancement Support System. Those in the other group (Comprehensive Health Enhancement Support System + Clinician Report) received access to Comprehensive Health Enhancement Support System plus an online symptom reporting system called the Clinician Report. Clinicians of patients in the Comprehensive Health Enhancement Support System + Clinician Report group received e-mail alerts notifying them when a symptom distress was reported over a predetermined threshold. Setting/Participants Dyads (n=235) of advanced-stage lung, breast, and prostate cancer patients and their adult caregivers were recruited at five outpatient oncology clinics in the United States. Results Caregivers in the Comprehensive Health Enhancement Support System + Clinician Report group reported less negative mood than those in the Comprehensive Health Enhancement Support System-Only group at both 6 months (p=0.009) and 12 months (p=0.004). Groups were not significantly different on caregiver preparedness or physical burden at either time point. Conclusions This study provides new evidence that by using an online symptom reporting system, caregivers may experience less emotional distress due to the Clinician Report’s timely communication of caregiving needs in symptom management to clinicians. PMID:22988042

  12. Little association between the interleukin 10-3575T/A polymorphism and cancer risk: pooled analysis of 15608 cancer cases and 17539 controls

    PubMed Central

    Zhu, Biyuan; Xiao, Chaolie; Zhu, Biqing; Zheng, Zhiwen; Liang, Jingjing

    2015-01-01

    The aim of the present work was to evaluate the association between the interleukin 10 (IL-10) -3575T/A (rs1800890) polymorphism and cancer risk. We performed a met-analysis based on 15 studies, including 15608 cancer cases and 17539 controls. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association, and performed sensitivity analyses. In the stratified analyses by all included studies, no association between IL-10-3575T/A (rs1800890) polymorphism and cancer risk (OR=0.966, 95% CI=0.889-1.05, P=0.417 for A vs. T; OR=1.035, 95% CI=0.975-1.1, P=0.257 for AA vs. AT+TT; OR=1.008, 95% CI=0.964-1.054, P=0.723 for AA+AT vs. TT) was observed. In the stratified analyses by cancer type of lymphoma and non-lymphoma, no association between them was also detected (Lymphoma: OR=1.021, 95% CI=0.962-1.083, P=0.496 for A vs. T; OR=1.029, 95% CI=0.967-1.095, P=0.363 for AA vs. AT+TT; OR=1.017, 95% CI=0.952-1.086, P=0.626 for AA+AT vs. TT; Non-lymphoma: OR=0.966 95% CI=0.889-1.51, P=0.245 for A vs. T; OR=1.035, 95% CI=0.975-1.1, P=0.287 for AA vs. AT+TT; OR=1.017, 95% CI=0.948-1.091, P=0.967 for AA+AT vs. TT). The results were the same by sensitivity analyses. No publication bias was existed in the analysis. The interleukin 10-3575T/A polymorphism may have no association with cancer risk. PMID:26550419

  13. Intrathecal administration of trastuzumab for the treatment of meningeal carcinomatosis in HER2-positive metastatic breast cancer: a systematic review and pooled analysis.

    PubMed

    Zagouri, Flora; Sergentanis, Theodoros N; Bartsch, Rupert; Berghoff, Anna S; Chrysikos, Dimosthenis; de Azambuja, Evandro; Dimopoulos, Meletios-Athanassios; Preusser, Matthias

    2013-05-01

    Leptomeningeal carcinomatosis (MC) represents an uncommon, but devasting manifestation of metastatic breast cancer. This is the first systematic review/pooled analysis to synthesize all available data evaluating the efficacy and safety of intrathecal (IT) administration of trastuzumab for the treatment of MC in HER2-positive breast cancer patients. This study was performed in accordance with the PRISMA guidelines. A total of 13 articles (17 patients) were eligible. The mean age of patients at IT trastuzumab administration was 48.2 years (SD 8.4, range 38-66). The mean total dose was 399.8 mg (SD 325.4, range 35-1,110 mg). IT trastuzumab alone or as part of combination therapies seemed to be safe; no serious adverse events were reported in 88.2 % of cases. In 68.8 % of cases, a significant clinical improvement was observed, while stabilization or progression of the disease was noticed in 31.2 % of cases. Cerebrospinal fluid (CSF) response was noted in 66.7 % of cases. The median overall survival was 13.5 months, whereas the median central nervous system progression-free survival (CNS-PFS) was 7.5 months. In 23.5 % of cases, IT trastuzumab was administered beyond CNS progression with a response noticed in 75 % of cases and a CNS-PFS of 9.4 months. The cumulative dose of IT trastuzumab given was 1,040 mg (SD 697.9, median 1,215, range 55-1,675). The protective effect of prior radio- or neurosurgery upon CNS-PFS was sizeable but did not reach formal statistical significance (HR 0.28, 95 % CI 0.06-1.37). Clinical improvement (HR 0.14, 95 % CI 0.02-0.91) and CSF response (HR 0.09, 95 % CI 0.01-0.89) were associated with longer CNS-PFS. IT trastuzumab administration seems to represent a safe and in some cases effective option for the treatment of HER2-positive breast cancer patients with leptomeningeal involvement. However, clinical trials are urgently needed to establish the definite role of IT trastuzumab in HER2-positive metastatic breast cancer patients with MC. PMID:23588955

  14. Pooled analysis of the accuracy of five cervical cancer screening tests assessed in eleven studies in Africa and India.

    PubMed

    Arbyn, Marc; Sankaranarayanan, Rengaswamy; Muwonge, Richard; Keita, Namory; Dolo, Amadou; Mbalawa, Charles Gombe; Nouhou, Hassan; Sakande, Boblewende; Wesley, Ramani; Somanathan, Thara; Sharma, Anjali; Shastri, Surendra; Basu, Parthasarathy

    2008-07-01

    Cervical cancer is the main cancer among women in sub-Saharan Africa, India and other parts of the developing world. Evaluation of screening performance of effective, feasible and affordable early detection and management methods is a public health priority. Five screening methods, naked eye visual inspection of the cervix uteri after application of diluted acetic acid (VIA), or Lugol's iodine (VILI) or with a magnifying device (VIAM), the Pap smear and human papillomavirus testing with the high-risk probe of the Hybrid Capture-2 assay (HC2), were evaluated in 11 studies in India and Africa. More than 58,000 women, aged 25-64 years, were tested with 2-5 screening tests and outcome verification was done on all women independent of the screen test results. The outcome was presence or absence of cervical intraepithelial neoplasia (CIN) of different degrees or invasive cervical cancer. Verification was based on colposcopy and histological interpretation of colposcopy-directed biopsies. Negative colposcopy was accepted as a truly negative outcome. VIA showed a sensitivity of 79% (95% CI 73-85%) and 83% (95% CI 77-89%), and a specificity of 85% (95% CI 81-89%) and 84% (95% CI 80-88%) for the outcomes CIN2+ or CIN3+, respectively. VILI was on average 10% more sensitive and equally specific. VIAM showed similar results as VIA. The Pap smear showed lowest sensitivity, even at the lowest cutoff of atypical squamous cells of undetermined significance (57%; 95% CI 38-76%) for CIN2+ but the specificity was rather high (93%; 95% CI 89-97%). The HC2-assay showed a sensitivity for CIN2+ of 62% (95% CI 56-68%) and a specificity of 94% (95% CI 92-95%). Substantial interstudy variation was observed in the accuracy of the visual screening methods. Accuracy of visual methods and cytology increased over time, whereas performance of HC2 was constant. Results of visual tests and colposcopy were highly correlated. This study was the largest ever done that evaluates the cross-sectional accuracy of screening tests for cervical cancer precursors in developing countries. The merit of the study was that all screened subjects were submitted to confirmatory investigations avoiding to verification bias. A major finding was the consistently higher sensitivity but equal specificity of VILI compared with VIA. Nevertheless, some caution is warranted in the interpretation of observed accuracy measures, since a certain degree of gold standard misclassification cannot be excluded. Because of the correlation between visual screening tests and colposcopy and a certain degree of over-diagnosis of apparent CIN2+ by study pathologists, it is possible that both sensitivity and specificity of VIA and VILI were overestimated. Gold standard verification error could also explain the surprisingly low sensitivity of HC2, which contrasts with findings from other studies. PMID:18404671

  15. Associations between unprocessed red and processed meat, poultry, seafood and egg intake and the risk of prostate cancer: A pooled analysis of 15 prospective cohort studies.

    PubMed

    Wu, Kana; Spiegelman, Donna; Hou, Tao; Albanes, Demetrius; Allen, Naomi E; Berndt, Sonja I; van den Brandt, Piet A; Giles, Graham G; Giovannucci, Edward; Alexandra Goldbohm, R; Goodman, Gary G; Goodman, Phyllis J; Håkansson, Niclas; Inoue, Manami; Key, Timothy J; Kolonel, Laurence N; Männistö, Satu; McCullough, Marjorie L; Neuhouser, Marian L; Park, Yikyung; Platz, Elizabeth A; Schenk, Jeannette M; Sinha, Rashmi; Stampfer, Meir J; Stevens, Victoria L; Tsugane, Shoichiro; Visvanathan, Kala; Wilkens, Lynne R; Wolk, Alicja; Ziegler, Regina G; Smith-Warner, Stephanie A

    2016-05-15

    Reports relating meat intake to prostate cancer risk are inconsistent. Associations between these dietary factors and prostate cancer were examined in a consortium of 15 cohort studies. During follow-up, 52,683 incident prostate cancer cases, including 4,924 advanced cases, were identified among 842,149 men. Cox proportional hazard models were used to calculate study-specific relative risks (RR) and then pooled using random effects models. Results do not support a substantial effect of total red, unprocessed red and processed meat for all prostate cancer outcomes, except for a modest positive association for tumors identified as advanced stage at diagnosis (advanced(r)). For seafood, no substantial effect was observed for prostate cancer regardless of stage or grade. Poultry intake was inversely associated with risk of advanced and fatal cancers (pooled multivariable RR [MVRR], 95% confidence interval, comparing ≥45 vs. <5 g/day: advanced 0.83, 0.70-0.99; trend test p value 0.29), fatal, 0.69, 0.59-0.82, trend test p value 0.16). Participants who ate ≥25 versus <5 g/day of eggs (1 egg ∼ 50 g) had a significant 14% increased risk of advanced and fatal cancers (advanced 1.14, 1.01-1.28, trend test p value 0.01; fatal 1.14, 1.00-1.30, trend test p value 0.01). When associations were analyzed separately by geographical region (North America vs. other continents), positive associations between unprocessed red meat and egg intake, and inverse associations between poultry intake and advanced, advanced(r) and fatal cancers were limited to North American studies. However, differences were only statistically significant for eggs. Observed differences in associations by geographical region warrant further investigation. PMID:26685908

  16. Associations between unprocessed red and processed meat, poultry, seafood and egg intake and the risk of prostate cancer: A pooled analysis of 15 prospective cohort studies

    PubMed Central

    Wu, Kana; Spiegelman, Donna; Hou, Tao; Albanes, Demetrius; Allen, Naomi E.; Berndt, Sonja I.; van den Brandt, Piet A.; Giles, Graham G.; Giovannucci, Edward; Goldbohm, R. Alexandra; Goodman, Gary G.; Goodman, Phyllis J.; Håkansson, Niclas; Inoue, Manami; Key, Timothy J.; Kolonel, Laurence N.; Männistö, Satu; McCullough, Marjorie L.; Neuhouser, Marian L.; Park, Yikyung; Platz, Elizabeth A.; Schenk, Jeannette M.; Sinha, Rashmi; Stampfer, Meir J.; Stevens, Victoria L.; Tsugane, Shoichiro; Visvanathan, Kala; Wilkens, Lynne R.; Wolk, Alicja; Ziegler, Regina G.; Smith-Warner, Stephanie A.

    2016-01-01

    Reports relating meat intake to prostate cancer risk are inconsistent. Associations between these dietary factors and prostate cancer were examined in a consortium of 15 cohort studies. During follow-up, 52, 683 incident prostate cancer cases, including 4,924 advanced cases, were identified among 842, 149 men. Cox proportional hazard models were used to calculate study-specific relative risks (RR) and then pooled using random effects models. Results do not support a substantial effect of total red, unprocessed red and processed meat for all prostate cancer outcomes, except for a modest positive association for tumors identified as advanced stage at diagnosis (advanced(r)). For seafood, no substantial effect was observed for prostate cancer regardless of stage or grade. Poultry intake was inversely associated with risk of advanced and fatal cancers (pooled multivariable RR [MVRR], 95% confidence interval, comparing ≥45 vs. <5 g/day: advanced 0.83, 0.70–0.99; trend test p value 0.29), fatal, 0.69, 0.59–0.82, trend test p value 0.16). Participants who ate ≥25 versus <5 g/day of eggs (1 egg ~ 50 g) had a significant 14% increased risk of advanced and fatal cancers (advanced 1.14, 1.01–1.28, trend test p value 0.01; fatal 1.14, 1.00–1.30, trend test p value 0.01). When associations were analyzed separately by geographical region (North America vs. other continents), positive associations between unprocessed red meat and egg intake, and inverse associations between poultry intake and advanced, advanced(r) and fatal cancers were limited to North American studies. However, differences were only statistically significant for eggs. Observed differences in associations by geographical region warrant further investigation. PMID:26685908

  17. Nomograms for Prediction of Outcome With or Without Adjuvant Radiation Therapy for Patients With Endometrial Cancer: A Pooled Analysis of PORTEC-1 and PORTEC-2 Trials

    SciTech Connect

    Creutzberg, Carien L.; Stiphout, Ruud G.P.M. van; Nout, Remi A.; Lutgens, Ludy C.H.W.; Jürgenliemk-Schulz, Ina M.; Jobsen, Jan J.; Smit, Vincent T.H.B.M.; Lambin, Philippe

    2015-03-01

    Background: Postoperative radiation therapy for stage I endometrial cancer improves locoregional control but is without survival benefit. To facilitate treatment decision support for individual patients, accurate statistical models to predict locoregional relapse (LRR), distant relapse (DR), overall survival (OS), and disease-free survival (DFS) are required. Methods and Materials: Clinical trial data from the randomized Post Operative Radiation Therapy for Endometrial Cancer (PORTEC-1; N=714 patients) and PORTEC-2 (N=427 patients) trials and registered group (grade 3 and deep invasion, n=99) were pooled for analysis (N=1240). For most patients (86%) pathology review data were available; otherwise original pathology data were used. Trial variables which were clinically relevant and eligible according to data constraints were age, stage, given treatment (pelvic external beam radiation therapy (EBRT), vaginal brachytherapy (VBT), or no adjuvant treatment, FIGO histological grade, depth of invasion, and lymph-vascular invasion (LVSI). Multivariate analyses were based on Cox proportional hazards regression model. Predictors were selected based on a backward elimination scheme. Model results were expressed by the c-index (0.5-1.0; random to perfect prediction). Two validation sets (n=244 and 291 patients) were used. Results: Accuracy of the developed models was good, with training accuracies between 0.71 and 0.78. The nomograms validated well for DR (0.73), DFS (0.69), and OS (0.70), but validation was only fair for LRR (0.59). Ranking of variables as to their predictive power showed that age, tumor grade, and LVSI were highly predictive for all outcomes, and given treatment for LRR and DFS. The nomograms were able to significantly distinguish low- from high-probability patients for these outcomes. Conclusions: The nomograms are internally validated and able to accurately predict long-term outcome for endometrial cancer patients with observation, pelvic EBRT, or VBT after surgery. These models facilitate decision support in daily clinical practice and can be used for patient counseling and shared decision making, selecting patients who benefit most from adjuvant treatment, and generating new hypotheses.

  18. Preoperative Radiotherapy of Advanced Rectal Cancer With Capecitabine and Oxaliplatin With or Without Cetuximab: A Pooled Analysis of Three Prospective Phase I-II Trials

    SciTech Connect

    Weiss, Christian; Arnold, Dirk; Dellas, Kathrin; Liersch, Torsten; Hipp, Matthias; Fietkau, Rainer; Sauer, Rolf; Hinke, Axel; Roedel, Claus

    2010-10-01

    Purpose: A pooled analysis of three prospective trials of preoperative radiochemotherapy (RCT) for rectal cancer by using oxaliplatin and capecitabine with or without cetuximab was performed to evaluate the impact of additional cetuximab on pathologic complete response (pCR) rates and tumor regression (TRG) grades. Methods and Materials: Of 202 patients, 172 patients met the inclusion criteria (primary tumor stage II/III, M0). All patients received concurrent RCT, and 46 patients received additional cetuximab therapy. A correlation of pretreatment clinicopathologic factors and cetuximab treatment with early pCR rates (TRG > 50%) was performed with univariate and multivariate analyses. Toxicity data were recorded for all patients. Results: Of 172 patients, 24 (14%) patients achieved a pCR, and 84 of 172 (71%) patients showed a TRG of >50% in the surgical specimen assessment after preoperative treatment. Age, gender, and T/N stages, as well as localization of the tumor, were not associated with pCR or good TRG. The pCR rate was 16% after preoperative RCT alone and 9% with concurrent cetuximab therapy (p = 0.32). A significantly reduced TRG of >50% was found after RCT with cetuximab compared to RCT alone (p = 0.0035). This was validated by a multivariate analysis with all available clinical factors (p = 0.0037). Acute toxicity and surgical complications were not increased with additional cetuximab. Conclusions: Triple therapy with RCT and cetuximab seems to be feasible, with no unexpected toxicity. Early response assessment (TRG), however, suggests subadditive interaction. A longer follow-up (and finally randomized trials) is needed to draw any firm conclusions with respect to local and distant failure rates.

  19. Estimating and explaining the effect of education and income on head and neck cancer risk: INHANCE consortium pooled analysis of 31 case-control studies from 27 countries

    PubMed Central

    Conway, David I.; Brenner, Darren R.; McMahon, Alex D.; Macpherson, Lorna M.D.; Agudo, Antonio; Ahrens, Wolfgang; Bosetti, Cristina; Brenner, Hermann; Castellsague, Xavier; Chen, Chu; Curado, Maria Paula; Curioni, Otávio A.; Maso, Luigino Dal; Daudt, Alexander W.; de Gois Filho, José F.; D'Souza, Gypsyamber; Edefonti, Valeria; Fabianova, Eleonora; Fernandez, Leticia; Franceschi, Silvia; Gillison, Maura; Hayes, Richard B.; Healy, Claire M.; Herrero, Rolando; Holcatova, Ivana; Jayaprakash, Vijayvel; Kelsey, Karl; Kjaerheim, Kristina; Koifman, Sergio; La Vecchia, Carlo; Lagiou, Pagona; Lazarus, Philip; Levi, Fabio; Lissowska, Jolanta; Luce, Daniele; Macfarlane, Tatiana V.; Mates, Dana; Matos, Elena; McClean, Michael; Menezes, Ana M; Menvielle, Gwenn; Merletti, Franco; Morgenstern, Hal; Moysich, Kirsten; Müller, Heiko; Muscat, Joshua; Olshan, Andrew F.; Purdue, Mark P.; Ramroth, Heribert; Richiardi, Lorenzo; Rudnai, Peter; Schantz, Stimson; Schwartz, Stephen M.; Shangina, Oxana; Simonato, Lorenzo; Smith, Elaine; Stucker, Isabelle; Sturgis, Erich M.; Szeszenia-Dabrowska, Neonila; Talamini, Renato; Thomson, Peter; Vaughan, Thomas L.; Wei, Qingyi; Winn, Deborah M.; Wunsch-Filho, Victor; Yu, Guo-Pei; Zhang, Zuo-Feng; Zheng, Tongzhang; Znaor, Ariana; Boffetta, Paolo; Chuang, Shu-Chun; Ghodrat, Marianoosh; Lee, Yuan-Chin Amy; Hashibe, Mia; Brennan, Paul

    2015-01-01

    Low socioeconomic status has been reported to be associated with head and neck cancer risk. However, previous studies have been too small to examine the associations by cancer subsite, age, sex, global region and calendar time and to explain the association in terms of behavioral risk factors. Individual participant data of 23,964 cases with head and neck cancer and 31,954 controls from 31 studies in 27 countries pooled with random effects models. Overall, low education was associated with an increased risk of head and neck cancer (OR = 2.50; 95% CI = 2.02 – 3.09). Overall one-third of the increased risk was not explained by differences in the distribution of cigarette smoking and alcohol behaviors; and it remained elevated among never users of tobacco and nondrinkers (OR = 1.61; 95% CI = 1.13 – 2.31). More of the estimated education effect was not explained by cigarette smoking and alcohol behaviors: in women than in men, in older than younger groups, in the oropharynx than in other sites, in South/Central America than in Europe/North America and was strongest in countries with greater income inequality. Similar findings were observed for the estimated effect of low versus high household income. The lowest levels of income and educational attainment were associated with more than 2-fold increased risk of head and neck cancer, which is not entirely explained by differences in the distributions of behavioral risk factors for these cancers and which varies across cancer sites, sexes, countries and country income inequality levels. PMID:24996155

  20. Body Mass Index and Risk of Second Obesity-Associated Cancers After Colorectal Cancer: A Pooled Analysis of Prospective Cohort Studies

    PubMed Central

    Gibson, Todd M.; Park, Yikyung; Robien, Kim; Shiels, Meredith S.; Black, Amanda; Sampson, Joshua N.; Purdue, Mark P.; Beane Freeman, Laura E.; Andreotti, Gabriella; Weinstein, Stephanie J.; Albanes, Demetrius; Fraumeni, Joseph F.; Curtis, Rochelle E.; Berrington de Gonzalez, Amy; Morton, Lindsay M.

    2014-01-01

    Purpose To determine whether prediagnostic body mass index (BMI) is associated with risk of second obesity-associated cancers in colorectal cancer (CRC) survivors, and whether CRC survivors have increased susceptibility to obesity-associated cancer compared with cancer-free individuals. Patients and Methods Incident first primary CRC cases (N = 11,598) were identified from five prospective cohort studies. We used Cox proportional hazards regression models to examine associations between baseline (prediagnostic) BMI and risk of second obesity-associated cancers (postmenopausal breast, kidney, pancreas, esophageal adenocarcinoma, endometrium) in CRC survivors, and compared associations to those for first obesity-associated cancers in the full cohort. Results Compared with survivors with normal prediagnostic BMI (18.5-24.9 kg/m2), those who were overweight (25-29.9 kg/m2) or obese (30+ kg/m2) had greater risk of a second obesity-associated cancer (n = 224; overweight hazard ratio [HR], 1.39; 95% CI, 1.01 to 1.92; obese HR, 1.47; 95% CI, 1.02 to 2.12; per 5-unit change in BMI HR, 1.12; 95% CI, 0.98 to 1.29). The magnitude of risk for developing a first primary obesity-associated cancer was similar (overweight HR, 1.18; 95% CI, 1.14 to 1.21; obese HR, 1.61; 95% CI, 1.56 to 1.66; per 5-unit change in BMI HR, 1.23; 95% CI, 1.21 to 1.24). Before diagnosis CRC patients were somewhat more likely than the overall cohort to be overweight (44% v 41%) or obese (25% v 21%). Conclusion CRC survivors who were overweight or obese before diagnosis had increased risk of second obesity-associated cancers compared with survivors with normal weight. The risks were similar in magnitude to those observed for first cancers in this population, suggesting increased prevalence of overweight or obesity, rather than increased susceptibility, may contribute to elevated second cancer risks in colorectal cancer survivors compared with the general population. These results support emphasis of existing weight guidelines for this high-risk group. PMID:25267739

  1. Gene expression profiling of breast cancer survivability by pooled cDNA microarray analysis using logistic regression, artificial neural networks and decision trees

    PubMed Central

    2013-01-01

    Background Microarray technology can acquire information about thousands of genes simultaneously. We analyzed published breast cancer microarray databases to predict five-year recurrence and compared the performance of three data mining algorithms of artificial neural networks (ANN), decision trees (DT) and logistic regression (LR) and two composite models of DT-ANN and DT-LR. The collection of microarray datasets from the Gene Expression Omnibus, four breast cancer datasets were pooled for predicting five-year breast cancer relapse. After data compilation, 757 subjects, 5 clinical variables and 13,452 genetic variables were aggregated. The bootstrap method, Mann–Whitney U test and 20-fold cross-validation were performed to investigate candidate genes with 100 most-significant p-values. The predictive powers of DT, LR and ANN models were assessed using accuracy and the area under ROC curve. The associated genes were evaluated using Cox regression. Results The DT models exhibited the lowest predictive power and the poorest extrapolation when applied to the test samples. The ANN models displayed the best predictive power and showed the best extrapolation. The 21 most-associated genes, as determined by integration of each model, were analyzed using Cox regression with a 3.53-fold (95% CI: 2.24-5.58) increased risk of breast cancer five-year recurrence… Conclusions The 21 selected genes can predict breast cancer recurrence. Among these genes, CCNB1, PLK1 and TOP2A are in the cell cycle G2/M DNA damage checkpoint pathway. Oncologists can offer the genetic information for patients when understanding the gene expression profiles on breast cancer recurrence. PMID:23506640

  2. Serum 25-Hydroxyvitamin D Concentrations ≥40 ng/ml Are Associated with >65% Lower Cancer Risk: Pooled Analysis of Randomized Trial and Prospective Cohort Study

    PubMed Central

    McDonnell, Sharon L.; Baggerly, Carole; French, Christine B.; Baggerly, Leo L.; Garland, Cedric F.; Gorham, Edward D.; Lappe, Joan M.; Heaney, Robert P.

    2016-01-01

    Background Higher serum 25-hydroxyvitamin D [25(OH)D] concentrations have been associated with a lower risk of multiple cancer types across a range of 25(OH)D concentrations. Objectives To investigate whether the previously reported inverse association between 25(OH)D and cancer risk could be replicated, and if a 25(OH)D response region could be identified among women aged 55 years and older across a broad range of 25(OH)D concentrations. Methods Data from two cohorts representing different median 25(OH)D concentrations were pooled to afford a broader range of 25(OH)D concentrations than either cohort alone: the Lappe cohort (N = 1,169), a randomized clinical trial cohort (median 25(OH)D = 30 ng/ml) and the GrassrootsHealth cohort (N = 1,135), a prospective cohort (median 25(OH)D = 48 ng/ml). Cancer incidence over a multi-year period (median: 3.9 years) was compared according to 25(OH)D concentration. Kaplan-Meier plots were developed and the association between 25(OH)D and cancer risk was examined with multivariate Cox regression using multiple 25(OH)D measurements and spline functions. The study included all invasive cancers excluding skin cancer. Results Age-adjusted cancer incidence across the combined cohort (N = 2,304) was 840 cases per 100,000 person-years (1,020 per 100,000 person-years in the Lappe cohort and 722 per 100,000 person-years in the GrassrootsHealth cohort). Incidence was lower at higher concentrations of 25(OH)D. Women with 25(OH)D concentrations ≥40 ng/ml had a 67% lower risk of cancer than women with concentrations <20 ng/ml (HR = 0.33, 95% CI = 0.12–0.90). Conclusions 25(OH)D concentrations ≥40 ng/ml were associated with substantial reduction in risk of all invasive cancers combined. PMID:27049526

  3. Endometrial cancer survival after breast cancer in relation to tamoxifen treatment: Pooled results from three countries

    PubMed Central

    2012-01-01

    Introduction Tamoxifen is an effective treatment for breast cancer but an undesirable side-effect is an increased risk of endometrial cancer, particularly rare tumor types associated with poor prognosis. We investigated whether tamoxifen therapy increases mortality among breast cancer patients subsequently diagnosed with endometrial cancer. Methods We pooled case-patient data from the three largest case-control studies of tamoxifen in relation to endometrial cancer after breast cancer (1,875 patients: Netherlands, 765; United Kingdom, 786; United States, 324) and collected follow-up information on vital status. Breast cancers were diagnosed in 1972 to 2005 with endometrial cancers diagnosed in 1978 to 2006. We used Cox proportional hazards survival analysis to estimate hazard ratios (HRs) and 95% confidence intervals (CI). Results A total of 1,104 deaths occurred during, on average, 5.8 years following endometrial cancer (32% attributed to breast cancer, 25% to endometrial cancer). Mortality from endometrial cancer increased significantly with unfavorable non-endometrioid morphologies (P < 0.0001), International Federation of Gynaecology and Obstetrics staging system for gynecological malignancy (FIGO) stage (P < 0.0001) and age (P < 0.0001). No overall association was observed between tamoxifen treatment and endometrial cancer mortality (HR = 1.17 (95% CI: (0.89 to 1.55)). Tamoxifen use for at least five years was associated with increased endometrial cancer mortality (HR = 1.59 (1.13 to 2.25)). This association appeared to be due primarily to the excess of unfavorable histologies and advanced stage in women using tamoxifen for five or more years since the association with mortality was no longer significant after adjustment for morphological type and FIGO stage (HR = 1.37 (0.97 to 1.93)). Those patients with endometrioid tumors, who stopped tamoxifen use at least five years before their endometrial cancer diagnosis, had a greater mortality risk from endometrial cancer than endometrioid patients with no tamoxifen exposure (HR = 2.11 (1.13 to 3.94)). The explanation for this latter observation is not apparent. Conclusions Patients with endometrial cancer after breast cancer who received tamoxifen treatment for five years for breast cancer have greater endometrial cancer mortality risk than those who did not receive tamoxifen. This can be attributed to non-endometrioid histological subtypes with poorer prognosis among long term tamoxifen users. PMID:22691381

  4. Genital powder use and risk of ovarian cancer: a pooled analysis of 8,525 cases and 9,859 controls

    PubMed Central

    Terry, Kathryn L.; Karageorgi, Stalo; Shvetsov, Yurii B.; Merritt, Melissa A.; Lurie, Galina; Thompson, Pamela J.; Carney, Michael E.; Weber, Rachel Palmieri; Akushevich, Lucy; Lo-Ciganic, Wei-Hsuan; Cushing-Haugen, Kara; Sieh, Weiva; Moysich, Kirsten; Doherty, Jennifer A.; Nagle, Christina M.; Berchuck, Andrew; Pearce, Celeste L.; Pike, Malcolm; Ness, Roberta B.; Webb, Penelope M.; Rossing, Mary Anne; Schildkraut, Joellen; Risch, Harvey; Goodman, Marc T.

    2013-01-01

    Genital powder use has been associated with risk of epithelial ovarian cancer in some, but not all, epidemiologic investigations, possibly reflecting the carcinogenic effects of talc particles found in most of these products. Whether risk increases with number of genital-powder applications and for all histologic types of ovarian cancer also remains uncertain. Therefore, we estimated the association between self-reported genital powder use and epithelial ovarian cancer risk in eight population-based case-control studies. Individual data from each study was collected and harmonized. Lifetime number of genital-powder applications was estimated from duration and frequency of use. Pooled odds ratios were calculated using conditional logistic regression matched on study and age and adjusted for potential confounders. Subtype-specific risks were estimated according to tumor behavior and histology. 8,525 cases and 9,859 controls were included in the analyses. Genital powder use was associated with a modest increased risk of epithelial ovarian cancer (odds ratio 1.24, 95% confidence interval 1.15–1.33) relative to women who never used powder. Risk was elevated for invasive serous (1.20, 1.09–1.32), endometrioid (1.22, 1.04–1.43), and clear cell (1.24, 1.01–1.52) tumors, and for borderline serous tumors (1.46, 1.24–1.72). Among genital powder users, we observed no significant trend (p=0.17) in risk with increasing number of lifetime applications (assessed in quartiles). We noted no increase in risk among women who only reported non-genital powder use. In summary, genital powder use is a modifiable exposure associated with small-to-moderate increases in risk of most histologic subtypes of epithelial ovarian cancer. PMID:23761272

  5. Racial Differences in Clinical Outcomes From Metastatic Breast Cancer: A Pooled Analysis of CALGB 9342 and 9840—Cancer and Leukemia Group B

    PubMed Central

    Polite, Blase N.; Cirrincione, Constance; Fleming, Gini F.; Berry, Donald A.; Seidman, Andrew; Muss, Hyman; Norton, Larry; Shapiro, Charles; Bakri, Kamal; Marcom, Kelly; Lake, Diana; Schwartz, Joel H.; Hudis, Clifford; Winer, Eric P.

    2016-01-01

    Purpose African American women are more likely to be diagnosed with metastatic breast cancer at the time of presentation than whites, and have shorter survival once diagnosed. This study examines racial differences in clinical outcomes in the setting of two large cooperative group randomized clinical trials. Patients and Methods The study cohort consisted of 787 white (80%) and 195 African American (20%) patients with metastatic breast cancer enrolled in two successive Cancer and Leukemia Group B (CALGB) trials using taxanes in the metastatic setting. Differences in overall survival (OS), response incidence, and time to treatment failure (TTF) were examined by race. In addition, differences in the incidence of baseline and treatment-related toxicities were examined. Results With 779 deaths (166 African Americans and 613 whites), median OS was 14.3 months for African Americans and 18.75 months for whites (hazard ratio [HR] = 1.37; 95% CI, 1.15 to 1.63). When adjusted for prognostic factors, African Americans had a 24% increase in the hazard of death compared with whites (HR = 1.24; 95% CI, 1.02 to 1.51). No significant differences in TTF or overall response to therapy were seen. No clinically significant toxicity differences were seen. Conclusion African Americans with metastatic breast cancer have an increased hazard of death compared with whites despite the receipt of similar per-protocol treatment, but experience no differences in TTF or overall response to therapy. We hypothesize that more direct and robust measures of comorbidities, and perhaps other factors such as receipt of subsequent therapy could help further explain the observed survival difference. PMID:18509177

  6. Are Sitting Occupations Associated with Increased All-Cause, Cancer, and Cardiovascular Disease Mortality Risk? A Pooled Analysis of Seven British Population Cohorts

    PubMed Central

    Stamatakis, Emmanuel; Chau, Josephine Y.; Pedisic, Zeljko; Bauman, Adrian; Macniven, Rona; Coombs, Ngaire; Hamer, Mark

    2013-01-01

    Background There is mounting evidence for associations between sedentary behaviours and adverse health outcomes, although the data on occupational sitting and mortality risk remain equivocal. The aim of this study was to determine the association between occupational sitting and cardiovascular, cancer and all-cause mortality in a pooled sample of seven British general population cohorts. Methods The sample comprised 5380 women and 5788 men in employment who were drawn from five Health Survey for England and two Scottish Health Survey cohorts. Participants were classified as reporting standing, walking or sitting in their work time and followed up over 12.9 years for mortality. Data were modelled using Cox proportional hazard regression adjusted for age, waist circumference, self-reported general health, frequency of alcohol intake, cigarette smoking, non-occupational physical activity, prevalent cardiovascular disease and cancer at baseline, psychological health, social class, and education. Results In total there were 754 all-cause deaths. In women, a standing/walking occupation was associated with lower risk of all-cause (fully adjusted hazard ratio [HR] = 0.68, 95% CI 0.52–0.89) and cancer (HR = 0.60, 95% CI 0.43–0.85) mortality, compared to sitting occupations. There were no associations in men. In analyses with combined occupational type and leisure-time physical activity, the risk of all-cause mortality was lowest in participants with non-sitting occupations and high leisure-time activity. Conclusions Sitting occupations are linked to increased risk for all-cause and cancer mortality in women only, but no such associations exist for cardiovascular mortality in men or women. PMID:24086292

  7. Germline HOXB13 p.Gly84Glu mutation and cancer susceptibility: a pooled analysis of 25 epidemiological studies with 145,257 participates

    PubMed Central

    Cai, Qiliang; Wang, Xinpeng; Li, Xiaodong; Gong, Rui; Guo, Xuemei; Tang, Yang; Yang, Kuo; Niu, Yuanjie; Zhao, Yan

    2015-01-01

    Numerous studies have investigated association between the germline HOXB13 p.Gly84Glu mutation and cancer risk. However, the results were inconsistent. Herein, we performed this meta-analysis to get a precise conclusion of the associations. A comprehensive literature search was conducted through Medline (mainly Pubmed), Embase, Cochrane Library databases. Crude odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated by STATA 12.1 software to evaluate the association of HOXB13 p.Gly84Glu mutation and cancer susceptibility. Then, 25 studies including 51,390 cases and 93,867 controls were included, and there was significant association between HOXB13 p.Gly84Glu mutation and overall cancer risk (OR = 2.872, 95% CI = 2.121–3.888, P < 0.001), particularly in prostate cancer (OR = 3.248, 95% CI = 2.313–4.560, P < 0.001), while no association was found in breast (OR = 1.424, 95% CI = 0.776–2.613, P = 0.253) and colorectal cancers (OR = 2.070, 95% CI = 0.485–8.841, P = 0.326). When we stratified analysis by ethnicity, significant association was found in Caucasians (OR = 2.673, 95%CI = 1.920–3.720, P < 0.001). Further well-designed with large samples and other various cancers should be performed to validate our results. PMID:26517352

  8. Recent alcohol consumption and risk of incident ovarian carcinoma: a pooled analysis of 5,342 cases and 10,358 controls from the Ovarian Cancer Association Consortium

    PubMed Central

    2013-01-01

    Background Studies evaluating the association between alcohol intake and ovarian carcinoma (OC) are inconsistent. Because OC and ovarian borderline tumor histologic types differ genetically, molecularly and clinically, large numbers are needed to estimate risk associations. Methods We pooled data from 12 case-control studies in the Ovarian Cancer Association Consortium comprising 5,342 OC cases, 1,455 borderline tumors and 10,358 controls with quantitative information on recent alcohol intake to estimate odds ratios (OR) and 95% confidence intervals (CI) according to frequencies of average daily intakes of beer, wine, liquor and total alcohol. Results Total alcohol intake was not associated with all OC: consumption of >3 drinks per day compared to none, OR=0.92, 95% CI=0.76-1.10, P trend=0.27. Among beverage types, a statistically non-significant decreased risk was observed among women who consumed >8 oz/d of wine compared to none (OR=0.83, 95% CI=0.68-1.01, P trend=0.08). This association was more apparent among women with clear cell OC (OR, 0.43; 95% CI, 0.22-0.83; P trend=0.02), although based on only 10 cases and not statistically different from the other histologic types (P value for statistical heterogeneity between histologic types = 0.09). Statistical heterogeneity of the alcohol- and wine-OC associations was seen among three European studies, but not among eight North American studies. No statistically significant associations were observed in separate analyses evaluating risk with borderline tumors of serous or mucinous histology. Smoking status did not significantly modify any of the associations. Conclusions We found no evidence that recent moderate alcohol drinking is associated with increased risk for overall OC, or that variation in risk is associated strongly with specific histologic types. Understanding modifiable causes of these elusive and deadly cancers remains a priority for the research community. PMID:23339562

  9. Adjuvant external beam radiotherapy in the treatment of endometrial cancer (MRC ASTEC and NCIC CTG EN.5 randomised trials): pooled trial results, systematic review, and meta-analysis

    PubMed Central

    2009-01-01

    Summary Background Early endometrial cancer with low-risk pathological features can be successfully treated by surgery alone. External beam radiotherapy added to surgery has been investigated in several small trials, which have mainly included women at intermediate risk of recurrence. In these trials, postoperative radiotherapy has been shown to reduce the risk of isolated local recurrence but there is no evidence that it improves recurrence-free or overall survival. We report the findings from the ASTEC and EN.5 trials, which investigated adjuvant external beam radiotherapy in women with early-stage disease and pathological features suggestive of intermediate or high risk of recurrence and death from endometrial cancer. Methods Between July, 1996, and March, 2005, 905 (789 ASTEC, 116 EN.5) women with intermediate-risk or high-risk early-stage disease from 112 centres in seven countries (UK, Canada, Poland, Norway, New Zealand, Australia, USA) were randomly assigned after surgery to observation (453) or to external beam radiotherapy (452). A target dose of 40–46 Gy in 20–25 daily fractions to the pelvis, treating five times a week, was specified. Primary outcome measure was overall survival, and all analyses were by intention to treat. These trials were registered ISRCTN 16571884 (ASTEC) and NCT 00002807 (EN.5). Findings After a median follow-up of 58 months, 135 women (68 observation, 67 external beam radiotherapy) had died. There was no evidence that overall survival with external beam radiotherapy was better than observation, hazard ratio 1·05 (95% CI 0·75–1·48; p=0·77). 5-year overall survival was 84% in both groups. Combining data from ASTEC and EN.5 in a meta-analysis of trials confirmed that there was no benefit in terms of overall survival (hazard ratio 1·04; 95% CI 0·84–1·29) and can reliably exclude an absolute benefit of external beam radiotherapy at 5 years of more than 3%. With brachytherapy used in 53% of women in ASTEC/EN.5, the local recurrence rate in the observation group at 5 years was 6·1%. Interpretation Adjuvant external beam radiotherapy cannot be recommended as part of routine treatment for women with intermediate-risk or high-risk early-stage endometrial cancer with the aim of improving survival. The absolute benefit of external beam radiotherapy in preventing isolated local recurrence is small and is not without toxicity. Funding Medical Research Council, National Cancer Research Network, National Cancer Institute of Canada, with funds from the Canadian Cancer Society. PMID:19070891

  10. Hydrocarbon pool and vapor fire data analysis

    SciTech Connect

    Mudan, K.S.

    1984-10-01

    The flame geometry and thermal radiation data from a series of large scale experiments involving liquefied petroleum gas (LPG) and gasoline spills on water were analyzed. The experiments were conducted at the Naval Weapons Center, China Lake, California. Two types of fires have been studied; namely, pool fires and vapor fires. The spill quantity varied from 4 m/sup 3/ to approximately 6 m/sup 3/. The LPG pool fire flame height to diameter ratio were between 3.5 and 4.5. The gasoline flame height was about 2. The flame emissive powers for LPG pool fires ranged from 78 kW/m/sup 2/ to 115 kW/m/sup 2/. The average surface emissive power for gasoline pool fire was 40 kW/m/sup 2/. The LPG vapor fire emissive power ranged from 159 to 269 kW/m/sup 2/. 63 figures, 13 tables.

  11. Anthropometric and Hormonal Risk Factors for Male Breast Cancer: Male Breast Cancer Pooling Project Results

    PubMed Central

    Brinton, Louise A.

    2014-01-01

    Background The etiology of male breast cancer is poorly understood, partly because of its relative rarity. Although genetic factors are involved, less is known regarding the role of anthropometric and hormonally related risk factors. Methods In the Male Breast Cancer Pooling Project, a consortium of 11 case–control and 10 cohort investigations involving 2405 case patients (n = 1190 from case–control and n = 1215 from cohort studies) and 52013 control subjects, individual participant data were harmonized and pooled. Unconditional logistic regression generated study design–specific (case–control/cohort) odds ratios (ORs) and 95% confidence intervals (CIs), with exposure estimates combined using fixed effects meta-analysis. All statistical tests were two-sided. Results Risk was statistically significantly associated with weight (highest/lowest tertile: OR = 1.36; 95% CI = 1.18 to 1.57), height (OR = 1.18; 95% CI = 1.01 to 1.38), and body mass index (BMI; OR = 1.30; 95% CI = 1.12 to 1.51), with evidence that recent rather than distant BMI was the strongest predictor. Klinefelter syndrome (OR = 24.7; 95% CI = 8.94 to 68.4) and gynecomastia (OR = 9.78; 95% CI = 7.52 to 12.7) were also statistically significantly associated with risk, relations that were independent of BMI. Diabetes also emerged as an independent risk factor (OR = 1.19; 95% CI = 1.04 to 1.37). There were also suggestive relations with cryptorchidism (OR = 2.18; 95% CI = 0.96 to 4.94) and orchitis (OR = 1.43; 95% CI = 1.02 to 1.99). Although age at onset of puberty and histories of infertility were unrelated to risk, never having had children was statistically significantly related (OR = 1.29; 95% CI = 1.01 to 1.66). Among individuals diagnosed at older ages, a history of fractures was statistically significantly related (OR = 1.41; 95% CI = 1.07 to 1.86). Conclusions Consistent findings across case–control and cohort investigations, complemented by pooled analyses, indicated important roles for anthropometric and hormonal risk factors in the etiology of male breast cancer. Further investigation should focus on potential roles of endogenous hormones. PMID:24552677

  12. Hydrocarbon pool and vapor fire data analysis

    NASA Astrophysics Data System (ADS)

    Mudan, K. S.

    1984-10-01

    The flame geometry and thermal radiation data from a series of large scale experiments involving liquefied petroleum gas (LPG) and gasoline spills on water were analyzed. The spill quantity varied from 4 cu m to approximately 6 cu m. The LPG pool fire flame height to diameter ratio were between 3.5 and 4.5. The gasoline flame height was about 2. The flame emissive powers for LPG pool fires ranged from 78 kW/sq m to 115 kW/sq m. The average surface emissive power for gasoline pool fire was 40 kW/sq m. The LPG vapor fire emissive power ranged from 159 to 259 kW/sq m.

  13. Pooling breast cancer datasets has a synergetic effect on classification performance and improves signature stability

    PubMed Central

    van Vliet, Martin H; Reyal, Fabien; Horlings, Hugo M; van de Vijver, Marc J; Reinders, Marcel JT; Wessels, Lodewyk FA

    2008-01-01

    Background Michiels et al. (Lancet 2005; 365: 488–92) employed a resampling strategy to show that the genes identified as predictors of prognosis from resamplings of a single gene expression dataset are highly variable. The genes most frequently identified in the separate resamplings were put forward as a 'gold standard'. On a higher level, breast cancer datasets collected by different institutions can be considered as resamplings from the underlying breast cancer population. The limited overlap between published prognostic signatures confirms the trend of signature instability identified by the resampling strategy. Six breast cancer datasets, totaling 947 samples, all measured on the Affymetrix platform, are currently available. This provides a unique opportunity to employ a substantial dataset to investigate the effects of pooling datasets on classifier accuracy, signature stability and enrichment of functional categories. Results We show that the resampling strategy produces a suboptimal ranking of genes, which can not be considered to be a 'gold standard'. When pooling breast cancer datasets, we observed a synergetic effect on the classification performance in 73% of the cases. We also observe a significant positive correlation between the number of datasets that is pooled, the validation performance, the number of genes selected, and the enrichment of specific functional categories. In addition, we have evaluated the support for five explanations that have been postulated for the limited overlap of signatures. Conclusion The limited overlap of current signature genes can be attributed to small sample size. Pooling datasets results in more accurate classification and a convergence of signature genes. We therefore advocate the analysis of new data within the context of a compendium, rather than analysis in isolation. PMID:18684329

  14. Swimming Pools, Hot Rods, and Qualitative Analysis.

    ERIC Educational Resources Information Center

    Clyde, Dale D.

    1988-01-01

    Describes some reactions for the identification and application of cyanuric acid. Suggests students may find this applied chemistry interesting because of the use of cyanuric acid in swimming pools and diesel engines. Lists three tests for cyanate ion and two tests for cyanuric acid. (MVL)

  15. Spent fuel pool analysis using TRACE code

    SciTech Connect

    Sanchez-Saez, F.; Carlos, S.; Villanueva, J. F.; Martorell, S.

    2012-07-01

    The storage requirements of Spent Fuel Pools have been analyzed with the purpose to increase their rack capacities. In the past, the thermal limits have been mainly evaluated with conservative codes developed for this purpose, although some works can be found in which a best estimate code is used. The use of best estimate codes is interesting as they provide more realistic calculations and they have the capability of analyzing a wide range of transients that could affect the Spent Fuel Pool. Two of the most representative thermal-hydraulic codes are RELAP-5 and TRAC. Nowadays, TRACE code is being developed to make use of the more favorable characteristics of RELAP-5 and TRAC codes. Among the components coded in TRACE that can be used to construct the model, it is interesting to use the VESSEL component, which has the capacity of reproducing three dimensional phenomena. In this work, a thermal-hydraulic model of the Maine Yankee spent fuel pool using the TRACE code is developed. Such model has been used to perform a licensing calculation and the results obtained have been compared with experimental measurements made at the pool, showing a good agreement between the calculations predicted by TRACE and the experimental data. (authors)

  16. Decline in Tested and Self-Reported Cognitive Functioning After Prophylactic Cranial Irradiation for Lung Cancer: Pooled Secondary Analysis of Radiation Therapy Oncology Group Randomized Trials 0212 and 0214

    SciTech Connect

    Gondi, Vinai; University of Wisconsin Comprehensive Cancer Center, Madison, Wisconsin ; Paulus, Rebecca; Bruner, Deborah W.; Meyers, Christina A.; Gore, Elizabeth M.; Wolfson, Aaron; Werner-Wasik, Maria; Sun, Alexander Y.; Choy, Hak; Movsas, Benjamin

    2013-07-15

    Purpose: To assess the impact of prophylactic cranial irradiation (PCI) on self-reported cognitive functioning (SRCF), a functional scale on the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30). Methods and Materials: Radiation Therapy Oncology Group (RTOG) protocol 0214 randomized patients with locally advanced non-small cell lung cancer to PCI or observation; RTOG 0212 randomized patients with limited-disease small cell lung cancer to high- or standard-dose PCI. In both trials, Hopkins Verbal Learning Test (HVLT)-Recall and -Delayed Recall and SRCF were assessed at baseline (after locoregional therapy but before PCI or observation) and at 6 and 12 months. Patients developing brain relapse before follow-up evaluation were excluded. Decline was defined using the reliable change index method and correlated with receipt of PCI versus observation using logistic regression modeling. Fisher's exact test correlated decline in SRCF with HVLT decline. Results: Of the eligible patients pooled from RTOG 0212 and RTOG 0214, 410 (93%) receiving PCI and 173 (96%) undergoing observation completed baseline HVLT or EORTC QLQ-C30 testing and were included in this analysis. Prophylactic cranial irradiation was associated with a higher risk of decline in SRCF at 6 months (odds ratio 3.60, 95% confidence interval 2.34-6.37, P<.0001) and 12 months (odds ratio 3.44, 95% confidence interval 1.84-6.44, P<.0001). Decline on HVLT-Recall at 6 and 12 months was also associated with PCI (P=.002 and P=.002, respectively) but was not closely correlated with decline in SRCF at the same time points (P=.05 and P=.86, respectively). Conclusions: In lung cancer patients who do not develop brain relapse, PCI is associated with decline in HVLT-tested and self-reported cognitive functioning. Decline in HVLT and decline in SRCF are not closely correlated, suggesting that they may represent distinct elements of the cognitive spectrum.

  17. Obesity and survival in operable breast cancer patients treated with adjuvant anthracyclines and taxanes according to pathological subtypes: a pooled analysis

    PubMed Central

    2013-01-01

    Introduction Obesity is an unfavorable prognostic factor in breast cancer (BC) patients regardless of menopausal status and treatment received. However, the association between obesity and survival outcome by pathological subtype requires further clarification. Methods We performed a retrospective analysis including 5,683 operable BC patients enrolled in four randomized clinical trials (GEICAM/9906, GEICAM/9805, GEICAM/2003–02, and BCIRG 001) evaluating anthracyclines and taxanes as adjuvant treatments. Our primary aim was to assess the prognostic effect of body mass index (BMI) on disease recurrence, breast cancer mortality (BCM), and overall mortality (OM). A secondary aim was to detect differences of such prognostic effects by subtype. Results Multivariate survival analyses adjusting for age, tumor size, nodal status, menopausal status, surgery type, histological grade, hormone receptor status, human epidermal growth factor receptor 2 (HER2) status, chemotherapy regimen, and under-treatment showed that obese patients (BMI 30.0 to 34.9) had similar prognoses to that of patients with a BMI < 25 (reference group) in terms of recurrence (Hazard Ratio [HR] = 1.08, 95% Confidence Interval [CI] = 0.90 to 1.30), BCM (HR = 1.02, 0.81 to 1.29), and OM (HR = 0.97, 0.78 to 1.19). Patients with severe obesity (BMI ≥ 35) had a significantly increased risk of recurrence (HR = 1.26, 1.00 to 1.59, P = 0.048), BCM (HR = 1.32, 1.00 to 1.74, P = 0.050), and OM (HR = 1.35, 1.06 to 1.71, P = 0.016) compared to our reference group. The prognostic effect of severe obesity did not vary by subtype. Conclusions Severely obese patients treated with anthracyclines and taxanes present a worse prognosis regarding recurrence, BCM, and OM than patients with BMI < 25. The magnitude of the harmful effect of BMI on survival-related outcomes was similar across subtypes. PMID:24192331

  18. Quality of Patient-Reported Outcome (PRO) Reporting Across Cancer Randomized Controlled Trials According to the CONSORT PRO Extension: A Pooled Analysis of 557 Trials

    PubMed Central

    Efficace, Fabio; Fayers, Peter; Pusic, Andrea; Cemal, Yeliz; Yanagawa, Jane; Jacobs, Marc; la Sala, Andrea; Cafaro, Valentina; Whale, Katie; Rees, Jonathan; Blazeby, Jane

    2016-01-01

    Background The main objectives of this study were to identify the number of randomized controlled trials (RCTs) that have included a patient-reported outcome (PRO) endpoint across a wide range of cancer specialties and to evaluate completeness of PRO reporting according to the CONSORT PRO extension. Methods RCTs with a PRO endpoint, conducted across several cancer specialties and published between 2004 and 2013 were considered. Studies were evaluated based on previously defined criteria, including the CONSORT PRO extension and the Cochrane Collaboration's tool for assessing RCT Risk of Bias. Analyses were also conducted by type of PRO endpoint (primary versus secondary) and by cancer disease site. Results A total of 56,696 potentially eligible records were scrutinized and 557 RCTs with a PRO evaluation, enrolling overall 254,677 patients, were identified. PROs were most frequently used in RCTs of breast (N=123), lung (N=85) and colorectal (N=66) cancer. Overall, PROs were secondary endpoint in 421 (76%) RCTs. Four out of six CONSORT PRO items evaluated were documented in less than 50% of the RCTs. Level of reporting was higher in RCTs with PRO as a primary endpoint. Presence of a supplementary report was the only statistically significant factor associated with greater completeness of reporting for both RCTs with PRO as primary (β=0.19; P=0.001) or secondary endpoint (β=0.30; P<0.001). Conclusion Implementation of the CONSORT PRO extension is equally important across all cancer specialties. Its use can also contribute in revealing the robust PRO design of some studies, which might be obscured by poor outcome reporting. PMID:26079197

  19. 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. PMID:26621531

  20. UPDG: Utilities package for data analysis of Pooled DNA GWAS

    PubMed Central

    2012-01-01

    Background Despite being a well-established strategy for cost reduction in disease gene mapping, pooled DNA association study is much less popular than the individual DNA approach. This situation is especially true for pooled DNA genomewide association study (GWAS), for which very few computer resources have been developed for its data analysis. This motivates the development of UPDG (Utilities package for data analysis of Pooled DNA GWAS). Results UPDG represents a generalized framework for data analysis of pooled DNA GWAS with the integration of Unix/Linux shell operations, Perl programs and R scripts. With the input of raw intensity data from GWAS, UPDG performs the following tasks in a stepwise manner: raw data manipulation, correction for allelic preferential amplification, normalization, nested analysis of variance for genetic association testing, and summarization of analysis results. Detailed instructions, procedures and commands are provided in the comprehensive user manual describing the whole process from preliminary preparation of software installation to final outcome acquisition. An example dataset (input files and sample output files) is also included in the package so that users can easily familiarize themselves with the data file formats, working procedures and expected output. Therefore, UPDG is especially useful for users with some computer knowledge, but without a sophisticated programming background. Conclusions UPDG provides a free, simple and platform-independent one-stop service to scientists working on pooled DNA GWAS data analysis, but with less advanced programming knowledge. It is our vision and mission to reduce the hindrance for performing data analysis of pooled DNA GWAS through our contribution of UPDG. More importantly, we hope to promote the popularity of pooled DNA GWAS, which is a very useful research strategy. PMID:22252406

  1. KRAS Mutation Status and Clinical Outcome of Preoperative Chemoradiation With Cetuximab in Locally Advanced Rectal Cancer: A Pooled Analysis of 2 Phase II Trials

    SciTech Connect

    Kim, Sun Young; Shim, Eun Kyung; Yeo, Hyun Yang; Baek, Ji Yeon; Hong, Yong Sang; Kim, Dae Yong; Division of Translational and Clinical Research I, Research Institute and Hospital, National Cancer Center, Goyang ; Kim, Tae Won; Kim, Jee Hyun; Im, Seock-Ah; Jung, Kyung Hae; Chang, Hee Jin

    2013-01-01

    Purpose: Cetuximab-containing chemotherapy is known to be effective for KRAS wild-type metastatic colorectal cancer; however, it is not clear whether cetuximab-based preoperative chemoradiation confers an additional benefit compared with chemoradiation without cetuximab in patients with locally advanced rectal cancer. Methods and Materials: We analyzed EGFR, KRAS, BRAF, and PIK3CA mutation status with direct sequencing and epidermal growth factor receptor (EGFR) and Phosphatase and tensin homolog (PTEN) expression status with immunohistochemistry in tumor samples of 82 patients with locally advanced rectal cancer who were enrolled in the IRIX trial (preoperative chemoradiation with irinotecan and capecitabine; n=44) or the ERBIRIX trial (preoperative chemoradiation with irinotecan and capecitabine plus cetuximab; n=38). Both trials were similarly designed except for the administration of cetuximab; radiation therapy was administered at a dose of 50.4 Gy/28 fractions and irinotecan and capecitabine were given at doses of 40 mg/m{sup 2} weekly and 1650 mg/m{sup 2}/day, respectively, for 5 days per week. In the ERBIRIX trial, cetuximab was additionally given with a loading dose of 400 mg/m{sup 2} on 1 week before radiation, and 250 mg/m{sup 2} weekly thereafter. Results: Baseline characteristics before chemoradiation were similar between the 2 trial cohorts. A KRAS mutation in codon 12, 13, and 61 was noted in 15 (34%) patients in the IRIX cohort and 5 (13%) in the ERBIRIX cohort (P=.028). Among 62 KRAS wild-type cancer patients, major pathologic response rate, disease-free survival and pathologic stage did not differ significantly between the 2 cohorts. No mutations were detected in BRAF exon 11 and 15, PIK3CA exon 9 and 20, or EGFR exon 18-24 in any of the 82 patients, and PTEN and EGFR expression were not predictive of clinical outcome. Conclusions: In patients with KRAS wild-type locally advanced rectal cancer, the addition of cetuximab to the chemoradiation with irinotecan plus capecitabine regimen was not associated with improved clinical outcome compared with chemoradiation without cetuximab.

  2. Tumors with high-density tumor infiltrating lymphocytes constitute a favorable entity in breast cancer: a pooled analysis of four prospective adjuvant trials

    PubMed Central

    Kotoula, Vassiliki; Chatzopoulos, Kyriakos; Lakis, Sotiris; Alexopoulou, Zoi; Timotheadou, Eleni; Zagouri, Flora; Pentheroudakis, George; Gogas, Helen; Galani, Eleni; Efstratiou, Ioannis; Zaramboukas, Thomas; Koutras, Angelos; Aravantinos, Gerasimos; Samantas, Epaminontas; Psyrri, Amanda; Kourea, Helen; Bobos, Mattheos; Papakostas, Pavlos; Kosmidis, Paris; Pectasides, Dimitrios; Fountzilas, George

    2016-01-01

    Background Tumor infiltrating lymphocytes (TILs) are considered in the prognosis of breast cancer (BC) patients. Here, we investigated the prognostic/predictive effect of TILs in patients treated in the frame of four prospective trials with adjuvant anthracycline-based chemotherapy in the pre- and post-trastuzumab era. Methods TILs density was histologically assessed as percentage of stromal area on whole routine sections of 2613 BC (1563 Luminal A/B; 477 Luminal HER2; 246 HER2-enriched; 327 triple negative [TNBC]) and were evaluated as high/low at three cut-offs (c/o; 50% [lymphocytic predominance, LP], 35% and 25%), in separate training and validation sets. Results High TILs were present in 3.5%, 6.5% and 11.5% of all tumors, using the 50%, 35% and 25% c/o, respectively. TILs status did not interact with BC subtypes or trastuzumab treatment. LPBC patient outcome was not affected by nodal status, while high TILs were favorable in TNBC with unfavorable nodal status. When adjusted for standard clinicopathological parameters and treatment, high TILs independently predicted for favorable outcome, e.g., disease-free survival with the 35% c/o in the entire cohort (HR = 0.44, 95% CI 0.28-0.69, p < 0.001) and in specific subtypes. Conclusions High TILs tumors, especially LPBC seem worthy validating as a separate entity of favorable prognosis in breast cancer. PMID:26506242

  3. Pooled Analysis of Loss of Heterozygosity in Breast Cancer: a Genome Scan Provides Comparative Evidence for Multiple Tumor Suppressors and Identifies Novel Candidate Regions

    PubMed Central

    Miller, Brian J.; Wang, Daolong; Krahe, Ralf; Wright, Fred A.

    2003-01-01

    Somatic loss of heterozygosity (LOH) has been widely reported in breast cancer as a means of identifying putative tumor-suppressor genes. However, individual studies have rarely spanned more than a single chromosome, and the varying criteria used to declare LOH complicate efforts to formally differentiate regions of consistent versus sporadic (random) loss. We report here the compilation of an extensive database from 151 published LOH studies of breast cancer, with summary data from >15,000 tumors and primary allelotypes from >4,300 tumors. Allelic loss was evaluated at 1,168 marker loci, with large variation in the density of informative observations across the genome. Using studies in which primary allelotype information was available, we employed a likelihood-based approach with a formal chromosomal instability and selection model. The approach seeks direct evidence for preferential loss at each locus compared with nearby loci, accounts for heterogeneity across studies, and enables the direct comparison of candidate regions across the genome. Striking preferential loss was observed (in descending order of significance) in specific regions of chromosomes 7q, 16q, 13q, 17p, 8p, 21q, 3p, 18q, 2q, and 19p, as well as other regions, in many cases coinciding with previously identified candidate genes or known fragile sites. Many of these observations were not possible from any single LOH study, and our results suggest that many previously reported LOH results are not systematic or reproducible. Our approach provides a comparative framework for further investigation of regions exhibiting LOH and identifies broad genomic regions for which there exist few data. PMID:13680524

  4. Second- and third-generation aromatase inhibitors as first-line endocrine therapy in postmenopausal metastatic breast cancer patients: a pooled analysis of the randomised trials

    PubMed Central

    Ferretti, G; Bria, E; Giannarelli, D; Felici, A; Papaldo, P; Fabi, A; Di Cosimo, S; Ruggeri, E M; Milella, M; Ciccarese, M; Cecere, F L; Gelibter, A; Nuzzo, C; Cognetti, F; Terzoli, E; Carlini, P

    2006-01-01

    The purpose of this study was to estimate in all randomised trials the relative risk of overall response rate (ORR), clinical benefit (CB), time to progression (TTP), overall survival (OS), and toxicity of aromatase inhibitors (AI), compared with tamoxifen (Tam) as first-line endocrine therapy in postmenopausal metastatic breast cancer (PMBC) women. Prospective randomised studies were searched through computerised queries of MEDLINE, EMBASE, and the American Society of Clinical Oncology (ASCO) abstract database. Relative risk, 95% confidence interval, and heterogeneity were derived according to the inverse variance and Mantel–Haenszel method and Q statistics. Six phase III prospective randomised trials including 2787 women were gathered. A significant advantage in ORR (P=0.042), TTP (P=0.007), and CB (P=0.001) in favour of AI over Tam was detected at the fixed effects model. These results were not significant at the random effects model, owing to the significant heterogeneity. On the contrary, no difference was registered for OS (P=0.743) with no significant heterogeneity. Regarding toxicity, Tam caused more frequently thromboembolic events (P=0.005) and vaginal bleeding (P=0.001) compared with AI. Aromatase inhibitors appear to be superior to Tam as first-line endocrine option in PMBC women. Owing to a component of variability between the six studies analysed, the random effects estimates differed from corresponding fixed ones. Investigators should assess heterogeneity of trial results before deriving summary estimates of treatment effect. PMID:16736002

  5. Pooling fMRI Data: Meta-Analysis, Mega-Analysis and Multi-Center Studies

    PubMed Central

    Costafreda, Sergi G.

    2009-01-01

    The quantitative analysis of pooled data from related functional magnetic resonance imaging (fMRI) experiments has the potential to significantly accelerate progress in brain mapping. Such data-pooling can be achieved through meta-analysis (the pooled analysis of published results), mega-analysis (the pooled analysis of raw data) or multi-site studies, which can be seen as designed mega-analyses. Current limitations in function-location brain mapping and how data-pooling can be used to remediate them are reviewed, with particular attention to power aggregation and mitigation of false positive results. Some recently developed analysis tools for meta- and mega-analysis are also presented, and recommendations for the conduct of valid fMRI data pooling are formulated. PMID:19826498

  6. Lifetime Cigarette Smoking and Breast Cancer Prognosis in the After Breast Cancer Pooling Project

    PubMed Central

    2014-01-01

    Background There is controversy on whether former smokers have increased risk for breast cancer recurrence or all-cause mortality, regardless of how much they smoked. Methods Data were from three US cohorts in the After Breast Cancer Pooling Project, with detailed information on smoking among 9975 breast cancer survivors. Smoking was assessed an average of 2 years after diagnosis. Delayed entry Cox proportional hazards models were used to examine the relationships of smoking status, cigarettes per day, years of smoking, and pack years with breast cancer prognosis. Endpoints included breast cancer recurrence (n = 1727), breast cancer mortality (n = 1059), and overall mortality (n = 1803). Results Compared with never smokers, former smokers with less than 20 pack-years of exposure had no increased risk of any outcome. However, former smokers with 20 to less than 34.9 pack-years of exposure had a 22% increased risk of breast cancer recurrence (hazard ratio [HR] = 1.22; 95% confidence interval [CI] = 1.01 to 1.48) and a 26% increased risk of all-cause mortality (HR = 1.26; 95% CI = 1.07 to 1.48). For former smokers with 35 or more pack-years of exposure, the probability of recurrence increased by 37% (HR = 1.37; 95% CI = 1.13 to 1.66), breast cancer mortality increased by 54% (HR = 1.54; 95% CI = 1.24 to 1.91), and all-cause mortality increased by 68% (HR = 1.68; 95% CI = 1.44 to 1.96). Current smoking increased the probability of recurrence by 41% (HR = 1.41; 95% CI = 1.16 to 1.71), increased breast cancer mortality by 60% (HR = 1.61; 95% CI = 1.28 to 2.03), and doubled the risk of all-cause mortality (HR = 2.17; 95% CI = 1.85 to 2.54). Conclusions Lifetime cigarette smoking was statistically significantly associated with a poor prognosis among women diagnosed with breast cancer, dose-dependent increased risks of recurrence, and breast cancer and all-cause mortality. PMID:24317179

  7. NSAID Use and Risk of Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma: The Liver Cancer Pooling Project.

    PubMed

    Petrick, Jessica L; Sahasrabuddhe, Vikrant V; Chan, Andrew T; Alavanja, Michael C; Beane-Freeman, Laura E; Buring, Julie E; Chen, Jie; Chong, Dawn Q; Freedman, Neal D; Fuchs, Charles S; Gaziano, John Michael; Giovannucci, Edward; Graubard, Barry I; Hollenbeck, Albert R; Hou, Lifang; Jacobs, Eric J; King, Lindsay Y; Koshiol, Jill; Lee, I-Min; Linet, Martha S; Palmer, Julie R; Purdue, Mark P; Rosenberg, Lynn; Schairer, Catherine; Sesso, Howard D; Sigurdson, Alice J; Wactawski-Wende, Jean; Zeleniuch-Jacquotte, Anne; Campbell, Peter T; McGlynn, Katherine A

    2015-12-01

    Chronic inflammation plays a pivotal role in the pathogenesis of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), the two most common types of liver cancer. A number of prior experimental studies have suggested that nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin and ibuprofen, may potentially protect against liver cancer. However, no observational study has examined the association between aspirin duration and dose or other over-the-counter non-aspirin NSAIDs, such as ibuprofen, and liver cancer incidence. Furthermore, the association between NSAID use and risk of ICC is unclear. As part of the Liver Cancer Pooling Project, we harmonized data on 1,084,133 individuals (HCC = 679, ICC = 225) from 10 U.S.-based prospective cohort studies. Cox proportional hazards regression models were used to evaluate multivariable-adjusted HRs and 95% confidence intervals (CI). Current aspirin use, versus nonuse, was inversely associated with HCC (HR, 0.68; 95% CI, 0.57-0.81), which persisted when restricted to individuals not using non-aspirin NSAIDs and in a 5- and 10-year lag analysis. The association between aspirin use and HCC risk was stronger for users who reported daily use, longer duration use, and lower dosage. Ibuprofen use was not associated with HCC risk. Aspirin use was associated with a reduced ICC risk in men (HR, 0.64; 95% CI, 0.42-0.98) but not women (HR, 1.34; 95% CI, 0.89-2.01; P(interaction) = 0.01). The observed inverse association between aspirin use and liver cancer in our study, together with previous data, suggests the merit of future intervention studies of aspirin and other agents that affect chronic inflammatory pathways for HCC and possibly ICC. PMID:26391917

  8. Reciprocal regulation of autophagy and dNTP pools in human cancer cells.

    PubMed

    Chen, Wei; Zhang, Lisheng; Zhang, Keqiang; Zhou, Bingsen; Kuo, Mei-Ling; Hu, Shuya; Chen, Linling; Tang, Michelle; Chen, Yun-Ru; Yang, Lixin; Ann, David K; Yen, Yun

    2014-07-01

    Ribonucleotide reductase (RNR) plays a critical role in catalyzing the biosynthesis and maintaining the intracellular concentration of 4 deoxyribonucleoside triphosphates (dNTPs). Unbalanced or deficient dNTP pools cause serious genotoxic consequences. Autophagy is the process by which cytoplasmic constituents are degraded in lysosomes to maintain cellular homeostasis and bioenergetics. However, the role of autophagy in regulating dNTP pools is not well understood. Herein, we reported that starvation- or rapamycin-induced autophagy was accompanied by a decrease in RNR activity and dNTP pools in human cancer cells. Furthermore, downregulation of the small subunit of RNR (RRM2) by siRNA or treatment with the RNR inhibitor hydroxyurea substantially induced autophagy. Conversely, cancer cells with abundant endogenous intracellular dNTPs or treated with dNTP precursors were less responsive to autophagy induction by rapamycin, suggesting that autophagy and dNTP pool levels are regulated through a negative feedback loop. Lastly, treatment with si-RRM2 caused an increase in MAP1LC3B, ATG5, BECN1, and ATG12 transcript abundance in xenografted Tu212 tumors in vivo. Together, our results revealed a previously unrecognized reciprocal regulation between dNTP pools and autophagy in cancer cells. PMID:24905824

  9. Do socioeconomic inequalities in mortality vary between different Spanish cities? a pooled cross-sectional analysis

    PubMed Central

    2013-01-01

    Background The relationship between deprivation and mortality in urban settings is well established. This relationship has been found for several causes of death in Spanish cities in independent analyses (the MEDEA project). However, no joint analysis which pools the strength of this relationship across several cities has ever been undertaken. Such an analysis would determine, if appropriate, a joint relationship by linking the associations found. Methods A pooled cross-sectional analysis of the data from the MEDEA project has been carried out for each of the causes of death studied. Specifically, a meta-analysis has been carried out to pool the relative risks in eleven Spanish cities. Different deprivation-mortality relationships across the cities are considered in the analysis (fixed and random effects models). The size of the cities is also considered as a possible factor explaining differences between cities. Results Twenty studies have been carried out for different combinations of sex and causes of death. For nine of them (men: prostate cancer, diabetes, mental illnesses, Alzheimer’s disease, cerebrovascular disease; women: diabetes, mental illnesses, respiratory diseases, cirrhosis) no differences were found between cities in the effect of deprivation on mortality; in four cases (men: respiratory diseases, all causes of mortality; women: breast cancer, Alzheimer’s disease) differences not associated with the size of the city have been determined; in two cases (men: cirrhosis; women: lung cancer) differences strictly linked to the size of the city have been determined, and in five cases (men: lung cancer, ischaemic heart disease; women: ischaemic heart disease, cerebrovascular diseases, all causes of mortality) both kinds of differences have been found. Except for lung cancer in women, every significant relationship between deprivation and mortality goes in the same direction: deprivation increases mortality. Variability in the relative risks across cities was found for general mortality for both sexes. Conclusions This study provides a general overview of the relationship between deprivation and mortality for a sample of large Spanish cities combined. This joint study allows the exploration of and, if appropriate, the quantification of the variability in that relationship for the set of cities considered. PMID:23679869

  10. New England salt marsh pools: A quantitative analysis of geomorphic and geographic features

    USGS Publications Warehouse

    Adamowicz, S.C.; Roman, C.T.

    2005-01-01

    New England salt marsh pools provide important wildlife habitat and are the object of on-going salt marsh restoration projects; however, they have not been quantified in terms of their basic geomorphic and geographic traits. An examination of 32 ditched and unditched salt marshes from the Connecticut shore of Long Island Sound to southern Maine, USA, revealed that pools from ditched and unditched marshes had similar average sizes of about 200 m2, averaged 29 cm in depth, and were located about 11 m from the nearest tidal flow. Unditched marshes had 3 times the density (13 pools/ha), 2.5 times the pool coverage (83 m pool/km transect), and 4 times the total pool surface area per hectare (913 m2 pool/ha salt marsh) of ditched sites. Linear regression analysis demonstrated that an increasing density of ditches (m ditch/ha salt marsh) was negatively correlated with pool density and total pool surface area per hectare. Creek density was positively correlated with these variables. Thus, it was not the mere presence of drainage channels that were associated with low numbers of pools, but their type (ditch versus creek) and abundance. Tidal range was not correlated with pool density or total pool surface area, while marsh latitude had only a weak relationship to total pool surface area per hectare. Pools should be incorporated into salt marsh restoration planning, and the parameters quantified here may be used as initial design targets.

  11. Occupational lung cancer risk for men in Germany: results from a pooled case-control study.

    PubMed

    Brüske-Hohlfeld, I; Möhner, M; Pohlabeln, H; Ahrens, W; Bolm-Audorff, U; Kreienbrock, L; Kreuzer, M; Jahn, I; Wichmann, H E; Jöckel, K H

    2000-02-15

    Occupational exposures such as crystalline silica, diesel engine exhaust, polycyclic aromatic hydrocarbons, and man-made mineral fibers are strongly suspected to increase lung cancer risk. Two case-control studies in Germany conducted between 1988 and 1996 were pooled for a joint analysis. A total of 3,498 male cases and 3,541 male population controls, frequency matched for age and region, were included in the study. The lifelong history of all jobs and industries was coded and occupational exposures were evaluated by expert rating. Odds ratios, crude and adjusted for smoking and asbestos exposure, were calculated by conditional logistic regression. Job-related evaluation showed a statistically significant increased odds ratio adjusted for smoking among farmers; forestry workers, fishermen, and livestock workers; miners and quarrymen; chemical processors; cabinet makers and related wood workers; metal producers and processors; bricklayers and carpenters; road construction workers, pipelayers and well diggers; plasterers, insulators, and upholsterers; painters and lacquerers; stationary engine and heavy equipment operators; transport workers and freight handlers; and service workers. With regard to specific occupational exposures, elevated odds ratios (OR) (95% confidence intervals (CI)) for lung cancer risk adjusted for smoking and asbestos exposure were observed for man-made mineral fibers (OR = 1.48, 95% CI 1.17, 1.88); crystalline silica (OR = 1.41, 95% CI 1.22, 1.62); diesel engine exhaust (OR = 1.43, 95% CI 1.23, 1.67); and polycyclic aromatic hydrocarbons (OR = 1.53, 95% CI 1.14, 2.04). The risk of asbestos exposure, adjusted for smoking was also increased (OR = 1.41, 95% CI 1.24, 1.60). PMID:10695597

  12. 76 FR 72923 - Pool Corporation; Analysis To Aid Public Comment

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-28

    ... is the world's largest distributor of products used in the construction, renovation, repair, service...Corp used exclusionary acts and practices to maintain its monopoly power in the pool product... power in local geographic markets to prevent manufacturers from supplying pool products to new...

  13. [Pooled Analysis of RET/PTC Gene Rearrangement Rate in Sporadic and Radiogenic Thyroid Papillary Carcinoma].

    PubMed

    Ushenkova, L N; Koterov, A N; Biryukov, A P

    2015-01-01

    The database of publications on molecular epidemiology of RET/PTC rearrangements in sporadic and radiogenic thyroid papillary carcinoma has been formed (197 sources at the end of 2014; coverage of 100%). Based on this database a pooled analysis of data on the rates of RET/PTC1, RET/PTC3 and RET/PTC in total was conducted. Statistical approach involves a simple pooling, as well as calculations on the models of random and fixed effects. Since almost all the strata were characterized by heterogeneity, simple pooling and random effect models were adequate. Calculations using both models led to almost identical results. For rates of RET/PTC1, RET/PTC3 and RET/PTC in total with respect to formed carcinoma striations the following values (pooling, in %) were obtained: sporadic, total--13.2; 8.9; 21.2; sporadic, adults--13.3; 9.9; 21.1; sporadic, children--22.4; 17.5; 44.5; radiogenic, total--20.9; 20.3; 40.4; radiotherapy (exposure in childhood)--31.1; 11.8; 42.5; children affected after the Chernobyl accident--19.9; 23.6; 46.1; radiological incidents (exposure in adulthood)--19.9; 7.7; 18.4. Statistically proven is the reliability of differences of carcinoma indicators for children compared with adults (both sporadic and radiogenic tumors) and for radiogenic cancer compared with sporadic. The greatest increase in rate after irradiation was found for RET/PTC1, previously characterized in vitro as one of radiogenic types of RET/PTC. PMID:26601537

  14. Identifying Sexual Orientation Health Disparities in Adolescents: Analysis of Pooled Data From the Youth Risk Behavior Survey, 2005 and 2007

    PubMed Central

    Van Wagenen, Aimee; Birkett, Michelle; Eyster, Sandra; Corliss, Heather L.

    2014-01-01

    We studied sexual orientation disparities in health outcomes among US adolescents by pooling multiple Youth Risk Behavior Survey (YRBS) data sets from 2005 and 2007 for 14 jurisdictions. Here we describe the methodology for pooling and analyzing these data sets. Sexual orientation–related items assessed sexual orientation identity, gender of sexual contacts, sexual attractions, and harassment regarding sexual orientation. Wording of items varied across jurisdictions, so we created parallel variables and composite sexual minority variables. We used a variety of statistical approaches to address issues with the analysis of pooled data and to meet the aims of individual articles, which focused on a range of health outcomes and behaviors related to cancer, substance use, sexual health, mental health, violence, and injury. PMID:24328640

  15. Postdiagnosis cruciferous vegetable consumption and breast cancer outcomes: a report from the After Breast Cancer Pooling Project.

    PubMed

    Nechuta, Sarah; Caan, Bette J; Chen, Wendy Y; Kwan, Marilyn L; Lu, Wei; Cai, Hui; Poole, Elizabeth M; Flatt, Shirley W; Zheng, Wei; Pierce, John P; Shu, Xiao Ou

    2013-08-01

    Cruciferous vegetables are a major source of glucosinolate-derived bioactive compounds such as isothiocyanates, which have been shown in animal and in vitro studies to inhibit cancer growth and progression. Few studies have investigated cruciferous vegetable intake after diagnosis and breast cancer outcomes. Using data from the After Breast Cancer Pooling Project, which includes prospective data from U.S. and Chinese breast cancer survivors, we evaluated the association of cruciferous vegetables with breast cancer outcomes. Analyses included 11,390 women diagnosed with stage I-III invasive breast cancer (1990-2006) from four cohorts. Cruciferous vegetable intake (g/day) was assessed using food frequency questionnaires (mean of 22 months postdiagnosis). Study heterogeneity was evaluated by the Q statistic; hazard ratios (HRs) and 95% confidence intervals (CI) were estimated using delayed-entry Cox regression models stratified by study. After a median follow-up of 9.0 years, 1,725 deaths and 1,421 recurrences were documented. In pooled analyses using study-specific quartiles, cruciferous vegetable intake was not associated with breast cancer outcomes, adjusting for known clinical prognostic factors and selected lifestyle factors. HRs (95% CIs) by increasing quartiles (reference = lowest quartile) were 1.08 (0.93-1.25), 1.01 (0.87-1.18), and 1.10 (0.95-1.28) for recurrence (P(trend) = 0.34) and 1.01 (0.88-1.15), 0.97 (0.84-1.11), and 0.99 (0.86-1.13) for total mortality (P(trend) = 0.84). No associations were observed for subgroups defined by estrogen receptor status, stage, or tamoxifen therapy. Cruciferous vegetable intake at approximately two years after diagnosis was not associated with recurrence or mortality. Our results do not support an association between postdiagnosis cruciferous vegetable intake and breast cancer outcomes. PMID:23765086

  16. Post-diagnosis Cruciferous Vegetable Consumption and Breast Cancer Outcomes: a Report from the After Breast Cancer Pooling Project

    PubMed Central

    Nechuta, Sarah; Caan, Bette J.; Chen, Wendy Y.; Kwan, Marilyn L.; Lu, Wei; Cai, Hui; Poole, Elizabeth M.; Flatt, Shirley W.; Zheng, Wei; Pierce, John P.; Shu, Xiao Ou

    2013-01-01

    Cruciferous vegetables are a major source of glucosinolate-derived bioactive compounds such as isothiocyanates, which have been shown in animal and in vitro studies to inhibit cancer growth and progression. Few studies have investigated cruciferous vegetable intake after diagnosis and breast cancer outcomes. Using data from the After Breast Cancer Pooling Project, which includes prospective data from US and Chinese breast cancer survivors, we evaluated the association of cruciferous vegetables with breast cancer outcomes. Analyses included 11,390 women diagnosed with stage I–III invasive breast cancer (1990–2006) from four cohorts. Cruciferous vegetable intake (g/day) was assessed using food frequency questionnaires (mean of 22 months post-diagnosis). Study heterogeneity was evaluated by the Q statistic; hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using delayed-entry Cox regression models stratified by study. After a median follow-up of 9.0 years, 1,725 deaths and 1,421 recurrences were documented. In pooled analyses using study-specific quartiles, cruciferous vegetable intake was not associated with breast cancer outcomes, adjusting for known clinical prognostic factors and selected lifestyle factors. HRs (95%CIs) by increasing quartiles (reference=lowest quartile) were 1.08 (0.93–1.25), 1.01 (0.87–1.18), and 1.10 (0.95–1.28) for recurrence (Ptrend=0.34) and 1.01 (0.88–1.15), 0.97 (0.84–1.11), and 0.99 (0.86–1.13) for total mortality (Ptrend=0.84). No associations were observed for subgroups defined by ER status, stage, or tamoxifen therapy. Cruciferous vegetable intake at approximately two years after diagnosis was not associated with recurrence or mortality. Our results do not support an association between post-diagnosis cruciferous vegetable intake and breast cancer outcomes. PMID:23765086

  17. Hydrocarbon pool and vapor fire data analysis. Final report

    SciTech Connect

    Mudan, K.S.

    1984-10-01

    The flame geometry and thermal radiation data from a series of large scale experiments involving liquefied petroleum gas (LPG) and gasoline spills on water were analyzed. The experiments were conducted at the Naval Weapons Center, China Lake, California. Two types of fires have been studied; namely, pool fires and vapor fires. The spill quantity varied from 4 m/sup 3/ to approximately 6 m/sup 3/. The LPG pool fire flame height to diameter ratio were between 3.5 and 4.5. The gasoline flame height was about 2. The flame emissive powers for LPG pool fires ranged from 78 kW/m/sup 2/ to 115 kW/m/sup 2/. The average surface emissive power for gasoline pool fire was 40 kW/m/sup 2/. The LPG vapor fire emissive power ranged from 159 to 269 kW/m/sup 2/. 63 figures, 13 tables.

  18. Melanocortin-1 receptor, skin cancer and phenotypic characteristics (M-SKIP) project: study design and methods for pooling results of genetic epidemiological studies

    PubMed Central

    2012-01-01

    Background For complex diseases like cancer, pooled-analysis of individual data represents a powerful tool to investigate the joint contribution of genetic, phenotypic and environmental factors to the development of a disease. Pooled-analysis of epidemiological studies has many advantages over meta-analysis, and preliminary results may be obtained faster and with lower costs than with prospective consortia. Design and methods Based on our experience with the study design of the Melanocortin-1 receptor (MC1R) gene, SKin cancer and Phenotypic characteristics (M-SKIP) project, we describe the most important steps in planning and conducting a pooled-analysis of genetic epidemiological studies. We then present the statistical analysis plan that we are going to apply, giving particular attention to methods of analysis recently proposed to account for between-study heterogeneity and to explore the joint contribution of genetic, phenotypic and environmental factors in the development of a disease. Within the M-SKIP project, data on 10,959 skin cancer cases and 14,785 controls from 31 international investigators were checked for quality and recoded for standardization. We first proposed to fit the aggregated data with random-effects logistic regression models. However, for the M-SKIP project, a two-stage analysis will be preferred to overcome the problem regarding the availability of different study covariates. The joint contribution of MC1R variants and phenotypic characteristics to skin cancer development will be studied via logic regression modeling. Discussion Methodological guidelines to correctly design and conduct pooled-analyses are needed to facilitate application of such methods, thus providing a better summary of the actual findings on specific fields. PMID:22862891

  19. Admixture Aberration Analysis: Application to Mapping in Admixed Population Using Pooled DNA

    NASA Astrophysics Data System (ADS)

    Bercovici, Sivan; Geiger, Dan

    Admixture mapping is a gene mapping approach used for the identification of genomic regions harboring disease susceptibility genes in the case of recently admixed populations such as African Americans. We present a novel method for admixture mapping, called admixture aberration analysis (AAA), that uses a DNA pool of affected admixed individuals. We demonstrate through simulations that AAA is a powerful and economical mapping method under a range of scenarios, capturing complex human diseases such as hypertension and end stage kidney disease. The method has a low false-positive rate and is robust to deviation from model assumptions. Finally, we apply AAA on 600 prostate cancer-affected African Americans, replicating a known risk locus. Simulation results indicate that the method can yield over 96% reduction in genotyping. Our method is implemented as a Java program called AAAmap and is freely available.

  20. Structural analysis of a reflux pool-boiler solar receiver

    NASA Astrophysics Data System (ADS)

    Hoffman, E. L.; Stone, C. M.

    1991-06-01

    Coupled thermal-structural finite element calculations of a reflux pool-boiler solar receiver were performed to characterize the operating stresses and to address issues affecting the service life of the receiver. Analyses performed using shell elements provided information for receiver material selection and design optimization. Calculations based on linear elastic fracture mechanics principles were performed using continuum elements to assess the vulnerability of a seam-weld to fatigue crack growth. All calculations were performed using ABAQUS, a general purpose finite element code, and elements specifically formulated for coupled thermal-structural analysis. Two materials were evaluated: 316L SS and Haynes 230 alloys. The receiver response was simulated for a combination of structural and thermal loads that represent the startup and operating conditions of the receiver. For both materials, maximum stresses in the receiver developed shortly after startup due to uneven temperature distribution across the receiver surface. The largest effective stress was near yield in the 316L SS receiver and below 39 percent of yield in the Haynes 230 receiver. The calculations demonstrated that stress reductions of over 25 percent could be obtained by reducing the aft dome thickness to one closer to the absorber. The fatigue calculations demonstrated that the stress distribution near the seam-weld notch depends primarily on the structural load created by internal pressurization of the receiver rather than the thermal, indicating that the thermal loads can be neglected when assessing the stress intensity near the seam-weld notch. The stress intensity factor, computed using the J-integral method and crack opening-displacement field equations, was significantly below the fatigue threshold for most steels. The calculations indicated that the weld notch was always loaded in compression, a condition which is not conducive to fatigue crack growth.

  1. Structural analysis of a reflux pool-boiler solar receiver

    SciTech Connect

    Hoffman, E.L.; Stone, C.M.

    1991-06-01

    Coupled thermal-structural finite element calculations of a reflux pool-boiler solar receiver were performed to characterize the operating stresses and to address issues affecting the service life of the receiver. Analyses performed using shell elements provided information for receiver material selection and design optimization. Calculations based on linear elastic fracture mechanics principles were performed using continuum elements to assess the vulnerability of a seam-weld to fatigue crack growth. All calculations were performed using ABAQUS, a general purpose finite element code, and elements specifically formulated for coupled thermal-structural analysis. Two materials were evaluated: 316L SS and Haynes 230 alloys. The receiver response was simulated for a combination of structural and thermal loads that represent the startup and operating conditions of the receiver. For both materials, maximum stresses in the receiver developed shortly after startup due to uneven temperature distribution across the receiver surface. The largest effective stress was near yield in the 316L SS receiver and below 39 percent of yield in the Haynes 230 receiver. The calculations demonstrated that stress reductions of over 25 percent could be obtained by reducing the aft dome thickness to one closer to the absorber. The fatigue calculations demonstrated that the stress distribution near the seam-weld notch depends primarily on the structural load created by internal pressurization of the receiver rather than the thermal, indicating that the thermal loads can be neglected when assessing the stress intensity near the seam-weld notch. The stress intensity factor, computed using the J-integral method and crack opening-displacement field equations, was significantly below the fatigue threshold for most steels. The calculations indicated that the weld notch was always loaded in compression, a condition which is not conducive to fatigue crack growth. 15 refs., 30 figs., 3 tabs.

  2. The Cancer Genome Atlas ovarian cancer analysis

    Cancer.gov

    An analysis of genomic changes in ovarian cancer has provided the most comprehensive and integrated view of cancer genes for any cancer type to date. Ovarian serous adenocarcinoma tumors from 500 patients were examined by The Cancer Genome Atlas (TCGA) Re

  3. MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool.

    PubMed

    Gad, Helge; Koolmeister, Tobias; Jemth, Ann-Sofie; Eshtad, Saeed; Jacques, Sylvain A; Ström, Cecilia E; Svensson, Linda M; Schultz, Niklas; Lundbäck, Thomas; Einarsdottir, Berglind Osk; Saleh, Aljona; Göktürk, Camilla; Baranczewski, Pawel; Svensson, Richard; Berntsson, Ronnie P-A; Gustafsson, Robert; Strömberg, Kia; Sanjiv, Kumar; Jacques-Cordonnier, Marie-Caroline; Desroses, Matthieu; Gustavsson, Anna-Lena; Olofsson, Roger; Johansson, Fredrik; Homan, Evert J; Loseva, Olga; Bräutigam, Lars; Johansson, Lars; Höglund, Andreas; Hagenkort, Anna; Pham, Therese; Altun, Mikael; Gaugaz, Fabienne Z; Vikingsson, Svante; Evers, Bastiaan; Henriksson, Martin; Vallin, Karl S A; Wallner, Olov A; Hammarström, Lars G J; Wiita, Elisee; Almlöf, Ingrid; Kalderén, Christina; Axelsson, Hanna; Djureinovic, Tatjana; Puigvert, Jordi Carreras; Häggblad, Maria; Jeppsson, Fredrik; Martens, Ulf; Lundin, Cecilia; Lundgren, Bo; Granelli, Ingrid; Jensen, Annika Jenmalm; Artursson, Per; Nilsson, Jonas A; Stenmark, Pål; Scobie, Martin; Berglund, Ulrika Warpman; Helleday, Thomas

    2014-04-10

    Cancers have dysfunctional redox regulation resulting in reactive oxygen species production, damaging both DNA and free dNTPs. The MTH1 protein sanitizes oxidized dNTP pools to prevent incorporation of damaged bases during DNA replication. Although MTH1 is non-essential in normal cells, we show that cancer cells require MTH1 activity to avoid incorporation of oxidized dNTPs, resulting in DNA damage and cell death. We validate MTH1 as an anticancer target in vivo and describe small molecules TH287 and TH588 as first-in-class nudix hydrolase family inhibitors that potently and selectively engage and inhibit the MTH1 protein in cells. Protein co-crystal structures demonstrate that the inhibitors bind in the active site of MTH1. The inhibitors cause incorporation of oxidized dNTPs in cancer cells, leading to DNA damage, cytotoxicity and therapeutic responses in patient-derived mouse xenografts. This study exemplifies the non-oncogene addiction concept for anticancer treatment and validates MTH1 as being cancer phenotypic lethal. PMID:24695224

  4. Chromosomal aberration frequency in lymphocytes predicts the risk of cancer: results from a pooled cohort study of 22 358 subjects in 11 countries

    PubMed Central

    Bonassi, Stefano; Norppa, Hannu; Ceppi, Marcello; Strömberg, Ulf; Vermeulen, Roel; Znaor, Ariana; Cebulska-Wasilewska, Antonina; Fabianova, Eleonora; Fucic, Alexandra; Gundy, Sarolta; Hansteen, Inger-Lise; Knudsen, Lisbeth E.; Lazutka, Juozas; Rossner, Pavel; Sram, Radim J.; Boffetta, Paolo

    2008-01-01

    Mechanistic evidence linking chromosomal aberration (CA) to early stages of cancer has been recently supported by the results of epidemiological studies that associated CA frequency in peripheral lymphocytes of healthy individuals to future cancer incidence. To overcome the limitations of single studies and to evaluate the strength of this association, a pooled analysis was carried out. The pooled database included 11 national cohorts and a total of 22 358 cancer-free individuals who underwent genetic screening with CA for biomonitoring purposes during 1965–2002 and were followed up for cancer incidence and/or mortality for an average of 10.1 years; 368 cancer deaths and 675 incident cancer cases were observed. Subjects were classified within each laboratory according to tertiles of CA frequency. The relative risk (RR) of cancer was increased for subjects in the medium [RR = 1.31, 95% confidence interval (CI) = 1.07–1.60] and in the high (RR = 1.41; 95% CI = 1.16–1.72) tertiles when compared with the low tertile. This increase was mostly driven by chromosome-type aberrations. The presence of ring chromosomes increased the RR to 2.22 (95% CI = 1.34–3.68). The strongest association was found for stomach cancer [RRmedium = 1.17 (95% CI = 0.37–3.70), RRhigh = 3.13 (95% CI = 1.17–8.39)]. Exposure to carcinogens did not modify the effect of CA levels on overall cancer risk. These results reinforce the evidence of a link between CA frequency and cancer risk and provide novel information on the role of aberration subclass and cancer type. PMID:18356148

  5. MTHFR 677C>T Polymorphism and the Risk of Breast Cancer: Evidence from an Original Study and Pooled Data for 28031 Cases and 31880 Controls

    PubMed Central

    Sekhar, Deepa; Francis, Amirtharaj; Gupta, Nishi; Konwar, Rituraj; Kumar, Sandeep; Kumar, Surender; Thangaraj, Kumarasamy; Rajender, Singh

    2015-01-01

    Background Methylenetetrahydrofolate reductase (MTHFR) acts at an important metabolic point in the regulation of cellular methylation reaction. It assists in the conversion of 5, 10-methylenetetrahydrofolate to 5-methyltetrahydrofolate. The latter aids in remethylation of homocysteine to de novo methionine that is required for DNA synthesis. The objective of this study was to examine the effect of MTHFR 677 C>T polymorphism on the risk of breast cancer in the Indian sub-continent. Methods and Results We genotyped 677 C>T locus in 1096 individuals that were classified into cases (N=588) and controls (N=508). Genotype data were analyzed using chi-square test. No significant difference was observed in the distribution of genotypes between cases and controls in north Indian (P = 0.932), south Indian (P = 0.865), and pooled data (P = 0.680). To develop a consensus regarding the impact of 677C>T polymorphism on breast cancer risk, we also conducted a meta-analysis on 28031 cases and 31880 controls that were pooled from sixty one studies. The overall summary estimate upon meta-analysis suggested no significant correlation between the 677C>T substitution and breast cancer in the dominant model (Fixed effect model: OR = 0.97, P=0.072, Random effects model: OR = 0.96, P = 0.084) or the recessive model (Fixed effect model: OR = 1.05, P = 0.089; Random effects model: OR= 1.08, P= 0.067). Conclusion 677 C>T substitution does not affect breast cancer risk in the Indo-European and Dravidian populations of India. Analysis on pooled data further ruled out association between the 677 C>T polymorphism and breast cancer. Therefore, 677 C>T substitution does not appear to influence the risk of breast cancer. PMID:25803740

  6. Microbiological analysis in three diverse natural geothermal bathing pools in Iceland.

    PubMed

    Thorolfsdottir, Berglind Osk Th; Marteinsson, Viggo Thor

    2013-03-01

    Natural thermal bathing pools contain geothermal water that is very popular to bathe in but the water is not sterilized, irradiated or treated in any way. Increasing tourism in Iceland will lead to increasing numbers of bath guests, which can in turn affect the microbial flora in the pools and therefore user safety. Today, there is no legislation that applies to natural geothermal pools in Iceland, as the water is not used for consumption and the pools are not defined as public swimming pools. In this study, we conducted a microbiological analysis on three popular but different natural pools in Iceland, located at Lýsuhóll, Hveravellir and Landmannalaugar. Total bacterial counts were performed by flow cytometry, and with plate count at 22 °C, 37 °C and 50 °C. The presence of viable coliforms, Enterococcus spp. and pseudomonads were investigated by growth experiments on selective media. All samples were screened for noroviruses by real time PCR. The results indicate higher fecal contamination in the geothermal pools where the geothermal water flow was low and bathing guest count was high during the day. The number of cultivated Pseudomonas spp. was high (13,000-40,000 cfu/100 mL) in the natural pools, and several strains were isolated and classified as opportunistic pathogens. Norovirus was not detected in the three pools. DNA was extracted from one-liter samples in each pool and analyzed by partial 16S rRNA gene sequencing. Microbial diversity analysis revealed different microbial communities between the pools and they were primarily composed of alpha-, beta- and gammaproteobacteria. PMID:23493033

  7. Microbiological Analysis in Three Diverse Natural Geothermal Bathing Pools in Iceland

    PubMed Central

    Thorolfsdottir, Berglind Osk Th.; Marteinsson, Viggo Thor

    2013-01-01

    Natural thermal bathing pools contain geothermal water that is very popular to bathe in but the water is not sterilized, irradiated or treated in any way. Increasing tourism in Iceland will lead to increasing numbers of bath guests, which can in turn affect the microbial flora in the pools and therefore user safety. Today, there is no legislation that applies to natural geothermal pools in Iceland, as the water is not used for consumption and the pools are not defined as public swimming pools. In this study, we conducted a microbiological analysis on three popular but different natural pools in Iceland, located at Lýsuhóll, Hveravellir and Landmannalaugar. Total bacterial counts were performed by flow cytometry, and with plate count at 22 °C, 37 °C and 50 °C. The presence of viable coliforms, Enterococcus spp. and pseudomonads were investigated by growth experiments on selective media. All samples were screened for noroviruses by real time PCR. The results indicate higher fecal contamination in the geothermal pools where the geothermal water flow was low and bathing guest count was high during the day. The number of cultivated Pseudomonas spp. was high (13,000–40,000 cfu/100 mL) in the natural pools, and several strains were isolated and classified as opportunistic pathogens. Norovirus was not detected in the three pools. DNA was extracted from one-liter samples in each pool and analyzed by partial 16S rRNA gene sequencing. Microbial diversity analysis revealed different microbial communities between the pools and they were primarily composed of alpha-, beta- and gammaproteobacteria. PMID:23493033

  8. EQUILIBRIUM-ANALYSIS OF PROJECT CLIMATE CHANGE EFFECTS ON THE GLOBAL SOIL ORGANIC MATTER POOL

    EPA Science Inventory

    Increased rates of soil organic matter decomposition may represent a significant positive feedback to global warming. s a step towards assessing the potential magnitude of this response, an equilibrium analysis was performed in which representative carbon pools were associated wi...

  9. Human papillomavirus and breast cancer in Iran: a meta- analysis

    PubMed Central

    Haghshenas, Mohammad Reza; Mousavi, Tahoora; Moosazadeh, Mahmood; Afshari, Mahdi

    2016-01-01

    Objective(s): This study aims to investigate the relationship between human papillomavirus (HPV) and breast cancer using meta- analysis. Materials and Methods: Relevant studies were identified reviewing the national and international databases. We also increased the search sensitivity by investigating the references as well as interview with research centers and experts. Finally, quality assessment and implementation of inclusion/exclusion criteria determined the eligible articles for meta-analysis. Based on the heterogeneity observed among the results of the primary studies, random effects model was used to estimate the pooled prevalence of HPV infection and also pooled odds ratio between HPV and developing breast cancer using Stata SE V. 11 software. Results: This meta- analysis included 11 primary studies investigating the HPV infection prevalence among 1539 Iranian women. Pooled prevalence (95% confidence interval) of HPV infection among Iranian women with breast cancer was estimated as of 23.6% (6.7- 40.5), while, the odds ratio (95% confidence interval) between HPV infection and developing breast cancer was estimated as of 5.7% (0.7- 46.8). Conclusion: This meta- analysis showed a high prevalence of HPV infection among women with breast cancer. We also found that the odds of developing breast cancer among women with breast cancer was more than that of women without breast cancer. PMID:27114791

  10. Echinacoside induces apoptotic cancer cell death by inhibiting the nucleotide pool sanitizing enzyme MTH1.

    PubMed

    Dong, Liwei; Wang, Hongge; Niu, Jiajing; Zou, Mingwei; Wu, Nuoting; Yu, Debin; Wang, Ye; Zou, Zhihua

    2015-01-01

    Inhibition of the nucleotide pool sanitizing enzyme MTH1 causes extensive oxidative DNA damages and apoptosis in cancer cells and hence may be used as an anticancer strategy. As natural products have been a rich source of medicinal chemicals, in the present study, we used the MTH1-catalyzed enzymatic reaction as a high-throughput in vitro screening assay to search for natural compounds capable of inhibiting MTH1. Echinacoside, a compound derived from the medicinal plants Cistanche and Echinacea, effectively inhibited the catalytic activity of MTH1 in an in vitro assay. Treatment of various human cancer cell lines with Echinacoside resulted in a significant increase in the cellular level of oxidized guanine (8-oxoguanine), while cellular reactive oxygen species level remained unchanged, indicating that Echinacoside also inhibited the activity of cellular MTH1. Consequently, Echinacoside treatment induced an immediate and dramatic increase in DNA damage markers and upregulation of the G1/S-CDK inhibitor p21, which were followed by marked apoptotic cell death and cell cycle arrest in cancer but not in noncancer cells. Taken together, these studies identified a natural compound as an MTH1 inhibitor and suggest that natural products can be an important source of anticancer agents. PMID:26677335

  11. Echinacoside induces apoptotic cancer cell death by inhibiting the nucleotide pool sanitizing enzyme MTH1

    PubMed Central

    Dong, Liwei; Wang, Hongge; Niu, Jiajing; Zou, Mingwei; Wu, Nuoting; Yu, Debin; Wang, Ye; Zou, Zhihua

    2015-01-01

    Inhibition of the nucleotide pool sanitizing enzyme MTH1 causes extensive oxidative DNA damages and apoptosis in cancer cells and hence may be used as an anticancer strategy. As natural products have been a rich source of medicinal chemicals, in the present study, we used the MTH1-catalyzed enzymatic reaction as a high-throughput in vitro screening assay to search for natural compounds capable of inhibiting MTH1. Echinacoside, a compound derived from the medicinal plants Cistanche and Echinacea, effectively inhibited the catalytic activity of MTH1 in an in vitro assay. Treatment of various human cancer cell lines with Echinacoside resulted in a significant increase in the cellular level of oxidized guanine (8-oxoguanine), while cellular reactive oxygen species level remained unchanged, indicating that Echinacoside also inhibited the activity of cellular MTH1. Consequently, Echinacoside treatment induced an immediate and dramatic increase in DNA damage markers and upregulation of the G1/S-CDK inhibitor p21, which were followed by marked apoptotic cell death and cell cycle arrest in cancer but not in noncancer cells. Taken together, these studies identified a natural compound as an MTH1 inhibitor and suggest that natural products can be an important source of anticancer agents. PMID:26677335

  12. Distinct cholesterogenic and lipidogenic gene expression patterns in ovarian cancer - a new pool of biomarkers

    PubMed Central

    Pampalakis, Georgios; Politi, Angeliki-Louiza; Papanastasiou, Anastasios; Sotiropoulou, Georgia

    2015-01-01

    Cancer cells display different metabolic requirements compared to nonmalignant cells imposed by their need for rapid proliferation. Alterations in cellular metabolic pathways of lipid and cholesterol synthesis have been linked to tumorigenesis and cancer progression but have not been exploited in clinical diagnosis. Here, the expression of genes related to cholesterol/lipid metabolism was measured with semiquantitative and real-time RT-PCR in RNA isolated from normal, benign and cancer ovarian tissues. We found that both SREBF2 and its target gene DHCR7 are downregulated in ovarian cancer tissues. On the contrary, SREBF1c and its target SCD1 were upregulated. The steroidogenesis regulator PDE8B was found downregulated. Oncomine analysis supported these findings, and further revealed that in ovarian cancers, the SREBF1-regulated lipidogenic pathway is activated while the SREBF2-regulated cholesterogenic pathway is repressed based on expression profiles of HMGCR and DHCR7. In conclusion, we show that ovarian cancer cells display distinct lipidogenic and cholesterogenic gene expression profiles with potential applications in the development of new biomarkers and/or treatment of ovarian cancer. Reduced cholesterol and enhanced lipid synthesis and SCD1 expression may provide an explanation for the previously reported increased membrane fluidity of ovarian cancer cells, a finding that merits further investigation. PMID:26807200

  13. Self-expandable metal stents for malignant gastric outlet obstruction: A pooled analysis of prospective literature

    PubMed Central

    van Halsema, Emo E; Rauws, Erik AJ; Fockens, Paul; van Hooft, Jeanin E

    2015-01-01

    AIM: To provide an overview of the clinical outcomes of self-expandable metal stent (SEMS) placement for malignant gastric outlet obstruction (MGOO). METHODS: A systematic literature search was performed in PubMed of the literature published between January 2009 and March 2015. Only prospective studies that reported on the clinical success of stent placement for MGOO were included. The primary endpoint was clinical success, defined according to the definition used in the original article. Data were pooled and analyzed using descriptive statistics. Subgroup analyses were performed for partially covered SEMSs (PCSEMSs) and uncovered SEMSs (UCSEMSs) using Fisher’s exact test. RESULTS: A total of 19 studies, including 1281 patients, were included in the final analysis. Gastric (42%) and pancreatic (37%) cancer were the main causes of MGOO. UCSEMSs were used in 76% of patients and PCSEMSs in 24%. The overall pooled technical success rate was 97.3% and the clinical success rate was 85.7%. Stent dysfunction occurred in 19.6% of patients, mainly caused by re-obstruction (12.6%) and stent migration (4.3%), and was comparable between PCSEMSs and UCSEMSs (21.2% vs 19.1%, respectively, P = 0.412). Re-obstruction was more common with UCSEMSs (14.9% vs 5.1%, P < 0.001) and stent migration was more frequent after PCSEMS placement (10.9% vs 2.2%, P < 0.001). The overall perforation rate was 1.2%. Bleeding was reported in 4.1% of patients, including major bleeding in 0.8%. The median stent patency ranged from 68 to 307 d in five studies. The median overall survival ranged from 49 to 183 d in 13 studies. CONCLUSION: The clinical outcomes in this large population showed that enteral stent placement was feasible, effective and safe. Therefore, stent placement is a valid treatment option for the palliation of MGOO. PMID:26604654

  14. Pooled analysis indicates that the GSTT1 deletion, GSTM1 deletion, and GSTP1 Ile105Val polymorphisms do not modify breast cancer risk in BRCA1 and BRCA2 mutation carriers.

    PubMed

    Spurdle, Amanda B; Fahey, Paul; Chen, Xiaoqing; McGuffog, Lesley; Easton, Douglas; Peock, Susan; Cook, Margaret; Simard, Jacques; Rebbeck, Tim R; Antoniou, Antonis C; Chenevix-Trench, Georgia

    2010-07-01

    The GSTP1, GSTM1, and GSTT1 detoxification genes all have functional polymorphisms that are common in the general population. A single study of 320 BRCA1/2 carriers previously assessed their effect in BRCA1 or BRCA2 mutation carriers. This study showed no evidence for altered risk of breast cancer for individuals with the GSTT1 and GSTM1 deletion variants, but did report that the GSTP1 Ile105Val (rs1695) variant was associated with increased breast cancer risk in carriers. We investigated the association between these three GST polymorphisms and breast cancer risk using existing data from 718 women BRCA1 and BRCA2 mutation carriers from Australia, the UK, Canada, and the USA. Data were analyzed within a proportional hazards framework using Cox regression. There was no evidence to show that any of the polymorphisms modified disease risk for BRCA1 or BRCA2 carriers, and there was no evidence for heterogeneity between sites. These results support the need for replication studies to confirm or refute hypothesis-generating studies. PMID:19921428

  15. Pooled analysis indicates that the GSTT1 deletion, GSTM1 deletion, and GSTP1 Ile105Val polymorphisms do not modify breast cancer risk in BRCA1 and BRCA2 mutation carriers

    PubMed Central

    Spurdle, Amanda B.; Fahey, Paul; Chen, Xiaoqing; McGuffog, Lesley; Easton, Douglas; Peock, Susan; Cook, Margaret; Simard, Jacques; Rebbeck, Tim R.; Antoniou, Antonis C.

    2011-01-01

    The GSTP1, GSTM1, and GSTT1 detoxification genes all have functional polymorphisms that are common in the general population. A single study of 320 BRCA1/2 carriers previously assessed their effect in BRCA1 or BRCA2 mutation carriers. This study showed no evidence for altered risk of breast cancer for individuals with the GSTT1 and GSTM1 deletion variants, but did report that the GSTP1 Ile105Val (rs1695) variant was associated with increased breast cancer risk in carriers. We investigated the association between these three GST polymorphisms and breast cancer risk using existing data from 718 women BRCA1 and BRCA2 mutation carriers from Australia, the UK, Canada, and the USA. Data were analyzed within a proportional hazards framework using Cox regression. There was no evidence to show that any of the polymorphisms modified disease risk for BRCA1 or BRCA2 carriers, and there was no evidence for heterogeneity between sites. These results support the need for replication studies to confirm or refute hypothesis-generating studies. PMID:19921428

  16. Mirabegron for the treatment of overactive bladder: a prespecified pooled efficacy analysis and pooled safety analysis of three randomised, double-blind, placebo-controlled, phase III studies

    PubMed Central

    Nitti, V W; Khullar, V; Kerrebroeck, P; Herschorn, S; Cambronero, J; Angulo, J C; Blauwet, M B; Dorrepaal, C; Siddiqui, E; Martin, N E

    2013-01-01

    Introduction To examine pooled efficacy data from three, large phase III studies comparing mirabegron (50 and 100 mg) with placebo, and pooled safety data including additional mirabegron 25 mg and tolterodine extended release (ER) 4 mg results. Methods This prespecified pooled analysis of three randomised, double-blind, placebo-controlled, 12-week studies, evaluated efficacy and safety of once-daily mirabegron 25 mg (safety analysis), 50 or 100 mg (efficacy and safety analyses) and tolterodine ER 4 mg (safety analysis) for the treatment of symptoms of overactive bladder (OAB). Co-primary efficacy measures were change from baseline to Final Visit in the mean number of incontinence episodes/24 h and mean number of micturitions/24 h. Key secondary efficacy end-points included mean number of urgency episodes/24 h and mean volume voided/micturitions, while other end-points included patient-reported outcomes according to the Treatment Satisfaction-Visual Analogue Scale (TS-VAS) and responder analyses [dry rate (posttreatment), ≥ 50% reduction in incontinence episodes/24 h, ≤ 8 micturitions/24 h (post hoc analysis)]. The safety analysis included adverse event (AE) reporting, laboratory assessments, ECG, postvoid residual volume and vital signs (blood pressure, pulse rate). Results Mirabegron (50 and 100 mg once daily) demonstrated statistically significant improvements compared with placebo for the co-primary end-points, key secondary efficacy variables, TS-VAS and responder analyses (all comparisons p < 0.05). Mirabegron is well tolerated and demonstrates a good safety profile. The most common AEs (≥ 3%) included hypertension, nasopharyngitis and urinary tract infection (UTI); the incidence of hypertensive events and UTIs decreased with increasing dose. For mirabegron, the incidence of the bothersome antimuscarinic AE, dry mouth, was at placebo level and of a lesser magnitude than tolterodine. Conclusion The efficacy and safety of mirabegron are demonstrated in this large pooled clinical trial dataset in patients with OAB. PMID:23692526

  17. Imported malaria in pregnant women: a retrospective pooled analysis

    PubMed Central

    Käser, Annina K.; Arguin, Paul M.; Chiodini, Peter L.; Smith, Valerie; Delmont, Jean; Jiménez, Beatriz C.; Färnert, Anna; Kimura, Mikio; Ramharter, Michael; Grobusch, Martin P.; Schlagenhauf, Patricia

    2015-01-01

    Summary Background Data on imported malaria in pregnant women are scarce. Method A retrospective, descriptive study of pooled data on imported malaria in pregnancy was done, using data from 1977 to 2014 from 8 different collaborators in Europe, the United States and Japan. Most cases were from the period 1991–2014. National malaria reference centresas well as specialists on this topic were asked to search their archives for cases of imported malaria in pregnancy. A total of 632 cases were collated, providing information on Plasmodium species, region of acquisition, nationality, country of residence, reason for travel, age, gestational age, prophylactic measures and treatment used, as well as on complications and outcomes in mother and child. Results Datasets from some sources were incomplete. The predominant Plasmodium species was P. falciparum in 72% of cases. Among the 543 cases where information on the use of chemoprophylaxis was known, 471 (74.5%) did not use chemoprophylaxis or used incorrect or incomplete chemoprophylaxis. The main reason for travelling was “visiting friends and relatives” VFR (48.6%) and overall, most cases of malaria were imported from West Africa (85.9%). Severe anaemia was the most frequent complication in the mother. Data on offspring outcome was limited, but spontaneous abortion was a frequently reported foetal outcome (n = 14). A total of 50 different variants of malaria treatment regimens were reported. Conclusion Imported cases of malaria in pregnancy are mainly P. falciparum acquired in sub-Saharan Africa. Malaria prevention and treatment in pregnant travellers is a challenge for travel medicine due to few data on medication safety and maternal and foetal outcomes. International, collaborative efforts are needed to capture standardized data on imported malaria cases in pregnant women. PMID:26227740

  18. RELAP5 Analysis of the Hybrid Loop-Pool Design for Sodium Cooled Fast Reactors

    SciTech Connect

    Hongbin Zhang; Haihua Zhao; Cliff Davis

    2008-06-01

    An innovative hybrid loop-pool design for sodium cooled fast reactors (SFR-Hybrid) has been recently proposed. This design takes advantage of the inherent safety of a pool design and the compactness of a loop design to improve economics and safety of SFRs. In the hybrid loop-pool design, primary loops are formed by connecting the reactor outlet plenum (hot pool), intermediate heat exchangers (IHX), primary pumps and the reactor inlet plenum with pipes. The primary loops are immersed in the cold pool (buffer pool). Passive safety systems -- modular Pool Reactor Auxiliary Cooling Systems (PRACS) – are added to transfer decay heat from the primary system to the buffer pool during loss of forced circulation (LOFC) transients. The primary systems and the buffer pool are thermally coupled by the PRACS, which is composed of PRACS heat exchangers (PHX), fluidic diodes and connecting pipes. Fluidic diodes are simple, passive devices that provide large flow resistance in one direction and small flow resistance in reverse direction. Direct reactor auxiliary cooling system (DRACS) heat exchangers (DHX) are immersed in the cold pool to transfer decay heat to the environment by natural circulation. To prove the design concepts, especially how the passive safety systems behave during transients such as LOFC with scram, a RELAP5-3D model for the hybrid loop-pool design was developed. The simulations were done for both steady-state and transient conditions. This paper presents the details of RELAP5-3D analysis as well as the calculated thermal response during LOFC with scram. The 250 MW thermal power conventional pool type design of GNEP’s Advanced Burner Test Reactor (ABTR) developed by Argonne National Laboratory was used as the reference reactor core and primary loop design. The reactor inlet temperature is 355 °C and the outlet temperature is 510 °C. The core design is the same as that for ABTR. The steady state buffer pool temperature is the same as the reactor inlet temperature. The peak cladding, hot pool, cold pool and reactor inlet temperatures were calculated during LOFC. The results indicate that there are two phases during LOFC transient – the initial thermal equilibration phase and the long term decay heat removal phase. The initial thermal equilibration phase occurs over a few hundred seconds, as the system adjusts from forced circulation to natural circulation flow. Subsequently, during long-term heat removal phase all temperatures evolve very slowly due to the large thermal inertia of the primary and buffer pool systems. The results clearly show that passive safety PRACS can effectively transfer decay heat from the primary system to the buffer pool by natural circulation. The DRACS system in turn can effectively transfer the decay heat to the environment.

  19. Evaluation of High Ipsilateral Subventricular Zone Radiation Therapy Dose in Glioblastoma: A Pooled Analysis

    SciTech Connect

    Lee, Percy; UCLA Jonsson Comprehensive Cancer Center, Los Angeles, California ; Eppinga, Wietse; Lagerwaard, Frank; Cloughesy, Timothy; UCLA Jonsson Comprehensive Cancer Center, Los Angeles, California ; Slotman, Benjamin; Nghiemphu, Phioanh L.; UCLA Jonsson Comprehensive Cancer Center, Los Angeles, California ; Wang, Pin-Chieh; Kupelian, Patrick; Agazaryan, Nzhde; Demarco, John; Selch, Michael T.; Steinberg, Michael; UCLA Jonsson Comprehensive Cancer Center, Los Angeles, California ; Kang, Jung Julie

    2013-07-15

    Purpose: Cancer stem cells (CSCs) may play a role in the recurrence of glioblastoma. They are believed to originate from neural stem cells in the subventricular zone (SVZ). Because of their radioresistance, we hypothesized that high doses of radiation (>59.4 Gy) to the SVZ are necessary to control CSCs and improve progression-free survival (PFS) or overall survival (OS) in glioblastoma. Methods and Materials: 173 patients with glioblastoma pooled from 2 academic centers were treated with resection followed by chemoradiation therapy. The SVZ was segmented on computed tomography to calculate radiation doses delivered to the presumptive CSC niches. The relationships between high SVZ doses and PFS and OS were examined using Cox proportional hazards models. Five covariates were included to estimate their impact on PFS or OS: ipsilateral and contralateral SVZ doses, clinical target volume dose, age, and extent of resection. Results: Median PFS and OS were 10.4 and 19.6 months for the cohort. The mean ipsilateral SVZ, contralateral SVZ, and clinical target volume doses were 49.2, 35.2, and 60.1 Gy, respectively. Twenty-one patients who received high ipsilateral SVZ dose (>59.4 Gy) had significantly longer median PFS (12.6 vs 9.9 months, P=.042) and longer OS (25.8 vs 19.2 months, P=.173). On multivariate analysis, high radiation therapy doses to ipsilateral SVZ remained a statistically significant independent predictor of improved PFS but not of OS. The extent of surgery affected both PFS and OS on multivariate analysis. Conclusion: High radiation therapy doses to ipsilateral CSC niches are associated with improved PFS in glioblastoma.

  20. ViPAR: a software platform for the Virtual Pooling and Analysis of Research Data

    PubMed Central

    Carter, Kim W; Carter, KW; Francis, RW; Bresnahan, M; Gissler, M; Grønborg, TK; Gross, R; Gunnes, N; Hammond, G; Hornig, M; Hultman, CM; Huttunen, J; Langridge, A; Leonard, H; Newman, S; Parner, ET; Petersson, G; Reichenberg, A; Sandin, S; Schendel, DE; Schalkwyk, L; Sourander, A; Steadman, C; Stoltenberg, C; Suominen, A; Surén, P; Susser, E; Sylvester Vethanayagam, A; Yusof, Z

    2016-01-01

    Background: Research studies exploring the determinants of disease require sufficient statistical power to detect meaningful effects. Sample size is often increased through centralized pooling of disparately located datasets, though ethical, privacy and data ownership issues can often hamper this process. Methods that facilitate the sharing of research data that are sympathetic with these issues and which allow flexible and detailed statistical analyses are therefore in critical need. We have created a software platform for the Virtual Pooling and Analysis of Research data (ViPAR), which employs free and open source methods to provide researchers with a web-based platform to analyse datasets housed in disparate locations. Methods: Database federation permits controlled access to remotely located datasets from a central location. The Secure Shell protocol allows data to be securely exchanged between devices over an insecure network. ViPAR combines these free technologies into a solution that facilitates ‘virtual pooling’ where data can be temporarily pooled into computer memory and made available for analysis without the need for permanent central storage. Results: Within the ViPAR infrastructure, remote sites manage their own harmonized research dataset in a database hosted at their site, while a central server hosts the data federation component and a secure analysis portal. When an analysis is initiated, requested data are retrieved from each remote site and virtually pooled at the central site. The data are then analysed by statistical software and, on completion, results of the analysis are returned to the user and the virtually pooled data are removed from memory. Conclusions: ViPAR is a secure, flexible and powerful analysis platform built on open source technology that is currently in use by large international consortia, and is made publicly available at [http://bioinformatics.childhealthresearch.org.au/software/vipar/]. PMID:26452388

  1. Extra-binomial variation approach for analysis of pooled DNA sequencing data

    PubMed Central

    Wallace, Chris

    2012-01-01

    Motivation: The invention of next-generation sequencing technology has made it possible to study the rare variants that are more likely to pinpoint causal disease genes. To make such experiments financially viable, DNA samples from several subjects are often pooled before sequencing. This induces large between-pool variation which, together with other sources of experimental error, creates over-dispersed data. Statistical analysis of pooled sequencing data needs to appropriately model this additional variance to avoid inflating the false-positive rate. Results: We propose a new statistical method based on an extra-binomial model to address the over-dispersion and apply it to pooled case-control data. We demonstrate that our model provides a better fit to the data than either a standard binomial model or a traditional extra-binomial model proposed by Williams and can analyse both rare and common variants with lower or more variable pool depths compared to the other methods. Availability: Package ‘extraBinomial’ is on http://cran.r-project.org/ Contact: chris.wallace@cimr.cam.ac.uk Supplementary information: Supplementary data are available at Bioinformatics Online. PMID:22976083

  2. Vitamin D Pooling Project

    Cancer.gov

    The Vitamin D Pooling Project of Rarer Cancers brought together investigators from 10 cohorts to conduct a large prospective epidemiologic study of the association between vitamin D status and seven rarer cancers.

  3. Selenium Exposure and Cancer Risk: an Updated Meta-analysis and Meta-regression.

    PubMed

    Cai, Xianlei; Wang, Chen; Yu, Wanqi; Fan, Wenjie; Wang, Shan; Shen, Ning; Wu, Pengcheng; Li, Xiuyang; Wang, Fudi

    2016-01-01

    The objective of this study was to investigate the associations between selenium exposure and cancer risk. We identified 69 studies and applied meta-analysis, meta-regression and dose-response analysis to obtain available evidence. The results indicated that high selenium exposure had a protective effect on cancer risk (pooled OR = 0.78; 95%CI: 0.73-0.83). The results of linear and nonlinear dose-response analysis indicated that high serum/plasma selenium and toenail selenium had the efficacy on cancer prevention. However, we did not find a protective efficacy of selenium supplement. High selenium exposure may have different effects on specific types of cancer. It decreased the risk of breast cancer, lung cancer, esophageal cancer, gastric cancer, and prostate cancer, but it was not associated with colorectal cancer, bladder cancer, and skin cancer. PMID:26786590

  4. Selenium Exposure and Cancer Risk: an Updated Meta-analysis and Meta-regression

    PubMed Central

    Cai, Xianlei; Wang, Chen; Yu, Wanqi; Fan, Wenjie; Wang, Shan; Shen, Ning; Wu, Pengcheng; Li, Xiuyang; Wang, Fudi

    2016-01-01

    The objective of this study was to investigate the associations between selenium exposure and cancer risk. We identified 69 studies and applied meta-analysis, meta-regression and dose-response analysis to obtain available evidence. The results indicated that high selenium exposure had a protective effect on cancer risk (pooled OR = 0.78; 95%CI: 0.73–0.83). The results of linear and nonlinear dose-response analysis indicated that high serum/plasma selenium and toenail selenium had the efficacy on cancer prevention. However, we did not find a protective efficacy of selenium supplement. High selenium exposure may have different effects on specific types of cancer. It decreased the risk of breast cancer, lung cancer, esophageal cancer, gastric cancer, and prostate cancer, but it was not associated with colorectal cancer, bladder cancer, and skin cancer. PMID:26786590

  5. Seismic analysis of a 400-MWe pool-type fast reactor

    SciTech Connect

    Ma, D.C.; Gvildys, J.

    1987-01-01

    This paper presents a seismic analysis of a 400-MWe pool-type fast reactor subjected to horizontal support excitation. Two types of analyses are performed - the fluid-structure interaction analysis and the sloshing analysis. In the fluid-structure interaction analysis, the fluid coupling between various components are investigated. The maximum horizontal acceleration for the reactor core and the relative displacement between the reactor core and UIS (Upper Internal Structure) are examined. Seismic stresses at critical areas are calculated. In the sloshing analysis, the sloshing frequency and wave patterns are calculated. The maximum wave height and the sloshing forces exerted on the submerged components and the primary tank are evaluated.

  6. Interventions for non-metastatic squamous cell carcinoma of the skin: systematic review and pooled analysis of observational studies

    PubMed Central

    2013-01-01

    Objectives To assess the effects of treatments for non-metastatic invasive squamous cell carcinoma (SCC) of the skin using evidence from observational studies, given the paucity of evidence from randomised controlled trials. Design Systematic review of observational studies. Data sources Medline, Embase, to December 2012. Review methods Observational studies of interventions for primary, non-metastatic, invasive, SCC of the skin that reported recurrence during follow-up, quality of life, initial response to treatment, adverse events, cosmetic appearance, or death from disease. Studies were excluded if data for primary cutaneous SCC was not separable from other data. Data were extracted independently by two reviewers. Meta-analysis was performed where appropriate using a random effects model to estimate the pooled proportion of an event with 95% confidence intervals. Results 118 publications were included, covering seven treatment modalities. Pooled estimates of recurrence of SCCs were lowest after cryotherapy (0.8% (95% confidence interval 0.1% to 2%)) and curettage and electrodesiccation (1.7% (0.5% to 3.4%)), but most treated SCCs were small, low risk lesions. After Mohs micrographic surgery, the pooled estimate of local recurrence during variable follow-up periods from 10 studies was 3.0% (2.2% to 3.9%), which was non-significantly lower than the pooled average local recurrence of 5.4% (2.5% to 9.1%) after standard surgical excision (12 studies), and 6.4% (3.0% to 11.0%) after external radiotherapy (7 studies). After an apparently successful initial response of SCCs to photodynamic therapy, pooled average recurrence of 26.4% (12.3% to 43.7%; 8 studies) was significantly higher than other treatments. Evidence was limited for laser treatment (1 study) and for topical and systemic treatments (mostly single case reports or small non-comparative series with limited follow-up). Conclusions Many observational studies have looked at different treatment modalities for SCC, but the evidence base for the effectiveness of these interventions is poor. Comparison of outcomes after different treatments should be interpreted cautiously owing to biases inherent in the types of study included, and lack of direct comparisons to enable the estimation of relative treatment effect. Further evidence is needed to develop a prognostic model and stratify individuals at high risk of developing SCC, to improve the evidence base for this common cancer and to optimise clinical management. Protocol registration International Prospective Register of Systematic Reviews (PROSPERO) registration number CRD42011001450. PMID:24191270

  7. Exposure to UV radiation and risk of Hodgkin lymphoma: a pooled analysis.

    PubMed

    Monnereau, Alain; Glaser, Sally L; Schupp, Clayton W; Ekström Smedby, Karin; de Sanjosé, Silvia; Kane, Eleanor; Melbye, Mads; Forétova, Lenka; Maynadié, Marc; Staines, Anthony; Becker, Nikolaus; Nieters, Alexandra; Brennan, Paul; Boffetta, Paolo; Cocco, Pierluigi; Glimelius, Ingrid; Clavel, Jacqueline; Hjalgrim, Henrik; Chang, Ellen T

    2013-11-14

    Ultraviolet radiation (UVR) exposure has been inversely associated with Hodgkin lymphoma (HL) risk, but only inconsistently, only in a few studies, and without attention to HL heterogeneity. We conducted a pooled analysis of HL risk focusing on type and timing of UVR exposure and on disease subtypes by age, histology, and tumor-cell Epstein-Barr virus (EBV) status. Four case-control studies contributed 1320 HL cases and 6381 controls. We estimated lifetime, adulthood, and childhood UVR exposure and history of sunburn and sunlamp use. We used 2-stage estimation with mixed-effects models and weighted pooled effect estimates by inverse marginal variances. We observed statistically significant inverse associations with HL risk for UVR exposures during childhood and adulthood, sunburn history, and sunlamp use, but we found no significant dose-response relationships. Risks were significant only for EBV-positive HL (pooled odds ratio, 0.56; 95% confidence interval, 0.35 to 0.91 for the highest overall UVR exposure category), with a significant linear trend for overall exposure (P = .03). Pooled relative risk estimates were not heterogeneous across studies. Increased UVR exposure may protect against HL, particularly EBV-positive HL. Plausible mechanisms involving UVR induction of regulatory T cells or the cellular DNA damage response suggest opportunities for new prevention targets. PMID:24016459

  8. Exposure to UV radiation and risk of Hodgkin lymphoma: a pooled analysis

    PubMed Central

    Glaser, Sally L.; Schupp, Clayton W.; Ekström Smedby, Karin; de Sanjosé, Silvia; Kane, Eleanor; Melbye, Mads; Forétova, Lenka; Maynadié, Marc; Staines, Anthony; Becker, Nikolaus; Nieters, Alexandra; Brennan, Paul; Boffetta, Paolo; Cocco, Pierluigi; Glimelius, Ingrid; Clavel, Jacqueline; Hjalgrim, Henrik; Chang, Ellen T.

    2013-01-01

    Ultraviolet radiation (UVR) exposure has been inversely associated with Hodgkin lymphoma (HL) risk, but only inconsistently, only in a few studies, and without attention to HL heterogeneity. We conducted a pooled analysis of HL risk focusing on type and timing of UVR exposure and on disease subtypes by age, histology, and tumor-cell Epstein-Barr virus (EBV) status. Four case-control studies contributed 1320 HL cases and 6381 controls. We estimated lifetime, adulthood, and childhood UVR exposure and history of sunburn and sunlamp use. We used 2-stage estimation with mixed-effects models and weighted pooled effect estimates by inverse marginal variances. We observed statistically significant inverse associations with HL risk for UVR exposures during childhood and adulthood, sunburn history, and sunlamp use, but we found no significant dose-response relationships. Risks were significant only for EBV-positive HL (pooled odds ratio, 0.56; 95% confidence interval, 0.35 to 0.91 for the highest overall UVR exposure category), with a significant linear trend for overall exposure (P = .03). Pooled relative risk estimates were not heterogeneous across studies. Increased UVR exposure may protect against HL, particularly EBV-positive HL. Plausible mechanisms involving UVR induction of regulatory T cells or the cellular DNA damage response suggest opportunities for new prevention targets. PMID:24016459

  9. Genetic linkage analysis using pooled DNA and infrared detection of tailed STRP primer patterns

    NASA Astrophysics Data System (ADS)

    Oetting, William S.; Wildenberg, Scott C.; King, Richard A.

    1996-04-01

    The mapping of a disease locus to a specific chromosomal region is an important step in the eventual isolation and analysis of a disease causing gene. Conventional mapping methods analyze large multiplex families and/or smaller nuclear families to find linkage between the disease and a chromosome marker that maps to a known chromosomal region. This analysis is time consuming and tedious, typically requiring the determination of 30,000 genotypes or more. For appropriate populations, we have instead utilized pooled DNA samples for gene mapping which greatly reduces the amount of time necessary for an initial chromosomal screen. This technique assumes a common founder for the disease locus of interest and searches for a region of a chromosome shared between affected individuals. Our analysis involves the PCR amplification of short tandem repeat polymorphisms (STRP) to detect these shared regions. In order to reduce the cost of genotyping, we have designed unlabeled tailed PCR primers which, when combined with a labeled universal primer, provides for an alternative to synthesizing custom labeled primers. The STRP pattern is visualized with an infrared fluorescence based automated DNA sequencer and the patterns quantitated by densitometric analysis of the allele pattern. Differences in the distribution of alleles between pools of affected and unaffected individuals, including a reduction in the number of alleles in the affected pool, indicate the sharing of a region of a chromosome. We have found this method effective for markers 10 - 15 cM away from the disease locus for a recessive genetic disease.

  10. Mortality and cancer incidence in a pooled cohort of US firefighters from San Francisco, Chicago and Philadelphia (1950–2009)

    PubMed Central

    Daniels, Robert D; Kubale, Travis L; Yiin, James H; Dahm, Matthew M; Hales, Thomas R; Baris, Dalsu; Zahm, Shelia H; Beaumont, James J; Waters, Kathleen M; Pinkerton, Lynne E

    2015-01-01

    Objectives To examine mortality patterns and cancer incidence in a pooled cohort of 29 993 US career firefighters employed since 1950 and followed through 2009. Methods Mortality and cancer incidence were evaluated by life table methods with the US population referent. Standardised mortality (SMR) and incidence (SIR) ratios were determined for 92 causes of death and 41 cancer incidence groupings. Analyses focused on 15 outcomes of a priori interest. Sensitivity analyses were conducted to examine the potential for significant bias. Results Person-years at risk totalled 858 938 and 403 152 for mortality and incidence analyses, respectively. All-cause mortality was at expectation (SMR=0.99, 95% CI 0.97 to 1.01, n=12 028). There was excess cancer mortality (SMR=1.14, 95% CI 1.10 to 1.18, n=3285) and incidence (SIR=1.09, 95% CI 1.06 to 1.12, n=4461) comprised mainly of digestive (SMR=1.26, 95% CI 1.18 to 1.34, n=928; SIR=1.17, 95% CI 1.10 to 1.25, n=930) and respiratory (SMR=1.10, 95% CI 1.04 to 1.17, n=1096; SIR=1.16, 95% CI 1.08 to 1.24, n=813) cancers. Consistent with previous reports, modest elevations were observed in several solid cancers; however, evidence of excess lymphatic or haematopoietic cancers was lacking. This study is the first to report excess malignant mesothelioma (SMR=2.00, 95% CI 1.03 to 3.49, n=12; SIR=2.29, 95% CI 1.60 to 3.19, n=35) among US firefighters. Results appeared robust under differing assumptions and analytic techniques. Conclusions Our results provide evidence of a relation between firefighting and cancer. The new finding of excess malignant mesothelioma is noteworthy, given that asbestos exposure is a known hazard of firefighting. PMID:24142974

  11. One-Dimensional Analysis of Thermal Stratification in AHTR and SFR Coolant Pools

    SciTech Connect

    Haihua Zhao; Per F. Peterson

    2007-10-01

    Thermal stratification phenomena are very common in pool type reactor systems, such as the liquid-salt cooled Advanced High Temperature Reactor (AHTR) and liquid-metal cooled fast reactor systems such as the Sodium Fast Reactor (SFR). It is important to accurately predict the temperature and density distributions both for design optimation and accident analysis. Current major reactor system analysis codes such as RELAP5 (for LWR’s, and recently extended to analyze high temperature reactors), TRAC (for LWR’s), and SASSYS (for liquid metal fast reactors) only provide lumped-volume based models which can only give very approximate results and can only handle simple cases with one mixing source. While 2-D or 3-D CFD methods can be used to analyze simple configurations, these methods require very fine grid resolution to resolve thin substructures such as jets and wall boundaries, yet such fine grid resolution is difficult or impossible to provide for studying the reactor response to transients due to computational expense. Therefore, new methods are needed to support design optimization and safety analysis of Generation IV pool type reactor systems. Previous scaling has shown that stratified mixing processes in large stably stratified enclosures can be described using one-dimensional differential equations, with the vertical transport by free and wall jets modeled using standard integral techniques. This allows very large reductions in computational effort compared to three-dimensional numerical modeling of turbulent mixing in large enclosures. The BMIX++ (Berkeley mechanistic MIXing code in C++) code was originally developed at UC Berkeley to implement such ideas. This code solves mixing and heat transfer problems in stably stratified enclosures. The code uses a Lagrangian approach to solve 1-D transient governing equations for the ambient fluid and uses analytical or 1-D integral models to compute substructures. By including liquid salt properties, BMIX++ code is extended to analyze liquid salt pool systems in the current AHTR design, to provide an example of its application. Similar analysis is possible for liquid-metal cooled reactors. The current AHTR baseline design uses a large buffer salt tank to provide more thermal inertial and safety margin. Reactor vessel, intermediate heat exchangers, pool reactor auxiliary cooling system heat exchangers (PHX), and direct reactor auxiliary cooling system heat exchangers (DHX) are all immerged in the buffer salt pool. These structures provide major driving sources for vertical mixing and thermal stratification. Predication of the temperature distribution within the buffer salt tank directly affects the major safety systems design, such as the PHX and DHX, safety analysis results, and structure thermal stresses analysis. The BMIX++ code is used to predict mixing and thermal stratification in this pool system. This example shows the potential of 1-D analysis methods and BMIX++ to be included in system analysis codes for pool type of Gen-IV reactor systems.

  12. Testing Homeopathy in Mouse Emotional Response Models: Pooled Data Analysis of Two Series of Studies

    PubMed Central

    Bellavite, Paolo; Conforti, Anita; Marzotto, Marta; Magnani, Paolo; Cristofoletti, Mirko; Olioso, Debora; Zanolin, Maria Elisabetta

    2012-01-01

    Two previous investigations were performed to assess the activity of Gelsemium sempervirens (Gelsemium s.) in mice, using emotional response models. These two series are pooled and analysed here. Gelsemium s. in various homeopathic centesimal dilutions/dynamizations (4C, 5C, 7C, 9C, and 30C), a placebo (solvent vehicle), and the reference drugs diazepam (1 mg/kg body weight) or buspirone (5 mg/kg body weight) were delivered intraperitoneally to groups of albino CD1 mice, and their effects on animal behaviour were assessed by the light-dark (LD) choice test and the open-field (OF) exploration test. Up to 14 separate replications were carried out in fully blind and randomised conditions. Pooled analysis demonstrated highly significant effects of Gelsemium s. 5C, 7C, and 30C on the OF parameter “time spent in central area” and of Gelsemium s. 5C, 9C, and 30C on the LD parameters “time spent in lit area” and “number of light-dark transitions,” without any sedative action or adverse effects on locomotion. This pooled data analysis confirms and reinforces the evidence that Gelsemium s. regulates emotional responses and behaviour of laboratory mice in a nonlinear fashion with dilution/dynamization. PMID:22548123

  13. A meta-analysis of experimental warming effects on terrestrial nitrogen pools and dynamics.

    PubMed

    Bai, Edith; Li, Shanlong; Xu, Wenhua; Li, Wei; Dai, Weiwei; Jiang, Ping

    2013-07-01

    Global warming may have profound effects on terrestrial ecosystems. However, a comprehensive evaluation of the effects of warming on ecosystem nitrogen (N) pools and dynamics is not available. Here, we compiled data of 528 observations from 51 papers and carried out a meta-analysis of experimental warming effects on 13 variables related to terrestrial N pools and dynamics. We found that, on average, net N mineralization and net nitrification rate were increased by 52.2 and 32.2%, respectively, under experimental warming treatment. N pools were also increased by warming, although the magnitude of this increase was less than that of N fluxes. Soil microbial N and N immobilization were not changed by warming, probably because microbes are limited by carbon sources. Grassland and shrubland/heathland were less responsive to warming than forest, probably because the reduction of soil moisture by warming offset the temperature effect in these areas. Soil heating cable and all-day treatment appeared to be the most effective method on N cycling among all treatment methods. Results of this meta-analysis are useful for better understanding the response of N cycling to global warming and the underlying mechanism of warming effects on plants and ecosystem functions. PMID:23550663

  14. Testing homeopathy in mouse emotional response models: pooled data analysis of two series of studies.

    PubMed

    Bellavite, Paolo; Conforti, Anita; Marzotto, Marta; Magnani, Paolo; Cristofoletti, Mirko; Olioso, Debora; Zanolin, Maria Elisabetta

    2012-01-01

    Two previous investigations were performed to assess the activity of Gelsemium sempervirens (Gelsemium s.) in mice, using emotional response models. These two series are pooled and analysed here. Gelsemium s. in various homeopathic centesimal dilutions/dynamizations (4C, 5C, 7C, 9C, and 30C), a placebo (solvent vehicle), and the reference drugs diazepam (1 mg/kg body weight) or buspirone (5 mg/kg body weight) were delivered intraperitoneally to groups of albino CD1 mice, and their effects on animal behaviour were assessed by the light-dark (LD) choice test and the open-field (OF) exploration test. Up to 14 separate replications were carried out in fully blind and randomised conditions. Pooled analysis demonstrated highly significant effects of Gelsemium s. 5C, 7C, and 30C on the OF parameter "time spent in central area" and of Gelsemium s. 5C, 9C, and 30C on the LD parameters "time spent in lit area" and "number of light-dark transitions," without any sedative action or adverse effects on locomotion. This pooled data analysis confirms and reinforces the evidence that Gelsemium s. regulates emotional responses and behaviour of laboratory mice in a nonlinear fashion with dilution/dynamization. PMID:22548123

  15. First microbiota assessments of children's paddling pool waters evaluated using 16S rRNA gene-based metagenome analysis.

    PubMed

    Sawabe, Toko; Suda, Wataru; Ohshima, Kenshiro; Hattori, Masahira; Sawabe, Tomoo

    2016-01-01

    Insufficient chloric sterilization of children's paddling pool waters increases the risk of diarrheal illness. Therefore, we investigated the microbiota changes after children use pools. First, we applied 16S rRNA gene-based metagenome analysis to understand the dynamics of microbiota in pool water, especially with respect to the bio-contamination by potential pathogens. Proteobacteria were major taxa detected in every pool water sample after children spent time in the pool. In more detail, Gammaproteobacteria comprised the dominant class, which was followed by Betaproteobacteria. Five phyla, Bacteroidetes, Firmicutes, Actinobacteria and Deinococcus-Thermus phyla were minor groups. The pool water microbiota are likely to be a consortium of intestinal and skin microbiota from humans. Interestingly, the ratio of Gammaproteobacteria and Betaproteobacteria differed according to the age of the children who used the pool, which means the pool water was additionally contaminated by soil microbiota as a result of the children's behavior. Furthermore, potential pathogens, such as Campylobacter spp., Comamonas testosteroni and Burkholderia pseudomallei, were also found. Considering the standard plate counts, the abundances of these human pathogens are unlikely to be a sufficiently infectious dose. We suggest the importance of sanitary measures in paddling pool waters to reduce bio-contamination from both humans and the environment. PMID:26671497

  16. Fourier analysis of a gated blood-pool study during atrial flutter

    SciTech Connect

    Makler, P.T. Jr.; McCarthy, D.M.; London, J.W.; Sandler, M.S.; Alavi, A.

    1983-08-01

    First-harmonic Fourier analysis of a gated blood-pool study is based on the assumption that the cardiac chambers contract once per cardiac cycle. In atrial arrhythmias this condition may not exist for the atria. We recently studied a patient with atrial flutter and 2:1 artioventricular conduction. There were predictable alterations in the first-harmonic Fourier phase and amplitude images. The observed changes from first-harmonic Fourier analysis were: (a) very low atrial amplitude values, and (b) absence of identifiable atrial regions on the phase image.

  17. Pooled analysis of the prognostic relevance of progesterone receptor status in five German cohort studies.

    PubMed

    Salmen, Jessica; Neugebauer, Julia; Fasching, Peter A; Haeberle, Lothar; Huober, Jens; Wckel, Achim; Rauh, Claudia; Schuetz, Florian; Weissenbacher, Tobias; Kost, Bernd; Stickeler, Elmar; Klar, Maximilian; Orlowska-Volk, Marzenna; Windfuhr-Blum, Marisa; Heil, Joerg; Rom, Joachim; Sohn, Christof; Fehm, Tanja; Mohrmann, Svjetlana; Loehberg, Christian R; Hein, Alexander; Schulz-Wendtland, Ruediger; Hartkopf, Andreas D; Brucker, Sara Y; Wallwiener, Diethelm; Friese, Klaus; Hartmann, Arndt; Beckmann, Matthias W; Janni, Wolfgang; Rack, Brigitte

    2014-11-01

    The progesterone receptor (PR) has been increasingly well described as an important mediator of the pathogenesis and progression of breast cancer. The aim of this study was to assess the role of PR status as a prognostic factor in addition to other well-established prognostic factors. Data from five independent German breast cancer centers were pooled. A total of 7,965 breast cancer patients were included for whom information about their PR status was known, as well as other patient and tumor characteristics commonly used as prognostic factors. Cox proportional hazards models were built to compare the predictive value of PR status in addition to age at diagnosis, tumor size, nodal status, grading, and estrogen receptor (ER) status. PR status significantly increased the accuracy of prognostic predictions with regard to overall survival, distant disease-free survival, and local recurrence-free survival. There were differences with regard to its prognostic value relative to subgroups such as nodal status, ER status, and grading. The prognostic value of PR status was greatest in patients with a positive nodal status, negative ER status, and low grading. The PR-status adds prognostic value in addition to ER status and should not be omitted from clinical routine testing. The significantly greater prognostic value in node-positive and high-grade tumors suggests a greater role in the progression of advanced and aggressive tumors. PMID:25253172

  18. Swimming Pools.

    ERIC Educational Resources Information Center

    Ministry of Housing and Local Government, London (England).

    Technical and engineering data are set forth on the design and construction of swimming pools. Consideration is given to site selection, pool construction, the comparative merits of combining open air and enclosed pools, and alternative uses of the pool. Guidelines are presented regarding--(1) pool size and use, (2) locker and changing rooms, (3)

  19. Swimming Pools.

    ERIC Educational Resources Information Center

    Ministry of Housing and Local Government, London (England).

    Technical and engineering data are set forth on the design and construction of swimming pools. Consideration is given to site selection, pool construction, the comparative merits of combining open air and enclosed pools, and alternative uses of the pool. Guidelines are presented regarding--(1) pool size and use, (2) locker and changing rooms, (3)…

  20. A pooled analysis of body mass index and mortality among African Americans.

    PubMed

    Cohen, Sarah S; Park, Yikyung; Signorello, Lisa B; Patel, Alpa V; Boggs, Deborah A; Kolonel, Laurence N; Kitahara, Cari M; Knutsen, Synnove F; Gillanders, Elizabeth; Monroe, Kristine R; Berrington de Gonzalez, Amy; Bethea, Traci N; Black, Amanda; Fraser, Gary; Gapstur, Susan; Hartge, Patricia; Matthews, Charles E; Park, Song-Yi; Purdue, Mark P; Singh, Pramil; Harvey, Chinonye; Blot, William J; Palmer, Julie R

    2014-01-01

    Pooled analyses among whites and East Asians have demonstrated positive associations between all-cause mortality and body mass index (BMI), but studies of African Americans have yielded less consistent results. We examined the association between BMI and all-cause mortality in a sample of African Americans pooled from seven prospective cohort studies: NIH-AARP, 1995-2009; Adventist Health Study 2, 2002-2008; Black Women's Health Study, 1995-2009; Cancer Prevention Study II, 1982-2008; Multiethnic Cohort Study, 1993-2007; Prostate, Lung, Colorectal and Ovarian Screening Trial, 1993-2009; Southern Community Cohort Study, 2002-2009. 239,526 African Americans (including 100,175 never smokers without baseline heart disease, stroke, or cancer), age 30-104 (mean 52) and 71% female, were followed up to 26.5 years (mean 11.7). Hazard ratios (HR) and 95% confidence intervals (CI) for mortality were derived from multivariate Cox proportional hazards models. Among healthy, never smokers (11,386 deaths), HRs (CI) for BMI 25-27.4, 27.5-29.9, 30-34.9, 35-39.9, 40-49.9, and 50-60 kg/m(2) were 1.02 (0.92-1.12), 1.06 (0.95-1.18), 1.32 (1.18-1.47), 1.54 (1.29-1.83), 1.93 (1.46-2.56), and 1.93 (0.80-4.69), respectively among men and 1.06 (0.99-1.15), 1.15 (1.06-1.25), 1.24 (1.15-1.34), 1.58 (1.43-1.74), 1.80 (1.60-2.02), and 2.31 (1.74-3.07) respectively among women (reference category 22.5-24.9). HRs were highest among those with the highest educational attainment, longest follow-up, and for cardiovascular disease mortality. Obesity was associated with a higher risk of mortality in African Americans, similar to that observed in pooled analyses of whites and East Asians. This study provides compelling evidence to support public health efforts to prevent excess weight gain and obesity in African Americans. PMID:25401742

  1. Impact of Genetic Notification on Smoking Cessation: Systematic Review and Pooled-Analysis

    PubMed Central

    de Viron, Sylviane; Van der Heyden, Johan; Ambrosino, Elena; Arbyn, Marc; Brand, Angela; Van Oyen, Herman

    2012-01-01

    Objectives This study aimed to evaluate the impact of genetic notification of smoking-related disease risk on smoking cessation in the general population. Secondary objectives were to assess the impact of genetic notification on intention-to-quit smoking and on emotional outcomes as well as the understanding and the recall of this notification. Methods A systematic review of articles from inception to August 2011 without language restriction was realized using PubMed, Embase, Scopus, Web of Science, PsycINFO and Toxnet. Other publications were identified using hand search. The pooled-analysis included only randomized trials. Comparison groups were (i) high and low genetic risk versus control, and (ii) high versus low genetic risk. For the pooled-analysis random effect models were applied and sensitivity analyses were conducted. Results Eight papers from seven different studies met the inclusion criteria of the review. High genetic risk notification was associated with short-term increased depression and anxiety. Four randomized studies were included in the pooled-analysis, which revealed a significant impact of genetic notification on smoking cessation in comparison to controls (clinical risk notification or no intervention) in short term follow-up less than 6 months (RR = 1.55, 95% CI 1.09–2.21). Conclusions In short term follow-up, genetic notification increased smoking cessation in comparison to control interventions. However, there is no evidence of long term effect (up to 12 month) on smoking cessation. Further research is needed to assess more in depth how genetic notification of smoking-related disease could contribute to smoking cessation. PMID:22808123

  2. A Pooled Analysis of Melanocytic Naevus Phenotype and the Risk of Cutaneous Melanoma at Different Latitudes

    PubMed Central

    Chang, Yu-mei; Newton-Bishop, Julia A; Bishop, D Timothy; Armstrong, Bruce K; Bataille, Veronique; Bergman, Wilma; Berwick, Marianne; Bracci, Paige M; Elwood, J Mark; Ernstoff, Marc S; Green, Adèle C; Gruis, Nelleke A; Holly, Elizabeth A; Ingvar, Christian; Kanetsky, Peter A; Karagas, Margaret R; Le Marchand, Loïc; Mackie, Rona M; Olsson, Håkan; Østerlind, Anne; Rebbeck, Timothy R; Reich, Kristian; Sasieni, Peter; Siskind, Victor; Swerdlow, Anthony J; Titus-Ernstoff, Linda; Zens, Michael S; Ziegler, Andreas; Barrett, Jennifer H

    2008-01-01

    An abnormal naevus phenotype is associated with an increased risk of melanoma. We report a pooled analysis conducted using individual naevus data from 15 case-control studies (5,421 melanoma cases and 6,966 controls). The aims were to quantify better the risk, and to determine whether relative risk varied by latitude. Bayesian unconditional logistic random coefficients models were employed to study the risk associated with naevus characteristics. Participants with whole body naevus counts in the highest of four population-based categories had a greatly increased risk of melanoma compared with those in the lowest category (pooled odds ratio (pOR) 6.9 (95% confidence interval (CI): 4.4, 11.2) for those aged <50 years and pOR 5.1 (95% CI: 3.6, 7.5) for those aged ≥50). The pOR for presence compared with absence of any clinically atypical naevi was 4.0 (95% CI: 2.8, 5.8). The pORs for 1–2 and ≥3 large naevi on the body compared with none were 2.9 (95% CI: 1.9, 4.3) and 7.1 (95% CI: 4.7, 11.6), respectively. The relative heterogeneities among studies were small for most measures of naevus phenotype, except for the analysis of naevus counts on the arms, which may have been due to methodological differences among studies. The pooled analysis also suggested that an abnormal naevus phenotype is associated most with melanomas on intermittently sun-exposed sites. The presence of increased numbers of naevi, large naevi and clinically atypical naevi on the body are robust risk factors for melanoma showing little variation in relative risk among studies performed at different latitudes. PMID:18792098

  3. 3-Bromopyruvate induces rapid human prostate cancer cell death by affecting cell energy metabolism, GSH pool and the glyoxalase system.

    PubMed

    Valenti, Daniela; Vacca, Rosa A; de Bari, Lidia

    2015-12-01

    3-bromopyruvate (3-BP) is an anti-tumour drug effective on hepatocellular carcinoma and other tumour cell types, which affects both glycolytic and mitochondrial targets, depleting cellular ATP pool. Here we tested 3-BP on human prostate cancer cells showing, differently from other tumour types, efficient ATP production and functional mitochondrial metabolism. We found that 3-BP rapidly induced cultured androgen-insensitive (PC-3) and androgen-responsive (LNCaP) prostate cancer cell death at low concentrations (IC(50) values of 50 and 70 ?M, respectively) with a multimodal mechanism of action. In particular, 3-BP-treated PC-3 cells showed a selective, strong reduction of glyceraldeide 3-phosphate dehydrogenase activity, due to the direct interaction of the drug with the enzyme. Moreover, 3-BP strongly impaired both glutamate/malate- and succinate-dependent mitochondrial respiration, membrane potential generation and ATP synthesis, concomitant with the inhibition of respiratory chain complex I, II and ATP synthase activities. The drastic reduction of cellular ATP levels and depletion of GSH pool, associated with significant increase in cell oxidative stress, were found after 3-BP treatment of PC-3 cells. Interestingly, the activity of both glyoxalase I and II, devoted to the elimination of the cytotoxic methylglyoxal, was strongly inhibited by 3-BP. Both N-acetylcysteine and aminoguanidine, GSH precursor and methylglyoxal scavenger, respectively, prevented 3-BP-induced PC-3 cell death, showing that impaired cell antioxidant and detoxifying capacities are crucial events leading to cell death. The provided information on the multi-target cytotoxic action of 3-BP, finally leading to PC-3 cell necrosis, might be useful for future development of 3-BP as a therapeutic option for prostate cancer treatment. PMID:26530987

  4. Pirfenidone for idiopathic pulmonary fibrosis: analysis of pooled data from three multinational phase 3 trials.

    PubMed

    Noble, Paul W; Albera, Carlo; Bradford, Williamson Z; Costabel, Ulrich; du Bois, Roland M; Fagan, Elizabeth A; Fishman, Robert S; Glaspole, Ian; Glassberg, Marilyn K; Lancaster, Lisa; Lederer, David J; Leff, Jonathan A; Nathan, Steven D; Pereira, Carlos A; Swigris, Jeffrey J; Valeyre, Dominique; King, Talmadge E

    2016-01-01

    Pirfenidone is an antifibrotic agent that has been evaluated in three multinational phase 3 trials in patients with idiopathic pulmonary fibrosis (IPF). We analysed pooled data from the multinational trials to obtain the most precise estimates of the magnitude of treatment effect on measures of disease progression.All patients randomised to pirfenidone 2403 mg·day(-1) or placebo in the CAPACITY or ASCEND studies were included in the analysis. Pooled analyses of outcomes at 1 year were based on the pre-specified end-points and analytic methods described in the ASCEND study protocol.A total of 1247 patients were included in the analysis. At 1 year, pirfenidone reduced the proportion of patients with a ≥10% decline in per cent predicted forced vital capacity or death by 43.8% (95% CI 29.3-55.4%) and increased the proportion of patients with no decline by 59.3% (95% CI 29.0-96.8%). A treatment benefit was also observed for progression-free survival, 6-min walk distance and dyspnoea. Gastrointestinal and skin-related adverse events were more common in the pirfenidone group, but rarely led to discontinuation.Analysis of data from three phase 3 trials demonstrated that treatment with pirfenidone for 1 year resulted in clinically meaningful reductions in disease progression in patients with IPF. PMID:26647432

  5. Pirfenidone for idiopathic pulmonary fibrosis: analysis of pooled data from three multinational phase 3 trials

    PubMed Central

    Albera, Carlo; Bradford, Williamson Z.; Costabel, Ulrich; du Bois, Roland M.; Fagan, Elizabeth A.; Fishman, Robert S.; Glaspole, Ian; Glassberg, Marilyn K.; Lancaster, Lisa; Lederer, David J.; Leff, Jonathan A.; Nathan, Steven D.; Pereira, Carlos A.; Swigris, Jeffrey J.; Valeyre, Dominique; King, Talmadge E.

    2016-01-01

    Pirfenidone is an antifibrotic agent that has been evaluated in three multinational phase 3 trials in patients with idiopathic pulmonary fibrosis (IPF). We analysed pooled data from the multinational trials to obtain the most precise estimates of the magnitude of treatment effect on measures of disease progression. All patients randomised to pirfenidone 2403 mg·day−1 or placebo in the CAPACITY or ASCEND studies were included in the analysis. Pooled analyses of outcomes at 1 year were based on the pre-specified end-points and analytic methods described in the ASCEND study protocol. A total of 1247 patients were included in the analysis. At 1 year, pirfenidone reduced the proportion of patients with a ≥10% decline in per cent predicted forced vital capacity or death by 43.8% (95% CI 29.3–55.4%) and increased the proportion of patients with no decline by 59.3% (95% CI 29.0–96.8%). A treatment benefit was also observed for progression-free survival, 6-min walk distance and dyspnoea. Gastrointestinal and skin-related adverse events were more common in the pirfenidone group, but rarely led to discontinuation. Analysis of data from three phase 3 trials demonstrated that treatment with pirfenidone for 1 year resulted in clinically meaningful reductions in disease progression in patients with IPF. PMID:26647432

  6. β-Blockers Reduce Breast Cancer Recurrence and Breast Cancer Death: A Meta-Analysis.

    PubMed

    Childers, W Kurtis; Hollenbeak, Christopher S; Cheriyath, Pramil

    2015-12-01

    The normal physiologic stress mechanism, mediated by the sympathetic nervous system, causes a release of the neurotransmitters epinephrine and norepinephrine. Preclinical data have demonstrated an effect on tumor progression and metastasis via the sympathetic nervous system mediated primarily through the β-adrenergic receptor (β-AR) pathway. In vitro data have shown an increase in tumor growth, migration, tumor angiogenesis, and metastatic spread in breast cancer through activation of the β-AR. Retrospective cohort studies on the clinical outcomes of β-blockers in breast cancer outcomes showed no clear consensus. The purpose of this study was to perform a systematic review and meta-analysis of the effect of β-blockers on breast cancer outcomes. A systematic review was performed using the Cochrane library and PubMed. Publications between the dates of January 2010 and December 2013 were identified. Available hazard ratios (HRs) were extracted for breast cancer recurrence, breast cancer death, and all-cause mortality and pooled using a random effects meta-analysis. A total of 7 studies contained results for at least 1 of the outcomes of breast cancer recurrence, breast cancer death, or all-cause mortality in breast cancer patients receiving β-blockers. In the 5 studies that contained results for breast cancer recurrence, there was no statistically significant risk reduction (HR, 0.67; 95% confidence interval [CI], 0.39-1.13). Breast cancer death results were contained in 4 studies, which also suggested a significant reduction in risk (HR, 0.50; 95% CI, 0.32-0.80). Among the 4 studies that reported all-cause mortality, there was no significant effect of β-blockers on risk (HR, 1.02; 95% CI, 0.75-1.37). Results of this systematic review and meta-analysis suggest that the use of β-blockers significantly reduced risk of breast cancer death among women with breast cancer. PMID:26516037

  7. Monitoring organic loading to swimming pools by fluorescence excitation-emission matrix with parallel factor analysis (PARAFAC).

    PubMed

    Seredyńska-Sobecka, Bożena; Stedmon, Colin A; Boe-Hansen, Rasmus; Waul, Christopher K; Arvin, Erik

    2011-03-01

    Fluorescence Excitation-Emission Matrix spectroscopy combined with parallel factor analysis was employed to monitor water quality and organic contamination in swimming pools. The fluorescence signal of the swimming pool organic matter was low but increased slightly through the day. The analysis revealed that the organic matter fluorescence was characterised by five different components, one of which was unique to swimming pool organic matter and one which was specific to organic contamination. The latter component had emission peaks at 420 nm and was found to be a sensitive indicator of organic loading in swimming pool water. The fluorescence at 420 nm gradually increased during opening hours and represented material accumulating through the day. PMID:21310459

  8. Atopic disease and risk of non-Hodgkin lymphoma: an InterLymph pooled analysis

    PubMed Central

    Vajdic, Claire M.; Falster, Michael O.; Sanjose, Silvia de; Martínez-Maza, Otoniel; Becker, Nikolaus; Bracci, Paige M.; Melbye, Mads; Smedby, Karin Ekström; Engels, Eric A.; Turner, Jennifer; Vineis, Paolo; Costantini, Adele Seniori; Holly, Elizabeth A.; Kane, Eleanor; Spinelli, John J.; Vecchia, Carlo La; Zheng, Tongzhang; Chiu, Brian C.-H.; Maso, Luigino Dal; Cocco, Pierluigi; Maynadié, Marc; Foretova, Lenka; Staines, Anthony; Brennan, Paul; Davis, Scott; Severson, Richard; Cerhan, James R.; Breen, Elizabeth C.; Birmann, Brenda; Cozen, Wendy; Grulich, Andrew E.

    2009-01-01

    We performed a pooled analysis of data on atopic disease and risk of non-Hodgkin lymphoma (NHL) from 13 case-control studies, including13,535 NHL cases and 16,388 controls. Self-reported atopic diseases diagnosed two or more years before NHL diagnosis (cases) or interview (controls) were analyzed. Pooled odds ratios (OR) and 95% confidence intervals were computed in two-stage random-effects or joint fixed-effects models, adjusted for age, sex, and study center. When modeled individually, lifetime history of asthma, hay fever, a specific allergy (excluding hay fever, asthma and eczema), and food allergy were associated with a significant reduction in NHL risk, and there was no association for eczema. When each atopic condition was included in the same model, reduced NHL risk was only associated with history of allergy (OR 0.80, 95% CI 0.68–0.94), and reduced B-cell NHL risk was associated with history of hay fever (OR 0.85, 95% CI 0.77–0.95) and allergy (OR 0.84, 95% CI 0.76–0.93). Significant reductions in B-cell NHL risk were also observed in individuals who were likely to be truly or highly atopic - those with hay fever, allergy or asthma and at least one other atopic condition over their lifetime. The inverse associations were consistent for the diffuse large B-cell and follicular subtypes. Eczema was positively associated with lymphomas of the skin; misdiagnosis of lymphoma as eczema is likely, but progression of eczema to cutaneous lymphoma cannot be excluded. This pooled study demonstrates evidence of a modest but consistent reduction in the risk of B-cell NHL associated with atopy. PMID:19654312

  9. [Evaluation of zygomycosis cases by pooled analysis method reported from Turkey].

    PubMed

    Zeka, Arzu Nazlı; Taşbakan, Meltem; Pullukçu, Hüsnü; Sipahi, Oğuz Reşat; Yamazhan, Tansu; Arda, Bilgin

    2013-10-01

    Zygomycosis is a rapidly-progressive invasive fungal disease with high mortality rates. Mucor, Rhizopus, Rhizomucor and Absidia species classified in Mucorales order, are the main causative agents of zygomycosis. Uncontrolled diabetes, hematologic malignancies, long term corticosteroid use and immunosuppressive therapies are the main predisposing factors for mucormycosis. In this study, we aimed to evaluate the mucormycosis cases from Turkey published in national and international databases in the last 17 years by means of age, gender, co-morbidities, signs and symptoms, diagnostic methods, therapeutic modalities, and mortality rate by pooling analysis. In our study, two national (http://uvt.ulakbim.gov.tr, http://www.turkmedline.net) and two international (www.ncbi.nlm.nih.gov, http://apps.webofknowledge.com) databases were used. A total of 64 manuscript (34 from national and 30 from international databases) published between 1995 and 2012, which were eligible for the study criteria and accessible as full text were included in the study. A total of 151 mucormycosis patients (71 female, 80 male; mean age: 45.4 ± 21.4 years) from these studies, with definitive diagnosis of invasive fungal infections according to the criteria of European Organization for Research and Treatment of Cancer (EORTC) have been evaluated. Of 151 patients 91 (60%) were diagnosed as rhinocerebral, 42 (%27.8) were sinoorbital, 7 (4.6%) were pulmonary, 6 (3.9%) were disseminated, 3 (1.9%) were skin, and 2 (1.3%) were gastrointestinal mycormycosis. The most common symptoms and signs were; swelling of eye and face (n= 95, 63%), fever (n= 72, 48%), nasal obstruction (n= 60, 40%), headache (n= 58, 38%) and opthtalmoplegia (n= 48, 32%). The most common co-morbidity was diabetes (49%) followed by hematological malignancies (39.7%). Mycological cultures were performed for 82 patients, and fungal growth were detected in the clinical specimens of 51 cases. The distribution of strains isolated in culture were as follows: Mucor spp. (n= 19, 37.2%), Rhizopus spp. (n= 13, 25.5%), Zygomycetes (n= 9, 17.6%), Rhizopus oryzae (n= 4, 7.8%), Rhizopus spp. + yeast (n= 3, 5.9%), Rhizomucor spp. (n= 2, 3.9%) and Rhizosporium spp. (n= 1, 1.9%). In 133 patients, histopathological investigation and in 126 patients radiological examinations were performed for diagnosis. Both surgical debridement and antifungal therapy were employed in 115 patients. Four patients had received only surgical debridement and 30 only antifungal therapies. Classical amphotericin B (AMP-B) therapy for 77 cases, liposomal AMP-B for 60 cases, liposomal AMP-B + posaconazole for six cases and lipid complex AMP-B for two cases have been started as antifungal therapies. Total mortality rate was detected as 54.3% (82/151). In conclusion, despite new diagnostic tools and therapeutic agents, mortality rates in mucormycosis are still very high. For the management, mucormycosis should be considered early in risky patients, and surgical debridement together with effective antifungal therapy should be applied as soon as possible. PMID:24237440

  10. Patterns of ventricular emptying by Fourier analysis of gated blood-pool studies

    SciTech Connect

    Links, J.M.; Douglass, K.H.; Wagner, H.N. Jr.

    1980-10-01

    Temporal Fourier analysis was applied to the processing of ECG-gated cardiac blood-pool studies on a pixel-by-pixel basis, to yield information about the pattern of ventricular emptying in normal hearts and in others with conduction abnormalities. The transform data at the fundamental frequency (the heart rate) were used to construct two types of display: (a) a distribution histogram of the pixel phase values, and (b) a cinematic display of the wave of emptying as it spread over the cardiac chambers. Preliminary results indicate that temporal Fourier analysis permits visualization of the pattern of ventricular emptying, which may prove useful in the study of motion abnormalities and asynergies, including those resulting from myocardial hypertrophy or conduction abnormalities, and as an aid in the optimum placement of pacemakers.

  11. PWR core and spent fuel pool analysis using scale and nestle

    SciTech Connect

    Murphy, J. E.; Maldonado, G. I.; St Clair, R.; Orr, D.

    2012-07-01

    The SCALE nuclear analysis code system [SCALE, 2011], developed and maintained at Oak Ridge National Laboratory (ORNL) is widely recognized as high quality software for analyzing nuclear systems. The SCALE code system is composed of several validated computer codes and methods with standard control sequences, such as the TRITON/NEWT lattice physics sequence, which supplies dependable and accurate analyses for industry, regulators, and academia. Although TRITON generates energy-collapsed and space-homogenized few group cross sections, SCALE does not include a full-core nodal neutron diffusion simulation module within. However, in the past few years, the open-source NESTLE core simulator [NESTLE, 2003], originally developed at North Carolina State Univ. (NCSU), has been updated and upgraded via collaboration between ORNL and the Univ. of Tennessee (UT), so it now has a growingly seamless coupling to the TRITON/NEWT lattice physics [Galloway, 2010]. This study presents the methodology used to couple lattice physics data between TRITON and NESTLE in order to perform a three-dimensional full-core analysis employing a 'real-life' Duke Energy PWR as the test bed. The focus for this step was to compare the key parameters of core reactivity and radial power distribution versus plant data. Following the core analysis, following a three cycle burn, a spent fuel pool analysis was done using information generated from NESTLE for the discharged bundles and was compared to Duke Energy spent fuel pool models. The KENO control module from SCALE was employed for this latter stage of the project. (authors)

  12. Risk factors for MRSA in fattening pig herds - a meta-analysis using pooled data.

    PubMed

    Fromm, Sabine; Beißwanger, Elena; Käsbohrer, Annemarie; Tenhagen, Bernd-Alois

    2014-11-01

    The importance of livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) as an infectious agent for humans has increased in recent years in Germany. Although it is well known that the prevalence of MRSA in pig farms is high, risk factors for the presence of MRSA in herds of fattening pigs are still poorly understood. The aim of this study was to evaluate available data from previous studies on MRSA in fattening pigs in a meta-analysis to answer the question: What are the factors associated with the occurrence of MRSA in fattening pig herds? The studies on MRSA in pigs that were identified by literature research were heterogeneous with respect to the risk factors investigated and the type of herds focused on. Therefore we decided to carry out a pooling analysis on herd level rather than a typical meta-analysis. Eligible herd data were identified based on the published literature and communication with the authors. The final data set covered 400 fattening pig herds from 10 different studies and 12 risk factors. The prevalence of MRSA in the 400 fattening pig herds was 53.5%. Data were analyzed using generalized estimating equations (GEE). The resulting multivariate model confirmed previously identified risk factors for MRSA in pig herds (herd size and herd type). It also identified further risk factors: group treatment of fattening pigs with antimicrobial drugs (OR=1.79) and housing fattening pig herds on at least partially slatted floors (OR=2.39) compared to plain floor. In contrast, according to the model, fattening pig herds on farms keeping other livestock along with pigs were less likely to harbor MRSA (OR=0.54). The results underline the benefits from a pooling analysis and cooperative re-evaluation of published data. PMID:25241618

  13. Unbiased metabolite profiling indicates that a diminished thymidine pools is the underlying mechanism of colon cancer chemoprevention by alpha-difluoromethylornithine (DFMO)

    PubMed Central

    Witherspoon, Mavee; Chen, Qiuying; Kopelovich, Levy; Gross, Steven S.; Lipkin, Steven

    2013-01-01

    The ornithine decarboxylase (ODC) inhibitor, ?-difluoromethylornithine (DFMO), is a highly effective chemopreventative agent for colorectal cancer (CRC) thought to act via polyamine depletion. However, in DFMO treated patients, mucosal polyamine levels do not directly correlate with CRC risk. Untargeted metabolite profiling was used to broadly survey DFMO actions on colon cancer cell metabolism. Some studies revealed that DFMO treatment of ApcMin intestinal tumors and human CRC cells is associated with reduced levels of folate-dependent metabolites, including S-adenosylmethionine (SAM), thymidine pools and related pathway intermediates. We hypothesized that unrestrained SAM consumption/regeneration constitutes a futile DFMO-triggered cascade that can steal tetrahydrofolate (THF) from thymidylate synthase and thereby diminishing thymidine pools. In accord with this hypothesis, DFMO-treatment altered the folate cofactor balance and thymidine supplementation prevented DFMO-elicited cytostasis without restoring polyamine levels. These findings suggest that thymidine metabolite pool insufficiency is a fundamental mechanism of DFMO cytostatic activity. PMID:23771434

  14. Population pharmacokinetics of intravenous artesunate: a pooled analysis of individual data from patients with severe malaria.

    PubMed

    Zaloumis, S G; Tarning, J; Krishna, S; Price, R N; White, N J; Davis, T M E; McCaw, J M; Olliaro, P; Maude, R J; Kremsner, P; Dondorp, A; Gomes, M; Barnes, K; Simpson, J A

    2014-01-01

    There are ~660,000 deaths from severe malaria each year. Intravenous artesunate (i.v. ARS) is the first-line treatment in adults and children. To optimize the dosing regimen of i.v. ARS, the largest pooled population pharmacokinetic study to date of the active metabolite dihydroartemisinin (DHA) was performed. The pooled dataset consisted of 71 adults and 195 children with severe malaria, with a mixture of sparse and rich sampling within the first 12 h after drug administration. A one-compartment model described the population pharmacokinetics of DHA adequately. Body weight had the greatest impact on DHA pharmacokinetics, resulting in lower DHA exposure for smaller children (6-10 kg) than adults. Post hoc estimates of DHA exposure were not significantly associated with parasitological outcomes. Comparable DHA exposure in smaller children and adults after i.v. ARS was achieved under a dose modification for intramuscular ARS proposed in a separate analysis of children. PMID:25372510

  15. Dermatologic adverse events in pediatric patients receiving targeted anticancer therapies: a pooled analysis

    PubMed Central

    Pratilas, Christine A.; Sibaud, Vincent; Boralevi, Franck; Lacouture, Mario E.

    2015-01-01

    BACKGROUND The dermatologic adverse events (AEs) of various molecularly targeted therapies are well-described in adult cancer patients. Little has been reported on the incidence and clinical presentation of such AEs in pediatric patients with cancer. To address this gap, we analyzed the dermatologic AEs reported across clinical trials of targeted anticancer therapies in pediatric patients. METHODS We conducted an electronic literature search (PubMed, American Society of Clinical Oncology annual meetings’ abstracts, ClinicalTrials.gov, NCI’s Pediatric Oncology Branch webpage) to identify clinical trials involving targeted anticancer therapies that reported dermatologic AEs in their safety data. Studies were limited to the pediatric population, monotherapy trials (oncology), and English language publications. RESULTS Pooled data from 19 clinical studies investigating 11 targeted anticancer agents (alemtuzumab, rituximab, imatinib, dasatinib, erlotinib, vandetanib, sorafenib, cabozantinib, pazopanib, everolimus, and temsirolimus) were analyzed. The most frequently encountered dermatologic AEs were rash (127/660; 19%), xerosis (18/100; 18%), mucositis (68/402; 17%) and pruritus (12/169; 7%). Other AEs included pigmentary abnormalities of the skin/hair (13%), hair disorders (trichomegaly, hypertrichosis, alopecia and madarosis; 14%), urticaria (7%), palmoplantar erythrodysesthesia (7%), erythema, acne, purpura, skin fissures, other ‘unknown skin changes’, exanthem, infection, flushing, telangiectasia, and photosensitivity. CONCLUSION This study describes the dermatologic manifestations of targeted anticancer therapy-related AEs in the pediatric population. Since these AEs are often associated with significant morbidity, it is imperative that pediatric oncologists be familiar with their recognition and management, to avoid unnecessary dose modifications and/or termination, and to prevent impairments in patients’ quality of life. PMID:25683226

  16. Methods for Cancer Epigenome Analysis

    PubMed Central

    Nagarajan, Raman P.; Fouse, Shaun D.; Bell, Robert J.A.; Costello, Joseph F.

    2014-01-01

    Accurate detection of epimutations in tumor cells is crucial for understanding the molecular pathogenesis of cancer. Alterations in DNA methylation in cancer are functionally important and clinically relevant, but even this well-studied area is continually re-evaluated in light of unanticipated results, including a strong connection between aberrant DNA methylation in adult tumors and polycomb group profiles in embryonic stem cells, cancer-associated genetic mutations in epigenetic regulators such as DNMT3A and TET family genes, and the discovery of abundant 5-hydroxymethylcytosine, a product of TET proteins acting on 5-methylcytosine, in human tissues. The abundance and distribution of covalent histone modifications in primary cancer tissues relative to normal cells is a largely uncharted area, although there is good evidence for a mechanistic role of cancer-specific alterations in epigenetic marks in tumor etiology, drug response and tumor progression. Meanwhile, the discovery of new epigenetic marks continues, and there are many useful methods for epigenome analysis applicable to primary tumor samples, in addition to cancer cell lines. For DNA methylation and hydroxymethylation, next-generation sequencing allows increasingly inexpensive and quantitative whole-genome profiling. Similarly, the refinement and maturation of chromatin immunoprecipitation with next-generation sequencing (ChIP-seq) has made possible genome-wide mapping of histone modifications, open chromatin and transcription factor binding sites. Computational tools have been developed apace with these epigenome methods to better enable the accuracy and interpretation of the data from the profiling methods. PMID:22956508

  17. CPAP: Cancer Panel Analysis Pipeline.

    PubMed

    Huang, Po-Jung; Yeh, Yuan-Ming; Gan, Ruei-Chi; Lee, Chi-Ching; Chen, Ting-Wen; Lee, Cheng-Yang; Liu, Hsuan; Chen, Shu-Jen; Tang, Petrus

    2013-10-01

    Targeted sequencing using next-generation sequencing technologies is currently being rapidly adopted for clinical sequencing and cancer marker tests. However, no existing bioinformatics tool is available for the analysis and visualization of multiple targeted sequencing datasets. In the present study, we use cancer panel targeted sequencing datasets generated by the Life Technologies Ion Personal Genome Machine Sequencer as an example to illustrate how to develop an automated pipeline for the comparative analyses of multiple datasets. Cancer Panel Analysis Pipeline (CPAP) uses standard output files from variant calling software to generate a distribution map of SNPs among all of the samples in a circular diagram generated by Circos. The diagram is hyperlinked to a dynamic HTML table that allows the users to identify target SNPs by using different filters. CPAP also integrates additional information about the identified SNPs by linking to an integrated SQL database compiled from SNP-related databases, including dbSNP, 1000 Genomes Project, COSMIC, and dbNSFP. CPAP only takes 17 min to complete a comparative analysis of 500 datasets. CPAP not only provides an automated platform for the analysis of multiple cancer panel datasets but can also serve as a model for any customized targeted sequencing project. PMID:23893859

  18. Equilibrium analysis of carbon pools and fluxes of forest biomes in the former Soviet Union

    SciTech Connect

    Kolchugina, T.P.; Vinson, T.S.

    1993-01-01

    Forests are an important component of the biosphere and sequestration of carbon in boreal forests may represent one of the few realistic alternatives to ameliorate changes in atmospheric chemistry. The former Soviet Union has the greatest expanse of boreal forests in the world; however, the role of these forests in the terrestrial carbon cycle is not fully understood because the carbon budget of the Soviet forest sector has not been established. In recognition of the need to determine the role of these forests in the global carbon cycle, the carbon budget of forest biomes in the former Soviet Union was assessed based on an equilibrium analysis of carbon cycle pools and fluxes. Net primary productivity was used to identify the rate of carbon turnover in the forest biomes.

  19. Diclofenac topical solution compared with oral diclofenac: a pooled safety analysis

    PubMed Central

    Roth, Sanford H; Fuller, Philip

    2011-01-01

    Background Topical nonsteroidal anti-inflammatory drug (NSAID) formulations, which produce less systemic exposure compared with oral formulations, are an option for the management of osteoarthritis (OA). However, the overall safety and efficacy of these agents compared with oral or systemic therapy remains controversial. Methods Two 12-week, double-blind, double-dummy, randomized, controlled, multicenter studies compared the safety and efficacy profiles of diclofenac topical solution (TDiclo) with oral diclofenac (ODiclo). Each study independently showed that TDiclo had similar efficacy to ODiclo. To compare the safety profiles of TDiclo and ODiclo, a pooled safety analysis was performed for 927 total patients who had radiologically confirmed symptomatic OA of the knee. This pooled analysis included patients treated with TDiclo, containing 45.5% dimethyl sulfoxide (DMSO), and those treated with ODiclo. Safety assessments included monitoring of adverse events (AEs), recording of vital signs, dermatologic evaluation of the study knee, and clinical laboratory evaluation. Results AEs occurred in 312 (67.1%) patients using TDiclo versus 298 (64.5%) of those taking ODiclo. The most common AE with TDiclo was dry skin at the application site (24.1% vs 1.9% with ODiclo; P < 0.0001). Fewer gastrointestinal (25.4% vs 39.0%; P < 0.0001) and cardiovascular (1.5% vs 3.5%; P = 0.055) AEs occurred with TDiclo compared with ODiclo. ODiclo was associated with significantly greater increases in liver enzymes and creatinine, and greater decreases in creatinine clearance and hemoglobin (P < 0.001 for all). Conclusions These findings suggest that TDiclo represents a useful alternative to oral NSAID therapy in the management of OA, with a more favorable safety profile. PMID:21811391

  20. Arteriovenous malformations of the corpus callosum: Pooled analysis and systematic review of literature

    PubMed Central

    Pabaney, Aqueel H.; Ali, Rushna; Kole, Maximillian; Malik, Ghaus M.

    2016-01-01

    Background: Arteriovenous malformations (AVMs) of the corpus callosum (CC) are rare entities. We performed a systematic review of the available literature to better define the natural history, patient characteristics, and treatment options for these lesions. Methods: A MEDLINE, Google Scholar, and The Cochrane Library search were performed for studies published through June 2015. Data from all eligible studies were used to examine epidemiology, natural history, clinical features, treatment strategies, and outcomes of patients with CC-AVMs. A systematic review and pooled analysis of the literature were performed. Results: Our search yielded 37 reports and 230 patients. Mean age at presentation was 26.8 years (±13.12 years). AVMs were most commonly located in the splenium (43%), followed by the body (31%), and then the genu (23%) of the CC. A Spetzler-Martin grade of III was the most common (37%). One hundred eighty-seven (81.3%) patients presented with hemorrhage, 91 (40%) underwent microsurgical excision, and 87 (38%) underwent endovascular embolization. Radiosurgery was performed on 57 (25%) patients. Complete obliteration of the AVM was achieved in 102 (48.1%) patients and approximately twice as often when microsurgery was performed alone or in combination with other treatment modalities (94% vs. 49%; P < 0.001). Mean modified Rankin Scale (mRS) at presentation was 1.54 and mean mRS at last follow-up was 1.31. This difference was not statistically significant (P = 0.35). Conclusion: We present an analysis of the pooled data in the form of a systematic review focusing on management of CC-AVMs. This review aims to provide a valuable tool to aid in decision making when dealing with this particular subtype of AVM. PMID:27127713

  1. Predictors of Local Recurrence Following Accelerated Partial Breast Irradiation: A Pooled Analysis

    SciTech Connect

    Shah, Chirag; Wilkinson, John Ben; Lyden, Maureen; Beitsch, Peter; Vicini, Frank A.

    2012-04-01

    Purpose: To analyze a pooled set of nearly 2,000 patients treated on the American Society of Breast Surgeons (ASBS) Mammosite Registry Trial and at William Beaumont Hospital (WBH) to identify factors associated with local recurrence following accelerated partial breast irradiation (APBI). Methods and Materials: A total of 1,961 women underwent partial breast irradiation between April 1993 and November 2010 as part of the ASBS Registry Trial or at WBH. Rates of ipsilateral breast tumor recurrence (IBTR), regional recurrence (RR), distant metastases (DM), disease-free survival (DFS), cause-specific survival (CSS), and overall survival (OS) were analyzed for each group and for the pooled cohort. Clinical, pathologic, and treatment-related variables were analyzed including age, tumor stage/size, estrogen receptor status, surgical margins, and lymph node status to determine their association with IBTR. Results: The two groups weres similar, but WBH patients were more frequently node positive, had positive margins, and were less likely to be within the American Society for Radiation Oncology-unsuitable group. At 5 years, the rates of IBTR, RR, DM, DFS, CSS, and OS for the pooled group of patients were 2.9%, 0.5%, 2.4%, 89.1%, 98.5%, and 91.8%, respectively. The 5-year rate of true recurrence/marginal miss was 0.8%. Univariate analysis of IBTR found that negative estrogen receptor status (odds ratio [OR], 2.83, 95% confidence interval 1.55-5.13, p = 0.0007) was the only factor significantly associated with IBTR, while a trend was seen for age less than 50 (OR 1.80, 95% confidence interval 0.90-3.58, p = 0.10). Conclusions: Excellent 5-year outcomes were seen following APBI in over 1,900 patients. Estrogen receptor negativity was the only factor associated with IBTR, while a trend for age less than 50 was noted. Significant differences in factors associated with IBTR were noted between cohorts, suggesting that factors driving IBTR may be predicated based on the risk stratification of the patients being treated.

  2. Biology Pool

    ERIC Educational Resources Information Center

    Keller, M.

    1975-01-01

    Describes the conversion of an old swimming pool on the school grounds into a biology pool for the creation of a pond community which became both a useful teaching resource and an attractive part of the school environment. (BR)

  3. Community analysis of plant biomass-degrading microorganisms from Obsidian Pool, Yellowstone National Park.

    PubMed

    Vishnivetskaya, Tatiana A; Hamilton-Brehm, Scott D; Podar, Mircea; Mosher, Jennifer J; Palumbo, Anthony V; Phelps, Tommy J; Keller, Martin; Elkins, James G

    2015-02-01

    The conversion of lignocellulosic biomass into biofuels can potentially be improved by employing robust microorganisms and enzymes that efficiently deconstruct plant polysaccharides at elevated temperatures. Many of the geothermal features of Yellowstone National Park (YNP) are surrounded by vegetation providing a source of allochthonic material to support heterotrophic microbial communities adapted to utilize plant biomass as a primary carbon and energy source. In this study, a well-known hot spring environment, Obsidian Pool (OBP), was examined for potential biomass-active microorganisms using cultivation-independent and enrichment techniques. Analysis of 33,684 archaeal and 43,784 bacterial quality-filtered 16S rRNA gene pyrosequences revealed that archaeal diversity in the main pool was higher than bacterial; however, in the vegetated area, overall bacterial diversity was significantly higher. Of notable interest was a flooded depression adjacent to OBP supporting a stand of Juncus tweedyi, a heat-tolerant rush commonly found growing near geothermal features in YNP. The microbial community from heated sediments surrounding the plants was enriched in members of the Firmicutes including potentially (hemi)cellulolytic bacteria from the genera Clostridium, Anaerobacter, Caloramator, Caldicellulosiruptor, and Thermoanaerobacter. Enrichment cultures containing model and real biomass substrates were established at a wide range of temperatures (55-85 °C). Microbial activity was observed up to 80 °C on all substrates including Avicel, xylan, switchgrass, and Populus sp. Independent of substrate, Caloramator was enriched at lower (<65 °C) temperatures while highly active cellulolytic bacteria Caldicellulosiruptor were dominant at high (>65 °C) temperatures. PMID:25319238

  4. Systems analysis of iron metabolism: the network of iron pools and fluxes

    PubMed Central

    2010-01-01

    Background Every cell of the mammalian organism needs iron as trace element in numerous oxido-reductive processes as well as for transport and storage of oxygen. The very versatility of ionic iron makes it a toxic entity which can catalyze the production of radicals that damage vital membranous and macromolecular assemblies in the cell. The mammalian organism maintains therefore a complex regulatory network of iron uptake, excretion and intra-body distribution. Intracellular regulation in different cell types is intertwined with a global hormonal signalling structure. Iron deficiency as well as excess of iron are frequent and serious human disorders. They can affect every cell, but also the organism as a whole. Results Here, we present a kinematic model of the dynamic system of iron pools and fluxes. It is based on ferrokinetic data and chemical measurements in C57BL6 wild-type mice maintained on iron-deficient, iron-adequate, or iron-loaded diet. The tracer iron levels in major tissues and organs (16 compartment) were followed for 28 days. The evaluation resulted in a whole-body model of fractional clearance rates. The analysis permits calculation of absolute flux rates in the steady-state, of iron distribution into different organs, of tracer-accessible pool sizes and of residence times of iron in the different compartments in response to three states of iron-repletion induced by the dietary regime. Conclusions This mathematical model presents a comprehensive physiological picture of mice under three different diets with varying iron contents. The quantitative results reflect systemic properties of iron metabolism: dynamic closedness, hierarchy of time scales, switch-over response and dynamics of iron storage in parenchymal organs. Therefore, we could assess which parameters will change under dietary perturbations and study in quantitative terms when those changes take place. PMID:20704761

  5. Tiotropium HandiHaler® and Respimat® in COPD: a pooled safety analysis

    PubMed Central

    Halpin, David MG; Dahl, Ronald; Hallmann, Christoph; Mueller, Achim; Tashkin, Donald

    2015-01-01

    Introduction Tiotropium is prescribed for the treatment of chronic obstructive pulmonary disease (COPD) and delivered via HandiHaler® (18 μg once daily) or Respimat® Soft Mist™ inhaler (5 μg once daily). The recent TIOtropium Safety and Performance In Respimat® (TIOSPIR™) study demonstrated that both exhibit similar safety profiles. This analysis provides an updated comprehensive safety evaluation of tiotropium® using data from placebo-controlled HandiHaler® and Respimat® trials. Methods Pooled analysis of adverse event (AE) data from tiotropium HandiHaler® 18 μg and Respimat® 5 μg randomized, double-blind, parallel-group, placebo-controlled, clinical trials in patients with COPD (treatment duration ≥4 weeks). Incidence rates, rate ratios (RRs), and 95% confidence intervals (CIs) were determined for HandiHaler® and Respimat® trials, both together and separately. Results In the 28 HandiHaler® and 7 Respimat® trials included in this analysis, 11,626 patients were treated with placebo and 12,929 with tiotropium, totaling 14,909 (12,469 with HandiHaler®; 2,440 with Respimat®) patient-years of tiotropium exposure. Mean age was 65 years, and mean prebronchodilator forced expiratory volume in 1 second (FEV1) was 1.16 L (41% predicted). The risk (RR [95% CI]) of AEs (0.90 [0.87, 0.93]) and of serious AEs (SAEs) (0.94 [0.89, 0.99]) was significantly lower in the tiotropium than in the placebo group (HandiHaler® and Respimat® pooled results), and there was a numerically lower risk of fatal AEs (FAEs) (0.90 [0.79, 1.01]). The risk of cardiac AEs (0.93 [0.85, 1.02]) was numerically lower in the tiotropium group. Incidences of typical anticholinergic AEs, but not SAEs, were higher with tiotropium. Analyzed separately by inhaler, the risks of AE and SAE in the tiotropium groups remained lower than in placebo and similarly for FAEs. Conclusion This analysis indicates that tiotropium is associated with lower rates of AEs, SAEs, and similar rates of FAEs than placebo when delivered via HandiHaler® or Respimat® (overall and separately) in patients with COPD. PMID:25709423

  6. External beam radiotherapy for palliation of painful bone metastases: pooled data bioeffect dose response analysis of dose fractionation

    NASA Astrophysics Data System (ADS)

    Naveen, T.; Supe, Sanjay S.; Ganesh, K. M.; Samuel, Jacob

    2009-01-01

    Bone metastases develop in up to 70% of newly diagnosed cancer patients and result in immobility, anxiety, and depression, severely diminishing the patients quality of life. Radiotherapy is a frequently used modality for bone metastasis and has been shown to be effective in reducing metastatic bone pain and in some instances, causing tumor shrinkage or growth inhibition. There is controversy surrounding the optimal fractionation schedule and total dose of external beam radiotherapy, despite many randomized trials and overviews addressing the issue. This study was undertaken to apply BED to clinical fractionation data of radiotherapeutic management of bone metastases in order to arrive at optimum BED values for acceptable level of response rate. A computerised literature search was conducted to identify all prospective clinical studies that addressed the issue of fractionation for the treatment of bone metastasis. The results of these studies were pooled together to form the database for the analysis. A total of 4111 number of patients received radiation dose ranging from 4 to 40.5 Gy in 1 to 15 fractions with dose per fraction ranging from 2 to 10 Gy. Single fraction treatments were delivered in 2013 patients and the dose varied from 4 to 10 Gy. Multifraction treatments were delivered in 2098 patients and the dose varied from 15 to 40.5 Gy. The biological effective dose (BED) was evaluated for each fractionation schedule using the linear quadratic model and an α/β value of 10 Gy. Response rate increased significantly beyond a BED value of 14.4 Gy (p < 0.01). Based on our analysis and indications from the literature about higher retreatment and fracture rate of single fraction treatments, minimum BED value of 14.4 Gy is recommended.

  7. Safety and tolerability of sitagliptin in patients with type 2 diabetes: a pooled analysis

    PubMed Central

    Williams-Herman, Debora; Round, Elizabeth; Swern, Arlene S; Musser, Bret; Davies, Michael J; Stein, Peter P; Kaufman, Keith D; Amatruda, John M

    2008-01-01

    Background Sitagliptin, a highly selective dipeptidyl peptidase-4 inhibitor, is the first in a new class of oral antihyperglycemic agents (AHAs) for the treatment of patients with type 2 diabetes. Type 2 diabetes is a life-long disease requiring chronic treatment and management. Therefore, robust assessment of the long-term safety and tolerability of newer therapeutic agents is of importance. The purpose of this analysis was to assess the safety and tolerability of sitagliptin by pooling 12 large, double-blind, Phase IIb and III studies up to 2 years in duration. Methods: This analysis included 6139 patients with type 2 diabetes receiving either sitagliptin 100 mg/day (N = 3415) or a comparator agent (placebo or an active comparator) (N = 2724; non-exposed group). The 12 studies from which this pooled population was drawn represent the double-blind, randomized, Phase IIB and III studies that included patients treated with the clinical dose of sitagliptin (100 mg/day) for at least 18 weeks up to 2 years and that were available in a single safety database as of November 2007. These 12 studies assessed sitagliptin as monotherapy, initial combination therapy with metformin, or add-on combination therapy with other oral AHAs (metformin, pioglitazone, sulfonylurea, sulfonylurea + metformin, or metformin + rosiglitazone). Patients in the non-exposed group were taking placebo, pioglitazone, metformin, sulfonylurea, sulfonylurea + metformin, or metformin + rosiglitazone. This safety analysis used patient-level data from each study to evaluate clinical and laboratory adverse experiences. Results For clinical adverse experiences, the incidence rates of adverse experiences overall, serious adverse experiences, and discontinuations due to adverse experiences were similar in the sitagliptin and non-exposed groups. The incidence rates of specific adverse experiences were also generally similar in the two groups, with the exception of an increased incidence rate of hypoglycemia observed in the non-exposed group. The incidence rates of drug-related adverse experiences overall and discontinuations due to drug-related adverse experiences were higher in the non-exposed group, primarily due to the increased incidence rate of hypoglycemia in this group. For cardiac- and ischemia-related adverse experiences (including serious events), there were no meaningful between-group differences. No meaningful differences between groups in laboratory adverse experiences, either summary measures or specific adverse experiences, were observed. Conclusion In patients with type 2 diabetes, sitagliptin 100 mg/day was well tolerated in clinical trials up to 2 years in duration. PMID:18954434

  8. Genome-wide Association Study of Subtype-Specific Epithelial Ovarian Cancer Risk Alleles Using Pooled DNA

    PubMed Central

    Earp, Madalene A.; Kelemen, Linda E.; Magliocco, Anthony M.; Swenerton, Kenneth D.; Chenevix–Trench, Georgia; Lu, Yi; Hein, Alexander; Ekici, Arif B.; Beckmann, Matthias W.; Fasching, Peter A.; Lambrechts, Diether; Despierre, Evelyn; Vergote, Ignace; Lambrechts, Sandrina; Doherty, Jennifer A.; Rossing, Mary Anne; Chang-Claude, Jenny; Rudolph, Anja; Friel, Grace; Moysich, Kirsten B.; Odunsi, Kunle; Sucheston-Campbell, Lara; Lurie, Galina; Goodman, Marc T.; Carney, Michael E.; Thompson, Pamela J.; Runnebaum, Ingo B.; Dürst, Matthias; Hillemanns, Peter; Dörk, Thilo; Antonenkova, Natalia; Bogdanova, Natalia; Leminen, Arto; Nevanlinna, Heli; Pelttari, Liisa M.; Butzow, Ralf; Bunker, Clareann H.; Modugno, Francesmary; Edwards, Robert P.; Ness, Roberta B.; du Bois, Andreas; Heitz, Florian; Schwaab, Ira; Harter, Philipp; Karlan, Beth Y.; Walsh, Christine; Lester, Jenny; Jensen, Allan; Kjær, Susanne K.; Høgdall, Claus K.; Høgdall, Estrid; Lundvall, Lene; Sellers, Thomas A.; Fridley, Brooke L.; Goode, Ellen L.; Cunningham, Julie M.; Vierkant, Robert A.; Giles, Graham G.; Baglietto, Laura; Severi, Gianluca; Southey, Melissa C.; Liang, Dong; Wu, Xifeng; Lu, Karen; Hildebrandt, Michelle A.T.; Levine, Douglas A.; Bisogna, Maria; Schildkraut, Joellen M.; Iversen, Edwin S.; Weber, Rachel Palmieri; Berchuck, Andrew; Cramer, Daniel W.; Terry, Kathryn L.; Poole, Elizabeth M.; Tworoger, Shelley S.; Bandera, Elisa V.; Chandran, Urmila; Orlow, Irene; Olson, Sara H.; Wik, Elisabeth; Salvesen, Helga B.; Bjorge, Line; Halle, Mari K.; van Altena, Anne M.; Aben, Katja K.H.; Kiemeney, Lambertus A.; Massuger, Leon F.A.G.; Pejovic, Tanja; Bean, Yukie T.; Cybulski, Cezary; Gronwald, Jacek; Lubinski, Jan; Wentzensen, Nicolas; Brinton, Louise A.; Lissowska, Jolanta; Garcia–Closas, Montserrat; Dicks, Ed; Dennis, Joe; Easton, Douglas F.; Song, Honglin; Tyrer, Jonathan P.; Pharoah, Paul D. P.; Eccles, Diana; Campbell, Ian G.; Whittemore, Alice S.; McGuire, Valerie; Sieh, Weiva; Rothstein, Joseph H.; Flanagan, James M.; Paul, James; Brown, Robert; Phelan, Catherine M.; Risch, Harvey A.; McLaughlin, John R.; Narod, Steven A.; Ziogas, Argyrios; Anton-Culver, Hoda; Gentry-Maharaj, Aleksandra; Menon, Usha; Gayther, Simon A.; Ramus, Susan J.; Wu, Anna H.; Pearce, Celeste L.; Pike, Malcolm C.; Dansonka-Mieszkowska, Agnieszka; Rzepecka, Iwona K; Szafron, Lukasz M; Kupryjanczyk, Jolanta; Cook, Linda S.; Le, Nhu D.; Brooks–Wilson, Angela

    2014-01-01

    Epithelial ovarian cancer (EOC) is a heterogeneous cancer with both genetic and environmental risk factors. Variants influencing the risk of developing the less-common EOC subtypes have not been fully investigated. We performed a genome-wide association study (GWAS) of EOC according to subtype by pooling genomic DNA from 545 cases and 398 controls of European descent, and testing for allelic associations. We evaluated for replication 188 variants from the GWAS (56 variants for mucinous, 55 for endometrioid and clear cell, 53 for low malignant potential (LMP) serous, and 24 for invasive serous EOC), selected using pre-defined criteria. Genotypes from 13,188 cases and 23,164 controls of European descent were used to perform unconditional logistic regression under the log-additive genetic model; odds ratios (OR) and 95% confidence intervals are reported. Nine variants tagging 6 loci were associated with subtype-specific EOC risk at P<0.05, and had an OR that agreed in direction of effect with the GWAS results. Several of these variants are in or near genes with a biological rationale for conferring EOC risk, including ZFP36L1 and RAD51B for mucinous EOC (rs17106154, OR=1.17, P=0.029, n=1,483 cases), GRB10 for endometrioid and clear cell EOC (rs2190503, P=0.014, n=2,903 cases), and C22orf26/BPIL2 for LMP serous EOC (rs9609538, OR=0.86, P=0.0043, n=892 cases). In analyses that included the 75 GWAS samples, the association between rs9609538 (OR=0.84, P=0.0007) and LMP serous EOC risk remained statistically significant at P<0.0012 adjusted for multiple testing. Replication in additional samples will be important to verify these results for the less-common EOC subtypes. PMID:24190013

  9. Clinicopathological significance of Sox2 expression in patients with breast cancer: a meta-analysis

    PubMed Central

    Zheng, Yan; Qin, Biyong; Li, Fang; Xu, Shengzhen; Wang, Shanshan; Li, Li

    2015-01-01

    Sex-determining region Y-box protein 2 (Sox2), an embryonic transcription factor located at chromosome 3q26.33, has been frequently demonstrated to be an important prognostic marker for various tumors, including breast cancer. However, its clinicopathological role in breast cancer has not been fully elucidated. To derive a more precise evaluation, we here performed a meta-analysis focusing on the association between Sox2 expression and various clinicopathological characteristics of breast cancer. Relevant publications were identified and retrieved using PubMed, Embase, Cochrane Library, Web of Science, Chinese National Knowledge Infrastructure, and Chinese Biomedical databases. Ten studies with a total of 1713 patients with breast cancer were included in our meta-analysis. Reported odds ratios (OR) and the corresponding 95% confidence intervals (95% CI) were pooled to assess the strengths of the analyzed associations. Our results revealed significant positive associations between Sox2 expression and increased tumor size (pooled OR=2.61, 95% CI=1.91-3.58), histological grade (pooled OR=2.28, 95% CI=1.72-3.03), lymph node metastasis (pooled OR=4.17, 95% CI=1.20-14.45), and the highly aggressive triple-negative phenotype (pooled OR=2.64, 95% CI=1.11-6.29). However, no associations were observed for TNM stage and estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 statuses. Overall, the results of this meta-analysis indicate that Sox2 may be considered as a prognostic marker for breast cancer. More well-designed studies with larger sample sizes are warranted to clarify the prognostic significance of Sox2 in breast cancer. PMID:26885218

  10. Analysis of urine from pooled urinals - a novel method for the detection of novel psychoactive substances.

    PubMed

    Archer, J R H; Hudson, S; Wood, D M; Dargan, P I

    2013-06-01

    Current data on the epidemiology of recreational drug use is largely based on population and self-population surveys of drug use. In addition, increasingly, particularly for novel psychoactive substances, data collected from web monitoring systems is used to collect information on early trends in the use of NPS and the drugs available to users. All of these indicators rely on users self-report of the drug(s) that they are using, or more accurately the drugs that they perceive they are using. Numerous recent studies have demonstrated significant variation in the content of both classical recreational drugs and novel psychoactive substances. The technique of waste-water analysis has allowed estimation of population level use of a number of established recreational drugs such as cocaine and MDMA. However this technique is limited for novel psychoactive substances because of limitations in the knowledge of the stability and metabolism of these compounds. Our group has developed a technique that involves the collection and analysis of pooled-urine from standalone portable urinals and demonstrated that this technique can be used to detect the use of both classical, established recreational drugs and novel psychoactive substances. We discuss this technique in this paper and the ways in which this can be further developed to allow detection of use of new NPS and trends in use of these substances over time and across geographical regions. PMID:24308525

  11. RAPID ANALYSIS OF CYNANURIC ACID IN SWIMMING POOL WATERS BY HIGH PERFORMANCE LIQUID CHROMATOGRAPHY USING POROUS GRAPHITIC CARBON COLUMN

    EPA Science Inventory

    An innovative approach is presented for reducing analysis times of cyanuric acid in swimming pool waters by high performance liquid chromatography (HPLC). The HPLC method exploits the unique selectivity of porous graphitic carbon (PGC) to fully resolve cyanuric acid from other p...

  12. RAPID ANALYSIS OF CYANURIC ACID IN SWIMMING POOL WATERS BY HIGH PERFORMANCE LIQUID CHROMATOGRAPHY USING POROUS GRAPHITIC CARBON

    EPA Science Inventory

    An innovative approach is presented for reducing analysis times of cynuric acid in swimming pool waters by high performance liquid chromatography (HPLC). The HPLC method exploits the unique selectivity of porous graphitic carbon (PGC) to fully resolve within 10 minutes cyanuric ...

  13. Weld pool development during GTA and laser beam welding of Type 304 stainless steel; Part I - theoretical analysis

    SciTech Connect

    Zacharia, T.; David, S.A.; Vitek, J.M. ); Debroy, T. )

    1989-12-01

    A computational and experimental study was carried out to quantitatively understand the influence of the heat flow and the fluid flow in the transient development of the weld pool during gas tungsten arc (GTA) and laser beam welding of Type 304 stainless steel. Stationary gas tungsten arc and laser beam welds were made on two heats of Type 304 austenitic stainless steels containing 90 ppm sulfur and 240 ppm sulfur. A transient heat transfer model was utilized to simulate the heat flow and fluid flow in the weld pool. In this paper, the results of the heat flow and fluid flow analysis are presented.

  14. Vitamin D intake, blood 25(OH)D levels, and breast cancer risk or mortality: a meta-analysis

    PubMed Central

    Kim, Y; Je, Y

    2014-01-01

    Background: Experimental studies suggest potential anti-carcinogenic properties of vitamin D against breast cancer risk, but the epidemiological evidence to date is inconsistent. Methods: We searched MEDLINE and EMBASE databases along with a hand search for eligible studies to examine the association between vitamin D status (based on diet and blood 25-hydroxyvitamin D (25(OH)D)) and breast cancer risk or mortality in a meta-analysis. A random-effect model was used to calculate a pooled adjusted relative risk (RR). Results: A total of 30 prospective studies (nested case-control or cohort) were included for breast cancer incidence (n=24 studies; 31?867 cases) or mortality (n=6 studies; 870 deaths) among 6092 breast cancer patients. The pooled RRs of breast cancer incidence for the highest vs the lowest vitamin D intake and blood 25(OH)D levels were 0.95 (95% CI: 0.881.01) and 0.92 (95% CI: 0.831.02), respectively. Among breast cancer patients, high blood 25(OH)D levels were significantly associated with lower breast cancer mortality (pooled RR=0.58, 95% CI: 0.400.85) and overall mortality (pooled RR=0.61, 95% CI: 0.480.79). There was no evidence of heterogeneity and publication bias. Conclusions: Our findings suggest that high vitamin D status is weakly associated with low breast cancer risk but strongly associated with better breast cancer survival. PMID:24714744

  15. Monitoring of high-power fiber laser welding based on principal component analysis of a molten pool configuration

    NASA Astrophysics Data System (ADS)

    Xiangdong, Gao; Qian, Wen

    2013-12-01

    There exists plenty of welding quality information on a molten pool during high-power fiber laser welding. An approach for monitoring the high-power fiber laser welding status based on the principal component analysis (PCA) of a molten pool configuration is investigated. An infrared-sensitive high-speed camera was used to capture the molten pool images during laser butt-joint welding of Type 304 austenitic stainless steel plates with a high-power (10 kW) continuous wave fiber laser. In order to study the relationship between the molten pool configuration and the welding status, a new method based on PCA is proposed to analyze the welding stability by comparing the situation when the laser beam spot moves along, and when it deviates from the weld seam. Image processing techniques were applied to process the molten pool images and extract five characteristic parameters. Moreover, the PCA method was used to extract a composite indicator which is the linear combination of the five original characteristics to analyze the different status during welding. Experimental results showed that the extracted composite indicator had a close relationship with the actual welding results and it could be used to evaluate the status of the high-power fiber laser welding, providing a theoretical basis for the monitoring of laser welding quality.

  16. Analysis of Bubble Flow in the Deep-Penetration Molten Pool of Vacuum Electron Beam Welding

    NASA Astrophysics Data System (ADS)

    Luo, Yi; Wan, Rui; Zhu, Yang; Xie, Xiaojian

    2015-03-01

    Based on the vacuum electron beam welding with deep-penetration process, the convection phenomenon of the bubble flow in partially penetrated and fully penetrated molten pool of AZ91D magnesium alloy was simulated under the unsteady-state conditions. At the same time, the distributions of the cavity-type defects in deep-penetration weld were studied. The results showed that the cavity-type defects are more prone to distribute at the bottom of the weld and accumulate along the axis of the weld for the partially penetrated weld seam; there is a high incidence of cavity-type defects in the middle of the weld for the fully penetrated weld seam. As a smooth escape channel for the gas phase is formed in the fully penetrated molten pool, the possibility of gas escaping is much higher than that in the partially penetrated molten pool. A high liquid convection velocity is more conducive to the escape of the gas in molten pool. The liquid convection velocity in the fully penetrated molten pool is higher than that in the partially penetrated molten pool. So, the final gas fraction in the fully penetrated molten pool is low. Therefore, the appearance of cavity-type defects in the fully penetrated weld seam is less than that in the partially penetrated weld seam.

  17. Biogenic and non-biogenic Si pools in terrestrial ecosystems: results from a novel analysis method

    NASA Astrophysics Data System (ADS)

    Barao, Lucia; Vandevenne, Floor; Clymans, Wim; Meire, Patrick; Frings, Patrick; Conley, Daniel; Struyf, Eric

    2015-04-01

    Silicon (Si) is a chemical element frequently associated with highly abundant silicate minerals in the Earth crust. Over millions of years, the interaction of such minerals with the atmosphere and hydrosphere produces a myriad of processed compounds, and the mineral weathering consumes CO2 during the process. The weathering of minerals also triggers the export of dissolved Si (DSi) to coastal waters and the ocean. Here, DSi is deposited in diatom frustules, in an amorphous biogenic form (BSi). Diatoms account for 50% of the primary production and are crucial for the export of carbon into the deep sea. In recent years, it was acknowledged that terrestrial systems filter the Si transition from the terrestrial mineral to the marine and coastal biological pool, by the incorporation of DSi into plants. In this process, DSi is taken up by roots together with other nutrients and precipitates in plant cells in amorphous structures named phytoliths. After dead, plant tissues become mixed in the top soil, where BSi is available for dissolution and will control the DSi availability in short time scales. Additionally, Si originated from soil forming processes can also significantly interfere with the global cycle. The Si cycle in terrestrial ecosystems is a key factor to coastal ecology, plant ecology, biogeochemistry and agro-sciences, but the high variability of different biogenic and non-biogenic Si pools remains as an obstacle to obtain accurate measurements. The traditional methods, developed to isolate diatoms in ocean sediments, only account for simple mineral corrections. In this dissertation we have adapted a novel continuous analysis method (during alkaline extraction) that uses Si-Al ratios and reactivity to differ biogenic from non-biogenic fractions. The method was originally used in marine sediments, but we have developed it to be applicable in a wide range of terrestrial, aquatic and coastal ecosystems. We first focused on soils under strong human impact in temperate (European) zones, since cultivation influences the Si cycle with multiple consequences for the environment. Results showed that the intensity of the human pressure in the agricultural systems defines the level of BSi depletion, but parent material and weathering degree can also provide the soil with other reactive non BSi fractions. Secondly we analysed the influence of non-BSi pools of volcanic origin in soils and sediments subjected to volcanic activity. Results showed that a separation method is fundamental in these systems with volcanic shards and strongly weathered products, both of which are also significantly prone to dissolution in the common alkaline sequential extractions. We conclude that the application of a method that discriminates between Si fractions is mandatory to correctly understand the Si dynamics in terrestrial ecosystems. Although time-consuming and subjected to some limitations, the continuous analysis can be used for this purpose. Future challenges remain however for identifying fractions that cannot be differentiated on either reactivity or Si-Al ratio and for correlating the reactivity of fractions extracted in alkaline environments with the availability in situ.

  18. Diagnostic performance of serum macrophage inhibitory cytokine-1 in pancreatic cancer: a meta-analysis and meta-regression analysis.

    PubMed

    Chen, Yan-Zhi; Liu, Dan; Zhao, Yu-Xia; Wang, He-Tong; Gao, Ya; Chen, Ying

    2014-06-01

    Many existing studies have demonstrated that the macrophage inhibitory cytokine-1 (MIC-1) might be a powerful diagnostic biomarker in patients with pancreatic cancer; but individually published results are inconclusive. This meta-analysis aimed to derive a more precise estimation of the diagnostic performance of serum MIC-1 in pancreatic cancer. We searched CISCOM, CINAHL, Web of Science, PubMed, Google Scholar, EBSCO, Cochrane Library, China BioMedicine (CBM), and China National Knowledge Infrastructure (CNKI) databases from their inception through August 1st, 2013. Meta-analysis was performed using Meta-Disc version 1.4 and STATA version 12.0 software. Crude standardized mean difference (SMD) and their 95% confidence intervals (CI) were estimated. Data from selected studies were pooled to yield summary sensitivity, specificity, positive and negative likelihood ratio (LR), diagnostic odds ratio (DOR), and receiver operating characteristic (SROC) curve. Ten case-control studies were included in this meta-analysis with a total of 1235 pancreatic cancer patients and 730 healthy subjects. Our meta-analysis results revealed that serum MIC-1 levels in pancreatic patients were higher than those of healthy subjects (SMD=1.38, 95% CI=1.15-1.62, p<0.001). The area under the SROC curve was 0.92 (SE=0.020); the pooled sensitivity was 0.79 (95% CI=0.77-0.82); and the pooled specificity was 0.86 (95% CI=0.84-0.88). The pooled positive LR was 6.20 (95% CI=1.24-30.91); the pooled DOR was 35.73 (95% CI=18.52-68.93). In conclusion, the present meta-analysis suggests that serum MIC-1 may be a useful diagnostic biomarker with high sensitivity and specificity for identifying pancreatic cancer. PMID:24592997

  19. Furazolidone-based Therapies for Helicobacter pylori Infection: A Pooled-data Analysis

    PubMed Central

    Zullo, Angelo; Ierardi, Enzo; Hassan, Cesare; Francesco, Vincenzo De

    2012-01-01

    Background/Aim: Furazolidone-based therapies are used in developing countries to cure Helicobacter pylori infection due to its low cost. The low bacterial resistance toward furazolidone may render appealing the use of this drug even in developed countries. However, some relevant safety concerns do exist in using furazolidone. Patients and Methods: This was a systematic review with pooled-data analysis of data regarding both eradication rate and safety of furazolidone-based therapies for H. pylori infection. Intention-to-treat (ITT) and per-protocol (PP) eradication rates were calculated. Results: Following furazolidone-based first-line therapy, H. pylori eradication rates were 75.7% and 79.6% at ITT and PP analysis, respectively (P<0.001). The overall incidence of side effects and severe side effects were 33.2% and 3.8%, respectively. At multivariate analysis, only high-dose furazolidone was associated with increased therapeutic success (OR: 1.5, 95% CI: 1.3-2.7; P<0.001), while occurrence of side effects was relevant following treatment for a long duration (OR: 2.9, 95% CI: 2.2-4.1; P<0.001), high-dose furazolidone (OR: 2.3, 95% CI: 1.7-3.2; P<0.001) and bismuth-containing regimens (OR: 2.1, 95% CI: 1.5-2.8; P<0.001). Conclusions: Furazolidone-based regimens usually achieve low eradication rates. Only a high-dose regimen improves the cure rate, but simultaneously increases the incidence of severe side effects. Therefore, we suggest that patients have to be clearly informed about the possible genotoxic and carcinogenetic effects for which furazolidone use is not approved in developed countries. PMID:22249086

  20. Personal hair dye use and bladder cancer: a meta-analysis.

    PubMed

    Turati, Federica; Pelucchi, Claudio; Galeone, Carlotta; Decarli, Adriano; La Vecchia, Carlo

    2014-02-01

    Despite considerable research, the issue of hair dyes and bladder cancer is still open to discussion. In January 2013, we searched in PubMed/EMBASE to identify observational studies investigating the association between personal use of hair dyes and bladder cancer incidence/mortality. Pooled relative risks (RRs) and corresponding 95% confidence intervals (CIs) were calculated using random-effects models. Fifteen case-control and two cohort studies were available for meta-analysis (8504 cases/deaths, 14,102 controls, and 617,937 persons at risk). Compared with no use, the pooled RR of bladder cancer for personal use of any type of hair dyes was 0.93 (95% CI, 0.82-1.05), with moderate heterogeneity among studies (I(2) = 34.1%, P = .07). Similar RRs were found for females (RR = 0.95) and males (RR = 0.81). Based on seven studies, the pooled RR for personal use of permanent hair dyes was 0.92 (95% CI, 0.77-1.09). Compared with no use, no association was observed for the highest categories of duration of use and lifetime frequency of use of both any type of dyes and permanent dyes. The pooled RR from four studies reporting results for use of dark-colored dyes was 1.29 (95% CI, 0.98-1.71). This meta-analysis allows to definitively exclude any appreciable excess risk of bladder cancer among personal hair dye users. PMID:24342029

  1. A pooled cross-section analysis of the health care expenditures of the OECD countries.

    PubMed

    Gerdtham, U G; Søgaard, J; Jönsson, B; Andersson, F

    1992-01-01

    This paper has two purposes. The first, empirical purpose is to estimate and evaluate the effects of aggregate income, institutional and socio-demographic factors on health care expenditures in the OECD countries. The second purpose is methodological, and comprises assessment of temporal instability, the choice of functional form, and misspecification of the estimated relationships. Data compiled over three years (1974, 1980 and 1987) from 19 OECD countries are used in a pooled cross-section regression analysis. Like previous studies, this one concludes that aggregate income measured by Gross Domestic Product per capita is the statistically most important factor in cross-national variation in health care expenditures, and that the aggregate income elasticity exceeds one. However, the data analyzed in this study also show some evidence that public financing of health care services is associated with lower expenditures per capita, and that countries with fee for service as the dominant form of remuneration have higher expenditures. The examined relationships appear to be temporally stable over the three years except for upward shifts, and there is no indication of statistical misspecification. This does not necessarily imply a correct specification, and we do note the presence of measurement errors in some of the variables. Moreover, the selected log-linear functional form appears to be non-optimal according to a likelihood criterion, and is rejected against a quadratic form. Based on the analyses from this study the results do not appear to be sensitive to use of the quadratic form specification. PMID:10172496

  2. CHROMATIC TEMPORAL INTEGRATION AND RETINAL ECCENTRICITY: PSYCHOPHYSICS, NEUROMETRIC ANALYSIS AND CORTICAL POOLING

    PubMed Central

    Swanson, William H.; Pan, Fei; Lee, Barry B.

    2008-01-01

    Psychophysical chromatic sensitivity deteriorates in peripheral retina, even after appropriate size scaling of targets. This decrease is more marked for stimuli targeted at the long- (L) to middle-wavelength (M) cone opponent system than for stimuli targeted at short-wavelength (S) pathways. Foveal chromatic mechanisms integrate over several hundred milliseconds for pulse detection. If the time course for integration were shorter in the periphery, this might account for sensitivity loss. Psychophysical chromatic temporal integration (critical duration) for human observers was estimated as a function of eccentricity. Critical duration decreased by a factor of 2 (from ~200 to ~100 msec) from the fovea to 20° eccentricity. This partly (but not completely) accounts for the decrease in |L-M| sensitivity in the periphery, but almost completely accounts for the decrease in S-cone sensitivity. Some loss of |L-M|I sensitivity thus has a cortical locus. In a physiological analysis, we consider how the |L-M| cone parvocellular pathway integrates chromatic signals. Neurometric contrast sensitivities of individual retinal ganglion cells decreased with the square-root of stimulus duration (as expected from Poisson statistics of ganglion cell firing). In contrast, psychophysical data followed an inverse linear relationship (Bloch’s law). Models of cortical pooling mechanisms incorporating uncertainty as to stimulus onset and duration can at least partially account for this discrepancy. PMID:18417185

  3. Staphylococcus aureus bloodstream infection: A pooled analysis of five prospective, observational studies

    PubMed Central

    Kaasch, Achim J.; Barlow, Gavin; Edgeworth, Jonathan D.; Fowler, Vance G.; Hellmich, Martin; Hopkins, Susan; Kern, Winfried V.; Llewelyn, Martin J.; Rieg, Siegbert; Rodriguez-Baño, Jesús; Scarborough, Matthew; Seifert, Harald; Soriano, Alex; Tilley, Robert; Tőrők, M. Estée; Weiβ, Verena; Wilson, A. Peter R.; Thwaites, Guy E.

    2014-01-01

    Summary Objectives Staphylococcus aureus bacteraemia is a common, often fatal infection. Our aim was to describe how its clinical presentation varies between populations and to identify common determinants of outcome. Methods We conducted a pooled analysis on 3395 consecutive adult patients with S. aureus bacteraemia. Patients were enrolled between 2006 and 2011 in five prospective studies in 20 tertiary care centres in Germany, Spain, United Kingdom, and United States. Results The median age of participants was 64 years (interquartile range 50–75 years) and 63.8% were male. 25.4% of infections were associated with diabetes mellitus, 40.7% were nosocomial, 20.6% were caused by methicillin-resistant S. aureus (MRSA), although these proportions varied significantly across studies. Intravenous catheters were the commonest identified infective focus (27.7%); 8.3% had endocarditis. Crude 14 and 90-day mortality was 14.6% and 29.2%, respectively. Age, MRSA bacteraemia, nosocomial acquisition, endocarditis, and pneumonia were independently associated with death, but a strong association was with an unidentified infective focus (adjusted hazard ratio for 90-day mortality 2.92; 95% confidence interval 2.33 to 3.67, p < 0.0001). Conclusion The baseline demographic and clinical features of S. aureus bacteraemia vary significantly between populations. Mortality could be reduced by assiduous MRSA control and early identification of the infective focus. PMID:24247070

  4. Treatment of unresectable intrahepatic cholangiocarcinoma with yttrium-90 radioembolization: A systematic review and pooled analysis

    PubMed Central

    Al-Adra, D.P.; Gill, R.S.; Axford, S.J.; Shi, X.; Kneteman, N.; Liau, S.-S.

    2015-01-01

    Radioembolization with yttrium-90 microspheres offers an alternative treatment option for patients with unresectable intrahepatic cholangiocarcinoma (ICC). However, the rarity and heterogeneity of ICC makes it difficult to draw firm conclusions about treatment efficacy. Therefore, the goal of the current study is to systematically review the existing literature surrounding treatment of unresectable ICCs with yttrium-90 microspheres and provide a comprehensive review of the current experience and clinical outcome of this treatment modality. We performed a comprehensive search of electronic databases for ICC treatment and identified 12 studies with relevant data regarding radioembolization therapy with yttrium-90 microspheres. Based on pooled analysis, the overall weighted median survival was 15.5 months. Tumour response based on radiological studies demonstrated a partial response in 28% and stable disease in 54% of patients at three months. Seven patients were able to be downstaged to surgical resection. The complication profile of radioembolization is similar to that of other intra-arterial treatment modalities. Overall survival of patients with ICC after treatment with yttrium-90 microspheres is higher than historical survival rates and shows similar survival to those patients treated with systemic chemotherapy and/or trans-arterial chemoembolization therapy. Therefore, the use of yttrium-90 microspheres should be considered in the list of available treatment options for ICC. However, future randomized trials comparing systemic chemotherapy, TACE and local radiation will be required to identify the optimal treatment modality for unresectable ICC. PMID:25449754

  5. Treatment of unresectable intrahepatic cholangiocarcinoma with yttrium-90 radioembolization: a systematic review and pooled analysis.

    PubMed

    Al-Adra, D P; Gill, R S; Axford, S J; Shi, X; Kneteman, N; Liau, S-S

    2015-01-01

    Radioembolization with yttrium-90 microspheres offers an alternative treatment option for patients with unresectable intrahepatic cholangiocarcinoma (ICC). However, the rarity and heterogeneity of ICC makes it difficult to draw firm conclusions about treatment efficacy. Therefore, the goal of the current study is to systematically review the existing literature surrounding treatment of unresectable ICCs with yttrium-90 microspheres and provide a comprehensive review of the current experience and clinical outcome of this treatment modality. We performed a comprehensive search of electronic databases for ICC treatment and identified 12 studies with relevant data regarding radioembolization therapy with yttrium-90 microspheres. Based on pooled analysis, the overall weighted median survival was 15.5 months. Tumour response based on radiological studies demonstrated a partial response in 28% and stable disease in 54% of patients at three months. Seven patients were able to be downstaged to surgical resection. The complication profile of radioembolization is similar to that of other intra-arterial treatment modalities. Overall survival of patients with ICC after treatment with yttrium-90 microspheres is higher than historical survival rates and shows similar survival to those patients treated with systemic chemotherapy and/or trans-arterial chemoembolization therapy. Therefore, the use of yttrium-90 microspheres should be considered in the list of available treatment options for ICC. However, future randomized trials comparing systemic chemotherapy, TACE and local radiation will be required to identify the optimal treatment modality for unresectable ICC. PMID:25449754

  6. Highly-multiplexed barcode sequencing: an efficient method for parallel analysis of pooled samples

    PubMed Central

    Smith, Andrew M.; Heisler, Lawrence E.; St.Onge, Robert P.; Farias-Hesson, Eveline; Wallace, Iain M.; Bodeau, John; Harris, Adam N.; Perry, Kathleen M.; Giaever, Guri; Pourmand, Nader; Nislow, Corey

    2010-01-01

    Next-generation sequencing has proven an extremely effective technology for molecular counting applications where the number of sequence reads provides a digital readout for RNA-seq, ChIP-seq, Tn-seq and other applications. The extremely large number of sequence reads that can be obtained per run permits the analysis of increasingly complex samples. For lower complexity samples, however, a point of diminishing returns is reached when the number of counts per sequence results in oversampling with no increase in data quality. A solution to making next-generation sequencing as efficient and affordable as possible involves assaying multiple samples in a single run. Here, we report the successful 96-plexing of complex pools of DNA barcoded yeast mutants and show that such ‘Bar-seq’ assessment of these samples is comparable with data provided by barcode microarrays, the current benchmark for this application. The cost reduction and increased throughput permitted by highly multiplexed sequencing will greatly expand the scope of chemogenomics assays and, equally importantly, the approach is suitable for other sequence counting applications that could benefit from massive parallelization. PMID:20460461

  7. A Probabilistic Analysis of Sparse Coded Feature Pooling and Its Application for Image Retrieval.

    PubMed

    Zhang, Yunchao; Chen, Jing; Huang, Xiujie; Wang, Yongtian

    2015-01-01

    Feature coding and pooling as a key component of image retrieval have been widely studied over the past several years. Recently sparse coding with max-pooling is regarded as the state-of-the-art for image classification. However there is no comprehensive study concerning the application of sparse coding for image retrieval. In this paper, we first analyze the effects of different sampling strategies for image retrieval, then we discuss feature pooling strategies on image retrieval performance with a probabilistic explanation in the context of sparse coding framework, and propose a modified sum pooling procedure which can improve the retrieval accuracy significantly. Further we apply sparse coding method to aggregate multiple types of features for large-scale image retrieval. Extensive experiments on commonly-used evaluation datasets demonstrate that our final compact image representation improves the retrieval accuracy significantly. PMID:26132080

  8. A Probabilistic Analysis of Sparse Coded Feature Pooling and Its Application for Image Retrieval

    PubMed Central

    Zhang, Yunchao; Chen, Jing; Huang, Xiujie; Wang, Yongtian

    2015-01-01

    Feature coding and pooling as a key component of image retrieval have been widely studied over the past several years. Recently sparse coding with max-pooling is regarded as the state-of-the-art for image classification. However there is no comprehensive study concerning the application of sparse coding for image retrieval. In this paper, we first analyze the effects of different sampling strategies for image retrieval, then we discuss feature pooling strategies on image retrieval performance with a probabilistic explanation in the context of sparse coding framework, and propose a modified sum pooling procedure which can improve the retrieval accuracy significantly. Further we apply sparse coding method to aggregate multiple types of features for large-scale image retrieval. Extensive experiments on commonly-used evaluation datasets demonstrate that our final compact image representation improves the retrieval accuracy significantly. PMID:26132080

  9. Identification of Distinct Breast Cancer Stem Cell Populations Based on Single-Cell Analyses of Functionally Enriched Stem and Progenitor Pools

    PubMed Central

    Akrap, Nina; Andersson, Daniel; Bom, Eva; Gregersson, Pernilla; Ståhlberg, Anders; Landberg, Göran

    2016-01-01

    Summary The identification of breast cancer cell subpopulations featuring truly malignant stem cell qualities is a challenge due to the complexity of the disease and lack of general markers. By combining extensive single-cell gene expression profiling with three functional strategies for cancer stem cell enrichment including anchorage-independent culture, hypoxia, and analyses of low-proliferative, label-retaining cells derived from mammospheres, we identified distinct stem cell clusters in breast cancer. Estrogen receptor (ER)α+ tumors featured a clear hierarchical organization with switch-like and gradual transitions between different clusters, illustrating how breast cancer cells transfer between discrete differentiation states in a sequential manner. ERα− breast cancer showed less prominent clustering but shared a quiescent cancer stem cell pool with ERα+ cancer. The cellular organization model was supported by single-cell data from primary tumors. The findings allow us to understand the organization of breast cancers at the single-cell level, thereby permitting better identification and targeting of cancer stem cells. PMID:26771357

  10. Estimation of the relative sensitivity of qPCR analysis using pooled samples.

    PubMed

    Muniesa, Ana; Ferreira, Chelo; Fuertes, Héctor; Halaihel, Nabil; de Blas, Ignacio

    2014-01-01

    The high sensitivity of qPCR makes it a desirable diagnostic method in epidemiological surveillance programs. However, due to high costs, the use of pooling has been suggested. In this paper, an algorithm based on the Montecarlo method has been designed and implemented. The algorithm had been tested in many different situations, and finally it was validated with a real dataset. Moreover, based on the results obtained and depending on pooling conditions, a drastic decrease of sensitivity is observed. PMID:24722485

  11. Estimation of the Relative Sensitivity of qPCR Analysis Using Pooled Samples

    PubMed Central

    Muniesa, Ana; Ferreira, Chelo; Fuertes, Héctor; Halaihel, Nabil; de Blas, Ignacio

    2014-01-01

    The high sensitivity of qPCR makes it a desirable diagnostic method in epidemiological surveillance programs. However, due to high costs, the use of pooling has been suggested. In this paper, an algorithm based on the Montecarlo method has been designed and implemented. The algorithm had been tested in many different situations, and finally it was validated with a real dataset. Moreover, based on the results obtained and depending on pooling conditions, a drastic decrease of sensitivity is observed. PMID:24722485

  12. Volatile disinfection by-product analysis from chlorinated indoor swimming pools.

    PubMed

    Weaver, William A; Li, Jing; Wen, Yuli; Johnston, Jessica; Blatchley, Michael R; Blatchley, Ernest R

    2009-07-01

    Chlorination of indoor swimming pools is practiced for disinfection and oxidation of reduced compounds that are introduced to water by swimmers. However, there is growing concern associated with formation for chlorinated disinfection by-products (DBPs) in these settings. Volatile DBPs are of particular concern because they may promote respiratory ailments and other adverse health effects among swimmers and patrons of indoor pool facilities. To examine the scope of this issue, water samples were collected from 11 pools over a 6month period and analyzed for free chlorine and their volatile DBP content. Eleven volatile DBPs were identified: monochloramine (NH(2)Cl), dichloramine (NHCl(2)), trichloramine (NCl(3)), chloroform (CHCl(3)), bromoform (CHBr(3)), dichlorobromomethane (CHBrCl(2)), dibromochloromethane (CHBr(2)Cl), cyanogen chloride (CNCl), cyanogen bromide (CNBr), dichloroacetonitrile (CNCHCl(2)), and dichloromethylamine (CH(3)NCl(2)). Of these 11 DBPs, 10 were identified as regularly occurring, with CHBrCl(2) only appearing sporadically. Pool water samples were analyzed for residual chlorine compounds using the DPD colorimetric method and by membrane introduction mass spectrometry (MIMS). These two methods were chosen as complementary measures of residual chlorine, and to allow for comparisons between the methods. The DPD method was demonstrated to consistently overestimate inorganic chloramine content in swimming pools. Pairwise correlations among the measured volatile DBPs allowed identification of dichloromethylamine and dichloroacetonitrile as potential swimming pool water quality indicator compounds. PMID:19501873

  13. Fractionated BNCT for locally recurrent head and neck cancer: experience from a phase I/II clinical trial at Tsing Hua Open-Pool Reactor.

    PubMed

    Wang, Ling-Wei; Chen, Yi-Wei; Ho, Ching-Yin; Hsueh Liu, Yen-Wan; Chou, Fong-In; Liu, Yuan-Hao; Liu, Hong-Ming; Peir, Jinn-Jer; Jiang, Shiang-Huei; Chang, Chi-Wei; Liu, Ching-Sheng; Wang, Shyh-Jen; Chu, Pen-Yuan; Yen, Sang-Hue

    2014-06-01

    To introduce our experience of treating locally and regionally recurrent head and neck cancer patients with BNCT at Tsing Hua Open-Pool Reactor in Taiwan, 12 patients (M/F=10/2, median age 55.5 Y/O) were enrolled and 11 received two fractions of treatment. Fractionated BNCT at 30-day interval with adaptive planning according to changed T/N ratios was feasible, effective and safe for selected recurrent head and neck cancer in this trial. PMID:24369888

  14. BNCT for locally recurrent head and neck cancer: preliminary clinical experience from a phase I/II trial at Tsing Hua Open-Pool Reactor.

    PubMed

    Wang, L W; Wang, S J; Chu, P Y; Ho, C Y; Jiang, S H; Liu, Y W H; Liu, Y H; Liu, H M; Peir, J J; Chou, F I; Yen, S H; Lee, Y L; Chang, C W; Liu, C S; Chen, Y W; Ono, K

    2011-12-01

    To introduce our preliminary experience of treating locally and regionally recurrent Head and Neck cancer patients at Tsing Hua Open-Pool Reactor in Taiwan, four patients (M/F=3/1, median age 68 Y/O) were enrolled. BNCT with BPA (400 mg/kg) injected in 2 phases and prescription dose of 12-35 Gy (Eq.)/fraction for 2 fractions at 30 day interval can be given with sustained blood boron concentration and tolerable early toxicities for recurrent H & N cancer. PMID:21478023

  15. Pool Purification

    NASA Technical Reports Server (NTRS)

    1988-01-01

    Caribbean Clear, Inc. used NASA's silver ion technology as a basis for its automatic pool purifier. System offers alternative approach to conventional purification chemicals. Caribbean Clear's principal markets are swimming pool owners who want to eliminate chlorine and bromine. Purifiers in Caribbean Clear System are same silver ions used in Apollo System to kill bacteria, plus copper ions to kill algae. They produce spa or pool water that exceeds EPA Standards for drinking water.

  16. Maternal Age at Birth and Childhood Type 1 Diabetes: A Pooled Analysis of 30 Observational Studies

    PubMed Central

    Cardwell, Chris R.; Stene, Lars C.; Joner, Geir; Bulsara, Max K.; Cinek, Ondrej; Rosenbauer, Joachim; Ludvigsson, Johnny; Jané, Mireia; Svensson, Jannet; Goldacre, Michael J.; Waldhoer, Thomas; Jarosz-Chobot, Przemysława; Gimeno, Suely G.A.; Chuang, Lee-Ming; Parslow, Roger C.; Wadsworth, Emma J.K.; Chetwynd, Amanda; Pozzilli, Paolo; Brigis, Girts; Urbonaitė, Brone; Šipetić, Sandra; Schober, Edith; Devoti, Gabriele; Ionescu-Tirgoviste, Constantin; de Beaufort, Carine E.; Stoyanov, Denka; Buschard, Karsten; Patterson, Chris C.

    2010-01-01

    OBJECTIVE The aim if the study was to investigate whether children born to older mothers have an increased risk of type 1 diabetes by performing a pooled analysis of previous studies using individual patient data to adjust for recognized confounders. RESEARCH DESIGN AND METHODS Relevant studies published before June 2009 were identified from MEDLINE, Web of Science, and EMBASE. Authors of studies were contacted and asked to provide individual patient data or conduct prespecified analyses. Risk estimates of type 1 diabetes by maternal age were calculated for each study, before and after adjustment for potential confounders. Meta-analysis techniques were used to derive combined odds ratios and to investigate heterogeneity among studies. RESULTS Data were available for 5 cohort and 25 case-control studies, including 14,724 cases of type 1 diabetes. Overall, there was, on average, a 5% (95% CI 2–9) increase in childhood type 1 diabetes odds per 5-year increase in maternal age (P = 0.006), but there was heterogeneity among studies (heterogeneity I2 = 70%). In studies with a low risk of bias, there was a more marked increase in diabetes odds of 10% per 5-year increase in maternal age. Adjustments for potential confounders little altered these estimates. CONCLUSIONS There was evidence of a weak but significant linear increase in the risk of childhood type 1 diabetes across the range of maternal ages, but the magnitude of association varied between studies. A very small percentage of the increase in the incidence of childhood type 1 diabetes in recent years could be explained by increases in maternal age. PMID:19875616

  17. Genome-wide association study of subtype-specific epithelial ovarian cancer risk alleles using pooled DNA.

    PubMed

    Earp, Madalene A; Kelemen, Linda E; Magliocco, Anthony M; Swenerton, Kenneth D; Chenevix-Trench, Georgia; Lu, Yi; Hein, Alexander; Ekici, Arif B; Beckmann, Matthias W; Fasching, Peter A; Lambrechts, Diether; Despierre, Evelyn; Vergote, Ignace; Lambrechts, Sandrina; Doherty, Jennifer A; Rossing, Mary Anne; Chang-Claude, Jenny; Rudolph, Anja; Friel, Grace; Moysich, Kirsten B; Odunsi, Kunle; Sucheston-Campbell, Lara; Lurie, Galina; Goodman, Marc T; Carney, Michael E; Thompson, Pamela J; Runnebaum, Ingo B; Dürst, Matthias; Hillemanns, Peter; Dörk, Thilo; Antonenkova, Natalia; Bogdanova, Natalia; Leminen, Arto; Nevanlinna, Heli; Pelttari, Liisa M; Butzow, Ralf; Bunker, Clareann H; Modugno, Francesmary; Edwards, Robert P; Ness, Roberta B; du Bois, Andreas; Heitz, Florian; Schwaab, Ira; Harter, Philipp; Karlan, Beth Y; Walsh, Christine; Lester, Jenny; Jensen, Allan; Kjær, Susanne K; Høgdall, Claus K; Høgdall, Estrid; Lundvall, Lene; Sellers, Thomas A; Fridley, Brooke L; Goode, Ellen L; Cunningham, Julie M; Vierkant, Robert A; Giles, Graham G; Baglietto, Laura; Severi, Gianluca; Southey, Melissa C; Liang, Dong; Wu, Xifeng; Lu, Karen; Hildebrandt, Michelle A T; Levine, Douglas A; Bisogna, Maria; Schildkraut, Joellen M; Iversen, Edwin S; Weber, Rachel Palmieri; Berchuck, Andrew; Cramer, Daniel W; Terry, Kathryn L; Poole, Elizabeth M; Tworoger, Shelley S; Bandera, Elisa V; Chandran, Urmila; Orlow, Irene; Olson, Sara H; Wik, Elisabeth; Salvesen, Helga B; Bjorge, Line; Halle, Mari K; van Altena, Anne M; Aben, Katja K H; Kiemeney, Lambertus A; Massuger, Leon F A G; Pejovic, Tanja; Bean, Yukie T; Cybulski, Cezary; Gronwald, Jacek; Lubinski, Jan; Wentzensen, Nicolas; Brinton, Louise A; Lissowska, Jolanta; Garcia-Closas, Montserrat; Dicks, Ed; Dennis, Joe; Easton, Douglas F; Song, Honglin; Tyrer, Jonathan P; Pharoah, Paul D P; Eccles, Diana; Campbell, Ian G; Whittemore, Alice S; McGuire, Valerie; Sieh, Weiva; Rothstein, Joseph H; Flanagan, James M; Paul, James; Brown, Robert; Phelan, Catherine M; Risch, Harvey A; McLaughlin, John R; Narod, Steven A; Ziogas, Argyrios; Anton-Culver, Hoda; Gentry-Maharaj, Aleksandra; Menon, Usha; Gayther, Simon A; Ramus, Susan J; Wu, Anna H; Pearce, Celeste L; Pike, Malcolm C; Dansonka-Mieszkowska, Agnieszka; Rzepecka, Iwona K; Szafron, Lukasz M; Kupryjanczyk, Jolanta; Cook, Linda S; Le, Nhu D; Brooks-Wilson, Angela

    2014-05-01

    Epithelial ovarian cancer (EOC) is a heterogeneous cancer with both genetic and environmental risk factors. Variants influencing the risk of developing the less-common EOC subtypes have not been fully investigated. We performed a genome-wide association study (GWAS) of EOC according to subtype by pooling genomic DNA from 545 cases and 398 controls of European descent, and testing for allelic associations. We evaluated for replication 188 variants from the GWAS [56 variants for mucinous, 55 for endometrioid and clear cell, 53 for low-malignant potential (LMP) serous, and 24 for invasive serous EOC], selected using pre-defined criteria. Genotypes from 13,188 cases and 23,164 controls of European descent were used to perform unconditional logistic regression under the log-additive genetic model; odds ratios (OR) and 95 % confidence intervals are reported. Nine variants tagging six loci were associated with subtype-specific EOC risk at P < 0.05, and had an OR that agreed in direction of effect with the GWAS results. Several of these variants are in or near genes with a biological rationale for conferring EOC risk, including ZFP36L1 and RAD51B for mucinous EOC (rs17106154, OR = 1.17, P = 0.029, n = 1,483 cases), GRB10 for endometrioid and clear cell EOC (rs2190503, P = 0.014, n = 2,903 cases), and C22orf26/BPIL2 for LMP serous EOC (rs9609538, OR = 0.86, P = 0.0043, n = 892 cases). In analyses that included the 75 GWAS samples, the association between rs9609538 (OR = 0.84, P = 0.0007) and LMP serous EOC risk remained statistically significant at P < 0.0012 adjusted for multiple testing. Replication in additional samples will be important to verify these results for the less-common EOC subtypes. PMID:24190013

  18. Nanomechanical analysis of cells from cancer patients

    NASA Astrophysics Data System (ADS)

    Cross, Sarah E.; Jin, Yu-Sheng; Rao, Jianyu; Gimzewski, James K.

    2007-12-01

    Change in cell stiffness is a new characteristic of cancer cells that affects the way they spread. Despite several studies on architectural changes in cultured cell lines, no ex vivo mechanical analyses of cancer cells obtained from patients have been reported. Using atomic force microscopy, we report the stiffness of live metastatic cancer cells taken from the body (pleural) fluids of patients with suspected lung, breast and pancreas cancer. Within the same sample, we find that the cell stiffness of metastatic cancer cells is more than 70% softer, with a standard deviation over five times narrower, than the benign cells that line the body cavity. Different cancer types were found to display a common stiffness. Our work shows that mechanical analysis can distinguish cancerous cells from normal ones even when they show similar shapes. These results show that nanomechanical analysis correlates well with immunohistochemical testing currently used for detecting cancer.

  19. Fuel Burnup and Fuel Pool Shielding Analysis for Bushehr Nuclear Reactor VVER-1000

    NASA Astrophysics Data System (ADS)

    Hadad, Kamal; Ayobian, Navid

    Bushehr Nuclear power plant (BNPP) is currently under construction. The VVER-1000 reactor will be loaded with 126 tons of about 4% enriched fuel having 3-years life cycle. The spent fuel (SF) will be transferred into the spent fuel pool (SPF), where it stays for 8 years before being transferred to Russia. The SPF plays a crucial role during 8 years when the SP resides in there. This paper investigates the shielding of this structure as it is designed to shield the SF radiation. In this study, the SF isotope inventory, for different cycles and with different burnups, was calculated using WIMS/4D transport code. Using MCNP4C nuclear code, the intensity of γ rays was obtained in different layers of SFP shields. These layers include the water above fuel assemblies (FA) in pool, concrete wall of the pool and water laid above transferring fuels. Results show that γ rays leakage from the shield in the mentioned layers are in agreement with the plant's PSAR data. Finally we analyzed an accident were the water height above the FA in the pool drops to 47 cm. In this case it was observed that exposure dose above pool, 10 and 30 days from the accident, are still high and in the levels of 1000 and 758 R/hr.

  20. Well-characterized open pool experiment data and analysis for model validation and development.

    SciTech Connect

    Sundberg, David W.; Brown, Alexander L.; Blanchat, Thomas K.

    2006-12-01

    Four Well-Characterized Open Pool fires were conducted by Fire Science and Technology Department. The focus of the Well-Characterized Open Pool fire series was to provide environmental information for open pool fires on a physics first principal basis. The experiments measured the burning rate of liquid fuel in an open pool and the resultant heat flux to a weapon-sized object and the surrounding environment with well-characterized boundary and initial conditions. Results presented in this report include a general description of test observation (pre- and post-test), wind measurements, fire plume topology, average fuel recession and heat release rates, and incident heat flux to the pool and to the calorimeters. As expected, results of the experiments show a strong correlation between wind conditions, fuel vaporization (mass loss) rate, and incident heat flux to the fuel and ground surface and calorimeters. Numerical fire simulations using both temporally- and spatially-dependant wind boundary conditions were performed using the Vulcan fire code. Comparisons of data to simulation predictions showed similar trends; however, simulation-predicted incident heat fluxes were lower than measured.

  1. Friends and Symptom Dimensions in Patients with Psychosis: A Pooled Analysis

    PubMed Central

    Giacco, Domenico; McCabe, Rose; Kallert, Thomas; Hansson, Lars; Fiorillo, Andrea; Priebe, Stefan

    2012-01-01

    Background Having friends is associated with more favourable clinical outcomes and a higher quality of life in mental disorders. Patients with schizophrenia have fewer friends than other mentally ill patients. No large scale studies have evaluated so far what symptom dimensions of schizophrenia are associated with the lack of friendships. Methods Data from four multi-centre studies on outpatients with schizophrenia and related disorders (ICD F20-29) were included in a pooled analysis (N?=?1396). We established whether patients had close friends and contact with friends by using the equivalent items on friendships of the Manchester Short Assessment of Quality of Life or of the Lancashire Quality of Life Profile. Symptoms were measured by the Brief Psychiatric Rating Scale or by the identical items included in the Positive and Negative Syndrome Scale. Results Seven hundred and sixty-nine patients (55.1%) had seen a friend in the previous week and 917 (65.7%) had someone they regarded as a close friend. Low levels of negative symptoms and hostility were significantly associated with having a close friend and contact with a friend. Overall, almost twice as many patients with absent or mild negative symptoms had met a friend in the last week, compared with those with moderate negative symptoms. Conclusions Higher levels of negative symptoms and hostility are specifically associated with the lack of friendships in patients with psychotic disorders. These findings suggest the importance of developing effective treatments for negative symptoms and hostility in order to improve the probability of patients with schizophrenia to have friends. PMID:23185552

  2. Biologic markers of sun exposure and melanoma risk in women: pooled case-control analysis.

    PubMed

    Olsen, Catherine M; Zens, Michael S; Green, Adele C; Stukel, Therese A; Holman, C D'Arcy J; Mack, Thomas; Elwood, J Mark; Holly, Elizabeth A; Sacerdote, Carlotta; Gallagher, Richard; Swerdlow, Anthony J; Armstrong, Bruce K; Rosso, Stefano; Kirkpatrick, Connie; Zanetti, Roberto; Bishop, Julia Newton; Bataille, Veronique; Chang, Yu-Mei; Mackie, Rona; Østerlind, Anne; Berwick, Marianne; Karagas, Margaret R; Whiteman, David C

    2011-08-01

    A model has been proposed whereby melanomas arise through two distinct pathways dependent on the relative influence of host susceptibility and sun exposure. Such pathways may explain site-specific patterns of melanoma occurrence. To explore this model, we investigated the relationship between melanoma risk and general markers of acute (recalled sunburns) and chronic (prevalent solar keratoses) sun exposure, stratified by anatomic site and host phenotype. Our working hypothesis was that head and neck melanomas have stronger associations with solar keratoses and weaker associations with sunburn than trunk melanomas. We conducted a collaborative analysis using original data from women subjects of 11 case-control studies of melanoma (2,575 cases, 3,241 controls). We adjusted for potential confounding effects of sunlamp use and sunbathing. The magnitude of sunburn associations did not differ significantly by melanoma site, nevus count or histologic subtype of melanoma. Across all sites, relative risk of melanoma increased with an increasing number of reported lifetime "painful" sunburns, lifetime "severe" sunburns and "severe" sunburns in youth (p(trend) < 0.001), with pooled odds ratios (pORs) for the highest category of sunburns versus no sunburns of 3.22 [95% confidence interval (CI) 2.04-5.09] for lifetime "painful" sunburns, 2.10 (95%CI 1.30-3.38) for lifetime "severe" sunburns and 2.43 (95%CI 1.61-3.65) for "severe" sunburns in youth. Solar keratoses strongly increased the risk of head and neck melanoma (pOR 4.91, 95%CI 2.10-11.46), but data were insufficient to assess risk for other sites. Reported sunburn is strongly associated with melanoma on all major body sites. PMID:20857492

  3. Biologic markers of sun exposure and melanoma risk in women: pooled case-control analysis

    PubMed Central

    Olsen, Catherine M.; Zens, Michael S.; Green, Adele C.; Stukel, Therese A.; Holman, C. D’Arcy J.; Mack, Thomas; Elwood, J. Mark; Holly, Elizabeth A.; Sacerdote, Carlotta; Gallagher, Richard; Swerdlow, Anthony J.; Armstrong, Bruce K.; Rosso, Stefano; Kirkpatrick, Connie; Zanetti, Roberto; Bishop, Julia Newton; Bataille, Veronique; Chang, Yu-Mei; Mackie, Rona; Østerlind, Anne; Berwick, Marianne; Karagas, Margaret R.; Whiteman, David C.

    2010-01-01

    A model has been proposed whereby melanomas arise through two distinct pathways dependent upon the relative influence of host susceptibility and sun exposure. Such pathways may explain site-specific patterns of melanoma occurrence. To explore this model, we investigated the relationship between melanoma risk and general markers of acute (recalled sunburns) and chronic (prevalent solar keratoses) sun exposure, stratified by anatomic site and host phenotype. Our working hypothesis was that head and neck melanomas have stronger associations with solar keratoses and weaker associations with sunburn than trunk melanomas. We conducted a collaborative analysis using original data from women subjects of 11 case–control studies of melanoma (2575 cases, 3241 controls). We adjusted for potential confounding effects of sunlamp use and sunbathing. The magnitude of sunburn associations did not differ significantly by melanoma site, nevus count or histologic sub-type of melanoma. Across all sites, relative risk of melanoma increased with an increasing number of reported lifetime ‘painful’ sunburns, lifetime ‘severe’ sunburns and ‘severe’ sunburns in youth (ptrend<0.001), with pooled odds ratios for the highest category of sunburns vs no sunburns of 3.22 (95%CI 2.04–5.09) for lifetime ‘painful’ sunburns, 2.10 (95%CI 1.30–3.38) for lifetime ‘severe’ sunburns, and 2.43 (95%CI 1.61–3.65) for ‘severe’ sunburns in youth. Solar keratoses strongly increased the risk of head and neck melanoma (pOR 4.91, 95% CI 2.10–11.46), but data were insufficient to assess risk for other sites. Reported sunburn is strongly associated with melanoma on all major body sites. PMID:20857492

  4. Prognostic value of Muc5AC in gastric cancer: A meta-analysis

    PubMed Central

    Zhang, Chuan-Tao; He, Ke-Cheng; Pan, Fei; Li, Yuan; Wu, Jiang

    2015-01-01

    AIM: To assess the correlation between decreased Muc5AC expression and patients’ survival and clinicopathological characteristics by conducting a meta-analysis. METHODS: Literature searches were performed in PubMed and EMBASE, and 11 studies met our criteria. Summary hazard ratios or odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to estimate the effect. For the pooled analysis of the correlation between decreased Muc5AC expression and clinicopathological characteristics (tumour invasion depth, lymph node metastasis, tumour-node-metastasis stage, tumour size, venous invasion and lymphatic invasion), ORs and their variance were combined to estimate the effect. RESULTS: Eleven retrospective cohort studies comprising 2135 patients were included to assess the association between Muc5AC expression and overall survival and/or clinicopathological characteristics. Decreased Muc5AC expression was significantly correlated with poor overall survival of gastric cancer patients (pooled HR = 1.35, 95%CI: 1.08-1.7). Moreover, decreased Muc5AC expression was also significantly associated with tumour invasion depth (pooled OR = 2.12, 95%CI: 1.56-2.87) and lymph node metastasis (pooled OR = 1.56, 95%CI: 1.00-2.44) in gastric cancer. CONCLUSION: Decreased Muc5AC expression might be a poor prognostic predictor for gastric cancer. PMID:26420972

  5. Development of a Self-Report Physical Function Instrument for Disability Assessment: Item Pool Construction and Factor Analysis

    PubMed Central

    McDonough, Christine M.; Jette, Alan M.; Ni, Pengsheng; Bogusz, Kara; Marfeo, Elizabeth E; Brandt, Diane E; Chan, Leighton; Meterko, Mark; Haley, Stephen M.; Rasch, Elizabeth K.

    2014-01-01

    Objectives To build a comprehensive item pool representing work-relevant physical functioning and to test the factor structure of the item pool. These developmental steps represent initial outcomes of a broader project to develop instruments for the assessment of function within the context of Social Security Administration (SSA) disability programs. Design Comprehensive literature review; gap analysis; item generation with expert panel input; stakeholder interviews; cognitive interviews; cross-sectional survey administration; and exploratory and confirmatory factor analyses to assess item pool structure. Setting In-person and semi-structured interviews; internet and telephone surveys. Participants A sample of 1,017 SSA claimants, and a normative sample of 999 adults from the US general population. Interventions Not Applicable. Main Outcome Measure Model fit statistics Results The final item pool consisted of 139 items. Within the claimant sample 58.7% were white; 31.8% were black; 46.6% were female; and the mean age was 49.7 years. Initial factor analyses revealed a 4-factor solution which included more items and allowed separate characterization of: 1) Changing and Maintaining Body Position, 2) Whole Body Mobility, 3) Upper Body Function and 4) Upper Extremity Fine Motor. The final 4-factor model included 91 items. Confirmatory factor analyses for the 4-factor models for the claimant and the normative samples demonstrated very good fit. Fit statistics for claimant and normative samples respectively were: Comparative Fit Index = 0.93 and 0.98; Tucker-Lewis Index = 0.92 and 0.98; Root Mean Square Error Approximation = 0.05 and 0.04. Conclusions The factor structure of the Physical Function item pool closely resembled the hypothesized content model. The four scales relevant to work activities offer promise for providing reliable information about claimant physical functioning relevant to work disability. PMID:23542402

  6. A pooled analysis to define vitamin D dose requirements for fracture prevention in seniors

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Meta-analyses reached conflicting results regarding vitamin D and fracture reduction. We pooled individual participant-level data from 11 double-blind RCTs of oral vitamin D supplementation (daily, weekly, 4-monthly) with or without calcium compared with placebo or calcium in seniors age 65 and olde...

  7. A meta-analysis of clinical trials assessing the effect of radiofrequency ablation for breast cancer

    PubMed Central

    Chen, Jiayan; Zhang, Chi; Li, Fei; Xu, Liping; Zhu, Hongcheng; Wang, Shui; Liu, Xiaoan; Zha, Xiaoming; Ding, Qiang; Ling, Lijun; Zhou, Wenbin; Sun, Xinchen

    2016-01-01

    Background Radiofrequency ablation (RFA) is a minimally invasive thermal ablation technique. We conducted a meta-analysis based on eligible studies to assess the efficacy and safety of RFA for treating patients with breast cancer. Methods A literature search was conducted in PubMed, Embase, and Web of Science databases. Eligible studies were clinical trials that assessed RFA in patients with breast cancer. The outcomes included complete ablation rate, recurrence rate, excellent or good cosmetic rates, and complication rate. A random-effects or fixed-effects model was used to pool the estimate, according to the heterogeneity among the included studies. Results Fifteen studies, with a total of 404 patients, were included in this meta-analysis. Pooled results showed that 89% (95% confidence interval: 85%–93%) of patients achieved a complete ablation after RFA treatment and 96% of patients reported a good-to-excellent cosmetic result. Although the pooled result for recurrence rate was 0, several cases of relapse were observed at different follow-up times. No RFA-related complications were recorded, except for skin burn with an incidence of 4% (95% confidence interval: 1%–6%). Conclusion This meta-analysis showed that RFA can be a promising alternative option for treating breast cancer since it produces a higher complete ablation rate with a low complication rate. Further well-designed randomized controlled trials are needed to confirm the efficacy and safety of RFA for breast cancer. PMID:27042126

  8. MicroRNA-18a as a promising biomarker for cancer detection: a meta-analysis.

    PubMed

    Jin, Shan; Tan, Shi-Sheng; Li, Hang

    2015-01-01

    Patients with cancer discovered at an early stage have relatively high survival rates. Increasing researches have shown the potential of detecting dysregulated microRNA-18a (miR-18a) to diagnose cancer. However, non-uniform results in previous studies were found. Thus, this meta-analysis was conducted to further explore the clinical applicability of miR-18a as an ideal biomarker for cancer detection. Suitable articles were obtained from online databases like PubMed, Embase, Cochrane, CBM and Wanfang. The Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool was used to evaluate the quality of our meta-analysis. The pooled diagnostic parameters like specificity, sensitivity, diagnostic odds ratio (DOR), positive and negative likelihood ratios (PLR and NLR) and area under the summary receiver operator characteristic curve (SROC) were pooled to assess the entire test accuracy. Overall, 10 studies from 9 articles, including 979 patients with cancer and 713 healthy controls were involved in our meta-analysis. The pooled sensitivity was 0.78 (95% CI: 0.70-0.84) and the corresponding specificity was 0.82 (95% CI: 0.73-0.89). The merged PLR was 4.3 (95% CI: 2.8-6.8), NLR was 0.27 (95% CI: 0.20-0.37), and DOR was 16 (95% CI: 8-31). The pooled AUC was 0.86 (95% CI: 0.83-0.89). Our meta-analysis suggested that miR-18a might open up a new field for novel clinical cancer screening with the merits of high accuracy, non-invasiveness, convenience and cheap cost. However, more reliable studies in larger cohort should be conducted before it is used. PMID:26550138

  9. Coffee consumption and risk of endometrial cancer: findings from a large up-to-date meta-analysis.

    PubMed

    Je, Youjin; Giovannucci, Edward

    2012-10-01

    Several epidemiological studies have examined the association between coffee drinking and risk of endometrial cancer. To provide a quantitative assessment of this association, we conducted a meta-analysis of observational studies published up to October 2011 through a search of MEDLINE and EMBASE databases and the reference lists of retrieved article. Pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated using a random-effects model, and generalized least square trend estimation was used to assess dose-response relationships. A total of 16 studies (10 case-control and six cohort studies) on coffee intake with 6,628 endometrial cancer cases were included in the meta-analysis. The pooled RR of endometrial cancer for the highest versus lowest categories of coffee intake was 0.71 (95% CI: 0.62-0.81; p for heterogeneity = 0.13). By study design, the pooled RRs were 0.69 (95% CI: 0.55-0.87) for case-control studies and 0.70 (95% CI: 0.61-0.80) for cohort studies. By geographic region, the inverse association was stronger for three Japanese studies (pooled RR = 0.40; 95% CI: 0.25-0.63) than five studies from USA/Canada (pooled RR = 0.69; 95% CI: 0.60-0.79) or eight studies from Europe (pooled RR = 0.79; 95% CI: 0.63-0.99). An increment of one cup per day of coffee intake conferred a pooled RR of 0.92 (95% CI: 0.90-0.95). In conclusion, our findings suggest that increased coffee intake is associated with a reduced risk of endometrial cancer, consistently observed for cohort and case-control studies. More large studies are needed to determine subgroups to obtain more benefits from coffee drinking in relation to endometrial cancer risk. PMID:22190017

  10. Analgesic use and the risk of kidney cancer: a meta-analysis of epidemiologic studies.

    PubMed

    Choueiri, Toni K; Je, Youjin; Cho, Eunyoung

    2014-01-15

    Analgesics are the most commonly used over-the-counter drugs worldwide with certain analgesics having cancer prevention effect. The evidence for an increased risk of developing kidney cancer with analgesic use is mixed. Using a meta-analysis design of available observational epidemiologic studies, we investigated the association between analgesic use and kidney cancer risk. We searched the MEDLINE and EMBASE databases to identify eligible case-control or cohort studies published in English until June 2012 for three categories of analgesics: acetaminophen, aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs). Study-specific effect estimates were pooled to compute an overall relative risk (RR) and its 95% confidence interval (CI) using a random-effects model for each category of the analgesics. We identified 20 studies (14 with acetaminophen, 13 with aspirin and five with other NSAIDs) that were performed in six countries, including 8,420 cases of kidney cancer. Use of acetaminophen and non-aspirin NSAIDs were associated with an increased risk of kidney cancer (pooled RR: 1.28; 95% CI: 1.15-1.44 and 1.25; 95% CI: 1.06-1.46, respectively). For aspirin use, we found no overall increased risk (pooled RR: 1.10; 95% CI: 0.95-1.28), except for non-US studies (five studies, pooled RR: 1.17; 95% CI: 1.04-1.33). Similar increases in risks were seen with higher analgesic intake. In this largest meta-analysis to date, we found that acetaminophen and non-aspirin NSAIDs are associated with a significant risk of developing kidney cancer. Further work is needed to elucidate biologic mechanisms behind these findings. PMID:23400756

  11. Is ioflupane I123 injection diagnostically effective in patients with movement disorders and dementia? Pooled analysis of four clinical trials

    PubMed Central

    O'Brien, John T; Oertel, Wolfgang H; McKeith, Ian G; Grosset, Donald G; Walker, Zuzana; Tatsch, Klaus; Tolosa, Eduardo; Sherwin, Paul F; Grachev, Igor D

    2014-01-01

    Objectives To pool clinical trials of similar design to assess overall sensitivity and specificity of ioflupane I123 injection (DaTSCAN or ioflupane (123I)) to detect or exclude a striatal dopaminergic deficit disorder (SDDD), such as parkinsonian syndrome and dementia with Lewy bodies. Design Pooled analysis of three phase 3 and one phase 4 clinical trials. These four trials were selected because they were the four studies used for the US new drug application to the Food and Drug Administration (FDA). Setting Multicentre, open-label, non-randomised. Participants Patients with either a movement disorder or dementia, and healthy volunteers. Interventions Ioflupane (123I) was administered. Outcome measures Images were assessed by panels of 35 blinded experts and/or on-site nuclear medicine physicians, classified as normal or abnormal and compared with clinical diagnosis (reference standard) to determine sensitivity and specificity. Results Pooling the four studies, 928 participants were enrolled, 849 were dosed and 764 completed their study. Across all studies, when images were assessed by on-site readers, ioflupane (123I) diagnostic effectiveness had an overall (95% CI) sensitivity of 91.9% (88.7% to 94.5%) and specificity of 83.6% (78.7% to 87.9%). When reads were conducted blindly by a panel of independent experts, the overall sensitivity was 88.7% (86.8% to 90.4%) and specificity was 91.2% (89.0% to 93.0%). Conclusions In this pooled analysis, the visual assessment of ioflupane (123I) images provided high levels of sensitivity and specificity in detecting the presence/absence of an SDDD. Ioflupane (123I) imaging has the potential to improve diagnostic accuracy in patients with signs and symptoms of a movement disorder and/or dementia. Trial registration number NCT00209456. PMID:24993764

  12. Selenium and Lung Cancer: A Systematic Review and Meta Analysis

    PubMed Central

    Fritz, Heidi; Kennedy, Deborah; Fergusson, Dean; Fernandes, Rochelle; Cooley, Kieran; Seely, Andrew; Sagar, Stephen; Wong, Raimond; Seely, Dugald

    2011-01-01

    Background Selenium is a natural health product widely used in the treatment and prevention of lung cancers, but large chemoprevention trials have yielded conflicting results. We conducted a systematic review of selenium for lung cancers, and assessed potential interactions with conventional therapies. Methods and Findings Two independent reviewers searched six databases from inception to March 2009 for evidence pertaining to the safety and efficacy of selenium for lung cancers. Pubmed and EMBASE were searched to October 2009 for evidence on interactions with chemo- or radiation-therapy. In the efficacy analysis there were nine reports of five RCTs and two biomarker-based studies, 29 reports of 26 observational studies, and 41 preclinical studies. Fifteen human studies, one case report, and 36 preclinical studies were included in the interactions analysis. Based on available evidence, there appears to be a different chemopreventive effect dependent on baseline selenium status, such that selenium supplementation may reduce risk of lung cancers in populations with lower baseline selenium status (serum<106 ng/mL), but increase risk of lung cancers in those with higher selenium (≥121.6 ng/mL). Pooling data from two trials yielded no impact to odds of lung cancer, OR 0.93 (95% confidence interval 0.61–1.43); other cancers that were the primary endpoints of these trials, OR 1.51 (95%CI 0.70–3.24); and all-cause-death, OR 0.93 (95%CI 0.79–1.10). In the treatment of lung cancers, selenium may reduce cisplatin-induced nephrotoxicity and side effects associated with radiation therapy. Conclusions Selenium may be effective for lung cancer prevention among individuals with lower selenium status, but at present should not be used as a general strategy for lung cancer prevention. Although promising, more evidence on the ability of selenium to reduce cisplatin and radiation therapy toxicity is required to ensure that therapeutic efficacy is maintained before any broad clinical recommendations can be made in this context. PMID:22073154

  13. Variation in cancer risk estimates for exposure to powerline frequency electromagnetic fields: A meta-analysis comparing EMF measurement methods

    SciTech Connect

    Miller, M.A.; Murphy, J.R.; MIller, T. I; Ruttenber, A.J.

    1995-04-01

    We used meta-analysis to synthesize the findings from eleven case-control studies on cancer risks in humans exposed to 50-60 Hertz powerline electromagnetic fields (EMFs). Pooled estimates of risk are derived for different EMF measurement methods and types of cancer. EMF measurement methods are classified as: wiring configuration codes, distance to power distribution equipment, spot measurements of magnetic fields, and calculated indices based on distance to power distribution equipment and historic load data. Pooled odds ratios depicting the risk of cancer by each measurement type are presented for all cancers combined, leukemia for all age groups and childhood leukemia. The wire code measurement technique was associated with a significantly increased risk for all three cancer types, while spot measures consistently showed non-significant odds ratios. Distance measures and the calculated indices produced risk estimates which were significant only for leukemia. 24 refs., 6 tabs.

  14. A keyhole volumetric model for weld pool analysis in Nd:YAG pulsed laser welding

    NASA Astrophysics Data System (ADS)

    Kuang, Jao-Hwa; Hung, Tsung-Pin; Chen, Chih-Kuan

    2012-07-01

    This study presents a new model for analyzing the temperature distribution and weld pool shape in Nd:YAG pulsed laser welding. In the proposed approach, a surface flux heat transfer model is applied in the low laser energy intensity region of the weld, while a keyhole heat transfer model based on a volumetric heat source is applied in the high laser energy intensity region of the weld. The correlation between the intensity of the laser input energy and the geometric parameters of the volumetric heat source is derived experimentally. A series of MARC finite element simulations based on the proposed single pulse model are performed to investigate the shape and size of the weld pool given different laser energy intensities. A good agreement is observed between the simulation results and the experimental results obtained under equivalent single pulse welding conditions. Thus, the basic validity of the proposed model is confirmed.

  15. An Innovative Hybrid Loop-Pool SFR Design and Safety Analysis Methods: Today and Tomorrow

    SciTech Connect

    Hongbin Zhang; Haihua Zhao; Vincent Mousseau

    2008-04-01

    Investment in commercial sodium cooled fast reactor (SFR) power plants will become possible only if SFRs achieve economic competitiveness as compared to light water reactors and other Generation IV reactors. Toward that end, we have launched efforts to improve the economics and safety of SFRs from the thermal design and safety analyses perspectives at Idaho National Laboratory. From the thermal design perspective, an innovative hybrid loop-pool SFR design has been proposed. This design takes advantage of the inherent safety of a pool design and the compactness of a loop design to further improve economics and safety. From the safety analyses perspective, we have initiated an effort to develop a high fidelity reactor system safety code.

  16. Prolactin receptor attenuation induces zinc pool redistribution through ZnT2 and decreases invasion in MDA-MB-453 breast cancer cells

    SciTech Connect

    Bostanci, Zeynep; Alam, Samina; Soybel, David I.; Kelleher, Shannon L.

    2014-02-15

    Prolactin receptor (PRL-R) activation regulates cell differentiation, proliferation, cell survival and motility of breast cells. Prolactin (PRL) and PRL-R over-expression are strongly implicated in breast cancer, particularly contributing to tumor growth and invasion in the more aggressive estrogen-receptor negative (ER−) disease. PRL-R antagonists have been suggested as potential therapeutic agents; however, mechanisms through which PRL-R antagonists exert their actions are not well-understood. Zinc (Zn) is a regulatory factor for over 10% of the proteome, regulating critical cell processes such as proliferation, cell signaling, transcription, apoptosis and autophagy. PRL-R signaling regulates Zn metabolism in breast cells. Herein we determined effects of PRL-R attenuation on cellular Zn metabolism and cell function in a model of ER-, PRL-R over-expressing breast cancer cells (MDA-MB-453). PRL-R attenuation post-transcriptionally increased ZnT2 abundance and redistributed intracellular Zn pools into lysosomes and mitochondria. ZnT2-mediated lysosomal Zn sequestration was associated with reduced matrix metalloproteinase 2 (MMP-2) activity and decreased invasion. ZnT2-mediated Zn accumulation in mitochondria was associated with increased mitochondrial oxidation. Our results suggest that PRL-R antagonism in PRL-R over-expressing breast cancer cells may reduce invasion through the redistribution of intracellular Zn pools critical for cellular function. - Highlights: • PRL-R attenuation increased ZnT2 expression. • PRL-R attenuation increased lysosomal and mitochondrial Zn accumulation. • PRL-R attenuation decreased MMP-2 and invasion. • PRL-R antagonists may modulate lysosomal and mitochondrial Zn pools.

  17. Non-Hodgkin lymphoma and Obesity: a pooled analysis from the InterLymph consortium

    PubMed Central

    Willett, Eleanor V.; Morton, Lindsay M.; Hartge, Patricia; Becker, Nikolaus; Bernstein, Leslie; Boffetta, Paolo; Bracci, Paige; Cerhan, James; Chiu, Brian C.-H.; Cocco, Pierluigi; Maso, Luigino Dal; Davis, Scott; De Sanjose, Silvia; Smedby, Karin Ekstrom; Ennas, Maria Grazia; Foretova, Lenka; Holly, Elizabeth A.; La Vecchia, Carlo; Matsuo, Keitaro; Maynadie, Marc; Melbye, Mads; Negri, Eva; Nieters, Alexandra; Severson, Richard; Slager, Susan L.; Spinelli, John J.; Staines, Anthony; Talamini, Renato; Vornanen, Martine; Weisenburger, Dennis D.; Roman, Eve

    2014-01-01

    Nutritional status is known to alter immune function, a suspected risk factor for non-Hodgkin lymphoma (NHL). To investigate whether long-term over, or under, nutrition is associated with NHL self-reported anthropometric data on weight and height from over 10000 cases of NHL and 16000 controls were pooled across 18 case-control studies identified through the International Lymphoma Epidemiology Consortium. Study-specific odds ratios (OR) were estimated using logistic regression and combined using a random-effects model. Severe obesity, defined as BMI of 40 kg m−2 or more, was not associated with NHL overall (pooled OR=1.00, 95% confidence interval (CI) 0.70–1.41) or the majority of NHL subtypes. An excess was however observed for diffuse large B-cell lymphoma (pooled OR=1.80, 95% CI 1.24–2.62), although not all study-specific ORs were raised. Among the overweight (BMI 25–29.9 kg m−2) and obese (BMI 30–39.9 kg m−2), associations were elevated in some studies and decreased in others, while no association was observed among the underweight (BMI<18.5 kg m−2). There was little suggestion of increasing ORs for NHL or its subtypes with every 5 kg m−2 rise in BMI above 18.5 kg m−2. BMI components height and weight were also examined, and the tallest men, but not women, were at marginally increased risk (pooled OR=1.19, 95% CI 1.06–1.34). In summary, whilst we conclude that there is no evidence to support the hypothesis that obesity is a determinant of all types of NHL combined, the association between severe obesity and diffuse large B-cell lymphoma may warrant further investigation. PMID:18167059

  18. NaK pool-boiler solar receiver durability bench test. Volume 2: Metallurgical analysis

    NASA Astrophysics Data System (ADS)

    Goods, S. H.; Bradshaw, R. W.

    1995-01-01

    The principal materials used in the construction of a NaK based pool-boiler were analyzed. The device, operated for 7500 hours, accumulated 1000 thermal cycles to a peak temperature of 750 C. Haynes 230, used to fabricate the pool-boiler vessel, was found to perform satisfactorily. Air-side corrosion of the pool-boiler vessel was insignificant. Internal surface of the alloy exhibited some NaK-induced elemental dissolution; this dissolution was somewhat more extensive where the alloy was exposed to the liquid metal compared to regions exposed only to NaK vapor; however, the corresponding metal loss in all regions was inconsequential, never exceeding more than a few microns. Autogenous seam welds of the alloy responded in a similar fashion, exhibiting only minimal metal loss over the course of the experiment. While there was 50% loss in ductility of the alloy there remained adequate ductility for the anticipated operating environment. An enhanced boiling nucleation surface comprised of stainless steel powder brazed to the vessel ID showed no change in its structure. It remained intact, showing no cracking after repeated thermal cycling. Other materials used in the experiment showed more extensive degradation after exposure to the NaK. IN 600, used to fabricate thermowells, exhibited extensive surface and intergranular dissolution. Grain boundary dissolution was sufficiently severe in one of the thermowells to cause an air leak, resulting in experiment termination. BNi-3, a brazing alloy used to join the pool-boiler vessel, endcaps and thermowells, showed some dissolution where it was exposed to the NaK as well as thermal aging effects. However, all brazes remained structurally sound. A nickel metal ribbon showed catastrophic dissolution, resulting in the formation of deep (greater than 30 (mu)m) pits and cavities. A zirconium metal foil used to getter oxygen from the NaK became extremely brittle.

  19. Fission matrix-based Monte Carlo criticality analysis of fuel storage pools

    SciTech Connect

    Farlotti, M.; Larsen, E. W.

    2013-07-01

    Standard Monte Carlo transport procedures experience difficulties in solving criticality problems in fuel storage pools. Because of the strong neutron absorption between fuel assemblies, source convergence can be very slow, leading to incorrect estimates of the eigenvalue and the eigenfunction. This study examines an alternative fission matrix-based Monte Carlo transport method that takes advantage of the geometry of a storage pool to overcome this difficulty. The method uses Monte Carlo transport to build (essentially) a fission matrix, which is then used to calculate the criticality and the critical flux. This method was tested using a test code on a simple problem containing 8 assemblies in a square pool. The standard Monte Carlo method gave the expected eigenfunction in 5 cases out of 10, while the fission matrix method gave the expected eigenfunction in all 10 cases. In addition, the fission matrix method provides an estimate of the error in the eigenvalue and the eigenfunction, and it allows the user to control this error by running an adequate number of cycles. Because of these advantages, the fission matrix method yields a higher confidence in the results than standard Monte Carlo. We also discuss potential improvements of the method, including the potential for variance reduction techniques. (authors)

  20. A comparative analysis of dietary intakes during pregnancy in Europe: a planned pooled analysis of birth cohort studies1234

    PubMed Central

    Kogevinas, Manolis

    2011-01-01

    Background: There is growing evidence that despite the absence of marked deficiencies, diet during pregnancy has important implications for maternal and child health in industrialized countries. At present, relatively little is known about prevailing patterns of intake across groups with diverse sociodemographic and lifestyle patterns in these settings. Objectives: The aims of this study were to develop methods for the standardization of food group intake data and to describe the process of applying these methods to existing pregnancy cohort studies, which included >200,000 women across Europe. Design: The study developed a detailed standardization protocol to harmonize intakes of selected food groups, which included fruit, vegetables, meats, seafood, and dairy products. Standardization is necessary to facilitate valid comparisons of intake patterns and disparities across countries and will lead to the development of harmonized databases for possible future pooled analyses. Results: On the basis of comparisons with previously coordinated multicountry studies, preliminary data suggest that the standardization process yielded sufficiently comparable intake data, which indicate differences in food cultures across the countries that participated. Conclusions: This project provides lessons on the feasibility of harmonizing dietary intake data from existing studies, which can be applied in future post hoc standardization efforts. The data yielded in this analysis will also provide useful information for the development of food and nutrition policies for pregnant women in Europe, including the identification of population subgroups in which dietary inadequacies during pregnancy may be widespread. PMID:21974890

  1. Higher dietary folate intake reduces the breast cancer risk: a systematic review and meta-analysis

    PubMed Central

    Chen, P; Li, C; Li, X; Li, J; Chu, R; Wang, H

    2014-01-01

    Background: Many epidemiological studies have investigated the association between folate intake, circulating folate level and risk of breast cancer; however, the findings were inconsistent between the studies. Methods: We searched the PubMed and MEDLINE databases updated to January, 2014 and performed the systematic review and meta-analysis of the published epidemiological studies to assess the associations between folate intake level, circulating folate level and the overall risk of breast cancer. Results: In all, 16 eligible prospective studies with a total of 744?068 participants and 26?205 breast cancer patients and 26 casecontrol studies with a total of 16?826 cases and 21?820 controls that have evaluated the association between folate intake and breast cancer risk were identified. Pooled analysis of the prospective studies and casecontrol studies suggested a potential nonlinearity relationship for dietary folate intake and breast cancer risk. Prospective studies indicated a U-shaped relationship for the dietary folate intake and breast cancer risk. Women with daily dietary folate intake between 153 and 400??g showed a significant reduced breast cancer risk compared with those <153??g, but not for those >400??g. The casecontrol studies also suggested a significantly negative correlation between the dietary folate intake level and the breast cancer risk. Increased dietary folate intake reduced breast cancer risk for women with higher alcohol intake level, but not for those with lower alcohol intake. No significant association between circulating folate level and breast cancer risk was found when the results of 8 identified studies with 5924 participants were pooled. Conclusions: Our studies suggested that folate may have preventive effects against breast cancer risk, especially for those with higher alcohol consumption level; however, the dose and timing are critical and more studies are warranted to further elucidate the questions. PMID:24667649

  2. The Cancer Genome Atlas Pan-Cancer analysis project.

    PubMed

    Weinstein, John N; Collisson, Eric A; Mills, Gordon B; Shaw, Kenna R Mills; Ozenberger, Brad A; Ellrott, Kyle; Shmulevich, Ilya; Sander, Chris; Stuart, Joshua M

    2013-10-01

    The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile. PMID:24071849

  3. Analysis of Pools of Targeted Salmonella Deletion Mutants Identifies Novel Genes Affecting Fitness during Competitive Infection in Mice

    PubMed Central

    Porwollik, Steffen; Choi, Sang-Ho; Long, Fred; Andrews-Polymenis, Helene L.; McClelland, Michael

    2009-01-01

    Pools of mutants of minimal complexity but maximal coverage of genes of interest facilitate screening for genes under selection in a particular environment. We constructed individual deletion mutants in 1,023 Salmonella enterica serovar Typhimurium genes, including almost all genes found in Salmonella but not in related genera. All mutations were confirmed simultaneously using a novel amplification strategy to produce labeled RNA from a T7 RNA polymerase promoter, introduced during the construction of each mutant, followed by hybridization of this labeled RNA to a Typhimurium genome tiling array. To demonstrate the ability to identify fitness phenotypes using our pool of mutants, the pool was subjected to selection by intraperitoneal injection into BALB/c mice and subsequent recovery from spleens. Changes in the representation of each mutant were monitored using T7 transcripts hybridized to a novel inexpensive minimal microarray. Among the top 120 statistically significant spleen colonization phenotypes, more than 40 were mutations in genes with no previously known role in this model. Fifteen phenotypes were tested using individual mutants in competitive assays of intraperitoneal infection in mice and eleven were confirmed, including the first two examples of attenuation for sRNA mutants in Salmonella. We refer to the method as Array-based analysis of cistrons under selection (ABACUS). PMID:19578432

  4. Cruciferous vegetables intake and the risk of colorectal cancer: a meta-analysis of observational studies

    PubMed Central

    Wu, Q. J.; Yang, Y.; Vogtmann, E.; Wang, J.; Han, L. H.; Li, H. L.; Xiang, Y. B.

    2013-01-01

    Background Epidemiological studies have reported inconsistent associations between cruciferous vegetable (CV) intake and colorectal cancer (CRC) risk. To our knowledge, a comprehensive and quantitative assessment of the association between CV intake and CRC has not been reported. Methods Relevant articles were identified by searching MEDLINE. We pooled the relative risks (RR) from individual studies using a random-effect model and carried out heterogeneity and publication bias analyses. Results Twenty-four case–control and 11 prospective studies were included in our analysis. When all studies were pooled, we yielded a significantly inverse association between CV (RR: 0.82; 95% confidence interval 0.75–0.90) intake and CRC risk. Specific analysis for cabbage and broccoli yielded similar result. When separately analyzed, case–control studies of CV intake yield similar results, and the results from the prospective studies showed borderline statistical significance. Moreover, significant inverse associations were also observed in colon cancer and its distal subsite both among prospective and case–control studies. Conclusions Findings from this meta-analysis provide evidence that high intake of CV was inversely associated with the risk of CRC and colon cancer in humans. Further analysis on other specific CV, food preparation methods, stratified results by anatomic cancer site, and subsite of colon cancer should be extended in future study. PMID:23211939

  5. Association of OPN rs11730582 polymorphism with cancer risk: a meta-analysis

    PubMed Central

    He, Lanlan; Wang, Yong

    2016-01-01

    Purpose Several molecular epidemiological studies have investigated the association between OPN rs11730582 C>T polymorphism and cancer risk, but the results are inconsistent. Hence, a meta-analysis was conducted to determine the association of this polymorphism with cancer risk. Materials and methods The related articles were searched in PubMed, Embase, and Chinese National Knowledge Infrastructure databases. Pooled odds ratios and 95% confidence intervals were calculated to evaluate the strength of the associations. A random-effects model or fixed-effects model was employed depending on the heterogeneity. Results A total of ten case-control studies involving 2,749 cancer cases and 3,398 controls were included in the meta-analysis. In overall analysis, OPN rs11730582 C.T polymorphism was not associated with cancer risk. In a stratified analysis by cancer type, no significant association was found between OPN rs11730582 C>T polymorphism and the risk of glioma, gastric cancer, and other cancers. Conclusion This meta-analysis suggests that OPN rs11730582 C.T polymorphism is not associated with cancer susceptibility. PMID:27022284

  6. Incorporating Network Structure in Integrative Analysis of Cancer Prognosis Data

    PubMed Central

    Liu, Jin; Huang, Jian; Ma, Shuangge

    2014-01-01

    In high-throughput cancer genomic studies, markers identified from the analysis of single datasets may have unsatisfactory properties because of low sample sizes. Integrative analysis pools and analyzes raw data from multiple studies, and can effectively increase sample size and lead to improved marker identification results. In this study, we consider the integrative analysis of multiple high-throughput cancer prognosis studies. In the existing integrative analysis studies, the interplay among genes, which can be described using the network structure, has not been effectively accounted for. In network analysis, tightly-connected nodes (genes) are more likely to have related biological functions and similar regression coefficients. The goal of this study is to develop an analysis approach that can incorporate the gene network structure in integrative analysis. To this end, we adopt an AFT (accelerated failure time) model to describe survival. A weighted least squares approach, which has low computational cost, is adopted for estimation. For marker selection, we propose a new penalization approach. The proposed penalty is composed of two parts. The first part is a group MCP penalty, and conducts gene selection. The second part is a Laplacian penalty, and smoothes the differences of coefficients for tightly-connected genes. A group coordinate descent approach is developed to compute the proposed estimate. Simulation study shows satisfactory performance of the proposed approach when there exist moderate to strong correlations among genes. We analyze three lung cancer prognosis datasets, and demonstrate that incorporating the network structure can lead to the identification of important genes and improved prediction performance. PMID:23161517

  7. Probabilistic risk analysis for Test Area North Hot Shop Storage Pool Facility

    SciTech Connect

    Meale, B.M.; Satterwhite, D.G.

    1990-01-01

    A storage pool facility used for storing spent fuel and radioactive debris from the Three Mile Island (TMI) accident was evaluated to determine the risk associated with its normal operations. Several hazards were identified and examined to determine if any any credible accident scenarios existed. Expected annual occurrence frequencies were calculated for hazards for which accident scenarios were identified through use of fault trees modeling techniques. Fault tree models were developed for two hazards: (1) increased radiation field and (2) spread of contamination. The models incorporated facets of the operations within the facility as well as the facility itself. 6 refs.

  8. Occupational exposure to diesel exhaust and lung cancer: a meta-analysis.

    PubMed Central

    Lipsett, M; Campleman, S

    1999-01-01

    OBJECTIVES: We undertook a meta-analysis of epidemiological studies investigating the relationship between occupational diesel exhaust exposure and lung cancer. METHODS: Thirty of 47 studies initially identified as potentially relevant met specified inclusion criteria. We extracted or calculated 39 independent estimates of relative risk and derived pooled estimates of risk for all studies and for numerous study subsets by using a random-effects model. We also examined interstudy heterogeneity by using linear metaregressions. RESULTS: There was substantial heterogeneity in the pooled risk estimates for all studies combined and for most subsets. Several factors consistent with higher study quality, however, contributed to increased pooled estimates of risk and lower heterogeneity, including (1) adjustment for confounding by cigarette smoking and other covariates, (2) having a lower likelihood of selection bias, and (3) having increased study power. CONCLUSION: This analysis provides quantitative support for prior qualitative reviews that have ascribed an etiologic role to occupational diesel exhaust exposure in lung cancer induction. Among study populations most likely to have had substantial exposure to diesel exhaust, the pooled smoking-adjusted relative risk was 1.47 (95% confidence interval = 1.29, 1.67). PMID:10394308

  9. Association between Breastfeeding and Endometrial Cancer Risk: Evidence from a Systematic Review and Meta-Analysis.

    PubMed

    Wang, Lianlian; Li, Jingxi; Shi, Zhan

    2015-07-01

    Quantification of the association between breastfeeding and risk of endometrial cancer is still conflicting. We therefore conducted a meta-analysis to assess the association between breastfeeding and endometrial cancer risk. Pertinent studies were identified by a search of PubMed and Web of Knowledge through April 2015. A random effect model was used to combine the data for analysis. Sensitivity analysis and publication bias were conducted. Dose-response relationships were assessed by restricted cubic spline and variance-weighted least squares regression analysis. Fourteen articles involving 5158 endometrial cancer cases and 706,946 participants were included in this meta-analysis. Pooled results suggested that breastfeeding significantly reduced the risk of endometrial cancer (summary relative risk (RR): 0.77, 95% CI: 0.62-0.96, I2: 63.0%), especially in North America (summary RR: 0.87, 95% CI: 0.79-0.95). A linear dose-response relationship was found, with the risk of endometrial cancer decreased by 2% for every one-month increase in the duration of breastfeeding (summary RR: 0.98, 95% CI: 0.97-0.99). Our analysis suggested that breastfeeding, particularly a longer duration of breastfeeding, was inversely associated with the risk of endometrial cancer, especially in North America, but not in Europe and Asia, probably due to the small number of cases included. Due to this limitation, further studies originating in other countries are required to assess the association between breastfeeding and endometrial cancer risk. PMID:26184301

  10. Association between tea and coffee consumption and risk of laryngeal cancer: a meta-analysis

    PubMed Central

    Ouyang, Zhiguo; Wang, Zhaoyan; Jin, Jian

    2014-01-01

    Objective: Epidemiological studies evaluating the association of tea and coffee consumption and the risk of laryngeal cancer have produced inconsistent results. Thus, we conducted a meta-analysis to assess the relationship between tea and coffee consumption and laryngeal cancer risk. Methods: Pertinent studies were identified by a search in PubMed, Web of Knowledge and Wan Fang Med Online. The random effect model was used based on heterogeneity test. Publication bias was estimated using Egger’s regression asymmetry test. As a result, 11 articles were included in this meta-analysis. Results: For tea consumption and laryngeal cancer, data from 8 studies including 2167 laryngeal cancer cases were used, and the pooled results suggested that highest tea consumption versus lowest level wasn’t associated with the risk of laryngeal cancer [summary RR = 0.909, 95% CI = 0.674-1.227]. Eight studies comprising 2596 laryngeal cancer cases for coffee consumption and laryngeal cancer risk were included, and no association was found (summary RR = 1.218, 95% CI = 0.915-1.622). Conclusions: Finding from this meta-analysis suggested that tea and coffee consumption weren’t associated with the risk of laryngeal cancer. Since the potential biases and confounders could not be ruled out completely in this meta-analysis, further studies are warranted to confirm this result. PMID:25664021

  11. Evaluation of prostate cancer antigen 3 for detecting prostate cancer: a systematic review and meta-analysis

    PubMed Central

    Cui, Yong; Cao, Wenzhou; Li, Quan; Shen, Hua; Liu, Chao; Deng, Junpeng; Xu, Jiangfeng; Shao, Qiang

    2016-01-01

    Previous studies indicate that prostate cancer antigen 3 (PCA3) is highly expressed in prostatic tumors. However, its clinical value has not been characterized. The aim of this study was to investigate the clinical value of the urine PCA3 test in the diagnosis of prostate cancer by pooling the published data. Clinical trials utilizing the urine PCA3 test for diagnosing prostate cancer were retrieved from PubMed and Embase. A total of 46 clinical trials including 12,295 subjects were included in this meta-analysis. The pooled sensitivity, specificity, positive likelihood ratio (+LR), negative likelihood ratio (−LR), diagnostic odds ratio (DOR) and area under the curve (AUC) were 0.65 (95% confidence interval [CI]: 0.63–0.66), 0.73 (95% CI: 0.72–0.74), 2.23 (95% CI: 1.91–2.62), 0.48 (95% CI: 0.44–0.52), 5.31 (95% CI: 4.19–6.73) and 0.75 (95% CI: 0.74–0.77), respectively. In conclusion, the urine PCA3 test has acceptable sensitivity and specificity for the diagnosis of prostate cancer and can be used as a non-invasive method for that purpose. PMID:27161545

  12. Human papillomavirus type-18 prevalence in oesophageal cancer in the Chinese population: a meta-analysis.

    PubMed

    Guo, L W; Zhang, S K; Liu, S Z; Chen, Q; Zhang, M; Quan, P L; Lu, J B; Sun, X B

    2016-02-01

    Globally, the prevalence of oesophageal cancer cases is particularly high in China. Since 1982, oncogenic human papillomavirus (HPV) has been hypothesized as a risk factor for oesophageal cancer, but no firm evidence of HPV infection in oesophageal cancer has been established to date. We aimed to conduct a meta-analysis to estimate the high-risk HPV-18 prevalence of oesophageal cancer in the Chinese population. Eligible studies published from 1 January 2005 to 12 July 2014 were retrieved via computer searches of English and Chinese literature databases (including Medline, EMBASE, Chinese National Knowledge Infrastructure and Wanfang Data Knowledge Service Platform). A random-effects model was used to calculate pooled prevalence and corresponding 95% confidence intervals (CIs). A total of 2556 oesophageal cancer cases from 19 studies were included in this meta-analysis. Overall, the pooled HPV-18 prevalence in oesophageal cancer cases was 4·1% (95% CI 2·7-5·5) in China, 6·1% (95% CI 2·9-9·3) in fresh or frozen biopsies and 4·0% (95% CI 2·3-5·8) in paraffin-embedded fixed biopsies, 8·2% (95% CI 4·6-11·7) by the E6/E7 region and 2·2% (95% CI 0·9-3·6) by the L1 region of the HPV gene. This meta-analysis indicated that China has a moderate HPV-18 prevalence of oesophageal cancer compared to cervical cancer, although there is variation between different variables. Further studies are needed to elucidate the role of HPV in oesophagus carcinogenesis with careful consideration of study design and laboratory detection method, providing more accurate assessment of HPV status in oesophageal cancer. PMID:26211663

  13. Analysis of trematode parasite communities in fish eye lenses by pyrosequencing of naturally pooled DNA.

    PubMed

    Rellstab, Christian; Louhi, Katja-Riikka; Karvonen, Anssi; Jokela, Jukka

    2011-08-01

    Infections by multiple parasite species are common in nature and have important consequences for between-species interactions and coevolutionary dynamics with the host populations. For example, ecological and evolutionary factors underlying the structure of parasite communities determine the range of hosts a parasite can infect and set the basis for both evolution of host defences and parasite virulence, as well as management of diseases. Studies investigating these factors have been facilitated in the recent past by genetic methods, which surmount difficulties of traditional morphological taxonomy in identifying individual parasite species. Here we take a step further and present a novel methodological approach to analyze parasite communities as a whole. We determined the relative frequencies of interspecific SNP alleles by pyrosequencing naturally pooled samples of closely related Diplostomum spp. trematodes infecting eye lenses of freshwater fish. Pyrosequencing allowed us to use naturally pooled community samples (lenses) to increase the sample size and statistical power, without sequencing single parasite specimens. In a case study, we applied this method to analyze the community structure of the eye flukes across fish host species of a freshwater system in Finland. We found that the fish species harboured significantly different parasite communities and that multiple species infections were common. Our study provides an example of how quantitative pyrosequencing can be used to answer evolutionary and ecological questions in natural communities of parasites. PMID:21554995

  14. Cave Pool

    A pool in the Caverns of Sonora. This cave, like many others, was formed by water combining with carbon dioxide to create a weak carbonic acid. This acid then dissolved the limestone to carve out chambers. The dissolved calcium from the limestone then combined with the carbon dioxide to create calci...

  15. Effects of Different Analysis Strategies on Paired Associative Stimulation. A Pooled Data Analysis from Three Research Labs.

    PubMed

    Lahr, Jacob; Paßmann, Sven; List, Jonathan; Vach, Werner; Flöel, Agnes; Klöppel, Stefan

    2016-01-01

    Paired associative stimulation (PAS) is a widely used transcranial magnetic stimulation (TMS) paradigm to non-invasively induce synaptic plasticity in the human brain in vivo. Altered PAS-induced plasticity has been demonstrated for several diseases. However, researchers are faced with a high inter- and intra-subject variability of the PAS response. Here, we pooled original data from nine PAS studies from three centers and analyzed the combined dataset of 190 healthy subjects with regard to age dependency, the role of stimulation parameters and the effect of different statistical methods. We observed no main effect of the PAS intervention over all studies (F(2;362) = 0.44; p = 0.644). The rate of subjects showing the expected increase of motor evoked potential (MEP) amplitudes was 53%. The PAS effect differed significantly between studies as shown by a significant interaction effect (F(16;362) = 1.77; p = 0.034) but post-hoc testing did not reveal significant effects after correction for multiple tests. There was a trend toward increased variability of the PAS effect in older subjects. Acquisition parameters differed across studies but without systematically influencing changes in MEP-size. The use of post/baseline quotients systematically indicated stronger PAS effects than post/baseline difference or the logarithm of the post/baseline quotient. The non-significant PAS effects across studies and a wide range of responder rates between studies indicate a high variability of this method. We were thus not able to replicate findings from a previous meta-analysis showing robust effects of PAS. No pattern emerged regarding acquisition parameters that at this point could guide future studies to reduce variability and help increase response rate. For future studies, we propose to report the responder rate and recommend the use of the logarithmized post/baseline quotient for further analyses to better address the possibility that results are driven by few extreme cases. PMID:27144307

  16. Effects of Different Analysis Strategies on Paired Associative Stimulation. A Pooled Data Analysis from Three Research Labs

    PubMed Central

    List, Jonathan; Vach, Werner; Flöel, Agnes; Klöppel, Stefan

    2016-01-01

    Paired associative stimulation (PAS) is a widely used transcranial magnetic stimulation (TMS) paradigm to non-invasively induce synaptic plasticity in the human brain in vivo. Altered PAS-induced plasticity has been demonstrated for several diseases. However, researchers are faced with a high inter- and intra-subject variability of the PAS response. Here, we pooled original data from nine PAS studies from three centers and analyzed the combined dataset of 190 healthy subjects with regard to age dependency, the role of stimulation parameters and the effect of different statistical methods. We observed no main effect of the PAS intervention over all studies (F(2;362) = 0.44; p = 0.644). The rate of subjects showing the expected increase of motor evoked potential (MEP) amplitudes was 53%. The PAS effect differed significantly between studies as shown by a significant interaction effect (F(16;362) = 1.77; p = 0.034) but post-hoc testing did not reveal significant effects after correction for multiple tests. There was a trend toward increased variability of the PAS effect in older subjects. Acquisition parameters differed across studies but without systematically influencing changes in MEP-size. The use of post/baseline quotients systematically indicated stronger PAS effects than post/baseline difference or the logarithm of the post/baseline quotient. The non-significant PAS effects across studies and a wide range of responder rates between studies indicate a high variability of this method. We were thus not able to replicate findings from a previous meta-analysis showing robust effects of PAS. No pattern emerged regarding acquisition parameters that at this point could guide future studies to reduce variability and help increase response rate. For future studies, we propose to report the responder rate and recommend the use of the logarithmized post/baseline quotient for further analyses to better address the possibility that results are driven by few extreme cases. PMID:27144307

  17. Pathway and Network Analysis of Cancer Genomes

    PubMed Central

    Haider, Syed; Wu, Guanming; Shibata, Tatsuhiro; Vazquez, Miguel; Mustonen, Ville; Gonzalez-Perez, Abel; Pearson, John; Sander, Chris; Raphael, Benjamin J.; Marks, Debora S.; Ouellette, B.F. Francis; Valencia, Alfonso; Bader, Gary D.; Boutros, Paul C.; Stuart, Joshua M.; Linding, Rune; Lopez-Bigas, Nuria; Stein, Lincoln D.

    2016-01-01

    Genomic information on tumors from 50 cancer types catalogued by The International Cancer Genome Consortium (ICGC) shows that only few well-studied driver genes are frequently mutated, in contrast to many infrequently mutated genes that may also contribute to tumor biology. Hence there has been large interest in developing pathway and network analysis methods that group genes and illuminate the processes involved. We provide an overview of these analysis techniques and show where they guide mechanistic and translational investigations. PMID:26125594

  18. Association among Dietary Flavonoids, Flavonoid Subclasses and Ovarian Cancer Risk: A Meta-Analysis

    PubMed Central

    You, Ruxu; Yang, Yu; Liao, Jing; Chen, Dongsheng; Yu, Lixiu

    2016-01-01

    Background Previous studies have indicated that intake of dietary flavonoids or flavonoid subclasses is associated with the ovarian cancer risk, but presented controversial results. Therefore, we conducted a meta-analysis to derive a more precise estimation of these associations. Methods We performed a search in PubMed, Google Scholar and ISI Web of Science from their inception to April 25, 2015 to select studies on the association among dietary flavonoids, flavonoid subclasses and ovarian cancer risk. The information was extracted by two independent authors. We assessed the heterogeneity, sensitivity, publication bias and quality of the articles. A random-effects model was used to calculate the pooled risk estimates. Results Five cohort studies and seven case-control studies were included in the final meta-analysis. We observed that intake of dietary flavonoids can decrease ovarian cancer risk, which was demonstrated by pooled RR (RR = 0.82, 95% CI = 0.68–0.98). In a subgroup analysis by flavonoid subtypes, the ovarian cancer risk was also decreased for isoflavones (RR = 0.67, 95% CI = 0.50–0.92) and flavonols (RR = 0.68, 95% CI = 0.58–0.80). While there was no compelling evidence that consumption of flavones (RR = 0.86, 95% CI = 0.71–1.03) could decrease ovarian cancer risk, which revealed part sources of heterogeneity. The sensitivity analysis indicated stable results, and no publication bias was observed based on the results of Funnel plot analysis and Egger’s test (p = 0.26). Conclusions This meta-analysis suggested that consumption of dietary flavonoids and subtypes (isoflavones, flavonols) has a protective effect against ovarian cancer with a reduced risk of ovarian cancer except for flavones consumption. Nevertheless, further investigations on a larger population covering more flavonoid subclasses are warranted. PMID:26960146

  19. Incidence of Cancer in ANCA-Associated Vasculitis: A Meta-Analysis of Observational Studies

    PubMed Central

    Shang, Weifeng; Ning, Yong; Xu, Xiu; Li, Menglan; Guo, Shuiming; Han, Min; Zeng, Rui; Ge, Shuwang; Xu, Gang

    2015-01-01

    Objective The purpose of this paper is to examine cancer incidence in patients with ANCA-associated vasculitis (AASV) derived from population-based cohort studies by means of meta-analysis. Methods Relevant electronic databases were searched for studies characterizing the associated risk of overall malignancy in patients with AASV. Standardized incidence rates (SIRs) with 95% confidence intervals (CIs) were used to evaluate the strength of association. We tested for publication bias and heterogeneity and stratified for site-specific cancers. Results Six studies (n = 2,578) were eventually identified, of which six provided the SIR for overall malignancy, five reported the SIR for non-melanoma skin cancer (NMSC), four for leukemia, five for bladder cancer, three for lymphoma, three for liver cancer, four for lung cancer, three for kidney cancer, four for prostate cancer, four for colon cancer and four for breast cancer. Overall, the pooled SIR of cancer in AASV patients was 1.74 (95%CI = 1.37–2.21), with moderate heterogeneity among these studies (I2 = 65.8%, P = 0.012). In sub-analyses for site-specific cancers, NMSC, leukemia and bladder cancer were more frequently observed in patients with AASV with SIR of 5.18 (95%CI = 3.47–7.73), 4.89 (95%CI = 2.93–8.16) and 3.84 (95%CI = 2.72–5.42) respectively. There was no significant increase in the risk of kidney cancer (SIR = 2.12, 95%CI = 0.66–6.85), prostate cancer (SIR = 1.45, 95%CI = 0.87–2.42), colon cancer (SIR = 1.26, 95%CI = 0.70–2.27), and breast cancer (SIR = 0.95, 95%CI = 0.50–1.79). Among these site-specific cancers, only NMSC showed moderate heterogeneity (I2 = 55.8%, P = 0.06). No publication bias was found by using the Begg’s test and Egger's test. Conclusions This meta-analysis shows that AASV patients treatment with cyclophosphamide (CYC) are at increased risk of late-occurring malignancies, particularly of the NMSC, leukemia and bladder cancer. However, there is no significant association between AASV and kidney cancer, prostate cancer, colon cancer and breast cancer. These findings emphasize monitoring and preventative management in AASV patients after cessation of CYC therapy is momentous. PMID:25973882

  20. Mutation Analysis of 18 Nephronophthisis-associated Ciliopathy Disease Genes using a DNA Pooling and Next-Generation Sequencing Strategy

    PubMed Central

    Otto, Edgar A.; Ramaswami, Gokul; Janssen, Sabine; Chaki, Moumita; Allen, Susan J.; Zhou, Weibin; Airik, Rannar; Hurd, Toby W.; Ghosh, Amiya K.; Wolf, Matthias T.; Hoppe, Bernd; Neuhaus, Thomas J.; Bockenhauer, Detlef; Milford, David V.; Soliman, Neveen A.; Saunier, Sophie; Johnson, Colin A.; Hildebrandt, Friedhelm

    2014-01-01

    Background Nephronophthisis-associated ciliopathies (NPHP-AC) comprise a group of autosomal recessive cystic kidney diseases that includes nephronophthisis (NPHP), Senior-Loken syndrome (SLS), Joubert syndrome (JBTS), and Meckel-Gruber syndrome (MKS). To date, causative mutations in NPHP-AC have been described for 18 different genes, rendering mutation analysis tedious and expensive. To overcome the broad genetic locus heterogeneity we devised a strategy of DNA pooling with consecutive massively parallel resequencing (MPR). Methods In 120 patients with severe NPHP-AC phenotypes we prepared 5 pools of genomic DNA with 24 patients each which were used as templates in order to PCR-amplify all 376 exons of 18 NPHP-AC genes (NPHP1, INVS, NPHP3, NPHP4, IQCB1, CEP290, GLIS2, RPGRIP1L, NEK8, TMEM67, INPP5E, TMEM216, AHI1, ARL13B, CC2D2A, TTC21B, MKS1, and XPNPEP3). PCR products were then subjected to MPR on a Illumina Genome-Analyzer and mutations were subsequently assigned to their respective mutation carrier via CEL I endonuclease-based heteroduplex screening and confirmed by Sanger sequencing. Results For proof of principle we used DNA from patients with known mutations and demonstrated the detection of 22 out of 24 different alleles (92% sensitivity). MPR led to the molecular diagnosis in 30/120 patients (25%) and we identified 54 pathogenic mutations (27 novel) in 7 different NPHP-AC genes. Additionally, in 24 patients we only found single heterozygous variants of unknown significance. Conclusions The combined approach of DNA pooling followed by MPR strongly facilitates mutation analysis in broadly heterogeneous single-gene disorders. The lack of mutations in 75% of patients in our cohort indicates further extensive heterogeneity in NPHP-AC. PMID:21068128

  1. 'Chain pooling' model selection as developed for the statistical analysis of a rotor burst protection experiment

    NASA Technical Reports Server (NTRS)

    Holms, A. G.

    1977-01-01

    A statistical decision procedure called chain pooling had been developed for model selection in fitting the results of a two-level fixed-effects full or fractional factorial experiment not having replication. The basic strategy included the use of one nominal level of significance for a preliminary test and a second nominal level of significance for the final test. The subject has been reexamined from the point of view of using as many as three successive statistical model deletion procedures in fitting the results of a single experiment. The investigation consisted of random number studies intended to simulate the results of a proposed aircraft turbine-engine rotor-burst-protection experiment. As a conservative approach, population model coefficients were chosen to represent a saturated 2 to the 4th power experiment with a distribution of parameter values unfavorable to the decision procedures. Three model selection strategies were developed.

  2. Plasma effect on weld pool surface reconstruction by shape-from-polarization analysis

    SciTech Connect

    Coniglio, N.; Mathieu, A.

    2014-03-31

    The polarimetric state of the thermal radiations emitted by the weld metal contains geometric information about the emitting surface. Even though the analysed thermal radiation has a wavelength corresponding to a blind spectral window of the arc plasma, the physical presence of the arc plasma itself interferes with the rays radiated by the weld pool surface before attaining the polarimeter, thus modifying the geometric information transported by the ray. In the present work, the effect of the arc plasma-surrounding zone on the polarimetric state and propagation direction of the radiated ray is analyzed. The interaction with the arc plasma zone induces a drop in ray intensity and a refraction of ray optical path.

  3. Analysis of gravity anomaly over coral-reef oil field: Wilfred Pool, Sullivan County, Indiana

    SciTech Connect

    Dana, S.W.

    1980-03-01

    To compare the measured and theoretical gravity anomaly of a typical coral-reef oil field, data were collected from the wilfred Pool, Sullivan County, Indiana. Densities of available core samples from the field were determined and the anomaly was calculated, taking into account the lateral and vertical variation of density and the geologic structure known from core studies and drilling-log records of lithologic types penetrated by the wells. Comparison of the theoretical and actual anomalies indicated a rough correspondence except for several sharp negative anomalies on the flanks of the measured gravity anomaly. Further studies indicated that the negative anomalies are possibly due to fluvial erosion that produced, on the surface of the youngest Pennsylvanian sediments, channels which were later filled with glacial till of lower density than the sediments. 13 figures.

  4. Analysis of the pool critical assembly pressure vessel benchmark using pentran

    SciTech Connect

    Edgar, C. A.; Sjoden, G. E.

    2012-07-01

    The internationally circulated Pool Critical Assembly (PCA) Pressure Vessel Benchmark was analyzed using the PENTRAN Parallel Sn code system for the geometry, material, and source specifications as described in the PCA Benchmark documentation. This research focused on utilizing the BUGLE-96 cross section library and accompanying reaction rates, while examining both adaptive differencing on a coarse mesh basis as well as Directional Theta Weighted Sn differencing in order to compare the calculated PENTRAN results to measured data. The results show good comparison with the measured data as well as to the calculated results provided from TORT for the BUGLE-96 cross sections and reaction rates, which suggests PENTRAN is a viable and reliable code system for calculation of light water reactor neutron shielding and dosimetry calculations. (authors)

  5. Prognostic role of microRNA-25 in cancers: evidence from a meta-analysis

    PubMed Central

    Qu, Jingjing; Li, Min; Zhong, Wen; Hu, Chengping

    2015-01-01

    Background: miRNAs have been participated in human carcinogenesis as tumor oncogenes or suppressors, and have a prognostic significant for patients with cancers. In recent years, miR-25 was found associated with clinical value of cancerous patients. Meanwhile the miR-25 showed a different expression in related studies. Therefore, we summarize the results from a variety of studies using a meta-analysis, in order to explain the prognostic value of miR-25 in many human cancers. Methods: The articles were retrieved from the on-line databases, PubMed, EMBASE and CNKI. We extracted and estimated the hazard ratios (HRs) for overall survival (OS), which compared the high and low expression levels of miR-25 in patients with a different of cancers. Pooled HRs and 95% confidence intervals (CIs) were calculated. Results: Eight studies of 868 patients were selected into the final meta-analysis after a strict filtering and qualifying process. Fixed model or random model method was chosen depending on the heterogeneity between the studies. For OS, higher miR-25 expression could significantly predict worse outcome with the pooled HR of 2.434 (95% CI 1.330-3.539, P=0.000). The subgroup analysis showed that high expressed miR-25 could worsen OS in Chinese patients with pooled HR of 1.895 (95% CI 1.096-2.693, P=0.007). The sensitive analysis showed that removing the document one by one, there no obvious change of HR of 0.823 (95% CI 0.385-1.260). No bias existed in the group. Conclusion: Our study indicates that high expression level of miR-25 corresponds with poor survival in cancerous patients, and the expression of miR-25 could be a promising prognostic biomarker in the future. PMID:26550209

  6. Association between S100B Levels and Long-Term Outcome after Aneurysmal Subarachnoid Hemorrhage: Systematic Review and Pooled Analysis

    PubMed Central

    Lai, Pui Man Rosalind; Du, Rose

    2016-01-01

    S100 calcium binding protein B (S100B), a well-studied marker for neurologic injury, has been suggested as a candidate for predicting outcome after subarachnoid hemorrhage. We performed a pooled analysis summarizing the associations between S100B protein in serum and cerebrospinal fluid (CSF) with radiographic vasospasm, delayed ischemic neurologic deficit (DIND), delayed cerebral infarction, and Glasgow Outcome Scale (GOS) outcome. A literature search using PubMed, the Cochrane Library, and the EMBASE databases was performed to identify relevant studies published up to May 2015. The weighted Stouffer’s Z method was used to perform a pooled analysis of outcome measures with greater than three studies. A total of 13 studies were included in this review. Higher serum S100B level was found to be associated with cerebral infarction as diagnosed by CT (padj = 3.1 x 10−4) and worse GOS outcome (padj = 5.5 x 10−11). There was no association found between serum and CSF S100B with radiographic vasospasm or DIND. S100B is a potential prognostic marker for aSAH outcome. PMID:27007976

  7. Pooling and Analysis of Published in Vitro Data: A Proof of Concept Study for the Grouping of Nanoparticles.

    PubMed

    Simkó, Myrtill; Tischler, Sonja; Mattsson, Mats-Olof

    2015-01-01

    The study aim was to test the applicability of pooling of nanomaterials-induced in vitro data for identifying the toxic capacity of specific (SiO₂, TiO₂, ZnO, CuO, CeO₂ and carbon nanotubes, [CNT]) nanoparticles (NP) and to test the usefulness for grouping purposes. Publication selection was based on specific criteria regarding experimental conditions. Two relevant biological endpoints were selected; generation of intracellular reactive oxygen species (ROS) and viability above 90%. The correlations of the ROS ratios with the NP parameters' size, concentration, and exposure time were analysed. The obtained data sets were then analysed with multiple regression analysis of variance (ANOVA) and the Tukey post-hoc test. The results show that this method is applicable for the selected metal oxide NP, but might need reconsideration and a larger data set for CNT. Several statistically significant correlations and results were obtained, thus validating the method. Furthermore, the relevance of the combination of ROS release with a cell viability test was shown. The data also show that it is advisable to compare ROS production of professional phagocytic with non-phagocytic cells. In conclusion, this is the first systematic analysis showing that pooling of available data into groups is a useful method for evaluation of data regarding NP induced toxicity in vitro. PMID:26540047

  8. Pooling and Analysis of Published in Vitro Data: A Proof of Concept Study for the Grouping of Nanoparticles

    PubMed Central

    Simkó, Myrtill; Tischler, Sonja; Mattsson, Mats-Olof

    2015-01-01

    The study aim was to test the applicability of pooling of nanomaterials-induced in vitro data for identifying the toxic capacity of specific (SiO2, TiO2, ZnO, CuO, CeO2 and carbon nanotubes, [CNT]) nanoparticles (NP) and to test the usefulness for grouping purposes. Publication selection was based on specific criteria regarding experimental conditions. Two relevant biological endpoints were selected; generation of intracellular reactive oxygen species (ROS) and viability above 90%. The correlations of the ROS ratios with the NP parameters’ size, concentration, and exposure time were analysed. The obtained data sets were then analysed with multiple regression analysis of variance (ANOVA) and the Tukey post-hoc test. The results show that this method is applicable for the selected metal oxide NP, but might need reconsideration and a larger data set for CNT. Several statistically significant correlations and results were obtained, thus validating the method. Furthermore, the relevance of the combination of ROS release with a cell viability test was shown. The data also show that it is advisable to compare ROS production of professional phagocytic with non-phagocytic cells. In conclusion, this is the first systematic analysis showing that pooling of available data into groups is a useful method for evaluation of data regarding NP induced toxicity in vitro. PMID:26540047

  9. Two chemically distinct light-absorbing pools of urban organic aerosols: A comprehensive multidimensional analysis of trends.

    PubMed

    Paula, Andreia S; Matos, João T V; Duarte, Regina M B O; Duarte, Armando C

    2016-02-01

    The chemical and light-absorption dynamics of organic aerosols (OAs), a master variable in the atmosphere, have yet to be resolved. This study uses a comprehensive multidimensional analysis approach for exploiting simultaneously the compositional changes over a molecular size continuum and associated light-absorption (ultraviolet absorbance and fluorescence) properties of two chemically distinct pools of urban OAs chromophores. Up to 45% of aerosol organic carbon (OC) is soluble in water and consists of a complex mixture of fluorescent and UV-absorbing constituents, with diverse relative abundances, hydrophobic, and molecular weight (Mw) characteristics between warm and cold periods. In contrast, the refractory alkaline-soluble OC pool (up to 18%) is represented along a similar Mw and light-absorption continuum throughout the different seasons. Results suggest that these alkaline-soluble chromophores may actually originate from primary OAs sources in the urban site. This work shows that the comprehensive multidimensional analysis method is a powerful and complementary tool for the characterization of OAs fractions. The great diversity in the chemical composition and optical properties of OAs chromophores, including both water-soluble and alkaline-soluble OC, may be an important contribution to explain the contrasting photo-reactivity and atmospheric behavior of OAs. PMID:26688258

  10. Prognostic Value of SPARC in Patients with Pancreatic Cancer: A Systematic Review and Meta-Analysis

    PubMed Central

    Chen, Min-bin; Lu, Rong-zhu; Wang, Hua-bing; Yu, Min; Shi, Chun-tao; Ding, Hou-zhong

    2016-01-01

    Objective There is a heated debate on whether the prognostic value of SPARC is favorable or unfavorable. Thus, we carried out a meta-analysis evaluating the relationship between SPARC expression and the prognosis of patients with pancreatic cancer. Methods We searched PubMed, EMBASE and Web of Science for relevant articles. The pooled hazard ratios (HRs) and corresponding 95%CI of overall survival (OS) were calculated to evaluate the prognostic value of SPARC expression in patients with pancreatic cancer. We also performed subgroup analyses. Results With 1623 patients pooled from 10 available studies, the incorporative HR showed an unfavorable prognosis of patients with pancreatic cancer in the multivariate analysis (HR = 1.55, 95%CI: 1.11–2.17, P = 0.01), but not in univariate analysis (HR = 1.41, 95%CI: 0.47–4.21, P = 0.54) and estimate (HR = 1.24, 95%CI: 0.72–2.13, P = 0.44). And this adverse impact could also be found in the subgroup analyses in multivariate analysis, especially in the stroma (HR = 1.53, 95%CI: 1.05–2.24, P = 0.03). However, the combined HR had the highly significant heterogeneity. No obvious publication bias was found. Conclusions SPARC might be an unfavorable indicator in patients with pancreatic cancer, especially in the stroma. More and further researches should be conducted to reveal the prognostic value of SPARC. PMID:26731428

  11. Work stress and risk of cancer: meta-analysis of 5700 incident cancer events in 116 000 European men and women

    PubMed Central

    Nyberg, Solja T; Theorell, Töres; Fransson, Eleonor I; Alfredsson, Lars; Bjorner, Jakob B; Bonenfant, Sébastien; Borritz, Marianne; Bouillon, Kim; Burr, Herman; Dragano, Nico; Geuskens, Goedele A; Goldberg, Marcel; Hamer, Mark; Hooftman, Wendela E; Houtman, Irene L; Joensuu, Matti; Knutsson, Anders; Koskenvuo, Markku; Koskinen, Aki; Kouvonen, Anne; Madsen, Ida E H; Magnusson Hanson, Linda L; Marmot, Michael G; Nielsen, Martin L; Nordin, Maria; Oksanen, Tuula; Pentti, Jaana; Salo, Paula; Rugulies, Reiner; Steptoe, Andrew; Suominen, Sakari; Vahtera, Jussi; Virtanen, Marianna; Väänänen, Ari; Westerholm, Peter; Westerlund, Hugo; Zins, Marie; Ferrie, Jane E; Singh-Manoux, Archana; Batty, G David; Kivimäki, Mika

    2013-01-01

    Objective To investigate whether work related stress, measured and defined as job strain, is associated with the overall risk of cancer and the risk of colorectal, lung, breast, or prostate cancers. Design Meta-analysis of pooled prospective individual participant data from 12 European cohort studies including 116 056 men and women aged 17-70 who were free from cancer at study baseline and were followed-up for a median of 12 years. Work stress was measured and defined as job strain, which was self reported at baseline. Incident cancers (all n=5765, colorectal cancer n=522, lung cancer n=374, breast cancer n=1010, prostate cancer n=865) were ascertained from cancer, hospital admission, and death registers. Data were analysed in each study with Cox regression and the study specific estimates pooled in meta-analyses. Models were adjusted for age, sex, socioeconomic position, body mass index (BMI), smoking, and alcohol intake Results A harmonised measure of work stress, high job strain, was not associated with overall risk of cancer (hazard ratio 0.97, 95% confidence interval 0.90 to 1.04) in the multivariable adjusted analyses. Similarly, no association was observed between job strain and the risk of colorectal (1.16, 0.90 to 1.48), lung (1.17, 0.88 to 1.54), breast (0.97, 0.82 to 1.14), or prostate (0.86, 0.68 to 1.09) cancers. There was no clear evidence for an association between the categories of job strain and the risk of cancer. Conclusions These findings suggest that work related stress, measured and defined as job strain, at baseline is unlikely to be an important risk factor for colorectal, lung, breast, or prostate cancers. PMID:23393080

  12. Myeloperoxidase Polymorphism, Menopausal Status, and Breast Cancer Risk: An Update Meta-Analysis

    PubMed Central

    Peng, Qi-Liu; Huang, Xiu-Li; Mo, Cui-Ju; Li, Shan; Zhao, Jin-Min

    2013-01-01

    Myeloperoxidase (MPO) is a metabolic/oxidative lysosomal enzyme secreted by reactive neutrophils at the sites of inflamed organs and tissues during phagocytosis. MPO has been either directly or indirectly linked to neoplasia, which is a well-established risk factor for many types of cancer. A large number of studies have reported the role of MPO G-463A polymorphism regarding breast-cancer risk. However, the published findings are inconsistent. Therefore, we conducted a meta-analysis to determine more precise estimations for the relationship. Eligible studies were identified by searching several electronic databases for relevant reports published before June 2012. According to the inclusion criteria and exclusion criteria, a total of five eligible studies were included in the pooled analyses. When the five eligible studies concerning MPO G-463A polymorphism were pooled into this meta-analysis, there was no evidence found for a significant association between MPO G-463A polymorphism and breast-cancer risk in any genetic model. We also categorized by ethnicity (Caucasian or Asian) for subgroup analysis; according to this subgroup analysis, we found no significant association between MPO G-463A polymorphism and breast-cancer risk in any genetic model. However, in the stratified analysis for the premenopausal group, women carrying the AA genotype were found to have a significantly reduced risk (OR = 0.56, 95% CI 0.34–0.94, p = 0.027). Under the recessive model, there was a significant association between MPO G-463A polymorphism and breast-cancer risk (OR = 0.57, 95% CI 0.34–0.93, p = 0.025). We conclude that MPO-G463A polymorphism might not be a good predictor of breast-cancer risk, though menopausal status modified women’s risk of developing breast cancer. PMID:23991124

  13. Distinct Biochemical Pools of Golgi Phosphoprotein 3 in the Human Breast Cancer Cell Lines MCF7 and MDA-MB-231.

    PubMed

    Tenorio, María J; Ross, Breyan H; Luchsinger, Charlotte; Rivera-Dictter, Andrés; Arriagada, Cecilia; Acuña, Diego; Aguilar, Marcelo; Cavieres, Viviana; Burgos, Patricia V; Ehrenfeld, Pamela; Mardones, Gonzalo A

    2016-01-01

    Golgi phosphoprotein 3 (GOLPH3) has been implicated in the development of carcinomas in many human tissues, and is currently considered a bona fide oncoprotein. Importantly, several tumor types show overexpression of GOLPH3, which is associated with tumor progress and poor prognosis. However, the underlying molecular mechanisms that connect GOLPH3 function with tumorigenicity are poorly understood. Experimental evidence shows that depletion of GOLPH3 abolishes transformation and proliferation of tumor cells in GOLPH3-overexpressing cell lines. Conversely, GOLPH3 overexpression drives transformation of primary cell lines and enhances mouse xenograft tumor growth in vivo. This evidence suggests that overexpression of GOLPH3 could result in distinct features of GOLPH3 in tumor cells compared to that of non-tumorigenic cells. GOLPH3 is a peripheral membrane protein mostly localized at the trans-Golgi network, and its association with Golgi membranes depends on binding to phosphatidylinositol-4-phosphate. GOLPH3 is also contained in a large cytosolic pool that rapidly exchanges with Golgi-associated pools. GOLPH3 has also been observed associated with vesicles and tubules arising from the Golgi, as well as other cellular compartments, and hence it has been implicated in several membrane trafficking events. Whether these and other features are typical to all different types of cells is unknown. Moreover, it remains undetermined how GOLPH3 acts as an oncoprotein at the Golgi. Therefore, to better understand the roles of GOLPH3 in cancer cells, we sought to compare some of its biochemical and cellular properties in the human breast cancer cell lines MCF7 and MDA-MB-231 with that of the non-tumorigenic breast human cell line MCF 10A. We found unexpected differences that support the notion that in different cancer cells, overexpression of GOLPH3 functions in diverse fashions, which may influence specific tumorigenic phenotypes. PMID:27123979

  14. Distinct Biochemical Pools of Golgi Phosphoprotein 3 in the Human Breast Cancer Cell Lines MCF7 and MDA-MB-231

    PubMed Central

    Luchsinger, Charlotte; Rivera-Dictter, Andrés; Arriagada, Cecilia; Acuña, Diego; Aguilar, Marcelo; Cavieres, Viviana; Burgos, Patricia V.; Ehrenfeld, Pamela; Mardones, Gonzalo A.

    2016-01-01

    Golgi phosphoprotein 3 (GOLPH3) has been implicated in the development of carcinomas in many human tissues, and is currently considered a bona fide oncoprotein. Importantly, several tumor types show overexpression of GOLPH3, which is associated with tumor progress and poor prognosis. However, the underlying molecular mechanisms that connect GOLPH3 function with tumorigenicity are poorly understood. Experimental evidence shows that depletion of GOLPH3 abolishes transformation and proliferation of tumor cells in GOLPH3-overexpressing cell lines. Conversely, GOLPH3 overexpression drives transformation of primary cell lines and enhances mouse xenograft tumor growth in vivo. This evidence suggests that overexpression of GOLPH3 could result in distinct features of GOLPH3 in tumor cells compared to that of non-tumorigenic cells. GOLPH3 is a peripheral membrane protein mostly localized at the trans-Golgi network, and its association with Golgi membranes depends on binding to phosphatidylinositol-4-phosphate. GOLPH3 is also contained in a large cytosolic pool that rapidly exchanges with Golgi-associated pools. GOLPH3 has also been observed associated with vesicles and tubules arising from the Golgi, as well as other cellular compartments, and hence it has been implicated in several membrane trafficking events. Whether these and other features are typical to all different types of cells is unknown. Moreover, it remains undetermined how GOLPH3 acts as an oncoprotein at the Golgi. Therefore, to better understand the roles of GOLPH3 in cancer cells, we sought to compare some of its biochemical and cellular properties in the human breast cancer cell lines MCF7 and MDA-MB-231 with that of the non-tumorigenic breast human cell line MCF 10A. We found unexpected differences that support the notion that in different cancer cells, overexpression of GOLPH3 functions in diverse fashions, which may influence specific tumorigenic phenotypes. PMID:27123979

  15. Prognostic significance of miR-126 in various cancers: a meta-analysis

    PubMed Central

    Dong, Yuanli; Fu, Chengrui; Guan, Hui; Zhang, Zicheng; Zhou, Tao; Li, Baosheng

    2016-01-01

    Objective Recent studies have demonstrated that microRNA-126 (miR-126) might be a promising prognostic factor for cancer patients. This meta-analysis was conducted to assess the effectiveness of miR-126 as a prognostic biomarker for various cancers. Methods The search of studies was performed by using PubMed and Embase until January 22, 2016. Pooled hazard ratio (HR) with 95% confidence interval (CI) for patients’ survival was calculated. A fixed-effect or random-effects model was applied according to heterogeneity. The trim and fill method was used to adjust pooled HR. Results In all 17 articles comprising of 2,437 participants were included in this meta-analysis. The results indicated that a high level of miR-126 played a favorable role in the overall survival (HR 0.70, 95% CI: 0.62–0.79, random-effects model), with a heterogeneity measure index of I2=63.2% (P<0.01). Subgroup analyses showed that pooled HR was more significant in patients with digestive system cancers (HR 0.70, 95% CI: 0.59–0.83, fixed-effects model) and respiratory system cancers (HR 0.71, 95% CI: 0.59–0.85, random-effects model). Owing to publication bias, HR was adjusted to 0.59 (0.463–0.752, P<0.01) by the trim and fill method. Conclusion miR-126 could be a promising biomarker for cancer prognosis prediction, especially in patients with digestive or respiratory system cancers.

  16. BAC-pool sequencing and analysis of large segments of A12 and D12 homoeologous chromosomes in upland cotton.

    PubMed

    Buyyarapu, Ramesh; Kantety, Ramesh V; Yu, John Z; Xu, Zhanyou; Kohel, Russell J; Percy, Richard G; Macmil, Simone; Wiley, Graham B; Roe, Bruce A; Sharma, Govind C

    2013-01-01

    Although new and emerging next-generation sequencing (NGS) technologies have reduced sequencing costs significantly, much work remains to implement them for de novo sequencing of complex and highly repetitive genomes such as the tetraploid genome of Upland cotton (Gossypium hirsutum L.). Herein we report the results from implementing a novel, hybrid Sanger/454-based BAC-pool sequencing strategy using minimum tiling path (MTP) BACs from Ctg-3301 and Ctg-465, two large genomic segments in A12 and D12 homoeologous chromosomes (Ctg). To enable generation of longer contig sequences in assembly, we implemented a hybrid assembly method to process ~35x data from 454 technology and 2.8-3x data from Sanger method. Hybrid assemblies offered higher sequence coverage and better sequence assemblies. Homology studies revealed the presence of retrotransposon regions like Copia and Gypsy elements in these contigs and also helped in identifying new genomic SSRs. Unigenes were anchored to the sequences in Ctg-3301 and Ctg-465 to support the physical map. Gene density, gene structure and protein sequence information derived from protein prediction programs were used to obtain the functional annotation of these genes. Comparative analysis of both contigs with Arabidopsis genome exhibited synteny and microcollinearity with a conserved gene order in both genomes. This study provides insight about use of MTP-based BAC-pool sequencing approach for sequencing complex polyploid genomes with limited constraints in generating better sequence assemblies to build reference scaffold sequences. Combining the utilities of MTP-based BAC-pool sequencing with current longer and short read NGS technologies in multiplexed format would provide a new direction to cost-effectively and precisely sequence complex plant genomes. PMID:24116150

  17. BAC-Pool Sequencing and Analysis of Large Segments of A12 and D12 Homoeologous Chromosomes in Upland Cotton

    PubMed Central

    Buyyarapu, Ramesh; Kantety, Ramesh V.; Yu, John Z.; Xu, Zhanyou; Kohel, Russell J.; Percy, Richard G.; Macmil, Simone; Wiley, Graham B.; Roe, Bruce A.; Sharma, Govind C.

    2013-01-01

    Although new and emerging next-generation sequencing (NGS) technologies have reduced sequencing costs significantly, much work remains to implement them for de novo sequencing of complex and highly repetitive genomes such as the tetraploid genome of Upland cotton (Gossypium hirsutum L.). Herein we report the results from implementing a novel, hybrid Sanger/454-based BAC-pool sequencing strategy using minimum tiling path (MTP) BACs from Ctg-3301 and Ctg-465, two large genomic segments in A12 and D12 homoeologous chromosomes (Ctg). To enable generation of longer contig sequences in assembly, we implemented a hybrid assembly method to process ~35x data from 454 technology and 2.8-3x data from Sanger method. Hybrid assemblies offered higher sequence coverage and better sequence assemblies. Homology studies revealed the presence of retrotransposon regions like Copia and Gypsy elements in these contigs and also helped in identifying new genomic SSRs. Unigenes were anchored to the sequences in Ctg-3301 and Ctg-465 to support the physical map. Gene density, gene structure and protein sequence information derived from protein prediction programs were used to obtain the functional annotation of these genes. Comparative analysis of both contigs with Arabidopsis genome exhibited synteny and microcollinearity with a conserved gene order in both genomes. This study provides insight about use of MTP-based BAC-pool sequencing approach for sequencing complex polyploid genomes with limited constraints in generating better sequence assemblies to build reference scaffold sequences. Combining the utilities of MTP-based BAC-pool sequencing with current longer and short read NGS technologies in multiplexed format would provide a new direction to cost-effectively and precisely sequence complex plant genomes. PMID:24116150

  18. A two-generation analysis of pollen pool genetic structure in flowering dogwood, Cornus florida (Cornaceae), in the Missouri Ozarks.

    PubMed

    Sork, Victoria L; Smouse, Peter E; Apsit, Victoria J; Dyer, Rodney J; Westfall, Robert D

    2005-02-01

    Anthropogenic landscape change can disrupt gene flow. As part of the Missouri Ozark Forest Ecosystem Project, this study examined whether silvicultural practices influence pollen-mediated gene movement in the insect-pollinated species, Cornus florida L., by comparing pollen pool structure (Φ(st)) among clear-cutting, selective cutting, and uncut regimes with the expectation that pollen movement should be least in the uncut regime. Using a sample of 1500 seedlings-10 each from 150 seed parents (43 in clear-cut, 74 in selective, and 33 in control sites) from six sites (each ranging from 266 to 527 ha), eight allozyme loci were analyzed with a pollen pool structure approach known as TwoGener (Smouse et al., 2001; Evolution 55: 260-271). This analysis revealed that pollen pool structure was less in clear-cut (Φ(C) = 0.090, P < 0.001) than in uncut areas (Φ(U) = 0.174, P < 0.001), with selective-cut intermediate (Φ(S) = 0.125, P < 0.001). These estimates translate into more effective pollen donors (N(ep)) in clear-cut (N(ep) = 5.56) and selective-cut (N(ep) = 4.00) areas than in uncut areas (N(ep) = 2.87). We demonstrate that Φ(C) ≤ Φ(S) ≤ Φ(U), with Φ(C) significantly smaller than Φ(U) (P < 0.034). The findings imply that, as long as a sufficiently large number of seed parents remain to provide adequate reproduction and to avoid a genetic bottleneck in the effective number of mothers, silvicultural management may not negatively affect the effective number of pollen parents, and hence subsequent genetic diversity in Cornus florida. PMID:21652403

  19. ATM rs189037 (G>A) polymorphism and risk of lung cancer and head and neck cancer: A meta-analysis

    PubMed Central

    Bhowmik, Aditi; Nath, Sayantan; Das, Sambuddha; Ghosh, Sankar Kumar; Choudhury, Yashmin

    2015-01-01

    A number of different epidemiological studies have measured the association between the risk of different cancers and polymorphism at promoter region of 5? untranslated region (5?-UTR) of the Ataxia-telangiectasia mutated (ATM) gene. However the results were contentious rather than conclusive. The current study was aimed at evaluating the association between the SNP (rs189037 G>A) and the risk of head and neck cancer and lung cancer by conducting a meta-analysis. A total of 9 casecontrol studies were considered for this quantitative analysis. Stats Direct Statistical software (version 2.7.2) was used to evaluate the crude odds ratio (OR) with their 95% confidence interval (CI). The dominant model (GG vs. GA+AA) showed no heterogeneity and the fixed effects pooled OR was found to be significant (OR=1.14, 95% CI=1.051.25) at p=0.003. The pooled OR for fixed effects of heterozygote and homozygote mutant allele (GA vs. AA) model was significant (OR=1.17, 95% CI=1.041.30, p=0.006) and no heterogeneity was observed for this model. The current meta-analysis manifested that ATM rs189037 G>A genetic polymorphism may contribute increased risk of head and neck and lung cancer. Moreover, the AA mutant allele was found to be related significantly with the prognosis of lung cancer and head and neck cancer. PMID:26504743

  20. XELOX vs. FOLFOX in metastatic colorectal cancer: An updated meta-analysis.

    PubMed

    Guo, Yu; Xiong, Bing-Hong; Zhang, Tao; Cheng, Yong; Ma, Li

    2016-02-01

    This meta-analysis aims to evaluate chemotherapy with XELOX (capecitabine plus oxaliplatin) versus FOLFOX (fluorouracil plus oxaliplatin) as a treatment for metastatic colorectal cancer (mCRC) in terms of efficacy and safety. Only randomized controlled trials (RCTs) comparing XELOX versus FOLFOX were included. A total of 4,363 patients from eight RCTs were available for analysis. Pooled analysis revealed that there were no statistical differences between both arms in OS, and ORR. XELOX arm had a higher incidence of thrombocytopenia, hand-foot syndrome, and diarrhea, whereas neutropenia had a higher incidence in the FOLFOX group. For mCRC, the effect of XELOX is similar to FOLFOX. PMID:26864862

  1. Self-reported history of infections and the risk of non-Hodgkin lymphoma: an InterLymph pooled analysis.

    PubMed

    Becker, Nikolaus; Falster, Michael O; Vajdic, Claire M; de Sanjose, Silvia; Martínez-Maza, Otoniel; Bracci, Paige M; Melbye, Mads; Smedby, Karin Ekström; Engels, Eric A; Turner, Jennifer; Vineis, Paolo; Costantini, Adele Seniori; Holly, Elizabeth A; Spinelli, John J; La Vecchia, Carlo; Zheng, Tongzhang; Chiu, Brian C-H; Montella, Maurizio; Cocco, Pierluigi; Maynadié, Marc; Foretova, Lenka; Staines, Anthony; Brennan, Paul; Davis, Scott; Severson, Richard; Cerhan, James R; Breen, Elizabeth C; Birmann, Brenda; Cozen, Wendy; Grulich, Andrew E; Newton, Robert

    2012-11-15

    We performed a pooled analysis of data on self-reported history of infections in relation to the risk of non-Hodgkin lymphoma (NHL) from 17 case-control studies that included 12,585 cases and 15,416 controls aged 16-96 years at recruitment. Pooled odds ratios (OR) and 95% confidence intervals (95% CI) were estimated in two-stage random-effect or joint fixed-effect models, adjusting for age, sex and study centre. Data from the 2 years before diagnosis (or date of interview for controls) were excluded. A self-reported history of infectious mononucleosis was associated with an excess risk of NHL (OR = 1.26, 95% CI = 1.01-1.57 based on data from 16 studies); study-specific results indicate significant (I(2) = 51%, p = 0.01) heterogeneity. A self-reported history of measles or whooping cough was associated with an approximate 15% reduction in risk. History of other infection was not associated with NHL. We find little clear evidence of an association between NHL risk and infection although the limitations of data based on self-reported medical history (particularly of childhood illness reported by older people) are well recognized. PMID:22266776

  2. Autoimmune disorders and risk of non-Hodgkin lymphoma subtypes: a pooled analysis within the InterLymph Consortium

    PubMed Central

    Vajdic, Claire M.; Falster, Michael; Engels, Eric A.; Martínez-Maza, Otoniel; Turner, Jennifer; Hjalgrim, Henrik; Vineis, Paolo; Seniori Costantini, Adele; Bracci, Paige M.; Holly, Elizabeth A.; Willett, Eleanor; Spinelli, John J.; La Vecchia, Carlo; Zheng, Tongzhang; Becker, Nikolaus; De Sanjosé, Silvia; Chiu, Brian C.-H.; Dal Maso, Luigino; Cocco, Pierluigi; Maynadié, Marc; Foretova, Lenka; Staines, Anthony; Brennan, Paul; Davis, Scott; Severson, Richard; Cerhan, James R.; Breen, Elizabeth C.; Birmann, Brenda; Grulich, Andrew E.; Cozen, Wendy

    2008-01-01

    Some autoimmune disorders are increasingly recognized as risk factors for non-Hodgkin lymphoma (NHL) overall, but large-scale systematic assessments of risk of NHL subtypes are lacking. We performed a pooled analysis of self-reported autoimmune conditions and risk of NHL and subtypes, including 29 423 participants in 12 case-control studies. We computed pooled odds ratios (OR) and 95% confidence intervals (CI) in a joint fixed-effects model. Sjögren syndrome was associated with a 6.5-fold increased risk of NHL, a 1000-fold increased risk of parotid gland marginal zone lymphoma (OR = 996; 95% CI, 216-4596), and with diffuse large B-cell and follicular lymphomas. Systemic lupus erythematosus was associated with a 2.7-fold increased risk of NHL and with diffuse large B-cell and marginal zone lymphomas. Hemolytic anemia was associated with diffuse large B-cell NHL. T-cell NHL risk was increased for patients with celiac disease and psoriasis. Results for rheumatoid arthritis were heterogeneous between studies. Inflammatory bowel disorders, type 1 diabetes, sarcoidosis, pernicious anemia, and multiple sclerosis were not associated with risk of NHL or subtypes. Thus, specific autoimmune disorders are associated with NHL risk beyond the development of rare NHL subtypes in affected organs. The pattern of associations with NHL subtypes may harbor clues to lymphomagenesis. PMID:18263783

  3. Follicular dendritic cell sarcoma of the head and neck: Case report, literature review, and pooled analysis of 97 cases

    PubMed Central

    Pang, John; Mydlarz, Wojciech K.; Gooi, Zhen; Waters, Kevin M.; Bishop, Justin; Sciubba, James J.; Kim, Young J.; Fakhry, Carole

    2015-01-01

    Background Follicular dendritic cell sarcoma (FDCS) is a rare lymphoid neoplasm presenting in the head and neck. There are no pooled analyses of head and neck FDCS cases in the English language literature. Methods A MEDLINE and PubMed review of cases from 1978 to February 2014 was performed. Demographics, clinicopathologic data, and outcomes were summarized. Results We presented 2 patients and analyzed 97 cases. The mean age was 42.7 years (SD = 16.3 years). Outcomes were available for 76 patients. Tumors ≤4 cm had better disease-free survival (63% vs 28% at 5 years; p = .0282). Locoregional recurrence was significantly less likely with surgery and radiation compared to surgery alone (15% vs 45%; p = .019) and in patients receiving a neck dissection (10% vs 43%; p = .046). Conclusion This pooled analysis provides the largest sample size of FDCS of the head and neck to date and suggests that radiation and neck dissection may be beneficial to locoregional oncologic control. PMID:25917851

  4. Patterns of Weight Change in Black Americans: Pooled Analysis from Three Behavioral Weight Loss Trials

    PubMed Central

    Morales, Knashawn H.; Kumanyika, Shiriki K.; Fassbender, Jennifer E.; Good, Jerene; Localio, A. Russell; Wadden, Thomas A.

    2014-01-01

    Objective Differentiating trajectories of weight change and identifying associated baseline predictors can provide insights for improving behavioral obesity treatment outcomes. Design and Methods Secondary, observational analyses using growth mixture models were conducted in pooled data for 604 black American, primarily female adults in three completed clinical trials. Covariates of identified patterns were evaluated. Results The best fitting model identified three patterns over 2 years: 1) mean weight loss of approximately 2 kg (n=519); 2) mean weight loss of approximately 3 kg at 1 year, followed by ~ 4 kg regain (n=61); and 3) mean weight loss of approximately 20 kg at 1 year followed by ~ 4 kg regain (n=24, with 23 from one study). In final multivariate analyses, higher BMI predicted having pattern 2 (OR[95% CI]) 1.10[1.03, 1.17]) or 3 (OR[95% CI] 1.42[1.25, 1.63]), and higher dietary fat score was predictive of a lower odds of having patterns 2 (OR[95% CI] 0.37[0.15, 0.94]) or 3 (OR[95% CI] 0.23[0.07, 0.79]). Conclusions Findings were consistent with moderate, clinically non-significant weight loss as the predominant pattern across all studies. Results underscore the need to develop novel and more carefully targeted and tailored approaches to facilitating weight loss in black American adults. PMID:25251464

  5. Computational Analysis of Energy Pooling to Harvest Low-Energy Solar Energy in Organic Photovoltaic Devices

    NASA Astrophysics Data System (ADS)

    Lacount, Michael; Shaheen, Sean; Rumbles, Garry; van de Lagemaat, Jao; Hu, Nan; Ostrowski, Dave; Lusk, Mark

    2014-03-01

    Current photovoltaic energy conversions do not typically utilize low energy sunlight absorption, leaving large sections of the solar spectrum untapped. It is possible, though, to absorb such radiation, generating low-energy excitons, and then pool them to create higher energy excitons, which can result in an increase in efficiency. Calculation of the rates at which such upconversion processes occur requires an accounting of all possible molecular quantum electrodynamics (QED) pathways. There are two paths associated with the upconversion. The cooperative mechanism involves a three-body interaction in which low energy excitons are transferred sequentially onto an acceptor molecule. The accretive pathway, requires that an exciton transfer its energy to a second exciton that subsequently transfers its energy to the acceptor molecule. We have computationally modeled both types of molecular QED obtaining rates using a combination of DFT and many-body Green function theory. The simulation platform is exercised by considering upconversion events associated with material composed of a high energy absorbing core of hexabenzocoronene (HBC) and low energy absorbing arms of oligothiophene. In addition, we make estimates for all competing processes in order to judge the relative efficiencies of these two processes.

  6. Respiratory viruses in lung transplant recipients: a critical review and pooled analysis of clinical studies.

    PubMed

    Vu, D-L; Bridevaux, P-O; Aubert, J-D; Soccal, P M; Kaiser, L

    2011-05-01

    Lung transplant recipients present an increased risk for severe complications associated with respiratory infections. We conducted a review of the literature examining the clinical relationship between viral respiratory infection and graft complications. Thirty-four studies describing the clinical impact of influenza, respiratory syncytial virus, parainfluenza, human metapneumovirus, rhinovirus, enterovirus, coronavirus, bocavirus or adenovirus were identified. The detection rate of respiratory viral infection ranged from 1.4% to 60%. Viruses were detected five times more frequently when respiratory symptoms were present [odds ratio (OR) = 4.97; 95% CI = 2.11-11.68]. Based on available observations, we could not observe an association between respiratory viral infection and acute rejection (OR = 1.35; 95% CI = 0.41-4.43). We found a pooled incidence of 18% (9/50) of bronchiolitis obliterans syndrome (BOS) in virus-positive cases compared to 11.6% (37/319) in virus-negative cases; however, limited number of BOS events did not allow to confirm the association. Our review confirms a causal relationship between respiratory viruses and respiratory symptoms, but cannot confirm a link between respiratory viruses and acute lung rejection. This is related in part to the heterogeneity and limitations of available studies. The link with BOS needs also to be reassessed in appropriate prospective studies. PMID:21521473

  7. Analysis of an open-air swimming pool solar heating system by using an experimentally validated TRNSYS model

    SciTech Connect

    Ruiz, Elisa; Martinez, Pedro J.

    2010-01-15

    In the case of private outdoor swimming pools, seldom larger than 100 m{sup 2}, conventional auxiliary heating systems are being installed less and less. Solar heating is an option to extend the swimming season. The temperature evolution of an open-air swimming pool highly depends on the wind speed directly on the water surface, which at the same time is influenced by the surroundings of the pool. In this paper, the TRNSYS model of a private open-air pool with a 50-m{sup 2} surface was validated by registering the water temperature evolution and the meteorological data at the pool site. Evaporation is the main component of energy loss in swimming pools. Six different sets of constants found in literature were considered to evaluate the evaporative heat transfer coefficient with the purpose of finding the most suitable one for the TRNSYS pool model. In order to do that, the evolution of the pool water temperature predicted by the TRNSYS pool model was compared with the experimentally registered one. The simulation with TRNSYS of the total system, including the swimming pool and the absorber circuit integrated into the existing filter circuit, provided information regarding the increase of the pool temperature for different collector areas during the swimming season. This knowledge, together with the economic costs, support the decision about the absorber field size. (author)

  8. Mediation by Peer Violence Victimization of Sexual Orientation Disparities in Cancer-Related Tobacco, Alcohol, and Sexual Risk Behaviors: Pooled Youth Risk Behavior Surveys

    PubMed Central

    Corliss, Heather L.; Everett, Bethany G.; Russell, Stephen T.; Buchting, Francisco O.; Birkett, Michelle A

    2014-01-01

    Objectives. We examined the role of adolescent peer violence victimization (PVV) in sexual orientation disparities in cancer-related tobacco, alcohol, and sexual risk behaviors. Methods. We pooled data from the 2005 and 2007 Youth Risk Behavior Surveys. We classified youths with any same-sex sexual attraction, partners, or identity as sexual minority and the remainder as heterosexual. We had 4 indicators of tobacco and alcohol use and 4 of sexual risk and 2 PVV factors: victimization at school and carrying weapons. We stratified associations by gender and race/ethnicity. Results. PVV was related to disparities in cancer-related risk behaviors of substance use and sexual risk, with odds ratios (ORs) of 1.3 (95% confidence interval [CI] = 1.03, 1.6) to 11.3 (95% CI = 6.2, 20.8), and to being a sexual minority, with ORs of 1.4 (95% CI = 1.1, 1.9) to 5.6 (95% CI = 3.5, 8.9). PVV mediated sexual orientation disparities in substance use and sexual risk behaviors. Findings were pronounced for adolescent girls and Asian/Pacific Islanders. Conclusions. Interventions are needed to reduce PVV in schools as a way to reduce sexual orientation disparities in cancer risk across the life span. PMID:24825215

  9. Sexual Orientation Disparities in Cancer-Related Risk Behaviors of Tobacco, Alcohol, Sexual Behaviors, and Diet and Physical Activity: Pooled Youth Risk Behavior Surveys

    PubMed Central

    Corliss, Heather L.; Everett, Bethany G.; Reisner, Sari L.; Austin, S. Bryn; Buchting, Francisco O.; Birkett, Michelle

    2014-01-01

    Objectives. We examined sexual orientation disparities in cancer-related risk behaviors among adolescents. Methods. We pooled data from the 2005 and 2007 Youth Risk Behavior Surveys. We classified youths with any same-sex orientation as sexual minority and the remainder as heterosexual. We compared the groups on risk behaviors and stratified by gender, age (< 15 years and > 14 years), and race/ethnicity. Results. Sexual minorities (7.6% of the sample) reported more risk behaviors than heterosexuals for all 12 behaviors (mean = 5.3 vs 3.8; P < .001) and for each risk behavior: odds ratios (ORs) ranged from 1.3 (95% confidence interval [CI] = 1.2, 1.4) to 4.0 (95% CI = 3.6, 4.7), except for a diet low in fruit and vegetables (OR = 0.7; 95% CI = 0.5, 0.8). We found sexual orientation disparities in analyses by gender, followed by age, and then race/ethnicity; they persisted in analyses by gender, age, and race/ethnicity, although findings were nuanced. Conclusions. Data on cancer risk, morbidity, and mortality by sexual orientation are needed to track the potential but unknown burden of cancer among sexual minorities. PMID:24328632

  10. Poultry consumption and prostate cancer risk: a meta-analysis

    PubMed Central

    He, Qian; Wan, Zheng-ce; Xu, Xiao-bing; Wu, Jing

    2016-01-01

    Background. Several kinds of foods are hypothesized to be potential factors contributing to the variation of prostate cancer (PCa) incidence. But the effect of poultry on PCa is still inconsistent and no quantitative assessment has been published up to date. So we conducted this meta-analysis to clarify the association between them. Materials and Methods. We conducted a literature search of PubMed and Embase for studies examining the association between poultry consumption and PCa up to June, 2015. Pooled risk ratio (RR) and corresponding 95% confidence interval (CI) of the highest versus lowest poultry consumption categories were calculated by fixed-effect model or random-effect model. Results. A total of 27 (12 cohort and 15 case-control) studies comprising 23,703 cases and 469,986 noncases were eligible for inclusion. The summary RR of total PCa incidence was 1.03 (95% CI [0.95–1.11]) for the highest versus lowest categories of poultry intake. The heterogeneity between studies was not statistically significant (P = 0.768, I2 = 28.5%). Synthesized analysis of 11 studies on high stage PCa and 8 studies on chicken exposure also demonstrated null association. We also did not obtain significant association in the subgroup of cohort study (RR = 1.04, 95% CI [0.98–1.10]), as well as in the subgroups of population-based case-control study and hospital-based case-control study. Then the studies were divided into three geographic groups: Western countries, Asia and South America. The pooled RRs in these areas did not reveal statistically significant association between poultry and PCa. Conclusions. This meta-analysis suggests no association between poultry consumption and PCa risk. Further well-designed studies are warranted to confirm the result. PMID:26855875

  11. Potential Role of MicroRNA-210 as Biomarker in Human Cancers Detection: A Meta-Analysis

    PubMed Central

    Lu, Jiongjiong; Xie, Feng; Geng, Li; Shen, Weifeng; Sui, Chengjun; Yang, Jiamei

    2015-01-01

    We conducted this meta-analysis aimed to evaluate diagnostic accuracy of miR-210 in human cancers. A total of 673 cancer patients and 606 cancer-free individuals from 13 studies were contained in this meta-analysis. The overall diagnostic results in our study showed that the pooled sensitivity was 0.70, specificity was 0.76, and the AUC was 0.80. In addition, the PLR and NLR were 2.9 and 0.39, with DOR of 8. After the outliner exclusion detected by sensitivity analysis, these parameters had minimal change, which confirmed the stability of our work. The results in our studies showed that the miR-210 assay yielded relatively moderate accuracy in cancer patients and cancer-free individual differentiation. More basic researches are needed to highlight its role as supplement in clinical treatment. PMID:26446394

  12. Pooled Analysis of Rofecoxib Placebo-Controlled Clinical Trial Data: Lessons for Post-Market Pharmaceutical Safety Surveillance

    PubMed Central

    Ross, Joseph S.; Madigan, David; Hill, Kevin P.; Egilman, David S.; Wang, Yongfei; Krumholz, Harlan M.

    2010-01-01

    Background In September 2004, rofecoxib was voluntarily withdrawn from the worldwide market. Our objective was to determine whether and when analysis of published and unpublished placebo-controlled trials could have revealed cardiovascular risk associated with rofecoxib before its withdrawal as an example to inform future post-market pharmaceutical safety surveillance efforts. Methods We conducted a cumulative subject-level pooled analysis of data from all randomized, placebo-controlled trials of rofecoxib conducted by the manufacturer before September 2004. Our main outcome measurement was incidence of any investigator-reported death from any cause or cardiovascular thromboembolic (CVT) adverse event. Results We identified 30 randomized, placebo-controlled trials of rofecoxib that enrolled 20,152 subjects. Trial duration ranged from 4 weeks to 4 years, enrollment ranged from 17 to 2586 subjects prescribed either rofecoxib or placebo, and rofecoxib dosage ranged from 12.5 mg to 50 mg. As of December 2000, 21 (70%) of these trials had been completed and the risk of CVT adverse event or death was greater among subjects assigned to rofecoxib, with the difference being borderline statistically significant (Rate Ratio [RR]=2.18, 95% Confidence Interval [CI], 0.93–5.81; p=0.07). Subsequently collected data strengthened the statistical association (as of June 2001: RR=1.35, 95% CI, 1.00–1.96; p=0.05; as of April 2002: RR=1.39, 95% CI, 1.07–1.80; p=0.02). Conclusion Cumulative pooled analysis of all randomized, placebo-controlled trials demonstrates a progressing trend toward increased cardiovascular risk associated with rofecoxib compared with placebo as early as December 2000, reaching a P value of 0.05 by June 2001, nearly 3 and a half years before the manufacturer’s voluntary market withdrawal. PMID:19933959

  13. A Pooled Multisite Analysis of the Effects of Female Reproductive Hormones on Glioma Risk

    PubMed Central

    Krishnamachari, Bhuma; Il’yasova, Dora; Scheurer, Michael E.; Bondy, Melissa; Wrensch, Margaret; Davis, Faith

    2014-01-01

    Purpose The association between female reproductive factors and glioma risk is unclear, but most published studies have been limited by small sample size. We conducted a pooled multisite study of pre- and post-menopausal women, investigating the effect of female reproductive factors, including hormonal medications. Methods Unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals assessing the effects of female reproductive factors and female hormonal medications in glioma cases and unrelated controls. Results Menarche over the age of 15 as compared to under 12 was associated with a statistically significant risk for glioma (OR = 2.00, 95% CI, 1.47–2.71). Use of Oral Contraceptive Pills (OCP) was inversely associated with risk of glioma (OR= 0.61, 95% CI, 0.50–0.74) and there was an inverse trend with longer duration of OCP use (p for trend< 0.0001). Use of Hormone Replacement Therapy (HRT) was also inversely associated with risk of glioma (OR=0.55, 95% CI, 0.44–0.68) and there was an inverse trend with longer duration of use (p for trend< 0.0001). Compared to those reporting neither OCP use nor HRT use, those who reported using both were less likely to have a diagnosis of glioma (OR = 0.34, 95% CI, 0.24–0.48). Conclusions Female reproductive hormones may decrease the risk for glioma. The association appears to be strongest with greater length of use and use of both HRT and OCP. PMID:24890803

  14. Tracking of accelerometry-measured physical activity during childhood: ICAD pooled analysis

    PubMed Central

    2012-01-01

    Background Understanding of physical activity (PA) tracking during childhood is important to predict PA behaviors and design appropriate interventions. We compared tracking of PA according to PA level and type of day (weekday/weekend) in a pool of five childrens cohort studies. Methods Data from ALSPAC, CLAN, Iowa Bone Development Study, HEAPS, PEACH were extracted from the International Childrens Accelerometry Database (ICAD), resulting in 5,016 participants with age, gender, and accelerometry data at both baseline and follow-up (mean age: 10.3?years at baseline, 12.5?years at follow-up). Daily minutes spent in moderate- and vigorous-intensity PA (MVPA) and vigorous-intensity PA (VPA) was categorized into quintiles. Multinomial logistic regression models were fit to predict follow-up (M)VPA from baseline (M)VPA (reference: 20-?

  15. Evaluation of the prognostic role of centromere 17 gain and HER2/topoisomerase II alpha gene status and protein expression in patients with breast cancer treated with anthracycline-containing adjuvant chemotherapy: pooled analysis of two Hellenic Cooperative Oncology Group (HeCOG) phase III trials

    PubMed Central

    2013-01-01

    Background The HER2 gene has been established as a valid biological marker for the treatment of breast cancer patients with trastuzumab and probably other agents, such as paclitaxel and anthracyclines. The TOP2A gene has been associated with response to anthracyclines. Limited information exists on the relationship of HER2/TOP2A gene status in the presence of centromere 17 (CEP17) gain with outcome of patients treated with anthracycline-containing adjuvant chemotherapy. Methods Formalin-fixed paraffin-embedded tumor tissue samples from 1031 patients with high-risk operable breast cancer, enrolled in two consecutive phase III trials, were assessed in a central laboratory by fluorescence in situ hybridization for HER2/TOP2A gene amplification and CEP17 gain (CEP17 probe). Amplification of HER2 and TOP2A were defined as a gene/CEP17 ratio of >2.2 and ?2.0, respectively, or gene copy number higher than 6. Additionally, HER2, TopoIIa, ER/PgR and Ki67 protein expression was assessed by immunohistochemistry (IHC) and patients were classified according to their IHC phenotype. Treatment consisted of epirubicin-based adjuvant chemotherapy followed by hormonal therapy and radiation, as indicated. Results HER2 amplification was found in 23.7% of the patients and TOP2A amplification in 10.1%. In total, 41.8% of HER2-amplified tumors demonstrated TOP2A co-amplification. The median (range) of HER2, TOP2A and CEP17 gain was 2.55 (0.70-45.15), 2.20 (0.70-26.15) and 2.00 (0.70-26.55), respectively. Forty percent of the tumors had CEP17 gain (51% of those with HER2 amplification). Adjusting for treatment groups in the Cox model, HER2 amplification, TOP2A amplification, CEP17 gain and HER2/TOP2A co-amplification were not associated with time to relapse or time to death. Conclusion HER2 amplification, TOP2A amplification, CEP17 gain and HER2/TOP2A co-amplification were not associated with outcome in high-risk breast cancer patients treated with anthracycline-based adjuvant chemotherapy. Trial registration Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12611000506998 and ACTRN12609001036202 PMID:23537287

  16. A factor analysis of posttraumatic stress disorder symptoms using data pooled from two venlafaxine extended-release clinical trials

    PubMed Central

    Stein, Dan J; Rothbaum, Barbara O; Baldwin, David S; Szumski, Annette; Pedersen, Ronald; Davidson, Jonathan R T

    2013-01-01

    Background Confirmatory factor analysis (CFA) of Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) (DSM-IV) three-factor posttraumatic stress disorder (PTSD) diagnostic criteria was conducted to determine fit for this patient population. An exploratory factor analysis (EFA) of alternate symptom structures was planned to identify symptoms that cluster in this population. The response of symptom factors to treatment with venlafaxine extended release (ER) was explored. Methods Baseline 17-item Clinician-Administered PTSD Scale (CAPS-SX17) data were pooled from patients enrolled in two double-blind, randomized, placebo-controlled trials. The CFA was conducted using maximum likelihood and weighted, least-squares factor extraction methods. The EFA was performed using a polychoric correlation covariance matrix and Pearson correlation matrix. Results Data from a pooled population of 685 patients (venlafaxine ER: n = 339; placebo: n = 346) were analyzed. CFA rejected the DSM-IV three-factor structure. The EFA identified a different three-factor structure as the best fit: factor 1 included reexperiencing symptoms, factor 2 included symptoms of altered mood and cognition, whereas factor 3 comprised avoidance and arousal symptoms. All DSM-IV symptom factors and all factors in the identified three-factor model responded positively to venlafaxine ER treatment. Conclusions Data are consistent with literature failing to confirm the three-factor structure of DSM-IV PTSD, and they support the DSM-5 inclusion of a symptom cluster addressing altered mood and cognition in PTSD. The efficacy of venlafaxine ER in reducing a range of symptom clusters in PTSD is consistent with its multiple mechanisms of action. PMID:24363976

  17. Alert but less alarmed: a pooled analysis of terrorism threat perception in Australia

    PubMed Central

    2011-01-01

    Background Previous Australian research has highlighted disparities in community perceptions of the threat posed by terrorism. A study with a large sample size is needed to examine reported concerns and anticipated responses of community sub-groups and to determine their consistency with existing Australian and international findings. Methods Representative samples of New South Wales (NSW) adults completed terrorism perception questions as part of computer assisted telephone interviews (CATI) in 2007 (N = 2081) and 2010 (N = 2038). Responses were weighted against the NSW population. Data sets from the two surveys were pooled and multivariate multilevel analyses conducted to identify health and socio-demographic factors associated with higher perceived risk of terrorism and evacuation response intentions, and to examine changes over time. Results In comparison with 2007, Australians in 2010 were significantly more likely to believe that a terrorist attack would occur in Australia (Adjusted Odd Ratios (AOR) = 1.24, 95%CI:1.06-1.45) but felt less concerned that they would be directly affected by such an incident (AOR = 0.65, 95%CI:0.55-0.75). Higher perceived risk of terrorism and related changes in living were associated with middle age, female gender, lower education and higher reported psychological distress. Australians of migrant background reported significantly lower likelihood of terrorism (AOR = 0.52, 95%CI:0.39-0.70) but significantly higher concern that they would be personally affected by such an incident (AOR = 1.57, 95%CI:1.21-2.04) and having made changes in the way they live due to this threat (AOR = 2.47, 95%CI:1.88-3.25). Willingness to evacuate homes and public places in response to potential incidents increased significantly between 2007 and 2010 (AOR = 1.53, 95%CI:1.33-1.76). Conclusion While an increased proportion of Australians believe that the national threat of terrorism remains high, concern about being personally affected has moderated and may reflect habituation to this threat. Key sub-groups remain disproportionately concerned, notably those with lower education and migrant groups. The dissonance observed in findings relating to Australians of migrant background appears to reflect wider socio-cultural concerns associated with this issue. Disparities in community concerns regarding terrorism-related threat require active policy consideration and specific initiatives to reduce the vulnerabilities of known risk groups, particularly in the aftermath of future incidents. PMID:21992446

  18. Development and optimization of SPECT gated blood pool cluster analysis for the prediction of CRT outcome

    SciTech Connect

    Lalonde, Michel Wassenaar, Richard; Wells, R. Glenn; Birnie, David; Ruddy, Terrence D.

    2014-07-15

    Purpose: Phase analysis of single photon emission computed tomography (SPECT) radionuclide angiography (RNA) has been investigated for its potential to predict the outcome of cardiac resynchronization therapy (CRT). However, phase analysis may be limited in its potential at predicting CRT outcome as valuable information may be lost by assuming that time-activity curves (TAC) follow a simple sinusoidal shape. A new method, cluster analysis, is proposed which directly evaluates the TACs and may lead to a better understanding of dyssynchrony patterns and CRT outcome. Cluster analysis algorithms were developed and optimized to maximize their ability to predict CRT response. Methods: About 49 patients (N = 27 ischemic etiology) received a SPECT RNA scan as well as positron emission tomography (PET) perfusion and viability scans prior to undergoing CRT. A semiautomated algorithm sampled the left ventricle wall to produce 568 TACs from SPECT RNA data. The TACs were then subjected to two different cluster analysis techniques, K-means, and normal average, where several input metrics were also varied to determine the optimal settings for the prediction of CRT outcome. Each TAC was assigned to a cluster group based on the comparison criteria and global and segmental cluster size and scores were used as measures of dyssynchrony and used to predict response to CRT. A repeated random twofold cross-validation technique was used to train and validate the cluster algorithm. Receiver operating characteristic (ROC) analysis was used to calculate the area under the curve (AUC) and compare results to those obtained for SPECT RNA phase analysis and PET scar size analysis methods. Results: Using the normal average cluster analysis approach, the septal wall produced statistically significant results for predicting CRT results in the ischemic population (ROC AUC = 0.73;p < 0.05 vs. equal chance ROC AUC = 0.50) with an optimal operating point of 71% sensitivity and 60% specificity. Cluster analysis results were similar to SPECT RNA phase analysis (ROC AUC = 0.78, p = 0.73 vs cluster AUC; sensitivity/specificity = 59%/89%) and PET scar size analysis (ROC AUC = 0.73, p = 1.0 vs cluster AUC; sensitivity/specificity = 76%/67%). Conclusions: A SPECT RNA cluster analysis algorithm was developed for the prediction of CRT outcome. Cluster analysis results produced results equivalent to those obtained from Fourier and scar analysis.

  19. Analysis of dose rates received around the storage pool for irradiated control rods in a BWR nuclear power plant.

    PubMed

    Ródenas, J; Abarca, A; Gallardo, S

    2011-08-01

    BWR control rods are activated by neutron reactions in the reactor. The dose produced by this activity can affect workers in the area surrounding the storage pool, where activated rods are stored. Monte Carlo (MC) models for neutron activation and dose assessment around the storage pool have been developed and validated. In this work, the MC models are applied to verify the expected reduction of dose when the irradiated control rod is hanged in an inverted position into the pool. PMID:21093278

  20. Analysis of the dose rate produced by control rods discharged from a BWR into the irradiated fuel pool.

    PubMed

    Ródenas, J; Gallardo, S; Abarca, A; Juan, V

    2010-01-01

    BWR control rods become activated by neutron reactions into the reactor. Therefore, when they are withdrawn from the reactor, they must be stored into the storage pool for irradiated fuel at a certain depth under water. Dose rates on the pool surface and the area surrounding the pool should be lower than limits for workers. The MCNP code based on the Monte Carlo method has been applied to model this situation and to calculate dose rates at points of interest. PMID:19836252

  1. Association between Class III Obesity (BMI of 4059 kg/m2) and Mortality: A Pooled Analysis of 20 Prospective Studies

    PubMed Central

    Kitahara, Cari M.; Flint, Alan J.; Berrington de Gonzalez, Amy; Bernstein, Leslie; Brotzman, Michelle; MacInnis, Robert J.; Moore, Steven C.; Robien, Kim; Rosenberg, Philip S.; Singh, Pramil N.; Weiderpass, Elisabete; Adami, Hans Olov; Anton-Culver, Hoda; Ballard-Barbash, Rachel; Buring, Julie E.; Freedman, D. Michal; Fraser, Gary E.; Beane Freeman, Laura E.; Gapstur, Susan M.; Gaziano, John Michael; Giles, Graham G.; Hkansson, Niclas; Hoppin, Jane A.; Hu, Frank B.; Koenig, Karen; Linet, Martha S.; Park, Yikyung; Patel, Alpa V.; Purdue, Mark P.; Schairer, Catherine; Sesso, Howard D.; Visvanathan, Kala; White, Emily; Wolk, Alicja; Zeleniuch-Jacquotte, Anne; Hartge, Patricia

    2014-01-01

    Background The prevalence of class III obesity (body mass index [BMI]?40 kg/m2) has increased dramatically in several countries and currently affects 6% of adults in the US, with uncertain impact on the risks of illness and death. Using data from a large pooled study, we evaluated the risk of death, overall and due to a wide range of causes, and years of life expectancy lost associated with class III obesity. Methods and Findings In a pooled analysis of 20 prospective studies from the United States, Sweden, and Australia, we estimated sex- and age-adjusted total and cause-specific mortality rates (deaths per 100,000 persons per year) and multivariable-adjusted hazard ratios for adults, aged 1983 y at baseline, classified as obese class III (BMI 40.059.9 kg/m2) compared with those classified as normal weight (BMI 18.524.9 kg/m2). Participants reporting ever smoking cigarettes or a history of chronic disease (heart disease, cancer, stroke, or emphysema) on baseline questionnaires were excluded. Among 9,564 class III obesity participants, mortality rates were 856.0 in men and 663.0 in women during the study period (19762009). Among 304,011 normal-weight participants, rates were 346.7 and 280.5 in men and women, respectively. Deaths from heart disease contributed largely to the excess rates in the class III obesity group (rate differences?=?238.9 and 132.8 in men and women, respectively), followed by deaths from cancer (rate differences?=?36.7 and 62.3 in men and women, respectively) and diabetes (rate differences?=?51.2 and 29.2 in men and women, respectively). Within the class III obesity range, multivariable-adjusted hazard ratios for total deaths and deaths due to heart disease, cancer, diabetes, nephritis/nephrotic syndrome/nephrosis, chronic lower respiratory disease, and influenza/pneumonia increased with increasing BMI. Compared with normal-weight BMI, a BMI of 4044.9, 4549.9, 5054.9, and 5559.9 kg/m2 was associated with an estimated 6.5 (95% CI: 5.77.3), 8.9 (95% CI: 7.410.4), 9.8 (95% CI: 7.412.2), and 13.7 (95% CI: 10.516.9) y of life lost. A limitation was that BMI was mainly ascertained by self-report. Conclusions Class III obesity is associated with substantially elevated rates of total mortality, with most of the excess deaths due to heart disease, cancer, and diabetes, and major reductions in life expectancy compared with normal weight. Please see later in the article for the Editors' Summary PMID:25003901

  2. Independent review of design and analysis for Holtec spent fuel storage racks of CPP 666 Pool 1

    SciTech Connect

    Miller, G.K.

    1996-03-01

    This document summarizes the analyses and review performed to develop and validate the design of the new fuel storage racks for the Idaho Chemical Processing Plant (ICPP) Fuel Storage Area (FSA). Holtec International is responsible for the design and fabrication of the storage racks. This report describes the issues raised in the review effort and the resolutions to these issues. The conclusion is reached that the review issues for the racks of Pool 1 have been satisfactorily resolved in the final design and analysis for these racks. Section 1 of this report gives a brief description of the project. Section 2 describes the approach that Holtec used in analyzing the racks and results from these analyses. Section 3 describes the independent review process. Section 4 discusses the identification of and resolution to comments on the design analysis. Section 5 describes additional analysis performed to address major concerns with the Holtec design analysis. Section 6 presents a summary of AEC`s independent review, which is based on AEC`s final review report. Finally, Section 7 gives the Lockheed Idaho Technologies Company (LITCO) position on the acceptability of Holtec`s design.

  3. Worldwide Prevalence of Human Papillomavirus and Relative Risk of Prostate Cancer: A Meta-analysis

    PubMed Central

    Yang, Lin; Xie, Shuanghua; Feng, Xiaoshuang; Chen, Yuheng; Zheng, Tongzhang; Dai, Min; Ke Zhou, Cindy; Hu, Zhibin; Li, Ni; Hang, Dong

    2015-01-01

    Despite the increasing number of studies conducted recently to evaluate the association between HPV infections and the risk of prostate cancer, the results remain inconclusive. Furthermore, the prevalence and distribution of overall and individual HPV types worldwide in prostate cancer has not been reported until now. Therefore, we estimated the prevalence of HPV in prostate cancer by pooling data of 46 studies with 4919 prostate cancer cases, taking into account the heterogeneity of major related parameters, including study region, specimen type, HPV DNA source, detection method, publication calendar period and Gleason score. Moreover, we tested the association of HPV infections with prostate cancer risks by a meta-analysis of 26 tissue-based case-control studies. We found that the prevalence of HPV infection was 18.93% (95% CI = 17.84–20.05%) in prostate cancer cases, and most of which were high-risk HPV types (17.73%, 95% CI = 16.52–18.99%). The prevalence varied by region, PCR primers used, publication calendar period and Gleason score. Our study also showed a significantly increased risk of prostate cancer with the positivity of overall HPV detected in prostate tissues (OR = 1.79, 95% CI = 1.29–2.49) and revealed the geographic variation of association strength (P < 0.001). In conclusion, HPV infections may contribute to the risk of prostate cancer. PMID:26441160

  4. Analysis and Optimal Design for Association Studies Using Next-Generation Sequencing With Case-Control Pools

    PubMed Central

    Liang, Wei E.; Thomas, Duncan C.; Conti, David V.

    2014-01-01

    With its potential to discover a much greater amount of genetic variation, next-generation sequencing is fast becoming an emergent tool for genetic association studies. However, the cost of sequencing all individuals in a large-scale population study is still high in comparison to most alternative genotyping options. While the ability to identify individual-level data is lost (without bar-coding), sequencing pooled samples can substantially lower costs without compromising the power to detect significant associations.We propose a hierarchical Bayesian model that estimates the association of each variant using pools of cases and controls, accounting for the variation in read depth across pools and sequencing error. To investigate the performance of our method across a range of number of pools, number of individuals within each pool, and average coverage, we undertook extensive simulations varying effect sizes, minor allele frequencies, and sequencing error rates. In general, the number of pools and pool size have dramatic effects on power while the total depth of coverage per pool has only a moderate impact. This information can guide the selection of a study design that maximizes power subject to cost, sample size, or other laboratory constraints. We provide an R package (hiPOD: hierarchical Pooled Optimal Design) to find the optimal design, allowing the user to specify a cost function, cost, and sample size limitations, and distributions of effect size, minor allele frequency, and sequencing error rate. PMID:22972696

  5. p53 codon 72 polymorphism and breast cancer risk: A meta-analysis

    PubMed Central

    HOU, JING; JIANG, YUAN; TANG, WENRU; JIA, SHUTING

    2013-01-01

    p53 is a tumor suppressor gene and plays important roles in the etiology of breast cancer. Studies have produced conflicting results concerning the role of p53 codon 72 polymorphism (G>C) on the risk of breast cancer; therefore, a meta-analysis was performed to estimate the association between the p53 codon 72 polymorphism and breast cancer. Screening of the PubMed database was conducted to identify relevant studies. Studies containing available genotype frequencies of the p53 codon 72 polymorphism were selected and a pooled odds ratio (OR) with 95% confidence interval (CI) was used to assess the association. Sixty-one published studies, including 28,539 breast cancer patients and 32,788 controls were identified. The results suggest that variant genotypes are not associated with breast cancer risk (Pro/Pro + Arg/Pro vs. Arg/Arg: OR=1.016, 95% CI=0.931–1.11, P=0.722). The symmetric funnel plot, Egger’s test (P=0.506) and Begg’s test (P=0.921) were all suggestive of the lack of publication bias. This meta-analysis suggests that the p53 codon 72 Pro/Pro + Arg/Pro genotypes are not associated with an increased risk of breast cancer. To validate the association between the p53 codon 72 polymorphism and breast cancer, further studies with larger numbers of participants worldwide are required. PMID:23737888

  6. Association of Vitamin E Intake with Reduced Risk of Kidney Cancer: A Meta-Analysis of Observational Studies

    PubMed Central

    Shen, Chongxing; Huang, Ying; Yi, Shanhong; Fang, Zhenqiang; Li, Longkun

    2015-01-01

    Background Several observational studies suggested that vitamin E intake is related to the risk of kidney cancer; however, the results of published studies are inconsistent. Material/Methods A meta-analysis was performed to assess the relationship between vitamin E intake and the risk of kidney cancer by searching PubMed and Medline through August 2015. We computed pooled relative risks (RR) and 95%CI of kidney cancer for the highest versus lowest level of vitamin E intake. Results A total of 13 observational studies (7 case-control and 6 cohort) were included. The pooled RR (95%CI) of kidney cancer for the highest vs. the lowest level of vitamin E intake was 0.81 (0.69–0.94). In subgroup-analysis, this study found an inverse relationship between vitamin E intake and kidney cancer risk, which was not significantly modified by study design, study population, or sex distribution except in the cohort studies. Conclusions Results of the present study suggest an inverse relationship between vitamin E intake and kidney cancer risk. However, additional well designed cohort studies and randomized controlled trials that focus on the relationship between vitamin E intake and kidney cancer risk are needed. PMID:26547129

  7. Outcomes in Ethnic Minority Renal Transplant Recipients Receiving Everolimus versus Mycophenolate: Comparative Risk Assessment Results From a Pooled Analysis

    PubMed Central

    Melancon, Keith; Mulgaonkar, Shamkant P.; Delcoro, Carlos; Wiland, Anne; McCague, Kevin; Shihab, Fuad S.

    2013-01-01

    Background Everolimus (EVR) has demonstrated good efficacy after renal transplantation. Racial disparities in clinical outcomes after de novo renal transplantation are well documented; whether the efficacy of EVR varies based on recipient ethnicity is unknown. We conducted a comparative risk assessment of EVR by ethnicity. Methods Data on 2004 renal transplant recipients from three EVR studies were pooled to identify the impact of ethnicity on efficacy outcomes across EVR dosing groups and control groups. Ethnic groups compared were African Americans, non-U.S. blacks, Asians, Hispanics, and Caucasians. EVR groups received either 1.5 or 3 mg per day, with either standard-dose cyclosporine or reduced-dose cyclosporine. Control groups received mycophenolic acid (MPA) with standard-dose cyclosporine. Composite efficacy failure endpoint was graft loss, death, biopsy-proven acute rejection, or lost to follow-up. Adjusted odds ratios were calculated using a logistic regression model. Results The proportion of renal transplant recipients who met the composite endpoint was African Americans (46%), non-U.S. black (35%), Caucasian (31%), Hispanic (28%), and Asian (25%). The odds of meeting the composite endpoint were significantly (P=0.0001) greater for African Americans versus Caucasians but did not differ among the other ethnic groups (ethnic groups were only compared with Caucasians). EVR and MPA were associated with similar efficacy among each of the ethnic groups. Conclusion In this pooled data analysis in more than 2000 renal transplant recipients, EVR versus MPA resulted in similar composite endpoint incidence events across ethnicities. Consistent with previously published data, African Americans had poorer clinical outcomes. EVR is efficacious regardless of ethnicity. PMID:24345868

  8. Exhaled breath analysis for lung cancer

    PubMed Central

    Sutedja, Tom G.; Zimmerman, Paul V.

    2013-01-01

    Early diagnosis of lung cancer results in improved survival compared to diagnosis with more advanced disease. Early disease is not reliably indicated by symptoms. Because investigations such as bronchoscopy and needle biopsy have associated risks and substantial costs, they are not suitable for population screening. Hence new easily applicable tests, which can be used to screen individuals at risk, are required. Biomarker testing in exhaled breath samples is a simple, relatively inexpensive, non-invasive approach. Exhaled breath contains volatile and non-volatile organic compounds produced as end-products of metabolic processes and the composition of such compounds varies between healthy subjects and subjects with lung cancer. Many studies have analysed the patterns of these compounds in exhaled breath. In addition studies have also reported that the exhaled breath condensate (EBC) can reveal gene mutations or DNA abnormalities in patients with lung cancer. This review has summarised the scientific evidence demonstrating that lung cancer has distinct chemical profiles in exhaled breath and characteristic genetic changes in EBC. It is not yet possible to accurately identify individuals with lung cancer in at risk populations by any of these techniques. However, analysis of both volatile organic compounds in exhaled breath and of EBC have great potential to become clinically useful diagnostic and screening tools for early stage lung cancer detection. PMID:24163746

  9. Exhaled breath analysis for lung cancer.

    PubMed

    Dent, Annette G; Sutedja, Tom G; Zimmerman, Paul V

    2013-10-01

    Early diagnosis of lung cancer results in improved survival compared to diagnosis with more advanced disease. Early disease is not reliably indicated by symptoms. Because investigations such as bronchoscopy and needle biopsy have associated risks and substantial costs, they are not suitable for population screening. Hence new easily applicable tests, which can be used to screen individuals at risk, are required. Biomarker testing in exhaled breath samples is a simple, relatively inexpensive, non-invasive approach. Exhaled breath contains volatile and non-volatile organic compounds produced as end-products of metabolic processes and the composition of such compounds varies between healthy subjects and subjects with lung cancer. Many studies have analysed the patterns of these compounds in exhaled breath. In addition studies have also reported that the exhaled breath condensate (EBC) can reveal gene mutations or DNA abnormalities in patients with lung cancer. This review has summarised the scientific evidence demonstrating that lung cancer has distinct chemical profiles in exhaled breath and characteristic genetic changes in EBC. It is not yet possible to accurately identify individuals with lung cancer in at risk populations by any of these techniques. However, analysis of both volatile organic compounds in exhaled breath and of EBC have great potential to become clinically useful diagnostic and screening tools for early stage lung cancer detection. PMID:24163746

  10. Serum Lipids and Breast Cancer Risk: A Meta-Analysis of Prospective Cohort Studies

    PubMed Central

    Gao, Rong

    2015-01-01

    Purpose Epidemiologic studies exploring causal associations between serum lipids and breast cancer risk have reported contradictory results. We conducted a meta-analysis of prospective cohort studies to evaluate these associations. Methods Relevant studies were identified by searching PubMed and EMBASE through April 2015. We included prospective cohort studies that reported relative risk (RR) estimates with 95% confidence intervals (CIs) for the associations of specific lipid components (i.e., total cholesterol [TC], high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C], and triglycerides [TG]) with breast cancer risk. Either a fixed- or a random-effects model was used to calculate pooled RRs. Results Fifteen prospective cohort studies involving 1,189,635 participants and 23,369 breast cancer cases were included in the meta-analysis. The pooled RRs of breast cancer for the highest versus lowest categories were 0.96 (95% CI: 0.86–1.07) for TC, 0.92 (95% CI: 0.73–1.16) for HDL-C, 0.90 (95% CI: 0.77–1.06) for LDL-C, and 0.93 (95% CI: 0.86–1.00) for TG. Notably, for HDL-C, a significant reduction of breast cancer risk was observed among postmenopausal women (RR = 0.77, 95% CI: 0.64–0.93) but not among premenopausal women. Similar trends of the associations were observed in the dose-response analysis. Conclusions Our findings suggest that serum levels of TG but not TC and LDL-C may be inversely associated with breast cancer risk. Serum HDL-C may also protect against breast carcinogenesis among postmenopausal women. PMID:26554382

  11. IGF-I CA19 repeat polymorphisms and cancer risk: a meta-analysis

    PubMed Central

    Guo, Qing; Shen, Feng; Zhang, Chi; Yang, Xi; Zhu, Hong-Cheng; Zhang, Qu; Shen, Shu-Tong; Sun, Xin-Chen; Dai, Sheng-Bin

    2015-01-01

    IGF-I CA repeat polymorphisms, especially the allele containing CA19 repeats, have been reported to be associated with the risk for various types of cancers. However, the results still remain controversial and ambiguous. This meta-analysis was performed to evaluate the association between IGF-I CA19 repeat polymorphisms and the risk of cancer. Total 18 studies with IGF-I CA19 repeat genotyping on 9,873 patients and 15,607 controls were analyzed. We used random-effects model with a pooled OR of 0.69 (95% CI = 0.60-0.79) for the recessive genetic model, 0.97 (95% CI = 0.86-1.10) for the dominant genetic model, 0.99 (95% CI = 0.86-1.14) for the homozygote comparison and 1.06 (95% CI = 0.91-1.23) for the heterozygote comparison. In the subgroup analysis of recessive model, OR (95% CI) was 0.65 (0.52-0.80) in breast cancer, 0.68 (0.53-0.86) in prostate cancer, and 0.71 (0.52-0.96) in Caucasian. In conclusion, IGF-1 CA19 repeat polymorphisms are unlikely to be a major determinant of susceptibility to cancer. However, the subgroup analysis of recessive model indicates that IGF-I CA19 repeat polymorphisms may reduce the risk of certain types of cancer or in a specific population. PMID:26884978

  12. Stakeholder analysis and social-biophysical interdependencies for common pool resource management: La Brava Wetland (Argentina) as a case study.

    PubMed

    Romanelli, Asunción; Massone, Héctor E; Escalante, Alicia H

    2011-09-01

    This article gives an account of the implementation of a stakeholder analysis framework at La Brava Wetland Basin, Argentina, in a common-pool resource (CPR) management context. Firstly, the context in which the stakeholder framework was implemented is described. Secondly, a four-step methodology is applied: (1) stakeholder identification, (2) stakeholder differentiation-categorization, (3) investigation of stakeholders' relationships, and (4) analysis of social-biophysical interdependencies. This methodology classifies stakeholders according to their level of influence on the system and their potential in the conservation of natural resources. The main influential stakeholders are La Brava Village residents and tourism-related entrepreneurs who are empowered to make the more important decisions within the planning process of the ecosystem. While these key players are seen as facilitators of change, there are other groups (residents of the inner basin and fishermen) which are seen mainly as key blockers. The applied methodology for the Stakeholder Analysis and the evaluation of social-biophysical interdependencies carried out in this article can be seen as an encouraging example for other experts in natural sciences to learn and use these methods developed in social sciences. Major difficulties and some recommendations of applying this method in the practice by non-experts are discussed. PMID:21667179

  13. Patient satisfaction with intravenous acetaminophen: a pooled analysis of five randomized, placebo-controlled studies in the acute postoperative setting.

    PubMed

    Apfel, Christian C; Souza, Kimberly; Portillo, Juan; Dalal, Poorvi; Bergese, Sergio D

    2015-01-01

    Intravenous (IV) acetaminophen has been shown to reduce postoperative pain and opioid consumption, which may lead to increased patient satisfaction. To determine the effect IV acetaminophen has on patient satisfaction, a pooled analysis from methodologically homogenous studies was conducted. We obtained patient-level data from five randomized, placebo-controlled studies in adults undergoing elective surgery in which patient satisfaction was measured using a 4-point categorical rating scale. The primary endpoint was "excellent" satisfaction and the secondary endpoint was "good" or "excellent" satisfaction at 24 hr after first study drug administration. Bivariate analyses were conducted using the chi-square test and Student's t-test and multivariable analyses were conducted using logistic regression analysis. Patients receiving IV acetaminophen were more than twice as likely as those who received placebo to report "excellent" patient satisfaction ratings (32.3% vs. 15.9%, respectively). Of all variables that remained statistically significant in the multivariable analysis (i.e., type of surgery, duration of anesthesia, last pain rating, and opioid consumption), IV acetaminophen had the strongest positive effect on "excellent" patient satisfaction with an odds ratio of 2.76 (95% CI 1.81-4.23). Results for "excellent" or "good" satisfaction were similar. When given as part of a perioperative analgesic regimen, IV acetaminophen was associated with significantly improved patient satisfaction. PMID:24433365

  14. Circulating tumour cells predict survival in gastric cancer patients: a meta-analysis

    PubMed Central

    Wang, Hui-Yu; Wei, Jia; Zou, Zheng-Yun; Qian, Xiao-Ping

    2016-01-01

    Aim of the study The prognostic value of the detection of circulating tumour cells (CTCs) in gastric cancer has been studied intensely in recent years. However, the application of different technologies led to inconsistent results between the studies. Here, we performed a meta-analysis of published studies to summarise the evidence. Material and methods Medline and ISI Web of Knowledge were searched up to March 2013 using “circulating tumor cells” and “gastric cancer” as search terms. Hazard ratio (HR) with 95% confidence intervals (CIs) for prognostic outcomes and clinical characteristics were extracted from each study. Pooled hazard ratios (HR) and odds ratios (OR) were calculated using random or fixed-effects models. Results Twelve studies enrolling 774 patients were included. The combined HR estimate for overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS) were 1.41 (95% CI: 1.28–1.62), 2.99 (95% CI: 2.01–4.45) and 1.64 (95% CI: 1.02–2.62), respectively. Subgroup analysis concerning detection methods and sampling time showed that results of RT-PCR for the OS group and RT-PCR for the DFS group suggest a prognostic significance of CTC detection (pooled HR [95% CI]: 1.45 [1.28–1.65], I2 = 38%, p = 0.13; 2.99 [2.01–4.45], I2 = 0%, p = 0.32). In addition, results of the baseline CTC detection group also indicated a significant prognostic value to predict OS and DFS (pooled HR [95% CI]: 1.47 [1.19–1.82], I2 = 38%, p = 0.14; 2.99 [2.01–4.45], I2 = 0%, p = 0.32). We simultaneously found that the detection of CTCs correlated with pathological stage (pooled OR [95% CI]: 2.95 [1.65–5.28], I2 = 56%, p = 0.03), lymph node status (pooled OR [95% CI]: 2.26 [1.50–3.41], I2 = 37%, p = 0.09), the depth of invasion (pooled OR [95% CI]: 3.21 [1.38–7.43], I2 = 72%, p = 0.002), and distant metastasis (pooled OR [95% CI]: 2.68 [1.25–5.73], I2 = 43%, p = 0.15). Conclusions Detection of CTCs is associated with poorer prognosis in gastric cancer patients. PMID:26843841

  15. Thermal analysis of cancerous breast model.

    PubMed

    Chanmugam, Arjun; Hatwar, Rajeev; Herman, Cila

    2012-01-01

    Breast cancer is one of the most common and dangerous cancers. Subsurface breast cancer lesions generate more heat and have increased blood supply when compared to healthy tissue, and this temperature rise is mirrored in the skin surface temperature. The rise in temperature on the skin surface, caused by the cancerous lesion, can be measured noninvasively using infrared thermography, which can be used as a diagnostic tool to detect the presence of a lesion. However, its diagnostic ability is limited when image interpretation relies on qualitative principles. In this study, we present a quantitative thermal analysis of breast cancer using a 3D computational model of the breast. The COMSOL FEM software was used to carry out the analysis. The effect of various parameters (tumor size, location, metabolic heat generation and blood perfusion rate) on the surface temperature distribution (which can be measured with infrared thermography) has been analyzed. Key defining features of the surface temperature profile have been identified, which can be used to estimate the size and location of the tumor based on (measured) surface temperature data. In addition, we employed a dynamic cooling process, to analyze surface temperature distributions during cooling and thermal recovery as a function of time. In this study, the effect of the cooling temperature on the enhancement of the temperature differences between normal tissue and cancerous lesions is evaluated. This study demonstrates that a quantification of temperature distributions by computational modeling, combined with thermographic imaging and dynamic cooling can be an important tool in the early detection of breast cancer. PMID:25328914

  16. More People Under 50 Getting Colon Cancer, Analysis Finds

    MedlinePlus

    ... html More People Under 50 Getting Colon Cancer, Analysis Finds Though guidelines suggest screening starts at 50, ... at which guidelines recommend screenings start, a new analysis shows. One in seven colon cancer patients is ...

  17. Analysis of HLA-DP association with beryllium disease susceptibility in pooled exposed populations

    SciTech Connect

    Cesare Saltini, Massimo Amicosante

    2009-12-19

    Berylliosis or Chronic Beryllium Disease is a chronic granulomatous disorder primarily involving the lung associated with the exposition to low doses of Beryllium (Be) in the workplace. Berylliosis risk has been associated with the presence of a glutamate at position 69 of the HLA-DP beta chain (HLA-DPbetaGlu69) that is expressed in about 97% of disease cases and in 27% of the unaffected Be-exposed controls (p<0.0001) (Richeldi et al. Science 1993; 262: 242-244.12). Since this first observation of an immunogenetic association between berylliosis and HLA-DPbetaGlu69 a number of studies have confirmed the role of this marker as the primary gene of susceptibility of berylliosis (Richeldi et al Am J Ind Med. 1997; 32:337-40; Wang et al J. Immunol. 1999; 163: 1647-53; Saltini et al Eur Respir J. 2001 18:677-84; Rossman et al Am J Respir Crit Care Med. 2002 165:788-94). Moreover, a structure/function interaction between HLA-DP molecules carrying Glu69 and beryllium in driving and developing the immune response against beryllium itself has been observed as: (1) Be-specific T-cells clones obtained from berylliosis patients recognize beryllium as antigen only when presented in the context of the HLA-DP{beta}Glu69 molecules but not in the context of HLA-DP allelic variants carrying Lys69 (Lombardi G et al. J Immunol 2001; 166: 3549-3555), and (2) beryllium presents an affinity for the HLA-DP2, carrying the berylliosis marker of susceptibility HLA-DPGlu69, from 40 to 100 times higher that the HLA-DP molecule carrying Lys69 (Amicosante M. et al Hum. Immunol. 2001; 62: 686-93). However, although the immunogenetic studies performed have been addressed a number of different questions about the genetic association between berylliosis and/or beryllium sensitization, exposure levels to beryllium and HLA markers, a number of questions are still open in the field mainly due to the limitation imposed by the low number of subjects carrying berylliosis or beryllium sensitization enrolled in each immunogenetic study. In this context, the populations of the study already performed in this field by the University of Modena and Rome (by Prof. C. Saltini) and the University of Pennsylvania (by Prof. M. Rossman) have been evaluated by using similar HLA molecular typing methodologies and that both populations have now been followed up for a period of 4 to 7 years. The general objective of this study has to generate a larger data base comprising the two population with which analyze gene disease association with greater statistical power and ascertain the effect of lesser common gener variants which may be missed when analyzing associations on small populations. In particular addressing the role suggested in previous study such as: (1) the role of HLA-DP rare alleles and polymorphisms, and (2) the role of the HLA markers in disease progression from sensitization. The two populations from the already published studies (Saltini et al Eur Respir J. 2001 18:677-84; Rossman et al Am J Respir Crit Care Med. 2002 165:788-94) present similar aspects about: ethnicity, type and length of exposure to Be dust, a broadly similar association between beryllium related abnormalities and HLA. The two population have been pooled and evaluated using common criteria of diagnosis (Sensitized subject: at least 2 positive BeLPT tests each with 2 positive wells; CBD-affected subject: identification of well formed non-caseating granulomas on biopsy), follow up and HLA typing technique (complete HLA-DRB, DQB, DPB high resolution typing using amplification with sequence specific primers or sequence based typing). The two populations included 137 subjects with Beryllium hypersensitized (BH) and 155 Be-exposed controls. Inclusion criteria were met by one hundred and six subjects with Be-hypersensitivity of whom 55 were affected by CBD (age 52 {+-} 11 years; 50 caucasians, 2 African-Americans 2 Hispanics and 1 Asian; 46 males and 9 females; mean duration of Be-exposure 15 {+-} 9 years) and 51 showed Be-sensitization without lung granulomas detected by trans-bronchial biopsy (age 54 {+-} 14 years; 47 Caucasians, 3 Hispanics and 1 Afro-American; 45 males and 6 females; mean age of Be-exposure 17 {+-} 10 years) and 129 Be-exposed controls (age 53 {+-} 14 years; 120 Caucasians, 4 African-American, 4 Hispanics, 1 Asian; 104 males and 25 females; mean duration of Be-exposure 16 {+-} 10 years). Mean follow-up of BH affected subjects was 7.0 {+-} 3.7 years from the first positive Be-LPT test.

  18. Smoking as a Risk Factor for Prostate Cancer: A Meta-Analysis of 24 Prospective Cohort Studies

    PubMed Central

    Haddock, K. Sue; Reid, Rodney; Kupelnick, Bruce

    2010-01-01

    Objectives. We evaluated the relationship between smoking and adenocarcinoma of the prostate. Methods. We pooled data from 24 cohort studies enrolling 21 579 prostate cancer case participants for a general variance-based meta-analysis. Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated separately for mortality and incidence studies. We tested the robustness of effect measures and evaluated statistical heterogeneity with sensitivity analyses. Results. In the pooled data, current smokers had no increased risk of incident prostate cancer (RR = 1.04; 95% CI = 0.87, 1.24), but in data stratified by amount smoked they had statistically significant elevated risk (cigarettes per day or years: RR = 1.22; 95% CI = 1.01, 1.46; pack years of smoking: RR = 1.11; 95% CI = 1.01, 1.22). Former smokers had an increased risk (RR = 1.09; 95% CI = 1.02, 1.16). Current smokers had an increased risk of fatal prostate cancer (RR = 1.14; 95% CI = 1.06, 1.19). The heaviest smokers had a 24% to 30% greater risk of death from prostate cancer than did nonsmokers. Conclusions. Observational cohort studies show an association of smoking with prostate cancer incidence and mortality. Ill-defined exposure categories in many cohort studies suggest that pooled data underestimate risk. PMID:19608952

  19. Analysis of a Pool of Small Plasmids from Soil Heterotrophic Cultivable Bacterial Communities

    PubMed Central

    Papaleo, Maria Cristiana; Fondi, Marco; Maida, Isabel; Perrin, Elena; Bevivino, Annamaria; Dalmastri, Claudia; Fani, Renato

    2015-01-01

    In this work the analysis of the plasmid presence on soil aerobic cultivable heterotrophic bacterial communities was carried out checking a panel of 1,200 isolates, in order to establish the frequency of plasmid presence as well as the degree of plasmid flow between strains affiliated to the same or different taxon. Bacterial communities were isolated from two different sites of a 13-year experimental field with a clay-silt texture. Plasmid molecules were detected at low frequency (27 isolates, 2%) with a size ranging between 2 Kb and 40 Kb. The RAPD analysis performed on the plasmid-harboring isolates and the phylogenetic analysis of the whole community using the 16S rRNA gene sequences revealed the existence of transfer of the same plasmids between strains belonging to the same species and, in some cases, to different species of the same genus. As it might be expected, even though the viable cells title did not differ significantly between the two samplings, the overall data disclosed an uneven distribution of both species and plasmid-harboring strains. PMID:26464609

  20. Analysis of a Pool of Small Plasmids from Soil Heterotrophic Cultivable Bacterial Communities.

    PubMed

    Papaleo, Maria Cristiana; Fondi, Marco; Maida, Isabel; Perrin, Elena; Bevivino, Annamaria; Dalmastri, Claudia; Fani, Renato

    2015-01-01

    In this work the analysis of the plasmid presence on soil aerobic cultivable heterotrophic bacterial communities was carried out checking a panel of 1,200 isolates, in order to establish the frequency of plasmid presence as well as the degree of plasmid flow between strains affiliated to the same or different taxon. Bacterial communities were isolated from two different sites of a 13-year experimental field with a clay-silt texture. Plasmid molecules were detected at low frequency (27 isolates, 2%) with a size ranging between 2 Kb and 40 Kb. The RAPD analysis performed on the plasmid-harboring isolates and the phylogenetic analysis of the whole community using the 16S rRNA gene sequences revealed the existence of transfer of the same plasmids between strains belonging to the same species and, in some cases, to different species of the same genus. As it might be expected, even though the viable cells title did not differ significantly between the two samplings, the overall data disclosed an uneven distribution of both species and plasmid-harboring strains. PMID:26464609

  1. Root and Shoot Respiration of Perennial Ryegrass Are Supplied by the Same Substrate Pools: Assessment by Dynamic 13C Labeling and Compartmental Analysis of Tracer Kinetics1[OA

    PubMed Central

    Lehmeier, Christoph Andreas; Lattanzi, Fernando Alfredo; Schufele, Rudi; Wild, Melanie; Schnyder, Hans

    2008-01-01

    The substrate supply system for respiration of the shoot and root of perennial ryegrass (Lolium perenne) was characterized in terms of component pools and the pools' functional properties: size, half-life, and contribution to respiration of the root and shoot. These investigations were performed with perennial ryegrass growing in constant conditions with continuous light. Plants were labeled with 13CO2/12CO2 for periods ranging from 1 to 600 h, followed by measurements of the rates and 13C/12C ratios of CO2 respired by shoots and roots in the dark. Label appearance in roots was delayed by approximately 1 h relative to shoots; otherwise, the tracer time course was very similar in both organs. Compartmental analysis of respiratory tracer kinetics indicated that, in both organs, three pools supplied 95% of all respired carbon (a very slow pool whose kinetics could not be characterized provided the remaining 5%). The pools' half-lives and relative sizes were also nearly identical in shoot and root (half-life < 15 min, approximately 3 h, and 33 h). An important role of short-term storage in supplying respiration was apparent in both organs: only 43% of respiration was supplied by current photosynthate (fixed carbon transferred directly to centers of respiration via the two fastest pools). The residence time of carbon in the respiratory supply system was practically the same in shoot and root. From this and other evidence, we argue that both organs were supplied by the same pools and that the residence time was controlled by the shoot via current photosynthate and storage deposition/mobilization fluxes. PMID:18715953

  2. Prognostic Value of SMAD4 in Pancreatic Cancer: A Meta-Analysis12

    PubMed Central

    Shugang, Xing; Hongfa, Yang; Jianpeng, Liu; Xu, Zheng; Jingqi, Feng; Xiangxiang, Li; Wei, Li

    2016-01-01

    PURPOSE: The prognostic value of SMAD4 in pancreatic cancer has been evaluated in several studies. However, the conclusions remain controversial. Therefore, we aimed to evaluate the association between SMAD4 expression and the outcome of pancreatic cancer patients by performing a meta-analysis. METHODS: We systematically searched for relevant studies evaluating the relationship between SMAD4 expression and the outcome of pancreatic cancer patients until May 2015. A meta-analysis was performed using STATA 12.0, and pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were used to estimate the strength of the association between SMAD4 expression and the prognosis of pancreatic cancer patients. RESULTS: The analysis included 1762 patients from 14 studies, with 1401 patients from 11 studies and 927 patients from 8 studies included in the univariate and multivariate analyses, respectively. Loss of SMAD4 expression was found to be significantly correlated with poor overall survival, with the combined HR (95% CI) of 1.20 (1.03-1.40). After adjusting for potential confounders using the Cox regression model, the pooled HR (95% CI) was 1.88 (1.31-2.70). In subgroup analysis, study region, number of patients, follow-up duration, and cutoff value were found to affect the significance of the association between loss of SMAD4 expression and poor prognosis. In addition, there was no evidence of publication bias, as suggested by Begg’s and Egger’s test. CONCLUSIONS: Loss of SMAD4 was associated with poor survival and was a negative prognostic indicator in patients with pancreatic cancer. PMID:26947875

  3. Identification of novel causative genes determining the complex trait of high ethanol tolerance in yeast using pooled-segregant whole-genome sequence analysis

    PubMed Central

    Swinnen, Steve; Schaerlaekens, Kristien; Pais, Thiago; Claesen, Jürgen; Hubmann, Georg; Yang, Yudi; Demeke, Mekonnen; Foulquié-Moreno, María R.; Goovaerts, Annelies; Souvereyns, Kris; Clement, Lieven; Dumortier, Françoise; Thevelein, Johan M.

    2012-01-01

    High ethanol tolerance is an exquisite characteristic of the yeast Saccharomyces cerevisiae, which enables this microorganism to dominate in natural and industrial fermentations. Up to now, ethanol tolerance has only been analyzed in laboratory yeast strains with moderate ethanol tolerance. The genetic basis of the much higher ethanol tolerance in natural and industrial yeast strains is unknown. We have applied pooled-segregant whole-genome sequence analysis to map all quantitative trait loci (QTL) determining high ethanol tolerance. We crossed a highly ethanol-tolerant segregant of a Brazilian bioethanol production strain with a laboratory strain with moderate ethanol tolerance. Out of 5974 segregants, we pooled 136 segregants tolerant to at least 16% ethanol and 31 segregants tolerant to at least 17%. Scoring of SNPs using whole-genome sequence analysis of DNA from the two pools and parents revealed three major loci and additional minor loci. The latter were more pronounced or only present in the 17% pool compared to the 16% pool. In the locus with the strongest linkage, we identified three closely located genes affecting ethanol tolerance: MKT1, SWS2, and APJ1, with SWS2 being a negative allele located in between two positive alleles. SWS2 and APJ1 probably contained significant polymorphisms only outside the ORF, and lower expression of APJ1 may be linked to higher ethanol tolerance. This work has identified the first causative genes involved in high ethanol tolerance of yeast. It also reveals the strong potential of pooled-segregant sequence analysis using relatively small numbers of selected segregants for identifying QTL on a genome-wide scale. PMID:22399573

  4. Identification of novel causative genes determining the complex trait of high ethanol tolerance in yeast using pooled-segregant whole-genome sequence analysis.

    PubMed

    Swinnen, Steve; Schaerlaekens, Kristien; Pais, Thiago; Claesen, Jürgen; Hubmann, Georg; Yang, Yudi; Demeke, Mekonnen; Foulquié-Moreno, María R; Goovaerts, Annelies; Souvereyns, Kris; Clement, Lieven; Dumortier, Françoise; Thevelein, Johan M

    2012-05-01

    High ethanol tolerance is an exquisite characteristic of the yeast Saccharomyces cerevisiae, which enables this microorganism to dominate in natural and industrial fermentations. Up to now, ethanol tolerance has only been analyzed in laboratory yeast strains with moderate ethanol tolerance. The genetic basis of the much higher ethanol tolerance in natural and industrial yeast strains is unknown. We have applied pooled-segregant whole-genome sequence analysis to map all quantitative trait loci (QTL) determining high ethanol tolerance. We crossed a highly ethanol-tolerant segregant of a Brazilian bioethanol production strain with a laboratory strain with moderate ethanol tolerance. Out of 5974 segregants, we pooled 136 segregants tolerant to at least 16% ethanol and 31 segregants tolerant to at least 17%. Scoring of SNPs using whole-genome sequence analysis of DNA from the two pools and parents revealed three major loci and additional minor loci. The latter were more pronounced or only present in the 17% pool compared to the 16% pool. In the locus with the strongest linkage, we identified three closely located genes affecting ethanol tolerance: MKT1, SWS2, and APJ1, with SWS2 being a negative allele located in between two positive alleles. SWS2 and APJ1 probably contained significant polymorphisms only outside the ORF, and lower expression of APJ1 may be linked to higher ethanol tolerance. This work has identified the first causative genes involved in high ethanol tolerance of yeast. It also reveals the strong potential of pooled-segregant sequence analysis using relatively small numbers of selected segregants for identifying QTL on a genome-wide scale. PMID:22399573

  5. Occupation and Risk of Non-Hodgkin Lymphoma and Its Subtypes: A Pooled Analysis from the InterLymph Consortium

    PubMed Central

    ‘t Mannetje, Andrea; De Roos, Anneclaire J.; Boffetta, Paolo; Vermeulen, Roel; Benke, Geza; Fritschi, Lin; Brennan, Paul; Foretova, Lenka; Maynadié, Marc; Becker, Nikolaus; Nieters, Alexandra; Staines, Anthony; Campagna, Marcello; Chiu, Brian; Clavel, Jacqueline; de Sanjose, Silvia; Hartge, Patricia; Holly, Elizabeth A.; Bracci, Paige; Linet, Martha S.; Monnereau, Alain; Orsi, Laurent; Purdue, Mark P.; Rothman, Nathaniel; Lan, Qing; Kane, Eleanor; Costantini, Adele Seniori; Miligi, Lucia; Spinelli, John J.; Zheng, Tongzhang; Cocco, Pierluigi; Kricker, Anne

    2015-01-01

    Background: Various occupations have been associated with an elevated risk of non-Hodgkin lymphoma (NHL), but results have been inconsistent across studies. Objectives: We investigated occupational risk of NHL and of four common NHL subtypes with particular focus on occupations of a priori interest. Methods: We conducted a pooled analysis of 10,046 cases and 12,025 controls from 10 NHL studies participating in the InterLymph Consortium. We harmonized the occupational coding using the 1968 International Standard Classification of Occupations (ISCO-1968) and grouped occupations previously associated with NHL into 25 a priori groups. Odds ratios (ORs) adjusted for center, age, and sex were determined for NHL overall and for the following four subtypes: diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), and peripheral T-cell lymphoma (PTCL). Results: We confirmed previously reported positive associations between NHL and farming occupations [field crop/vegetable farm workers OR = 1.26; 95% confidence interval (CI): 1.05, 1.51; general farm workers OR = 1.19; 95% CI: 1.03, 1.37]; we also confirmed associations of NHL with specific occupations such as women’s hairdressers (OR = 1.34; 95% CI: 1.02, 1.74), charworkers/cleaners (OR = 1.17; 95% CI: 1.01, 1.36), spray-painters (OR = 2.07; 95% CI: 1.30, 3.29), electrical wiremen (OR = 1.24; 95% CI: 1.00, 1.54), and carpenters (OR = 1.42; 95% CI: 1.04, 1.93). We observed subtype-specific associations for DLBCL and CLL/SLL in women’s hairdressers and for DLBCL and PTCL in textile workers. Conclusions: Our pooled analysis of 10 international studies adds to evidence suggesting that farming, hairdressing, and textile industry–related exposures may contribute to NHL risk. Associations with women’s hairdresser and textile occupations may be specific for certain NHL subtypes. Citation: ‘t Mannetje A, De Roos AJ, Boffetta P, Vermeulen R, Benke G, Fritschi L, Brennan P, Foretova L, Maynadié M, Becker N, Nieters A, Staines A, Campagna M, Chiu B, Clavel J, de Sanjose S, Hartge P, Holly EA, Bracci P, Linet MS, Monnereau A, Orsi L, Purdue MP, Rothman N, Lan Q, Kane E, Seniori Costantini A, Miligi L, Spinelli JJ, Zheng T, Cocco P, Kricker A. 2016. Occupation and risk of non-Hodgkin lymphoma and its subtypes: a pooled analysis from the InterLymph Consortium. Environ Health Perspect 124:396–405; http://dx.doi.org/10.1289/ehp.1409294 PMID:26340796

  6. Risks on N-acetyltransferase 2 and bladder cancer: a meta-analysis

    PubMed Central

    Zhu, Zongheng; Zhang, Jinshan; Jiang, Wei; Zhang, Xianjue; Li, Youkong; Xu, Xiaoming

    2015-01-01

    Background It is known that bladder cancer disease is closely related to aromatic amine compounds, which could cause cancer by regulating of N-acetylation and N-acetyltransferase 1 and 2 (NAT1 and NAT2). The NAT2 slowed acetylation and would increase the risk of bladder cancer, with tobacco smoke being regarded as a risk factor for this increased risk. However, the relationship between NAT2 slow acetylation and bladder cancer is still debatable at present. This study aims to explore preliminarily correlation of NAT2 slow acetylation and the risk of bladder cancer. Methods The articles were searched from PubMed, Cochran, McGrane English databases, CBM, CNKI, and other databases. The extraction of bladder cancer patients and a control group related with the NAT2 gene were detected by the state, and the referenced articles and publications were also used for data retrieval. Using a random effects model, the model assumes that the studies included in the analysis cases belong to the overall population in the study of random sampling, and considering the variables within and between studies. Data were analyzed using STATA Version 6.0 software, using the META module. According to the inclusion and exclusion criteria of the literature study, 20 independent studies are included in this meta-analysis. Results The results showed that the individual differences of bladder cancer susceptibility might be part of the metabolism of carcinogens. Slow acetylation status of bladder cancer associated with the pooled odds ratio was 1.31 (95% confidence interval: 1.11–1.55). Conclusion The status of NAT2 slow N-acetylation is associated with bladder cancer risks, and may increase the risk of bladder cancer. PMID:26715854

  7. Seismic analysis of a large pool-type LMR (liquid metal reactor)

    SciTech Connect

    Wang, C.Y.; Gvildys, J.

    1989-01-01

    This paper describes the seismic study of a 450-MWe liquid metal reactor (LMR) under 0.3-g SSE ground excitation. Two calculations were performed using the new design configuration. They deal with the seismic response of the reactor vessel, the guard vessel and support skirt, respectively. In both calculations, the stress and displacement fields at important locations of those components are investigated. Assessments are also made on the elastic and inelastic structural capabilities for other beyond-design basis seismic loads. Results of the reactor vessel analysis reveal that the maximum equivalent stress is only about half of the material yield stress. For the guard vessel and support skirt, the stress level is very small. Regarding the analysis if inelastic structural capability, solutions of the Newmark-Hall ductility modification method show that the reactor vessel can withstand seismics with ground ZPAs ranging from 1.015 to 1.31 g, which corresponds to 3.37 to 4.37 times the basic 0.3-g SSE. Thus, the reactor vessel and guard vessel are strong enough to resist seismic loads. 4 refs., 10 figs., 5 tabs.

  8. Proteomic analysis of phosphorylation in cancer.

    PubMed

    Ruprecht, Benjamin; Lemeer, Simone

    2014-06-01

    Constitutive activity of kinases is known to be crucial for a tumor to maintain its malignant phenotype, a phenomenon which is often referred to as oncogene addiction. The in-depth analysis of aberrant signaling pathways by the analysis of protein phosphorylation has become feasible through recent advances in proteomics technology. In this article we will review developments in the field of phosphoproteomics and its application in cancer research. The most widely used technologies for the generic enrichment of phosphopeptides are discussed as well as targeted approaches for the analysis of a specific subset of phosphopeptides. Validation experiments of phosphorylation sites using targeted mass spectrometry are also explained. Finally, we will highlight applications of phosphoproteomic technology in cancer research using cell lines and tissue. PMID:24666026

  9. CHEK2 mutation and risk of prostate cancer: a systematic review and meta-analysis

    PubMed Central

    Wang, Yue; Dai, Bo; Ye, Dingwei

    2015-01-01

    Background: CHEK2 encodes for a G2 checkpoint kinase which plays a critical role in DNA repair. Its mutation confers an increased risk of breast cancer. It has also been suggested to increase risks of prostate cancer, but its involvement with this type of cancer has not been confirmed. Methods: We performed a systematic review and meta-analysis to clarify the association between CHEK2 1100delC, IVS2+1G>A, I157T mutation and risk of Prostate Cancer. A comprehensive, computerized literature search of PubMed until December 27, 2014 was carried out. Eligible studies were included according to specific inclusion criteria. Pooled hazard ratio was estimated using the fixed effects model or random effects model according to heterogeneity between studies. Results: Eight eligible studies were included in the analysis, all were retrospective studies. The overall meta-analysis demonstrated that the CHEK2 1100delC mutation (OR 3.29; 95% confidence interval: 1.85-5.85; P = 0.00) and I157T missense mutation (OR 1.80; 95% confidence interval: 1.51-2.14; P = 0.00) was associated with higher risk of Prostate Cancer, and CHEK2 1100delC mutation is irrelevant to familial aggregation phenomenon of prostate cancer (OR 1.59; 95% confidence interval: 0.79-3.20; P = 0.20). The IVS2+1G>A mutation is also irrelevant to Prostate Cancer (OR = 1.59, 95% CI = 0.93-2.71, P = 0.09). None of the single studies materially altered the original results and no evidence of publication bias was found. Conclusion: CHEK2 1100delC mutation and I157T missense mutation in males indicates higher risk of Prostate Cancer, but theres no evidence to prove the CHEK2 1100delC mutation was associated with Familial prostate cancer. PMID:26629066

  10. Meta-analysis of diffusion-weighted magnetic resonance imaging in identification of colorectal cancer

    PubMed Central

    Jia, Hongyuan; Ma, Xuelei; Zhao, Yang; Zhao, Jingyi; Liu, Rongjun; Chen, Zihang; Chen, Jinna; Huang, Jingwen; Li, Yanyan; Zhang, Jing; Wang, Feng

    2015-01-01

    Purpose: This meta-analysis aimed to evaluate the performance of diffusion-weighted magnetic resonance imaging (DWI) in identification of colorectal cancer. Methods: A systematic literature search was performed for studies that evaluated the diagnostic accuracy of DWI in identification of colorectal cancer. Methodological quality was assessed by Quality Assessment for Studies of Diagnostic Accuracy 2 (QUADAS 2) tool. After extracting data, we estimated the pooled sensitivity, specificity, likelihood ratios, and constructed summary receiver operating characteristics (SROC) curve. Results: Ten studies involving 367 malignant lesions and 178 benign lesions were considered eligible after full-text review. The pooled sensitivity and specificity were 0.95 (95% CI: 0.90-0.97) and 0.93 (95% CI: 0.85-0.97), respectively. Positive likelihood ratio and negative likelihood ratio were 12.8 (95% CI: 5.99-27.4) and 0.06 (95% CI: 0.03-0.11), respectively. The area under SROC curve was 0.98. Conclusions: Our meta-analysis indicates that DWI is a highly accurate diagnostic method in identification of colorectal cancer. PMID:26770325

  11. Association between Breastfeeding and Endometrial Cancer Risk: Evidence from a Systematic Review and Meta-Analysis

    PubMed Central

    Wang, Lianlian; Li, Jingxi; Shi, Zhan

    2015-01-01

    Quantification of the association between breastfeeding and risk of endometrial cancer is still conflicting. We therefore conducted a meta-analysis to assess the association between breastfeeding and endometrial cancer risk. Pertinent studies were identified by a search of PubMed and Web of Knowledge through April 2015. A random effect model was used to combine the data for analysis. Sensitivity analysis and publication bias were conducted. Dose-response relationships were assessed by restricted cubic spline and variance-weighted least squares regression analysis. Fourteen articles involving 5158 endometrial cancer cases and 706,946 participants were included in this meta-analysis. Pooled results suggested that breastfeeding significantly reduced the risk of endometrial cancer (summary relative risk (RR): 0.77, 95% CI: 0.62–0.96, I2: 63.0%), especially in North America (summary RR: 0.87, 95% CI: 0.79–0.95). A linear dose-response relationship was found, with the risk of endometrial cancer decreased by 2% for every one-month increase in the duration of breastfeeding (summary RR: 0.98, 95% CI: 0.97–0.99). Our analysis suggested that breastfeeding, particularly a longer duration of breastfeeding, was inversely associated with the risk of endometrial cancer, especially in North America, but not in Europe and Asia, probably due to the small number of cases included. Due to this limitation, further studies originating in other countries are required to assess the association between breastfeeding and endometrial cancer risk. PMID:26184301

  12. Virtual pools for interactive analysis and software development through an integrated Cloud environment

    NASA Astrophysics Data System (ADS)

    Grandi, C.; Italiano, A.; Salomoni, D.; Calabrese Melcarne, A. K.

    2011-12-01

    WNoDeS, an acronym for Worker Nodes on Demand Service, is software developed at CNAF-Tier1, the National Computing Centre of the Italian Institute for Nuclear Physics (INFN) located in Bologna. WNoDeS provides on demand, integrated access to both Grid and Cloud resources through virtualization technologies. Besides the traditional use of computing resources in batch mode, users need to have interactive and local access to a number of systems. WNoDeS can dynamically select these computers instantiating Virtual Machines, according to the requirements (computing, storage and network resources) of users through either the Open Cloud Computing Interface API, or through a web console. An interactive use is usually limited to activities in user space, i.e. where the machine configuration is not modified. In some other instances the activity concerns development and testing of services and thus implies the modification of the system configuration (and, therefore, root-access to the resource). The former use case is a simple extension of the WNoDeS approach, where the resource is provided in interactive mode. The latter implies saving the virtual image at the end of each user session so that it can be presented to the user at subsequent requests. This work describes how the LHC experiments at INFN-Bologna are testing and making use of these dynamically created ad-hoc machines via WNoDeS to support flexible, interactive analysis and software development at the INFN Tier-1 Computing Centre.

  13. HiTSelect: a comprehensive tool for high-complexity-pooled screen analysis.

    PubMed

    Diaz, Aaron A; Qin, Han; Ramalho-Santos, Miguel; Song, Jun S

    2015-02-18

    Genetic screens of an unprecedented scale have recently been made possible by the availability of high-complexity libraries of synthetic oligonucleotides designed to mediate either gene knockdown or gene knockout, coupled with next-generation sequencing. However, several sources of random noise and statistical biases complicate the interpretation of the resulting high-throughput data. We developed HiTSelect, a comprehensive analysis pipeline for rigorously selecting screen hits and identifying functionally relevant genes and pathways by addressing off-target effects, controlling for variance in both gene silencing efficiency and sequencing depth of coverage and integrating relevant metadata. We document the superior performance of HiTSelect using data from both genome-wide RNAi and CRISPR/Cas9 screens. HiTSelect is implemented as an open-source package, with a user-friendly interface for data visualization and pathway exploration. Binary executables are available at http://sourceforge.net/projects/hitselect/, and the source code is available at https://github.com/diazlab/HiTSelect. PMID:25428347

  14. Immunoisolation of two synaptic vesicle pools from synaptosomes: a proteomics analysis.

    PubMed

    Morciano, Marco; Burré, Jacqueline; Corvey, Carsten; Karas, Michael; Zimmermann, Herbert; Volknandt, Walter

    2005-12-01

    The nerve terminal proteome governs neurotransmitter release as well as the structural and functional dynamics of the presynaptic compartment. In order to further define specific presynaptic subproteomes we used subcellular fractionation and a monoclonal antibody against the synaptic vesicle protein SV2 for immunoaffinity purification of two major synaptosome-derived synaptic vesicle-containing fractions: one sedimenting at lower and one sedimenting at higher sucrose density. The less dense fraction contains free synaptic vesicles, the denser fraction synaptic vesicles as well as components of the presynaptic membrane compartment. These immunoisolated fractions were analyzed using the cationic benzyldimethyl-n-hexadecylammonium chloride (BAC) polyacrylamide gel system in the first and sodium dodecyl sulfate-polyacrylamide gel electrophoresis in the second dimension. Protein spots were subjected to analysis by matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI TOF MS). We identified 72 proteins in the free vesicle fraction and 81 proteins in the plasma membrane-containing denser fraction. Synaptic vesicles contain a considerably larger number of protein constituents than previously anticipated. The plasma membrane-containing fraction contains synaptic vesicle proteins, components of the presynaptic fusion and retrieval machinery and numerous other proteins potentially involved in regulating the functional and structural dynamics of the nerve terminal. PMID:16269012

  15. HiTSelect: a comprehensive tool for high-complexity-pooled screen analysis

    PubMed Central

    Diaz, Aaron A.; Qin, Han; Ramalho-Santos, Miguel; Song, Jun S.

    2015-01-01

    Genetic screens of an unprecedented scale have recently been made possible by the availability of high-complexity libraries of synthetic oligonucleotides designed to mediate either gene knockdown or gene knockout, coupled with next-generation sequencing. However, several sources of random noise and statistical biases complicate the interpretation of the resulting high-throughput data. We developed HiTSelect, a comprehensive analysis pipeline for rigorously selecting screen hits and identifying functionally relevant genes and pathways by addressing off-target effects, controlling for variance in both gene silencing efficiency and sequencing depth of coverage and integrating relevant metadata. We document the superior performance of HiTSelect using data from both genome-wide RNAi and CRISPR/Cas9 screens. HiTSelect is implemented as an open-source package, with a user-friendly interface for data visualization and pathway exploration. Binary executables are available at http://sourceforge.net/projects/hitselect/, and the source code is available at https://github.com/diazlab/HiTSelect. PMID:25428347

  16. Meta-analysis of neuroimaging data: a comparison of image-based and coordinate-based pooling of studies.

    PubMed

    Salimi-Khorshidi, Gholamreza; Smith, Stephen M; Keltner, John R; Wager, Tor D; Nichols, Thomas E

    2009-04-15

    With the rapid growth of neuroimaging research and accumulation of neuroinformatic databases the synthesis of consensus findings using meta-analysis is becoming increasingly important. Meta-analyses pool data across many studies to identify reliable experimental effects and characterize the degree of agreement across studies. Coordinate-based meta-analysis (CBMA) methods are the standard approach, where each study entered into the meta-analysis has been summarized using only the (x, y, z) locations of peak activations (with or without activation magnitude) reported in published reports. Image-based meta-analysis (IBMA) methods use the full statistic images, and allow the use of hierarchical mixed effects models that account for differing intra-study variance and modeling of random inter-study variation. The purpose of this work is to compare image-based and coordinate-based meta-analysis methods applied to the same dataset, a group of 15 fMRI studies of pain, and to quantify the information lost by working only with the coordinates of peak activations instead of the full statistic images. We apply a 3-level IBMA mixed model for a "mega-analysis", and highlight important considerations in the specification of each model and contrast. We compare the IBMA result to three CBMA methods: ALE (activation likelihood estimation), KDA (kernel density analysis) and MKDA (multi-level kernel density analysis), for various CBMA smoothing parameters. For the datasets considered, we find that ALE at sigma=15 mm, KDA at rho=25-30 mm and MKDA at rho=15 mm give the greatest similarity to the IBMA result, and that ALE was the most similar for this particular dataset, though only with a Dice similarity coefficient of 0.45 (Dice measure ranges from 0 to 1). Based on this poor similarity, and the greater modeling flexibility afforded by hierarchical mixed models, we suggest that IBMA is preferred over CBMA. To make IBMA analyses practical, however, the neuroimaging field needs to develop an effective mechanism for sharing image data, including whole-brain images of both effect estimates and their standard errors. PMID:19166944

  17. Comparison of dust related respiratory effects in Dutch and Canadian grain handling industries: a pooled analysis.

    PubMed Central

    Peelen, S J; Heederik, D; Dimich-Ward, H D; Chan-Yeung, M; Kennedy, S M

    1996-01-01

    OBJECTIVES: Four previously conducted epidemiological studies in more than 1200 grain workers were used to compare exposure-response relations between exposure to grain dust and respiratory health. METHODS: The studies included Dutch workers from an animal feed mill and a transfer grain elevator and Canadian workers from a terminal grain elevator and the docks. Relations between forced expiratory volume in one second (FEV1) and exposure were analysed with multiple regression analysis corrected for smoking, age, and height. Exposure variables examined included cumulative and current dust exposure and the numbers of years a subject was employed in the industry. Sampling efficiencies of the Dutch and Canadian measurement techniques were compared in a pilot study. Results of this study were used to correct slopes of exposure-response relations for differences in dust fractions sampled by Dutch and Canadian personal dust samplers. RESULTS: Negative exposure-response relations were shown for regressions of FEV1 on cumulative and current exposure and years employed. Slopes of the exposure-response relations differed by a factor of three to five between industries, apart from results for cumulative exposure. Here the variation in slopes differed by a factor of 100, from -1 to -0.009 ml/mg.y/m3. The variation in slopes between industries reduced to between twofold to fivefold when the Dutch transfer elevator workers were not considered. There was evidence that the small exposure-response slope found for this group is caused by misclassification of exposure and a strong healthy worker effect. Alternative, but less likely explanations for the variation in slopes were differences in exposure concentrations, composition of grain dust, exposure characteristics, and measurement techniques. CONCLUSION: In conclusion, this study showed moderately similar negative exposure-response relations for four different populations from different countries, despite differences in methods of exposure assessment and exposure estimation. PMID:8983468

  18. Evidence of association of APOE with age-related macular degeneration: a pooled analysis of 15 studies.

    PubMed

    McKay, Gareth J; Patterson, Chris C; Chakravarthy, Usha; Dasari, Shilpa; Klaver, Caroline C; Vingerling, Johannes R; Ho, Lintje; de Jong, Paulus T V M; Fletcher, Astrid E; Young, Ian S; Seland, Johan H; Rahu, Mati; Soubrane, Gisele; Tomazzoli, Laura; Topouzis, Fotis; Vioque, Jesus; Hingorani, Aroon D; Sofat, Reecha; Dean, Michael; Sawitzke, Julie; Seddon, Johanna M; Peter, Inga; Webster, Andrew R; Moore, Anthony T; Yates, John R W; Cipriani, Valentina; Fritsche, Lars G; Weber, Bernhard H F; Keilhauer, Claudia N; Lotery, Andrew J; Ennis, Sarah; Klein, Michael L; Francis, Peter J; Stambolian, Dwight; Orlin, Anton; Gorin, Michael B; Weeks, Daniel E; Kuo, Chia-Ling; Swaroop, Anand; Othman, Mohammad; Kanda, Atsuhiro; Chen, Wei; Abecasis, Goncalo R; Wright, Alan F; Hayward, Caroline; Baird, Paul N; Guymer, Robyn H; Attia, John; Thakkinstian, Ammarin; Silvestri, Giuliana

    2011-12-01

    Age-related macular degeneration (AMD) is the most common cause of incurable visual impairment in high-income countries. Previous studies report inconsistent associations between AMD and apolipoprotein E (APOE), a lipid transport protein involved in low-density cholesterol modulation. Potential interaction between APOE and sex, and smoking status has been reported. We present a pooled analysis (n = 21,160) demonstrating associations between late AMD and APOε4 (odds ratio [OR] = 0.72 per haplotype; confidence interval [CI]: 0.65-0.74; P = 4.41×10(-11) ) and APOε2 (OR = 1.83 for homozygote carriers; CI: 1.04-3.23; P = 0.04), following adjustment for age group and sex within each study and smoking status. No evidence of interaction between APOE and sex or smoking was found. Ever smokers had significant increased risk relative to never smokers for both neovascular (OR = 1.54; CI: 1.38-1.72; P = 2.8×10(-15) ) and atrophic (OR = 1.38; CI: 1.18-1.61; P = 3.37×10(-5) ) AMD but not early AMD (OR = 0.94; CI: 0.86-1.03; P = 0.16), implicating smoking as a major contributing factor to disease progression from early signs to the visually disabling late forms. Extended haplotype analysis incorporating rs405509 did not identify additional risks beyond ε2 and ε4 haplotypes. Our expanded analysis substantially improves our understanding of the association between the APOE locus and AMD. It further provides evidence supporting the role of cholesterol modulation, and low-density cholesterol specifically, in AMD disease etiology. PMID:21882290

  19. Parameningeal rhabdomyosarcoma in pediatric age: results of a pooled analysis from North American and European cooperative groups

    PubMed Central

    Merks, J. H. M.; De Salvo, G. L.; Bergeron, C.; Bisogno, G.; De Paoli, A.; Ferrari, A.; Rey, A.; Oberlin, O.; Stevens, M. C. G.; Kelsey, A.; Michalski, J.; Hawkins, D. S.; Anderson, J. R.

    2014-01-01

    Background Parameningeal (PM) site is a well-known adverse prognostic factor in children with localized rhabdomyosarcoma (RMS). To identify risk factors associated with outcome at this site, we pooled data from 1105 patients treated in 10 studies conducted by European and North American cooperative groups between 1984 and 2004. Patients and methods Clinical factors including age, histology, size, invasiveness, nodal involvement, Intergroup Rhabdomyosarcoma Study (IRS) clinical group, site, risk factors for meningeal involvement (MI), study group, and application of radiotherapy (RT) were studied for their impact on event-free and overall survival (EFS and OS). Results Ten-year EFS and OS were 62.6 and 66.1% for the whole group. Patients without initial RT showed worse survival (10-year OS 40.8% versus 68.5% for RT treated patients). Multivariate analysis focusing on 862 patients who received RT as part of their initial treatment revealed four unfavorable prognostic factors: age <3 or >10 years, signs of MI, unfavorable site, and tumor size. Utilizing these prognostic factors, patients could be classified into different risk groups with 10-year OS ranging between 51.1 and 80.9%. Conclusions While, in general, PM localization is regarded as an adverse prognostic factor, the current analysis differentiates those with good prognosis (36% patients with 0–1 risk factor: 10-year OS 80.9%) from high-risk PM patients (28% with 3–4 factors: 10-year OS 51.1%). Furthermore, this analysis reinforces the necessity for RT in PM RMS. PMID:24356633

  20. Evidence of association of APOE with age-related macular degeneration - a pooled analysis of 15 studies

    PubMed Central

    McKay, Gareth J.; Patterson, Chris C.; Chakravarthy, Usha; Dasari, Shilpa; Klaver, Caroline C.; Vingerling, Johannes R.; Ho, Lintje; de Jong, Paulus T.V.M.; Fletcher, Astrid E.; Young, Ian S.; Seland, Johan H.; Rahu, Mati; Soubrane, Gisele; Tomazzoli, Laura; Topouzis, Fotis; Vioque, Jesus; Hingorani, Aroon D.; Sofat, Reecha; Dean, Michael; Sawitzke, Julie; Seddon, Johanna M.; Peter, Inga; Webster, Andrew R.; Moore, Anthony T.; Yates, John R.W.; Cipriani, Valentina; Fritsche, Lars G.; Weber, Bernhard H.F.; Keilhauer, Claudia N.; Lotery, Andrew J.; Ennis, Sarah; Klein, Michael L.; Francis, Peter J.; Stambolian, Dwight; Orlin, Anton; Gorin, Michael B.; Weeks, Daniel E.; Kuo, Chia-Ling; Swaroop, Anand; Othman, Mohammad; Kanda, Atsuhiro; Chen, Wei; Abecasis, Goncalo R.; Wright, Alan F.; Hayward, Caroline; Baird, Paul N.; Guymer, Robyn H.; Attia, John; Thakkinstian, Ammarin; Silvestri, Giuliana

    2011-01-01

    Age-related macular degeneration (AMD) is the most common cause of incurable visual impairment in high-income countries. Previous studies report inconsistent associations between AMD and apolipoprotein E (APOE), a lipid transport protein involved in low-density cholesterol modulation. Potential interaction between APOE and sex, and smoking status, has been reported. We present a pooled analysis (n=21,160) demonstrating associations between late AMD and APOε4 (OR=0.72 per haplotype; CI: 0.65–0.74; P=4.41×10−11) and APOε2 (OR=1.83 for homozygote carriers; CI: 1.04–3.23; P=0.04), following adjustment for age-group and sex within each study and smoking status. No evidence of interaction between APOE and sex or smoking was found. Ever smokers had significant increased risk relative to never smokers for both neovascular (OR=1.54; CI: 1.38–1.72; P=2.8×10−15) and atrophic (OR=1.38; CI: 1.18–1.61; P=3.37×10−5) AMD but not early AMD (OR=0.94; CI: 0.86–1.03; P=0.16), implicating smoking as a major contributing factor to disease progression from early signs to the visually disabling late forms. Extended haplotype analysis incorporating rs405509 did not identify additional risks beyondε2 and ε4 haplotypes. Our expanded analysis substantially improves our understanding of the association between the APOE locus and AMD. It further provides evidence supporting the role of cholesterol modulation, and low-density cholesterol specifically, in AMD disease etiology. PMID:21882290

  1. Oral rivaroxaban versus standard therapy for the treatment of symptomatic venous thromboembolism: a pooled analysis of the EINSTEIN-DVT and PE randomized studies

    PubMed Central

    2013-01-01

    Background Standard treatment for venous thromboembolism (VTE) consists of a heparin combined with vitamin K antagonists. Direct oral anticoagulants have been investigated for acute and extended treatment of symptomatic VTE; their use could avoid parenteral treatment and/or laboratory monitoring of anticoagulant effects. Methods A prespecified pooled analysis of the EINSTEIN-DVT and EINSTEIN-PE studies compared the efficacy and safety of rivaroxaban (15 mg twice-daily for 21 days, followed by 20 mg once-daily) with standard-therapy (enoxaparin 1.0 mg/kg twice-daily and warfarin or acenocoumarol). Patients were treated for 3, 6, or 12 months and followed for suspected recurrent VTE and bleeding. The prespecified noninferiority margin was 1.75. Results A total of 8282 patients were enrolled; 4151 received rivaroxaban and 4131 received standard-therapy. The primary efficacy outcome occurred in 86 (2.1%) rivaroxaban-treated patients compared with 95 (2.3%) standard-therapy-treated patients (hazard ratio, 0.89; 95% confidence interval [CI], 0.66–1.19; pnoninferiority < 0.001). Major bleeding was observed in 40 (1.0%) and 72 (1.7%) patients in the rivaroxaban and standard-therapy groups, respectively (hazard ratio, 0.54; 95% CI, 0.37–0.79; p = 0.002). In key subgroups, including fragile patients, cancer patients, patients presenting with large clots, and those with a history of recurrent VTE, the efficacy and safety of rivaroxaban were similar compared with standard-therapy. Conclusion The single-drug approach with rivaroxaban resulted in similar efficacy to standard-therapy and was associated with a significantly lower rate of major bleeding. Efficacy and safety results were consistent among key patient subgroups. Trial registration EINSTEIN-PE: ClinicalTrials.gov, NCT00439777; EINSTEIN-DVT: ClinicalTrials.gov, NCT00440193. PMID:24053656

  2. Depression and anxiety in ovarian cancer: a systematic review and meta-analysis of prevalence rates

    PubMed Central

    Watts, Sam; Prescott, Philip; Mason, Jessica; McLeod, Natalie; Lewith, George

    2015-01-01

    Objectives To systematically review the literature pertaining to the prevalence of depression and anxiety in patients with ovarian cancer as a function of treatment stage. Design Systematic review and meta-analysis. Participants 3623 patients with ovarian cancer from primary research investigations. Primary outcome measure The prevalence of depression and anxiety in patients with ovarian cancer as a function of treatment stage. Results We identified 24 full journal articles that met the inclusion criteria for entry into the meta-analysis resulting in a pooled sample size of 3623 patients. The meta-analysis of prevalence rates identified pretreatment, on-treatment and post-treatment depression prevalences of 25.34% (CI 22.79% to 28.07%), 22.99% (CI 19.85% to 26.46%) and 12.71% (CI 10.14% to 15.79%), respectively. Pretreatment, on-treatment and post-treatment anxiety prevalences were 19.12% (CI 17.11% to 21.30%), 26.23% (CI 22.30% to 30.56%) and 27.09% (CI 23.10% to 31.49%). Conclusions Our findings suggest that the prevalence of depression and anxiety in women with ovarian cancer, across the treatment spectrum, is significantly greater than in the healthy female population. With the growing emphasis on improving the management of survivorship and quality of life, we conclude that further research is warranted to ensure psychological distress in ovarian cancer is not underdiagnosed and undertreated. PMID:26621509

  3. Telmisartan/Hydrochlorothiazide combination therapy for the treatment of hypertension: a pooled analysis in older and younger patients.

    PubMed

    Kjeldsen, Sverre E; Schumacher, Helmut; Neldam, Steen; Guthrie, Robert M

    2013-06-01

    Older patients frequently receive angiotensin II receptor blocker/diuretic combinations to control blood pressure (BP), although there have been relatively few trials specifically examining this patient population. A pooled analysis was performed of data from 7 randomized trials of telmisartan/hydrochlorothiazide combinations or telmisartan monotherapy in older (65 years and older) and younger (younger than 65 years) patients to better understand the response of older patients to a telmisartan/hydrochlorothiazide combination. Telmisartan doses were 40 mg and 80 mg (T40 and T80). Hydrochlorothiazide doses were 12.5 mg and 25 mg (H12.5 and H25). A total of 3654 patients were included and the mean treatment duration was approximately 8 weeks. BP reductions with telmisartan/hydrochlorothiazide combinations were broadly similar in older and younger patients. In older patients, mean BP reductions from baseline were -30.1/-19.0 mm Hg with the T80/H25 combination and -21.7/-13.0 mm Hg with T80 monotherapy. Tolerability was similar regardless of age, and the incidence of adverse events in both older and younger patients was similar to placebo. The telmisartan/hydrochlorothiazide combination, particularly high-dose T80/H25, is effective and well tolerated in patients 65 years and older as well as in younger patients. PMID:23730986

  4. Robot-assisted laparoscopic liver resection: a systematic review and pooled analysis of minor and major hepatectomies

    PubMed Central

    Nota, Carolijn L.; Rinkes, Inne H. Borel; Molenaar, Izaak Q.; van Santvoort, Hjalmar C.; Fong, Yuman; Hagendoorn, Jeroen

    2015-01-01

    Background Robotic surgery has been introduced to overcome the limitations of conventional laparoscopy. A systematic review and meta-analysis were performed to assess the safety and feasibility for three subgroups of robot-assisted laparoscopic liver resection: (i) minor resections of easily accessible segments: 2/3, 4B, 5, 6, (ii) minor resections of difficult located segments: 1, 4A, 7, 8 and (iii) major resections: ≥ 4 segments. Methods A systematic search was performed in PubMed, EMBASE and Cochrane Library. Results Twelve observational, mostly retrospective studies reporting on 363 patients were included. Data were pooled and analyzed. For subgroup (i) (n = 81) the weighted mean operative time was 215 ± 65 min. One conversion (1%) to laparotomy was needed. Weighted mean operative time for subgroup (ii) (n = 17) was 220 ± 60 min. No conversions were needed. For subgroup (iii) (n = 99) the weighted mean operative time was 405 ± 100 min. In this subgroup 8 robotic procedures (8%) were converted to open surgery. Conclusion Data show that robot-assisted laparoscopic liver resection is feasible in minor resections of all segments and major resections. Larger, prospective studies are warranted to compare the possible advantages of robot-assisted surgery with conventional laparoscopy and open surgery. PMID:26902129

  5. Prenatal and Postnatal Exposure to Persistent Organic Pollutants and Infant Growth: A Pooled Analysis of Seven European Birth Cohorts

    PubMed Central

    Iszatt, Nina; Stigum, Hein; Verner, Marc-André; White, Richard A.; Govarts, Eva; Murinova, Lubica Palkovicova; Schoeters, Greet; Trnovec, Tomas; Legler, Juliette; Pelé, Fabienne; Botton, Jérémie; Chevrier, Cécile; Wittsiepe, Jürgen; Ranft, Ulrich; Vandentorren, Stéphanie; Kasper-Sonnenberg, Monika; Klümper, Claudia; Weisglas-Kuperus, Nynke; Polder, Anuschka

    2015-01-01

    Background Infant exposure to persistent organic pollutants (POPs) may contribute to obesity. However, many studies so far have been small, focused on transplacental exposure, used an inappropriate measure to assess postnatal exposure through breastfeeding if any, or did not discern between prenatal and postnatal effects. Objectives We investigated prenatal and postnatal exposure to POPs and infant growth (a predictor of obesity). Methods We pooled data from seven European birth cohorts with biomarker concentrations of polychlorinated biphenyl 153 (PCB-153) (n = 2,487), and p,p´-dichlorodiphenyldichloroethylene (p,p´-DDE) (n = 1,864), estimating prenatal and postnatal POPs exposure using a validated pharmacokinetic model. Growth was change in weight-for-age z-score between birth and 24 months. Per compound, multilevel models were fitted with either POPs total exposure from conception to 24 months or prenatal or postnatal exposure. Results We found a significant increase in growth associated with p,p´-DDE, seemingly due to prenatal exposure (per interquartile increase in exposure, adjusted β = 0.12; 95% CI: 0.03, 0.22). Due to heterogeneity across cohorts, this estimate cannot be considered precise, but does indicate that an association with infant growth is present on average. In contrast, a significant decrease in growth was associated with postnatal PCB-153 exposure (β = –0.10; 95% CI: –0.19, –0.01). Conclusion To our knowledge, this is the largest study to date of POPs exposure and infant growth, and it contains state-of-the-art exposure modeling. Prenatal p,p´-DDE was associated with increased infant growth, and postnatal PCB-153 with decreased growth at European exposure levels. Citation Iszatt N, Stigum H, Verner MA, White RA, Govarts E, Palkovicova Murinova L, Schoeters G, Trnovec T, Legler J, Pelé F, Botton J, Chevrier C, Wittsiepe J, Ranft U, Vandentorren S, Kasper-Sonnenberg M, Klümper C, Weisglas-Kuperus N, Polder A, Eggesbø M, OBELIX. 2015. Prenatal and postnatal exposure to persistent organic pollutants and infant growth: a pooled analysis of seven European birth cohorts. Environ Health Perspect 123:730–736; http://dx.doi.org/10.1289/ehp.1308005 PMID:25742056

  6. Sun exposure and melanoma risk at different latitudes: a pooled analysis of 5700 cases and 7216 controls

    PubMed Central

    Chang, Yu-mei; Barrett, Jennifer H; Bishop, D Timothy; Armstrong, Bruce K; Bataille, Veronique; Bergman, Wilma; Berwick, Marianne; Bracci, Paige M; Elwood, J Mark; Ernstoff, Marc S; Gallagher, Richard P; Green, Adèle C; Gruis, Nelleke A; Holly, Elizabeth A; Ingvar, Christian; Kanetsky, Peter A; Karagas, Margaret R; Lee, Tim K; Le Marchand, Loïc; Mackie, Rona M; Olsson, Håkan; Østerlind, Anne; Rebbeck, Timothy R; Sasieni, Peter; Siskind, Victor; Swerdlow, Anthony J; Titus-Ernstoff, Linda; Zens, Michael S; Newton-Bishop, Julia A

    2009-01-01

    Background Melanoma risk is related to sun exposure; we have investigated risk variation by tumour site and latitude. Methods We performed a pooled analysis of 15 case–control studies (5700 melanoma cases and 7216 controls), correlating patterns of sun exposure, sunburn and solar keratoses (three studies) with melanoma risk. Pooled odds ratios (pORs) and 95% Bayesian confidence intervals (CIs) were estimated using Bayesian unconditional polytomous logistic random-coefficients models. Results Recreational sun exposure was a risk factor for melanoma on the trunk (pOR = 1.7; 95% CI: 1.4–2.2) and limbs (pOR = 1.4; 95% CI: 1.1–1.7), but not head and neck (pOR = 1.1; 95% CI: 0.8–1.4), across latitudes. Occupational sun exposure was associated with risk of melanoma on the head and neck at low latitudes (pOR = 1.7; 95% CI: 1.0–3.0). Total sun exposure was associated with increased risk of melanoma on the limbs at low latitudes (pOR = 1.5; 95% CI: 1.0–2.2), but not at other body sites or other latitudes. The pORs for sunburn in childhood were 1.5 (95% CI: 1.3–1.7), 1.5 (95% CI: 1.3–1.7) and 1.4 (95% CI: 1.1–1.7) for melanoma on the trunk, limbs, and head and neck, respectively, showing little variation across latitudes. The presence of head and neck solar keratoses was associated with increased risk of melanoma on the head and neck (pOR = 4.0; 95% CI: 1.7–9.1) and limbs (pOR = 4.0; 95% CI: 1.9–8.4). Conclusion Melanoma risk at different body sites is associated with different amounts and patterns of sun exposure. Recreational sun exposure and sunburn are strong predictors of melanoma at all latitudes, whereas measures of occupational and total sun exposure appear to predict melanoma predominately at low latitudes. PMID:19359257

  7. Posttreatment human papillomavirus testing for residual or recurrent high-grade cervical intraepithelial neoplasia: a pooled analysis

    PubMed Central

    Yoshikawa, Hiroyuki

    2016-01-01

    Objective We conducted a pooled analysis of published studies to compare the performance of human papillomavirus (HPV) testing and cytology in detecting residual or recurrent diseases after treatment for cervical intraepithelial neoplasia grade 2 or 3 (CIN 2/3). Methods Source articles presenting data on posttreatment HPV testing were identified from the National Library of Medicine (PubMed) database. We included 5,319 cases from 33 articles published between 1996 and 2013. Results The pooled sensitivity of high-risk HPV testing (0.92; 95% confidence interval [CI], 0.90 to 0.94) for detecting posttreatment CIN 2 or worse (CIN 2+) was much higher than that of cytology (0.76; 95% CI, 0.71 to 0.80). Co-testing of HPV testing and cytology maximized the sensitivity (0.93; 95% CI, 0.87 to 0.96), while HPV genotyping (detection of the same genotype between pre- and posttreatments) did not improve the sensitivity (0.89; 95% CI, 0.82 to 0.94) compared with high-risk HPV testing alone. The specificity of high-risk HPV testing (0.83; 95% CI, 0.82 to 0.84) was similar to that of cytology (0.85; 95% CI, 0.84 to 0.87) and HPV genotyping (0.83; 95% CI, 0.81 to 0.85), while co-testing had reduced specificity (0.76; 95% CI, 0.75 to 0.78). For women with positive surgical margins, high-risk HPV testing provided remarkable risk discrimination between test-positives and test-negatives (absolute risk of residual CIN 2+ 74.4% [95% CI, 64.0 to 82.6] vs. 0.8% [95% CI, 0.15 to 4.6]; p<0.001). Conclusion Our findings recommend the addition of high-risk HPV testing, either alone or in conjunction with cytology, to posttreatment surveillance strategies. HPV testing can identify populations at greatest risk of posttreatment CIN 2+ lesions, especially among women with positive section margins. PMID:26463429

  8. Prognostic Role of Common MicroRNA Polymorphisms in Cancers: Evidence from a Meta-Analysis

    PubMed Central

    Xia, Lingzi; Ren, Yangwu; Fang, Xue; Yin, Zhihua; Li, Xuelian; Wu, Wei; Guan, Peng; Zhou, Baosen

    2014-01-01

    Background The morbidity and mortality of cancer increase remarkably every year. It's a heavy burden for family and society. The detection of prognostic biomarkers can help to improve the theraputic effect and prolong the lifetime of patients. microRNAs have an influential role in cancer prognosis. The results of articles discussing the relationship between microRNA polymorphisms and cancer prognosis are inconsistent. Methods We conduct a meta-analysis of 19 publications concerning the association of four common polymorphisms, mir-146a rs2910164, mir-149 rs2292832, mir-196a2 rs11614913 and mir-499 rs3746444, with cancer prognosis. Pooled Hazard Ratios with 95% Confidence Intervals for the relationship between four genetic polymorphisms and Overall Survival, Recurrence-free Survival, Disease-free survival, recurrence are calculated. Subgroup analysis by population and type of tumor are conducted. Results GG genotype of mir-146a may be the protective factor for overall survival, especially in Caucasian population. C-containing genotypes of mir-196a2 act as a risk role for overall survival. The same result exists in Asian population, in Non-Small Cell Lung Cancer and digestive cancer. The patients with C allele of mir-149 have a better overall survival, especially in Non-Small Cell Lung Cancer. No significant results are obtained for mir-499 polymorphisms. Conclusions Genetic polymorphisms in mir-146a, mir-196a2 and mir-149 may be associated with overall survival. This effect varies with different types of cancer. Genetic polymorphism in mir-499 may have nothing to do with cancer prognosis. PMID:25337946

  9. The Association between Telomere Length and Cancer Prognosis: Evidence from a Meta-Analysis

    PubMed Central

    Li, Lu; Zhou, Ying; Wang, Chao; Hou, Shuxun

    2015-01-01

    Background Telomeres are essential for chromosomal integrity and stability. Shortened telomere length (TL) has been associated with risk of cancers and aging-related diseases. Several studies have explored associations between TL and cancer prognosis, but the results are conflicting. Methods Prospective studies on the relationship between TL and cancer survival were identified by a search of PubMed up to May 25, 2015. There were no restrictions on the cancer type or DNA source. The quality of the included studies was assessed using the Newcastle-Ottawa Scale. Meta-analysis approaches were conducted to determine pooled relative risks and 95% confidence intervals. Results Thirty-three articles containing forty-five independent studies were ultimately involved in our meta-analysis, of which twenty-seven were about overall cancer survival and eighteen were about cancer progression. Short TL was associated with increased cancer mortality risk (RR = 1.30, 95%CI: 1.061.59) and poor cancer progression (RR = 1.44, 95%CI: 1.101.88), both with high levels of heterogeneity (I2 = 83.5%, P = 0.012for overall survival and I2 = 75.4%, P = 0.008 for progression). TL was an independent predictor of overall cancer survival and progression in chronic lymphocytic leukemia. Besides, short telomeres were also associated with increased colorectal cancer mortality and decreased overall survival of esophageal cancer, but not in other cancers. Cancer progression was associated with TL in Asian and America populations and short TL predicted poor cancer survival in older populations. Compared with tumor tissue cells, TL in blood lymphocyte cells was better for prediction. In addition, the associations remained significant when restricted to studies with adjustments for age, with larger sample sizes, measuring TL using southern blotting or estimating risk effects by hazard ratios. Conclusion Short TL demonstrated a significant association with poor cancer survival, suggesting the potential prognostic significance of TL. Additional large well-designed studies are needed to confirm our findings. PMID:26177192

  10. A pan-cancer analysis of prognostic genes

    PubMed Central

    Reon, Brian; Chen, Wei-Min; Bekiranov, Stefan

    2015-01-01

    Numerous studies have identified prognostic genes in individual cancers, but a thorough pan-cancer analysis has not been performed. In addition, previous studies have mostly used microarray data instead of RNA-SEQ, and have not published comprehensive lists of associations with survival. Using recently available RNA-SEQ and clinical data from The Cancer Genome Atlas for 6,495 patients, we have investigated every annotated and expressed gene’s association with survival across 16 cancer types. The most statistically significant harmful and protective genes were not shared across cancers, but were enriched in distinct gene sets which were shared across certain groups of cancers. These groups of cancers were independently recapitulated by both unsupervised clustering of Cox coefficients (a measure of association with survival) for individual genes, and for gene programs. This analysis has revealed unappreciated commonalities among cancers which may provide insights into cancer pathogenesis and rationales for co-opting treatments between cancers. PMID:27047702

  11. Statin use and breast cancer survival and risk: a systematic review and meta-analysis

    PubMed Central

    Li, Yuan-Yuan; Zhu, Jingjing; Qian, Ke-Qing; Li, Wen-Jing; Wu, Lang

    2015-01-01

    The purpose of this study is to determine the associations between statin use and breast cancer survival and risk by performing a systematic review and meta-analysis. We searched PubMed, Embase and Web of Science up to August 2015 for identifying relevant prospective or case-control studies, or randomized clinical trials. Five prospective studies involving 60,911 patients reported the association between statin use and breast cancer mortality. Eleven prospective studies, 12 case-control studies and 9 randomized clinical trials involving 83,919 patients reported the association between statin use and breast cancer risk. After pooling estimates from all available studies, there was a significantly negative association between pre-diagnosis statin use and breast cancer mortality (for overall survival (OS): hazard ratio (HR) = 0.68, 95% confidence interval (CI) 0.54–0.84; for disease specific survival (DSS): HR = 0.72, 95% CI 0.53–0.99). There was also a significant inverse association between post-diagnosis statin use and breast cancer DSS (HR = 0.65, 95% CI 0.43–0.98), although the association with breast cancer OS did not reach statistical significance (HR = 0.71, 95% CI 0.48–1.07). Additionally, there was a non-linear relationship for the duration of post-diagnosis statin use with breast cancer specific mortality. On the other hand, with regards to the relationship between statin use and breast cancer risk, no significant association was detected. Our analyses suggest that although statin use may not influence breast cancer risk, the use of statin may be associated with decrease mortality of breast cancer patients. Further large-scale studies are warranted to validate our findings. PMID:26472026

  12. Association between three exonuclease 1 polymorphisms and cancer risks: a meta-analysis

    PubMed Central

    Chen, Zi-Yu; Zheng, Si-Rong; Zhong, Jie-Hui; Zhuang, Xiao-Duan; Zhou, Jue-Yu

    2016-01-01

    To date, the results of studies exploring the relation between exonuclease 1 (Exo1) polymorphisms and cancer risks have differed. In this study, we performed a meta-analysis to investigate the effect of the three most extensively studied Exo1 polymorphisms (Pro757Leu, Glu589Lys, and Glu670Gly) on cancer susceptibility. The related studies published before August 5, 2015, were collected by searching the PubMed and EMBASE databases. We found 16 publications containing studies that were eligible for our study, including 10 studies for Pro757Leu polymorphism (4,093 cases and 3,834 controls), 12 studies for Glu589Lys polymorphism (6,479 cases and 6,550 controls), and 7 studies for Glu670Gly polymorphism (3,700 cases and 3,496 controls). Pooled odds ratios and 95% confidence intervals were used to assess the strength of the associations, and all the statistical analyses were calculated using the software program STATA version 12.0. Our results revealed that the Pro757Leu polymorphism was significantly associated with a reduced cancer risk, whereas an inverse association was found for the Glu589Lys polymorphism. Furthermore, subgroup analysis of smoking status indicated that the Glu589Lys polymorphism was significantly associated with an increased cancer risk in smokers, but not in nonsmokers. However, no evidence was found for an association between the Glu670Gly polymorphism and cancer risk. In conclusion, this meta-analysis suggests that the Pro757Leu polymorphism may provide protective effects against cancer, while the Glu589Lys polymorphism may be a risk factor for cancer. Moreover, the Glu670Gly polymorphism may have no influence on cancer susceptibility. In the future, large-scaled and well-designed studies are needed to achieve a more precise and comprehensive result. PMID:26966378

  13. Weight change during long-term treatment with lurasidone: pooled analysis of studies in patients with schizophrenia

    PubMed Central

    Mao, Yongcai; Pikalov, Andrei; Cucchiaro, Josephine; Loebel, Antony

    2015-01-01

    The objective of this analysis was to evaluate the effect of 12 months of treatment with lurasidone on weight in patients with schizophrenia. Post-hoc, observed-case analysis included pooled data from six studies on 40–160 mg/day lurasidone; two studies included active comparators (2–6 mg/day risperidone or 200–800 mg/day quetiapine XR). Overall, 593 patients completed 12 months of treatment (N=471 lurasidone, N=89 risperidone, N=33 quetiapine XR). The mean baseline weight was 72.8, 80.8, and 72.4 kg in the lurasidone, risperidone, and quetiapine XR groups, respectively. The mean weight change at month 12 was −0.4 kg with lurasidone, +2.6 kg with risperidone, and +1.2 kg with quetiapine XR. Weight gain of at least 7% from study baseline was observed in 16.0, 25.8, and 15.2% of patients, and weight loss of at least 7% was seen in 18.5, 6.7, and 9.1% of patients treated with lurasidone, risperidone, and quetiapine XR, respectively. A shift from normal/underweight baseline BMI status to overweight/obese at month 12 occurred in 10.2, 27.6, and 15.0% of patients in the lurasidone, risperidone, and quetiapine XR groups, respectively. Conversely, 14.3, 1.7, and 7.7% of patients, respectively, shifted from overweight/obese to normal/underweight. In summary, a low potential for clinically significant weight gain was observed in patients with schizophrenia treated continuously with lurasidone for 12 months. PMID:26196189

  14. Primary Hepatic Small Cell Carcinoma: Two Case Reports, Molecular Characterization and Pooled Analysis of Known Clinical Data.

    PubMed

    Shastri, Aditi; Msaouel, Pavlos; Montagna, Cristina; White, Sherry; Delio, Maria; Patel, Kunjan; Alexis, Karenza; Strakhan, Marianna; Elrafei, Tarek N; Reed, Louis Juden

    2016-01-01

    Primary hepatic small cell carcinoma (HSCC) is a rare malignancy that has previously been described in only few case reports. The clinicopathological course, natural history, molecular markers and ideal treatment strategy for this tumor have not been fully elucidated. Herein, we report on two cases of spontaneously arising, metastatic primary HSCC that were treated at our Institution. Both patients succumbed to their disease within two months of initial presentation. Both cases underwent postmortem examination and no evidence of a pulmonary or other non-hepatic small cell primary was found. Unlike pulmonary small cell tumors, these two hepatic primaries showed only locoregional spread and very few distant metastases. Formalin-fixed samples were obtained at autopsy and sequenced using single-nucleotide polymorphism arrays and whole-genome sequencing. Four mutations in the epidermal growth factor receptor (EGFR) gene known to be associated with response to tyrosine kinase inhibitors (TKIs) were detected in one of the two HSCC samples. A systematic review and pooled analysis of all previously reported cases of primary HSCCs was conducted. The median overall survival was estimated at 4 months. Surgical resection was significantly associated with longer overall survival (hazard ratio =0.13, 95% confidence interval=0.03-0.69). Although several case reports of primary HSCC have been reported prior to this publication, to our knowledge this is the first time that molecular and systematic analysis has been conducted in order to more fully characterize this rare disease. Our results indicate that surgical resection, when feasible, may be a valid option in primary HSCC, and that some tumors may respond to TKIs against EGFR. PMID:26722053

  15. Weight change during long-term treatment with lurasidone: pooled analysis of studies in patients with schizophrenia.

    PubMed

    Meyer, Jonathan M; Mao, Yongcai; Pikalov, Andrei; Cucchiaro, Josephine; Loebel, Antony

    2015-11-01

    The objective of this analysis was to evaluate the effect of 12 months of treatment with lurasidone on weight in patients with schizophrenia. Post-hoc, observed-case analysis included pooled data from six studies on 40-160 mg/day lurasidone; two studies included active comparators (2-6 mg/day risperidone or 200-800 mg/day quetiapine XR). Overall, 593 patients completed 12 months of treatment (N=471 lurasidone, N = 89 risperidone, N = 33 quetiapine XR). The mean baseline weight was 72.8, 80.8, and 72.4 kg in the lurasidone, risperidone, and quetiapine XR groups, respectively. The mean weight change at month 12 was -0.4 kg with lurasidone, +2.6 kg with risperidone, and +1.2 kg with quetiapine XR. Weight gain of at least 7% from study baseline was observed in 16.0, 25.8, and 15.2% of patients, and weight loss of at least 7% was seen in 18.5, 6.7, and 9.1% of patients treated with lurasidone, risperidone, and quetiapine XR, respectively. A shift from normal/underweight baseline BMI status to overweight/obese at month 12 occurred in 10.2, 27.6, and 15.0% of patients in the lurasidone, risperidone, and quetiapine XR groups, respectively. Conversely, 14.3, 1.7, and 7.7% of patients, respectively, shifted from overweight/obese to normal/underweight. In summary, a low potential for clinically significant weight gain was observed in patients with schizophrenia treated continuously with lurasidone for 12 months. PMID:26196189

  16. Risk of Primary Liver Cancer Associated with Gallstones and Cholecystectomy: A Meta-Analysis

    PubMed Central

    Liu, Yanqiong; He, Yu; Li, Taijie; Xie, Li; Wang, Jian; Qin, Xue; Li, Shan

    2014-01-01

    Background Recent epidemiological evidence points to an association between gallstones or cholecystectomy and the incidence risk of liver cancer, but the results are inconsistent. We present a meta-analysis of observational studies to explore this association. Methods We identified studies by a literature search of PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and relevant conference proceedings up to March 2014. A random-effects model was used to generate pooled multivariable adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Between-study heterogeneity was assessed using Cochran’s Q statistic and the I2. Results Fifteen studies (five case-control and 10 cohort studies) were included in this analysis. There were 4,487,662 subjects in total, 17,945 diagnoses of liver cancer, 328,420 exposed to gallstones, and 884,507 exposed to cholecystectomy. Pooled results indicated a significant increased risk of liver cancer in patients with a history of gallstones (OR = 2.54; 95% CI, 1.71–3.79; n = 11 studies), as well as cholecystectomy (OR = 1.62; 95% CI, 1.29–2.02; n = 12 studies), but there was considerable heterogeneity among these studies. The effects estimates did not vary markedly when stratified by gender, study design, study region, and study quality. The multivariate meta-regression analysis suggested that study region and study quality appeared to explain the heterogeneity observed in the cholecystectomy analysis. Conclusions Our results suggest that individuals with a history of gallstones and cholecystectomy may have an increased risk of liver cancer. PMID:25290940

  17. Meta-analysis of residential exposure to radon gas and lung cancer.

    PubMed Central

    Pavia, Maria; Bianco, Aida; Pileggi, Claudia; Angelillo, Italo F.

    2003-01-01

    OBJECTIVES: To investigate the relation between residential exposure to radon and lung cancer. METHODS: A literature search was performed using Medline and other sources. The quality of studies was assessed. Adjusted odds ratios with 95% confidence intervals (CI) for the risk of lung cancer among categories of levels of exposure to radon were extracted. For each study, a weighted log-linear regression analysis of the adjusted odds ratios was performed according to radon concentration. The random effect model was used to combine values from single studies. Separate meta-analyses were performed on results from studies grouped with similar characteristics or with quality scores above or equal to the median. FINDINGS: Seventeen case-control studies were included in the meta-analysis. Quality scoring for individual studies ranged from 0.45 to 0.77 (median, 0.64). Meta-analysis based on exposure at 150 Bq/m3 gave a pooled odds ratio estimate of 1.24 (95% CI, 1.11-1.38), which indicated a potential effect of residential exposure to radon on the risk of lung cancer. Pooled estimates of fitted odds ratios at several levels of randon exposure were all significantly different from unity--ranging from 1.07 at 50 Bq/m3 to 1.43 at 250 Bq/m3. No remarkable differences from the baseline analysis were found for odds ratios from sensitivity analyses of studies in which > 75% of eligible cases were recruited (1.12, 1.00-1.25) and studies that included only women (1.29, 1.04-1.60). CONCLUSION: Although no definitive conclusions may be drawn, our results suggest a dose-response relation between residential exposure to radon and the risk of lung cancer. They support the need to develop strategies to reduce human exposure to radon. PMID:14758433

  18. Diagnostic value of SHOX2 DNA methylation in lung cancer: a meta-analysis

    PubMed Central

    Zhao, Qing-Tao; Guo, Tao; Wang, Hui-En; Zhang, Xiao-Peng; Zhang, Hua; Wang, Zhi-Kang; Yuan, Zheng; Duan, Guo-Chen

    2015-01-01

    The diagnostic value of SHOX2 DNA methylation in patients with lung cancer remains controversial. Thus, we performed a systematic review and meta-analysis to assess diagnostic accuracy of SHOX2 DNA methylation in the lymph node, bronchial aspirates, pleural effusion, plasma, and tumor tissue for lung cancer. We conducted a comprehensive literature search in PubMed, Ovid, the Cochrane library, and Web of Science databases in May 2015. The diagnostic sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and summary receiver operating characteristic (SROC) curve were pooled using STATA 12.0 software. A total of 2,296 subjects included 1,129 lung cancer patients in eight studies were recruited in this meta-analysis. The summary estimates for SHOX2 DNA methylation in the diagnosis of lung cancer in these studies were pooled SEN =0.70 (95% confidence interval [CI]: 0.46–0.87), SPE =0.96 (95% CI: 0.91–0.99), PLR 20.01 (95% CI: 6.96–57.52), NLR 0.31 (95% CI: 0.15–0.64), and DOR 65.11 (95% CI: 13.10–323.61), and the area under the curve (AUC) was 0.96 (95% CI: 0.94–0.97). SHOX2 DNA methylation has greater diagnostic value in detecting lung cancer. In addition, considering the potential publication bias and high heterogeneity, further research studies with more well-designed and large sample sizes are needed in the future. PMID:26640383

  19. Blood glucose concentration and risk of pancreatic cancer: systematic review and dose-response meta-analysis

    PubMed Central

    Liao, Wei-Chih; Wu, Ming-Shiang; Lin, Jaw-Town; Wang, Hsiu-Po

    2015-01-01

    Objective To evaluate potential linear and non-linear dose-response relations between blood glucose and risk of pancreatic cancer. Design Systematic review and dose-response meta-analysis of prospective observational studies. Data sources Search of PubMed, Scopus, and related reviews before 30 November 2013 without language restriction. Eligibility criteria Prospective studies evaluating the association between blood glucose concentration and pancreatic cancer. Retrospective and cross sectional studies excluded to avoid reverse causality. Data extraction and synthesis Two reviewers independently extracted relevant information and assessed study quality with the Newcastle-Ottawa scale. Random effects dose-response meta-analysis was conducted to assess potential linear and non-linear dose-response relations. Results Nine studies were included for analysis, with a total of 2408 patients with pancreatic cancer. There was a strong linear dose-response association between fasting blood glucose concentration and the rate of pancreatic cancer across the range of prediabetes and diabetes. No non-linear association was detected. The pooled rate ratio of pancreatic cancer per 0.56 mmol/L (10 mg/dL) increase in fasting blood glucose was 1.14 (95% confidence interval 1.06 to 1.22; P<0.001) without significant heterogeneity. Sensitivity analysis excluding blood glucose categories in the range of diabetes showed similar results (pooled rate ratio per 0.56 mmol/L increase in fasting blood glucose was 1.15, 95% confidence interval 1.05 to 1.27; P=0.003), strengthening the association between prediabetes and pancreatic cancer. Conclusions Every 0.56 mmol/L increase in fasting blood glucose is associated with a 14% increase in the rate of pancreatic cancer. As prediabetes can be improved or even reversed through lifestyle changes, early detection of prediabetes coupled with lifestyle changes could represent a viable strategy to curb the increasing incidence of pancreatic cancer. PMID:25556126

  20. Metabolic Syndrome Is Associated with Increased Breast Cancer Risk: A Systematic Review with Meta-Analysis

    PubMed Central

    Bhandari, Ruchi; Kelley, George A.; Hartley, Tara A.; Rockett, Ian R. H.

    2014-01-01

    Background. Although individual metabolic risk factors are reported to be associated with breast cancer risk, controversy surrounds risk of breast cancer from metabolic syndrome (MS). We report the first systematic review and meta-analysis of the association between MS and breast cancer risk in all adult females. Methods. Studies were retrieved by searching four electronic reference databases [PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Science, and ProQuest through June 30, 2012] and cross-referencing retrieved articles. Eligible for inclusion were longitudinal studies reporting associations between MS and breast cancer risk among females aged 18 years and older. Relative risks and 95% confidence intervals were calculated for each study and pooled using random-effects models. Publication bias was assessed quantitatively (Trim and Fill) and qualitatively (funnel plots). Heterogeneity was examined using Q and I2 statistics. Results. Representing nine independent cohorts and 97,277 adult females, eight studies met the inclusion criteria. A modest, positive association was observed between MS and breast cancer risk (RR: 1.47, 95% CI, 1.15–1.87; z = 3.13; p = 0.002; Q = 26.28, p = 0.001; I2 = 69.55%). No publication bias was observed. Conclusions. MS is associated with increased breast cancer risk in adult women. PMID:25653879

  1. Association between Metformin Therapy and Breast Cancer Incidence and Mortality: Evidence from a Meta-Analysis

    PubMed Central

    Yang, Ting; Yang, Yuan

    2015-01-01

    Purpose Metformin may be associated with a decreased risk of breast cancer. We performed a meta-analysis to assess the effect of metformin intake on breast cancer risk and mortality. Methods We performed a PubMed and EMbase search for all available studies that described the risk of breast cancer and all-cause mortality in relation to the use of metformin among patients with type 2 diabetes mellitus. Pooled relative risks (RRs) were determined using a random effects model to assess the strength of association between metformin and the risk of breast cancer. Results Fifteen articles from PubMed satisfied the inclusion criteria, including a total of 838,333 participants. Compared with the control group, metformin use was not related to a reduced incidence of breast cancer (RR, 0.964; 95% confidence interval [CI], 0.761-1.221; p=0.761). However, metformin therapy was associated with decreased all-cause mortality (RR, 0.652; 95% CI, 0.488-0.873; p=0.004). No obvious publication bias was detected (incidence: pBegg=0.755, pEgger=0.008; mortality: pBegg=0.072, pEgger=0.185). Conclusion The present study suggested that metformin therapy may decrease the all-cause mortality of patients affected by breast cancer. However, this finding should be considered carefully and confirmed with further studies. PMID:26472977

  2. Occupational exposure to pesticides and prostate cancer: a systematic review and meta-analysis.

    PubMed

    Lewis-Mikhael, Anne-Mary; Bueno-Cavanillas, Aurora; Ofir Guiron, Talia; Olmedo-Requena, Rocío; Delgado-Rodríguez, Miguel; Jiménez-Moleón, José Juan

    2016-02-01

    Epidemiological studies on exposure to pesticides and risk of prostate cancer (PC) provide inconsistent results. We aimed to explore various potential sources of heterogeneity not previously assessed and to derive updated risk estimates from homogenous studies. We searched PubMed, Web of Science and Scopus databases for case-control and cohort studies published from 1985 to April 2014. We assessed the quality of the articles using the Newcastle-Ottawa Scale. Pooled estimates were calculated using random-effects models. Heterogeneity was explored using subset analyses and metaregression. Fifty-two studies were included in the review and 25 in the meta-analysis. No association was found between low exposure to pesticides and PC, but association was significant for high exposure, pooled OR 1.33 (1.02 to 1.63), I(2)=44.8%, p=0.024. Heterogeneity was explained by a number of variables including method used to assess exposure. Pooled OR was weak and non-significant for studies measuring serum pesticide level, 1.12 (0.74 to 1.50), I(2)=0.00%, p=0.966. For studies applying self-reporting of exposure, pooled estimate was 1.34 (0.91 to 1.77), I(2)=0.00%, p=0.493, while a high significant association was detected for grouped exposure assessment, 2.24 (1.36 to 3.11), I(2)=0.00%, p=0.955. In spite of a weak significant association detected when pooling ORs for high occupational exposure to pesticides, the magnitude of the association was related to the method of exposure assessment used by the original studies. A family history-pesticide exposure interaction was also observed for a number of pesticides. PMID:26644457

  3. Breastfeeding and ovarian cancer risk: a meta-analysis of epidemiologic studies1234

    PubMed Central

    Wu, Qi-Jun; Gong, Ting-Ting; Vogtmann, Emily; Wang, Yong-Lai; Lin, Bei

    2013-01-01

    Background: Epidemiologic studies have yielded inconsistent findings between breastfeeding and epithelial ovarian cancer (EOC) risk. Objective: We performed a meta-analysis to summarize available evidence of the association between breastfeeding and breastfeeding duration and EOC risk from published cohort and case-control studies. Design: Relevant published studies were identified by a search of MEDLINE through December 2012. Two authors (T-TG and Q-JW) independently performed the eligibility evaluation and data abstraction. Study-specific RRs from individual studies were pooled by using a random-effects model, and heterogeneity and publication-bias analyses were conducted. Results: Five prospective and 30 case-control studies were included in this analysis. The pooled RR for ever compared with never breastfeeding was 0.76 (95% CI: 0.69, 0.83), with moderate heterogeneity (Q = 69.4, P < 0.001, I2 = 55.3%). Risk of EOC decreased by 8% for every 5-mo increase in the duration of breastfeeding (RR: 0.92; 95% CI: 0.90, 0.95). The risk reduction was similar for borderline and invasive EOC and was consistent within case-control and cohort studies. Conclusions: Results of this meta-analysis support the hypothesis that ever breastfeeding and a longer duration of breastfeeding are associated with lower risks of EOC. Additional research is warranted to focus on the association with cancer grade and histologic subtypes of EOC. PMID:23966430

  4. Associations between polymorphisms of the XPC gene and lung cancer susceptibility: a meta-analysis.

    PubMed

    Zhu, Mei-Ling; Hua, Rui-Xi; Zheng, Leizhen

    2014-04-01

    Xeroderma pigmentosum complementation group C (XPC) gene plays a critical role in DNA damage recognition, and its functional single nucleotide polymorphisms (SNPs) may alter DNA repair capacity and cancer susceptibility. Numerous epidemiological studies have investigated the associations between XPC Lys939Gln and Ala499Val polymorphisms and lung cancer susceptibility, but the conclusions are inconclusive. We searched three electronic databases (MEDLINE, EMBASE and EBSCO) for eligible publications and performed a meta-analysis assessing the associations between XPC Lys939Gln and Ala499Val polymorphisms and lung cancer risk. We also analysed the genotype-mRNA expression correlation using the data of HapMap phase II release 23 with 270 individuals from 4 ethnicities for exploring biological plausibility of our findings. We included ten published studies of 3,882 cases and 5,219 controls for Lys939Gln, and five studies with 2,605 cases and 3,329 controls for Ala499Val. When all studies were pooled, we found a significantly increased overall lung cancer risk for Lys939Gln polymorphism (recessive model: OR = 1.14, 95 % CI = 1.01-1.29, P = 0.218 for heterogeneity). Stratification analysis also showed a higher lung cancer risk in Asian populations (recessive model: OR = 1.26, 95% CI = 1.04-1.52, P = 0.263 for heterogeneity). Interestingly, we found significant correlation between Lys939Gln genotypes and XPC mRNA expression for Asian populations as well. However, we did not observe any association between Ala499Val polymorphism and overall lung cancer risk, nor in further stratification analysis. This meta-analysis suggests that XPC Lys939Gln polymorphism may contribute to lung cancer risk, which needs further validation in single larger studies. PMID:24375193

  5. Polychlorinated biphenyls and breast cancer: A congener-specific meta-analysis.

    PubMed

    Leng, Ling; Li, Jing; Luo, Xiu-Mei; Kim, Jun-Young; Li, Yi-Meng; Guo, Xue-Mei; Chen, Xi; Yang, Qiao-Yun; Li, Guang; Tang, Nai-Jun

    2016-03-01

    The incidence of breast cancer is related to various risk factors, especially that the environmental and lifestyle factors account for major contribution at the rate of 70% to 95% over all. However, there still remains some controversy over the epidemiological evidence regarding the effects of environmental carcinogens on the risk of breast cancer. We conducted a quantitative meta-analysis aiming at full evaluation of the effects of polychlorinated biphenyls (PCBs) on breast cancer in a congener-specific fashion. Four online literature databases were systematically searched before 1st January 2015, for studies stating correlation between PCB congeners and breast cancer. The Newcastle-Ottawa Scale was used to evaluate the quality of the studies that were included in our analysis. Sixteen studies were included in our final meta-analysis after screening based on the priori inclusion criteria. Nine PCB congeners were reported by more than two studies and they were presented in detail. The pooled Odds Ratios (ORs) showed a significant increase in the risk of breast cancer in individuals with higher plasma/fat levels of PCB 99 (OR: 1.36; 95% CI: 1.02 to 1.80), PCB 183 (OR: 1.56; 95% CI: 1.25 to 1.95) and PCB 187 (OR: 1.18; 95% CI: 1.01 to 1.39). Besides, the outcomes did not support a relationship between dioxin-like PCB congeners and the risk of breast cancer. The results of our meta-analysis imply that PCB 99, PCB 183 and PCB 187 would increase the risk of breast cancer. The mechanism of this increased risk may be by the induction of the CYP2B family in cytochrome P450 enzymes. PMID:26735351

  6. Optical spectra analysis for breast cancer diagnostics

    NASA Astrophysics Data System (ADS)

    Belkov, S. A.; Kochemasov, G. G.; Lyubynskaya, T. E.; Maslov, N. V.; Nuzhny, A. S.; da Silva, L. B.; Rubenchik, A.

    2011-11-01

    Minimally invasive probe and optical biopsy system based on optical spectra recording and analysis seem to be a promising tool for early diagnostics of breast cancer. Light scattering and absorption spectra are generated continuously as far as the needle-like probe with one emitting and several collecting optical fibers penetrates through the tissues toward to the suspicious area. That allows analyzing not only the state of local site, but also the structure of tissues along the needle trace. The suggested method has the advantages of automated on-line diagnosing and minimal tissue destruction and in parallel with the conventional diagnostic procedures provides the ground for decision-making. 165 medical trials were completed in Nizhny Novgorod Regional Oncology Centre, Russia. Independent diagnoses were the results of fine biopsy and histology. Application of wavelet expansion and clasterization techniques for spectra analysis revealed several main spectral types for malignant and benign tumors. Automatic classification algorithm demonstrated specificity ˜90% and sensitivity ˜91%. Large amount of information, fuzziness in criteria and data noisiness make neural networks to be an attractive analytic tool. The model based on three-layer perceptron was tested over the sample of 29 `cancer' and 29 `non-cancer' cases and demonstrated total separation.

  7. Thalidomide in myelofibrosis with myeloid metaplasia: a pooled-analysis of individual patient data from five studies.

    PubMed

    Barosi, Giovanni; Giovanni, Barosi; Elliott, Michelle; Michelle, Elliott; Canepa, Letizia; Letizia, Canepa; Ballerini, Filippo; Filippo, Ballerini; Piccaluga, Pier Paolo; Pier Paolo, Piccaluga; Visani, Giuseppe; Giuseppe, Visani; Marchetti, Monia; Monia, Marchetti; Pozzato, Gabriele; Gabriele, Pozzato; Zorat, Francesca; Francesca, Zorat; Tefferi, Ayalew; Ayalew, Tefferi

    2002-12-01

    Trials to determine the effect of thalidomide in patients with Myelofibrosis with Myeloid Metaplasia (MMM) have produced inconclusive results due to different criteria for response and heterogeneous study participants. We undertook a pooled-analysis to assess the effects of such treatment on a larger series of cases and with a uniform assessment of response. We used updated data on 62 individual patients from 5 phase II trials that evaluated thalidomide therapy in MMM patients. Responsewas judged on individual disease parameters, on the improvement of the Dupriez risk categories and on the improvement of a 6 point "severity score" based on myeloproliferative and myelodepletive indexes of the disease. Overall, using standard dose of thalidomide, i.e. starting with no less than 100 mg/day, 49 patients (79%) had more than 4 weeks of therapy. Twenty-nine percent of patients with moderate to severe anemia showed an increase in hemoglobin or reduction/abolishment of blood transfusion requirements, 38% with moderate to severe thrombocytopenia had an increase in platelet counts, and 41% with high grade splenomegaly demonstrated a measurable reduction in splenic size. These effects led to an absolute decrease in the "severity" score in 44.9% of the patients. Major disease severity and high degrees of splenomegaly before therapy predicted response with a probability of 61.9%. However, worsening of the "severity" score was observed in 20.4% of the patients, 18% having a "myeloproliferative reaction" with leukocytosis and/or thrombocytosis. Sixty-six percent of the patients discontinued the drug before 6 months of treatment due to intolerance. In conclusion, there is a small but clear improvement of disease severity with thalidomide therapy in MMM. The potential for myeloproliferative reactions and the unfavorable dose-related toxicity profile argue for future studies using lower doses of this drug. PMID:12613516

  8. Ma-Pi 2 macrobiotic diet and type 2 diabetes mellitus: pooled analysis of short-term intervention studies.

    PubMed

    Porrata-Maury, C; Hernández-Triana, M; Ruiz-Álvarez, V; Díaz-Sánchez, M E; Fallucca, F; Bin, W; Baba-Abubakari, B; Pianesi, M

    2014-03-01

    The macrobiotic, Ma-Pi 2 diet (12% protein, 18% fat and 70% carbohydrate), has shown benefit in adults with type 2 diabetes mellitus (T2DM). This pooled analysis aims to confirm results from four, 21-day intervention studies with the Ma-Pi 2 diet, carried out in Cuba, China, Ghana and Italy. Baseline and end of study biochemical, body composition and blood pressure data, were compared using multivariate statistical methods and assessment of the Cohen effect size (d). Results showed that all measured indicators demonstrated significant changes (p < 0.001); most of them with a very high (d ≥ 1.30), or high (d = 0.80-1.29) effect size. The global effect size of the diet was Italy (1.96), China (1.79), Cuba (1.38) and Ghana (0.98). The magnitude of the individual effect on each variable by country, and the global effect by country, was independent of the sample size (p > 0.05). Similarly, glycemia and glycemic profiles in all four studies were independent of the sample size (p = 0.237). The Ma-Pi diet 2 significantly reduced glycemia, serum lipids, uremia and cardiovascular risk in adults with T2DM. These results suggest that the Ma-Pi 2 diet could be a valid alternative treatment for patients with T2DM and point to the need for further clinical studies. Mechanisms related to its benefits as a functional diet are discussed. PMID:24532293

  9. Personal history of diabetes, genetic susceptibility to diabetes, and risk of brain glioma: a pooled analysis of observational studies

    PubMed Central

    Kitahara, Cari M.; Linet, Martha S.; Brenner, Alina V.; Wang, Sophia S.; Melin, Beatrice S.; Wang, Zhaoming; Inskip, Peter D.; Beane Freeman, Laura E.; Braganza, Melissa Z.; Carreón, Tania; Feychting, Maria; Gaziano, J. Michael; Peters, Ulrike; Purdue, Mark P.; Ruder, Avima M.; Sesso, Howard D.; Shu, Xiao-Ou; Waters, Martha A.; White, Emily; Zheng, Wei; Hoover, Robert N.; Fraumeni, Joseph F.; Chatterjee, Nilanjan; Yeager, Meredith; Chanock, Stephen J.; Hartge, Patricia; Rajaraman, Preetha

    2013-01-01

    Background Brain glioma is a relatively rare and fatal malignancy in adulthood with few known risk factors. Some observational studies have reported inverse associations between diabetes and subsequent glioma risk, but possible mechanisms are unclear. Methods We conducted a pooled analysis of original data from five nested case-control studies and two case-control studies from the U.S. and China that included 962 glioma cases and 2,195 controls. We examined self-reported diabetes history in relation to glioma risk, as well as effect modification by seven glioma risk-associated single-nucleotide polymorphisms (SNPs). We also examined the associations between 13 diabetes risk-associated SNPs, identified from genome-wide association studies, and glioma risk. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multivariable-adjusted logistic regression models. Results We observed a 42% reduced risk of glioma for individuals with a history of diabetes (OR=0.58, 95% CI: 0.40–0.84). The association did not differ by sex, study design, or after restricting to glioblastoma, the most common histological sub-type. We did not observe any significant per-allele trends among the 13 diabetes-related SNPs examined in relation to glioma risk. Conclusion These results support an inverse association between diabetes history and glioma risk. The role of genetic susceptibility to diabetes cannot be excluded, and should be pursued in future studies together with other factors that might be responsible for the diabetes-glioma association. Impact These data suggest the need for studies that can evaluate, separately, the association between type 1 and type 2 diabetes and subsequent risk of adult glioma. PMID:24220915

  10. Donor-Site Morbidity Following Free Tissue Harvest from the Thigh: A Systematic Review and Pooled Analysis of Complications.

    PubMed

    Lakhiani, Chrisovalantis; DeFazio, Michael V; Han, Kevin; Falola, Reuben; Evans, Karen

    2016-06-01

    Background Donor-site morbidity significantly influences patient satisfaction and quality of life following reconstructive surgery. The relevant donor-site morbidities associated with more commonly utilized thigh-based flaps are reviewed. Methods A systematic search of the MEDLINE and Cochrane databases from 1994 to 2014 was conducted to identify all reports of "anterolateral thigh (ALT)," "vastus lateralis (VL)," "anteromedial thigh (AMT)," "transverse upper gracilis (TUG)," tensor fascia latae (TFL)," "gracilis," and "rectus femoris (RF)," flaps. Only studies that investigated donor-site outcomes related to pain, paresthesia, wound dehiscence, infection, hematoma, seroma, contour deformity, and/or objective functional performance were included. Case series or anecdotal reports with less than five flaps, non-English, and animal studies were excluded. Results A total of 116 articles representing 4,554 flaps were reviewed, including 2,922 ALT/VL, 148 AMT, 436 TUG, 278 TFL, 527 gracilis, and 243 RF flaps. The most frequently cited donor-site complication was paresthesia (range: 0-36.4%), followed by wound dehiscence (range: 0.9-8.3%), contour deformity (range: 0-5.2%), pain (range: 0-6.3%), and seroma (range: 0.4-2.0%). Despite mixed results regarding functional performance, pooled-analysis of dynamometric studies demonstrated a significant reduction in strength only after RF flap harvest (21%). Conclusions Donor-site morbidity for thigh-flaps is minimal and appears to be well-tolerated by the majority of patients. Nevertheless, the appropriate flap selection is highly individualized, and patients must be informed of potential complications and morbidities specific to each flap. We have established the most current review of donor-site morbidity for thigh-based flaps to aid the surgeon in this important discussion. PMID:27144952

  11. Enhancing cancer clonality analysis with integrative genomics

    PubMed Central

    2015-01-01

    Introduction It is understood that cancer is a clonal disease initiated by a single cell, and that metastasis, which is the spread of cancer from the primary site, is also initiated by a single cell. The seemingly natural capability of cancer to adapt dynamically in a Darwinian manner is a primary reason for therapeutic failures. Survival advantages may be induced by cancer therapies and also occur as a result of inherent cell and microenvironmental factors. The selected "more fit" clones outmatch their competition and then become dominant in the tumor via propagation of progeny. This clonal expansion leads to relapse, therapeutic resistance and eventually death. The goal of this study is to develop and demonstrate a more detailed clonality approach by utilizing integrative genomics. Methods Patient tumor samples were profiled by Whole Exome Sequencing (WES) and RNA-seq on an Illumina HiSeq 2500 and methylation profiling was performed on the Illumina Infinium 450K array. STAR and the Haplotype Caller were used for RNA-seq processing. Custom approaches were used for the integration of the multi-omic datasets. Results Reported are major enhancements to CloneViz, which now provides capabilities enabling a formal tumor multi-dimensional clonality analysis by integrating: i) DNA mutations, ii) RNA expressed mutations, and iii) DNA methylation data. RNA and DNA methylation integration were not previously possible, by CloneViz (previous version) or any other clonality method to date. This new approach, named iCloneViz (integrated CloneViz) employs visualization and quantitative methods, revealing an integrative genomic mutational dissection and traceability (DNA, RNA, epigenetics) thru the different layers of molecular structures. Conclusion The iCloneViz approach can be used for analysis of clonal evolution and mutational dynamics of multi-omic data sets. Revealing tumor clonal complexity in an integrative and quantitative manner facilitates improved mutational characterization, understanding, and therapeutic assignments. PMID:26424171

  12. Vitamin A and Retinoid Derivatives for Lung Cancer: A Systematic Review and Meta Analysis

    PubMed Central

    Fritz, Heidi; Kennedy, Deborah; Fergusson, Dean; Fernandes, Rochelle; Doucette, Steve; Cooley, Kieran; Seely, Andrew; Sagar, Stephen; Wong, Raimond; Seely, Dugald

    2011-01-01

    Background Despite reported antiproliferative activity of vitamin A and its common use for cancer, there is no comprehensive synthesis of its safety and efficacy in lung cancers. To address this issue we conducted a systematic review of the safety and efficacy of vitamin A for the treatment and prevention of lung cancers. Methods and Findings Two independent reviewers searched six electronic databases from inception to July 2009 for clinical, observational, and preclinical evidence pertaining to the safety and efficacy of vitamin A and related retinoids for lung cancers. 248 studies were included for full review and analysis. Five RCTs assessed treatment of lung cancers, three assessed primary prevention, and three looked at secondary prevention of lung cancers. Five surrogate studies, 26 phase I/II, 32 observational, and 67 preclinical studies were also included. 107 studies were included for interactions between vitamin A and chemo- or radiation- therapy. Although some studies demonstrated benefits, there was insufficient evidence overall to support the use of vitamin A or related retinoids for the treatment or prevention of lung cancers. Retinyl palmitate combined with beta carotene increased risk of lung cancer in smokers in the large CARET trial. Pooling of three studies pertaining to treatment and three studies on secondary prevention revealed no significant effects on response rate, second primary tumor, recurrence, 5-year survival, and mortality. There was a small improvement in event free survival associated with vitamin A compared to controls, RR 1.24 (95% CI 1.13–1.35). The synthetic rexinoid bexarotene increased survival significantly among a subset of patients in two RCTs (p<0.014, <0.087). Conclusions There is a lack of evidence to support the use of naturally occuring retinoids for the treatment and prevention of lung cancers. The rexinoid bexarotene may hold promise for use among a subset of patients, and deserves further study. PMID:21738614

  13. Efficacy of gemcitabine plus platinum agents for biliary tract cancers: a meta-analysis.

    PubMed

    Yang, Rui; Wang, Bing; Chen, Yong-jun; Li, Hong-bo; Hu, Jun-bo; Zou, Sheng-quan

    2013-09-01

    The objective of this study was to carry out a meta-analysis of the efficacy of gemcitabine+platinum agent regimens in the treatment of advanced biliary tract cancer (BTC). PubMed and Google Scholar were searched using the following combination of search terms: gemcitabine, oxaliplatin, cholangiocarcinoma, biliary, gallbladder, bile duct. Studies were eligible for inclusion in the meta-analysis if they were randomized trials on the use of gemcitabine plus a platinum agent for the treatment of advanced (unresectable or metastatic cancer) BTC. Outcomes of interest were response rate, overall survival, and progression-free survival. Pooled odds ratios/differences in median survival and 95% confidence intervals (CIs) were determined for each outcome. A total of 47 records were identified in the initial search. Ultimately, three open-label randomized trials (two phase 2 and one phase 3) met the eligibility criteria and were included in the meta-analysis. Two studies compared gemcitabine plus cisplatin with gemcitabine alone, whereas the other study compared gemcitabine plus oxaliplatin with fluorouracil-folinic acid. The total number of patients in the studies ranged from 54 to 410. The overall analyses revealed that all survival outcomes assessed were significantly more favorable for patients treated with gemcitabine plus platinum agents than for patients not treated with this combination. Response rates: odds ratio=2.639, 95% CI=1.210-5.757, Z=2.439, P=0.015; pooled difference in median overall survival=3.822 months, 95% CI=1.798-5.845 months, Z=3.702, P<0.001; pooled difference in median progression-free survival=3.268 months, 95% CI=1.996-4.541 months, Z=5.035, P<0.001. Patients with advanced BTC who are treated with gemcitabine plus platinum agents may experience better survival outcomes compared with patients who are not treated with this combination of chemotherapy. PMID:23799294

  14. APC methylation predicts biochemical recurrence of patients with prostate cancer: a meta-analysis

    PubMed Central

    Wang, Yi; Fan, Caibin; Yu, Jiang; Wang, Xizhi

    2015-01-01

    The promoter region of adenomatous polyposis coli (APC) has been found to be frequently methylated in prostate cancer. However, the prognostic role of APC methylation in prostate cancer was still debated. We performed a meta-analysis by searching PubMed and EMBASE databases. Pooled hazard ratios (HRs) and corresponding 95% confidence intervals (CI) were calculated. Seven studies (1227 patients) were included in this study. After calculation, the overall HR was 1.74 (95% CI: 1.31-2.31), implicating that APC methylation has an unfavorable impact on biochemical recurrence of prostate cancer. A subgroup analysis was performed with detection method, combined HR was 1.53 (95% CI: 1.19-1.96) for Methylation-Specific PCR (MSP), and 2.08 (95% CI: 1.18-3.64) for quantitative Methylation-Specific PCR (qMSP). Another subgroup analysis was conducted according to regions of the patients, combined HR was 2.02 (95% CI: 1.18-3.49) for North America, and 1.64 (95% CI: 1.14-2.36) for European. In conclusion, APC methylation is associated with biochemical recurrence of patients with prostate cancer. PMID:26629051

  15. Coffee Consumption and Risk of Gastric Cancer: A Large Updated Meta-Analysis of Prospective Studies

    PubMed Central

    Xie, Feiyue; Wang, Dan; Huang, Zhifang; Guo, Yajun

    2014-01-01

    The potential role of coffee consumption in the development of various types of cancer has been extensively investigated in epidemiologic studies. How coffee consumption may modulate risk of gastric cancer, however, remains a subject open for investigation. To better quantify this relation, we quantitatively summarized evidence from prospective studies. Eligible studies were identified on PubMed databases. The summary risk estimates were obtained using the random-effects model. Subgroup, sensitivity and dose-response analyses were conducted. The present meta-analysis included 12 prospective cohort studies. A pooled analysis of these studies suggested that coffee consumption (highest vs. lowest consumption) was not associated with risk of gastric cancer (RR = 1.12, 95% CI = 0.93–1.36). In the subgroup analysis, significant increased risk was detected in the U.S. studies (RR = 1.36, 95% CI = 1.06–1.74) and in the studies with <10 years of follow-up (RR = 1.24, 95% CI = 1.00–1.54), and the greatest increase in risk was observed in those studies without adjustment for smoking (RR = 1.48, 95% CI = 1.13–1.93). There was some evidence of publication bias (P for Egger’s test = 0.03). Cumulative evidence from prospective studies suggests that coffee consumption is not associated with risk of gastric cancer. The observed positive results may be confounded by smoking and need further investigation. PMID:25237829

  16. Coffee Consumption and Pancreatic Cancer Risk: An Update Meta-analysis of Cohort Studies

    PubMed Central

    Ran, Heng-Quan; Wang, Jun-Zhou; Sun, Chang-Qin

    2016-01-01

    Background & Objective: The results of epidemiologic studies on the relationship between the coffee consumption and pancreatic cancer risk were inconsistent. Thus, we performed an update meta-analysis of cohort studies to quantitatively summarize the association between coffee consumption and pancreatic cancer risk. Methods: We searched CBM (China Biology Medicine disc) and MEDLINE for studies of coffee consumption and pancreatic cancer risk up to June 2015. A total of 20 cohort studies were identified in this meta-analysis, and we analyzed these studies using random effects model. The dose-response analysis was conducted too. Results: The overall relative risk (RR) for highest coffee consumption versus lowest coffee consumption was 0.75 (95% Confidence Interval (CI), 0.63-0.86). Statistic significant heterogeneity was found among these studies (I2 =37.8%, P for heterogeneity =0.045). The pooled RR for increment of 1 cup/day of coffee consumption was 0.99 (95%CI, 0.96-1.03) for the nine studies, without statistically significant. Conclusions: High coffee consumption is associated with a reduced pancreatic cancer risk. However, the result should be accepted with caution, due to the potential confounder and bias could not be excluded. Further well designed studies are needed to confirm the finding. PMID:27022386

  17. Do deficits in cardiac care influence high mortality rates in schizophrenia? A systematic review and pooled analysis

    PubMed Central

    Mitchell, Alex J; Lord, Oliver

    2010-01-01

    We have previously documented inequalities in the quality of medical care provided to those with mental ill health but the implications for mortality are unclear. We aimed to test whether disparities in medical treatment of cardiovascular conditions, specifically receipt of medical procedures and receipt of prescribed medication, are linked with elevated rates of mortality in people with schizophrenia and severe mental illness. We undertook a systematic review of studies that examined medical procedures and a pooled analysis of prescribed medication in those with and without comorbid mental illness, focusing on those which recruited individuals with schizophrenia and measured mortality as an outcome. From 17 studies of treatment adequacy in cardiovascular conditions, eight examined cardiac procedures and nine examined adequacy of prescribed cardiac medication. Six of eight studies examining the adequacy of cardiac procedures found lower than average provision of medical care and two studies found no difference. Meta-analytic pooling of nine medication studies showed lower than average rates of prescribing evident for the following individual classes of medication; angiotensin converting enzyme inhibitors (n = 6, aOR = 0.779, 95% CI = 0.638–0.950, p = 0.0137), beta-blockers (n = 9, aOR = 0.844, 95% CI = 0.690–1.03, p = 0.1036) and statins (n = 5, aOR = 0.604, 95% CI = 0.408–0.89, p = 0.0117). No inequality was evident for aspirin (n = 7, aOR = 0.986, 95% CI = 0.7955–1.02, p = 0.382). Interestingly higher than expected prescribing was found for older non-statin cholesterol-lowering agents (n = 4, aOR = 1.55, 95% CI = 1.04–2.32, p = 0.0312). A search for outcomes in this sample revealed ten studies linking poor quality of care and possible effects on mortality in specialist settings. In half of the studies there was significantly higher mortality in those with mental ill health compared with controls but there was inadequate data to confirm a causative link. Nevertheless, indirect evidence supports the observation that deficits in quality of care are contributing to higher than expected mortality in those with severe mental illness (SMI) and schizophrenia. The quality of medical treatment provided to those with cardiac conditions and comorbid schizophrenia is often suboptimal and may be linked with avoidable excess mortality. Every effort should be made to deliver high-quality medical care to people with severe mental illness. PMID:20923922

  18. Prognostic Value of Ezrin in Various Cancers: A Systematic Review and Updated Meta-analysis

    PubMed Central

    Li, Jianwei; Wei, Kuanhai; Yu, Hailang; Jin, Dan; Wang, Gang; Yu, Bin

    2015-01-01

    More and more studies have investigated the effects of Ezrin expression level on the prognostic role in various tumors. However, the results remain controversial rather than conclusive. Here, we performed a systematic review and meta-analysis to evaluate the correlation of Ezrin expression with the prognosis in various tumors. the pooled hazard ratios (HR) with the corresponding 95% confidence intervals (95% CI) were calculated to evaluate the degree of the association. The overall results of fifty-five studies with 6675 patients showed that elevated Ezrin expression was associated with a worse prognosis in patients with cancers, with the pooled HRs of 1.86 (95% CI: 1.51–2.31, P < 0.001) for over survival (OS), 2.55 (95% CI: 2.14–3.05, P < 0.001) for disease-specific survival (DFS) and 2.02 (95% CI: 1.13–3.63, P = 0.018) for disease-specific survival (DSS)/metastasis-free survival (MFS) by the random, fixed and random effect model respectively. Similar results were also observed in the stratified analyses by tumor types, ethnicity background and sample source. This meta-analysis suggests that Ezrin may be a potential prognostic marker in cancer patients. High Ezrin is associated with a poor prognosis in a variety of solid tumors. PMID:26632332

  19. Analysis of framelets for breast cancer diagnosis.

    PubMed

    Thivya, K S; Sakthivel, P; Venkata Sai, P M

    2016-01-27

    Breast cancer is the second threatening tumor among the women. The effective way of reducing breast cancer is its early detection which helps to improve the diagnosing process. Digital mammography plays a significant role in mammogram screening at earlier stage of breast carcinoma. Even though, it is very difficult to find accurate abnormality in prevalent screening by radiologists. But the possibility of precise breast cancer screening is encouraged by predicting the accurate type of abnormality through Computer Aided Diagnosis (CAD) systems. The two most important indicators of breast malignancy are microcalcifications and masses. In this study, framelet transform, a multiresolutional analysis is investigated for the classification of the above mentioned two indicators. The statistical and co-occurrence features are extracted from the framelet decomposed mammograms with different resolution levels and support vector machine is employed for classification with k-fold cross validation. This system achieves 94.82% and 100% accuracy in normal/abnormal classification (stage I) and benign/malignant classification (stage II) of mass classification system and 98.57% and 100% for microcalcification system when using the MIAS database. PMID:26409529

  20. Duration, Pattern of Breastfeeding and Postnatal Transmission of HIV: Pooled Analysis of Individual Data from West and South African Cohorts

    PubMed Central

    Becquet, Renaud; Bland, Ruth; Leroy, Valériane; Rollins, Nigel C.; Ekouevi, Didier K.; Coutsoudis, Anna; Dabis, François; Coovadia, Hoosen M.; Salamon, Roger; Newell, Marie-Louise

    2009-01-01

    Background Both breastfeeding pattern and duration are associated with postnatal HIV acquisition; their relative contribution has not been reliably quantified. Methodology and Principal Findings Pooled data from 2 cohorts: in urban West Africa where breastfeeding cessation at 4 months was recommended but exclusive breastfeeding was rare (Ditrame Plus, DP); in rural South Africa where high rates of exclusive breastfeeding were achieved, but with longer duration (Vertical Transmission Study, VTS). 18-months HIV postnatal transmission (PT) was estimated by Kaplan-Meier in infants who were HIV negative, and assumed uninfected, at age >1 month. Censoring with (to assess impact of mode of breastfeeding) and without (to assess effect of breastfeeding duration) breastfeeding cessation considered as a competing event. Of 1195 breastfed infants, not HIV-infected perinatally, 38% DP and 83% VTS children were still breastfed at age 6 months. By age 3 months, 66% of VTS children were exclusively breastfed since birth and 55% of DP infants predominantly breastfed (breastmilk+water-based drinks). 18-month PT risk (95%CI) in VTS was double that in DP: 9% (7–11) and 5% (3–8), respectively (p = 0.03). However, once duration of breastfeeding was allowed for in a competing risk analysis assuming that all children would have been breastfed for 18-month, the estimated PT risk was 16% (8–28) in DP and 14% (10–18) in VTS (p = 0.32). 18-months PT risk was 3.9% (2.3–6.5) among infants breastfed for less than 6 months, and 8.7% (6.8–11.0) among children breastfed for more than 6 months; crude hazard ratio (HR): 2.1 (1.2–3.7), p = 0.02; adjusted HR 1.8 (0.9–3.4), p = 0.06. In individual analyses of PT rates for specific breastfeeding durations, risks among children exclusively breastfed were very similar to those in children predominantly breastfed for the same period. Children exposed to solid foods during the first 2 months of life were 2.9 (1.1–8.0) times more likely to be infected postnatally than children never exposed to solids this early (adjusted competing risk analysis, p = 0.04). Conclusions Breastfeeding duration is a major determinant of postnatal HIV transmission. The PT risk did not differ between exclusively and predominantly breastfed children; the negative effect of mixed breastfeeding with solids on PT were confirmed. PMID:19834601

  1. Proteomics Analysis of Bladder Cancer Exosomes*

    PubMed Central

    Welton, Joanne L.; Khanna, Sanjay; Giles, Peter J.; Brennan, Paul; Brewis, Ian A.; Staffurth, John; Mason, Malcolm D.; Clayton, Aled

    2010-01-01

    Exosomes are nanometer-sized vesicles, secreted by various cell types, present in biological fluids that are particularly rich in membrane proteins. Ex vivo analysis of exosomes may provide biomarker discovery platforms and form non-invasive tools for disease diagnosis and monitoring. These vesicles have never before been studied in the context of bladder cancer, a major malignancy of the urological tract. We present the first proteomics analysis of bladder cancer cell exosomes. Using ultracentrifugation on a sucrose cushion, exosomes were highly purified from cultured HT1376 bladder cancer cells and verified as low in contaminants by Western blotting and flow cytometry of exosome-coated beads. Solubilization in a buffer containing SDS and DTT was essential for achieving proteomics analysis using an LC-MALDI-TOF/TOF MS approach. We report 353 high quality identifications with 72 proteins not previously identified by other human exosome proteomics studies. Overrepresentation analysis to compare this data set with previous exosome proteomics studies (using the ExoCarta database) revealed that the proteome was consistent with that of various exosomes with particular overlap with exosomes of carcinoma origin. Interrogating the Gene Ontology database highlighted a strong association of this proteome with carcinoma of bladder and other sites. The data also highlighted how homology among human leukocyte antigen haplotypes may confound MASCOT designation of major histocompatability complex Class I nomenclature, requiring data from PCR-based human leukocyte antigen haplotyping to clarify anomalous identifications. Validation of 18 MS protein identifications (including basigin, galectin-3, trophoblast glycoprotein (5T4), and others) was performed by a combination of Western blotting, flotation on linear sucrose gradients, and flow cytometry, confirming their exosomal expression. Some were confirmed positive on urinary exosomes from a bladder cancer patient. In summary, the exosome proteomics data set presented is of unrivaled quality. The data will aid in the development of urine exosome-based clinical tools for monitoring disease and will inform follow-up studies into varied aspects of exosome manufacture and function. PMID:20224111

  2. Increased Risk of Pancreatic Cancer Related to Gallstones and Cholecystectomy: A Systematic Review and Meta-Analysis.

    PubMed

    Fan, Yonggang; Hu, Jie; Feng, Bing; Wang, Wei; Yao, Guoliang; Zhai, Jingming; Li, Xin

    2016-04-01

    To investigate the potential roles of gallstones and cholecystectomy in pancreatic carcinogenesis, we performed the first meta-analysis of all currently published studies by pooling relative risks (RRs) with 95% confidence intervals (95% CIs). Stratified analysis by ethnicity, study design, and common adjusted factors were also conducted. Individuals with a history of gallstones and cholecystectomy were at increased risk of pancreatic cancer (RR, 1.39; 95% CI, 1.28-1.52; P < 0.001). Gallstones and cholecystectomy were also associated with an elevated risk of pancreatic cancer, respectively (for gallstones: RR, 1.70; 95% CI, 1.30-2.21; P < 0.001; for cholecystectomy: RR, 1.31; 95% CI, 1.19-1.43; P < 0.001). The positive association is observed among not only the Asian population but also whites. The pooled findings were further confirmed by sensitivity analysis and stratified analyses in case-control and cohort studies. Stratified analyses by different adjusted factors further showed that the increased risk of pancreatic cancer was independent of confounders including diabetes, obesity, smoking, and follow-up years of postcholecystectomy. A history of gallstones and cholecystectomy is a robust risk factor for pancreatic cancer. Gallstone disease or cholecystectomy alone is also an independent risk factor for pancreatic carcinogenesis. PMID:26684857

  3. Effects of physical exercise during adjuvant breast cancer treatment on physical and psychosocial dimensions of cancer-related fatigue: A meta-analysis.

    PubMed

    van Vulpen, Jonna K; Peeters, Petra H M; Velthuis, Miranda J; van der Wall, Elsken; May, Anne M

    2016-03-01

    Cancer-related fatigue has a multidimensional nature and complaints typically increase during adjuvant treatment for breast cancer. Physical exercise might prevent or reduce cancer-related fatigue. So far, no meta-analysis has investigated the effects of physical exercise on different dimensions of fatigue. The aim of the present meta-analysis was to investigate the effects of physical exercise during adjuvant breast cancer treatment on physical and psychosocial dimensions of fatigue. We performed a systematic literature search in PubMed, Embase and the Cochrane Library in June 2015. Randomised controlled trials reporting the effects of physical exercise during adjuvant breast cancer treatment on different dimensions of fatigue were included. Pooled effects of 6 exercise programmes (including 784 patients) showed significant beneficial exercise effects on general fatigue (ES: -0.22, 95% CI -0.38; -0.05) and physical fatigue (ES: -0.35, 95% CI -0.49; -0.21). Effects on fatigue subscales 'reduced activity' (ES: -0.22, 95% CI -0.38; -0.05) and 'reduced motivation' (ES: -0.18, 95% CI -0.35; -0.01) were also in favour of physical exercise. No effects were found on cognitive and affective fatigue. Including only the supervised exercise programmes (n=4 studies), slightly larger pooled effect estimates were found on general fatigue (ES: -0.25, 95% CI -0.47; -0.04) and physical fatigue (-0.39, 95% CI -0.56; -0.23). In conclusion, physical exercise during adjuvant breast cancer treatment has beneficial effects on general fatigue, physical fatigue, 'reduced activity' and 'reduced motivation', but did not show effects on cognitive and affective fatigue. Largest effect sizes are found for physical fatigue, suggesting that this is the fatigue dimension most sensitive to physical exercise. PMID:26857888

  4. Institutional Boundaries and Common-Pool Resource Management: A Comparative Analysis of Water Management Programs in California

    ERIC Educational Resources Information Center

    Heikkila, Tanya

    2004-01-01

    Policymakers and academics often identify institutional boundaries as one of the factors that shape the capacity of jurisdictions to manage natural resources such as water, forests, and scenic lands. This article examines two key bodies of literature--common-pool resource management theory and local public economy theory--to explain how the…

  5. Institutional Boundaries and Common-Pool Resource Management: A Comparative Analysis of Water Management Programs in California

    ERIC Educational Resources Information Center

    Heikkila, Tanya

    2004-01-01

    Policymakers and academics often identify institutional boundaries as one of the factors that shape the capacity of jurisdictions to manage natural resources such as water, forests, and scenic lands. This article examines two key bodies of literature--common-pool resource management theory and local public economy theory--to explain how the

  6. Confirmatory Factor Analysis of the M5-50: An Implementation of the International Personality Item Pool Item Set

    ERIC Educational Resources Information Center

    Socha, Alan; Cooper, Christopher A.; McCord, David M.

    2010-01-01

    Goldberg's International Personality Item Pool (IPIP; Goldberg, 1999) provides researchers with public-domain, free-access personality measurement scales that are proxies of well-established published scales. One of the more commonly used IPIP sets employs 50 items to measure the 5 broad domains of the 5-factor model, with 10 items per factor. The…

  7. Living near nuclear power plants and thyroid cancer risk: A systematic review and meta-analysis.

    PubMed

    Kim, Jaeyoung; Bang, Yejin; Lee, Won Jin

    2016-02-01

    There has been public concern regarding the safety of residing near nuclear power plants, and the extent of risk for thyroid cancer among adults living near nuclear power plants has not been fully explored. In the present study, a systematic review and meta-analysis of epidemiologic studies was conducted to investigate the association between living near nuclear power plants and the risk of thyroid cancer. A comprehensive literature search was performed on studies published up to March 2015 on the association between nuclear power plants and thyroid cancer risk. The summary standardized incidence ratio (SIR), standardized mortality ratio (SMR), and 95% confidence intervals (CIs) were calculated using a random-effect model of meta-analysis. Sensitivity analyses were performed by study quality. Thirteen studies were included in the meta-analysis, covering 36 nuclear power stations in 10 countries. Overall, summary estimates showed no significant increased thyroid cancer incidence or mortality among residents living near nuclear power plants (summary SIR=0.98; 95% CI 0.87-1.11, summary SMR=0.80; 95% CI 0.62-1.04). The pooled estimates did not reveal different patterns of risk by gender, exposure definition, or reference population. However, sensitivity analysis by exposure definition showed that living less than 20 km from nuclear power plants was associated with a significant increase in the risk of thyroid cancer in well-designed studies (summary OR=1.75; 95% CI 1.17-2.64). Our study does not support an association between living near nuclear power plants and risk of thyroid cancer but does support a need for well-designed future studies. PMID:26638017

  8. Immunoglobulin E and cancer: a meta-analysis and a large Swedish cohort study.

    PubMed

    Van Hemelrijck, Mieke; Garmo, Hans; Binda, Elisa; Hayday, Adrian; Karagiannis, Sophia N; Hammar, Niklas; Walldius, Göran; Lambe, Mats; Jungner, Ingmar; Holmberg, Lars

    2010-10-01

    We quantified associations between IgE and cancer in a meta-analysis and cohort study. Pubmed and Embase were searched to extract information using predefined inclusion criteria. In the Apolipoprotein MOrtality RISk (AMORIS) database, 24,820 persons had IgE measurements. Multivariate Cox proportional hazard models were used to analyze associations between IgE and cancer. Twenty-seven studies were reviewed from which seven case-control studies were included for analysis. The pooled relative risk (random effects model) was 0.97 (95% CI 0.86-1.09). Cell types of tumor origin (mesenchymal tissue or cells of the nervous system, lymphatic or hematopoietic tissue, and epithelium) modified the effect. In the AMORIS cohort, 862 persons developed cancer. Hazard ratios comparing quartiles of IgE were similar to the findings in the meta-analysis (HR 0.87 (95% CI 0.72-1.06); 0.94 (0.78-1.14); 0.90 (0.74-1.10) for the 2nd, 3rd, and 4th quartile compared to the 1st quartile), but there was no pattern by tumor origin. Both studies showed a weak inverse association between IgE and cancer, but a pattern by cancer type was only seen in the meta-analysis. Our findings suggest the need for prospective studies studying IgE and cancer. Measurements of IgE should be combined with other information, e.g., bio-banked samples containing other key immunological discriminators. PMID:20533084

  9. A Healthy Dietary Pattern Reduces Lung Cancer Risk: A Systematic Review and Meta-Analysis

    PubMed Central

    Sun, Yanlai; Li, Zhenxiang; Li, Jianning; Li, Zengjun; Han, Jianjun

    2016-01-01

    Background: Diet and nutrients play an important role in cancer development and progress; a healthy dietary pattern has been found to be associated with several types of cancer. However, the association between a healthy eating pattern and lung cancer risk is still unclear. Objective: Therefore, we conducted a systematic review with meta-analysis to evaluate whether a healthy eating pattern might reduce lung cancer risk. Methods: We identified relevant studies from the PubMed and Embase databases up to October 2015, and the relative risks were extracted and combined by the fixed-effects model when no substantial heterogeneity was observed; otherwise, the random-effects model was employed. Subgroup and publication bias analyses were also performed. Results: Finally, eight observational studies were included in the meta-analysis. The pooled relative risk of lung cancer for the highest vs. lowest category of healthy dietary pattern was 0.81 (95% confidence interval, CI: 0.75–0.86), and no significant heterogeneity was detected. The relative risks (RRs) for non-smokers, former smokers and current smokers were 0.89 (95% CI: 0.63–1.27), 0.74 (95% CI: 0.62–0.89) and 0.86 (95% CI: 0.79–0.93), respectively. The results remained stable in subgroup analyses by other confounders and sensitivity analysis. Conclusions: The results of our meta-analysis suggest that a healthy dietary pattern is associated with a lower lung cancer risk, and they provide more beneficial evidence for changing the diet pattern in the general population. PMID:26959051

  10. Cancer Nursing Education: Literature Review and Documentary Analysis.

    ERIC Educational Resources Information Center

    Langton, Helen; Blunden, Gillian; Hek, Gill

    The knowledge and skills needed by cancer nurses and the content and strategies of England's existing cancer nursing education programs were examined. The study included a comprehensive literature review and an analysis of course documents from selected English National Board-approved post-qualifying cancer nursing and palliative care courses

  11. Cancer Nursing Education: Literature Review and Documentary Analysis.

    ERIC Educational Resources Information Center

    Langton, Helen; Blunden, Gillian; Hek, Gill

    The knowledge and skills needed by cancer nurses and the content and strategies of England's existing cancer nursing education programs were examined. The study included a comprehensive literature review and an analysis of course documents from selected English National Board-approved post-qualifying cancer nursing and palliative care courses…

  12. Occupational Exposure to Asbestos and Ovarian Cancer: A Meta-analysis

    PubMed Central

    Camargo, M. Constanza; Straif, Kurt; Reina, Margarita; Al-Alem, Umaima; Demers, Paul A.; Landrigan, Philip J.

    2011-01-01

    Objective: A recent Monographs Working Group of the International Agency for Research on Cancer (IARC) concluded that there is sufficient evidence for a causal association between exposure to asbestos and ovarian cancer. We performed a meta-analysis to quantitatively evaluate this association. Data sources: Searches of PubMed and unpublished data yielded a total of 18 cohort studies of women occupationally exposed to asbestos. Data extraction: Two authors independently abstracted data; any disagreement was resolved by consulting a third reviewer. Data synthesis: All but one study reported standardized mortality ratios (SMRs) comparing observed numbers of deaths with expected numbers for the general population; the exception was a study that reported standardized incidence ratios. For simplicity, we refer to all effect estimates as SMRs. The overall pooled SMR estimate for ovarian cancer was 1.77 (95% confidence interval, 1.37–2.28), with a moderate degree of heterogeneity among the studies (I2 = 35.3%, p = 0.061). Effect estimates were stronger for cohorts compensated for asbestosis, cohorts with estimated lung cancer SMRs > 2.0, and studies conducted in Europe compared with other geographic regions. Effect estimates were similar for studies with and without pathologic confirmation, and we found no evidence of publication bias (Egger’s test p-value = 0.162). Conclusions: Our study supports the IARC conclusion that exposure to asbestos is associated with increased risk of ovarian cancer. PMID:21642044

  13. The Seroprevalence of Toxoplasma gondii in Chinese Population With Cancer: A Systematic Review and Meta-analysis.

    PubMed

    Jiang, CaiXiao; Li, ZhanZhan; Chen, Peng; Chen, LiZhang

    2015-12-01

    Toxoplasmosis is fatal in the immunocompromised individuals such as cancer patients with chemotherapy. Clinical toxoplasmosis in cancer patients is a great public health concern in China. We performed this meta-analysis to assess the seroprevalence and odds ratios (ORs) of Toxoplasma gondii in Chinese population with cancer compared with those without. A methodical literature search was conducted with the help of the PubMed, Web of Knowledge, Embase, Chinese Web of Knowledge, Wanfang, and Chongqing VIP database. Case-control studies published from their inception until April 2015, reporting the seroprevalence of T. gondii in Chinese population with cancer, were covered as well. The nonweighted prevalence, pooled random-effects estimates of ORs, and 95% confidence intervals (CIs) were all calculated. Nineteen studies including 4493 cases and 6797 controls were incorporated in the meta-analysis. The overall seroprevalence of T. gondii was higher in population with cancer compared with those without ((20.59% vs 6.31%, P < 0.001; OR 3.90, 95% CI 3.00-5.07). The OR of T. gondii in cancer patients is further subgrouped according to publication year, sample size, and diagnostic methods. The pooled OR estimates were 4.80 (95% CI 2.57-8.99) from 1991 to 1999, 4.96 (95% CI 3.03-8.12) during 2000 to 2005, and 2.94 (95% CI 2.46-3.50) during 2006 to 2015. The pooled OR estimates were 6.16 (95% CI 3.87-9.78) when the sample size was below 400, 5.37 (95% CI 3.84-7.53) when the sample size was between 400 and 500, and 2.58 (95% CI 2.17-3.07) when the sample size was above 500. The pooled OR estimates were 5.50 (95% CI 3.98-7.62) by using indirect hemagglutination assay method, and 3.15 (95% CI 2.67-3.72) by using enzyme-linked immunosorbent assay method. The meta-analysis study found Chinese population with cancer had higher seroprevalence rates of T. gondii compared with those without. PMID:26683951

  14. Metformin therapy and prostate cancer risk: a meta-analysis of observational studies

    PubMed Central

    Wu, Gang-Feng; Zhang, Xiao-Long; Luo, Zhen-Gang; Yan, Jia-Jun; Pan, Shou-Hua; Ying, Xiang-Rong; Pan, Jian-Gang; Zhang, Guan-Fu

    2015-01-01

    Objective: Several observational studies have shown that metformin therapy may modify the risk of prostate cancer. We carried out a meta-analysis of relevant studies evaluating the effect of metformin therapy on prostate cancer risk. Methods: We searched pubmed database (January 1966-February 2014) for case-control and cohort studies that assessed metformin therapy and prostate cancer risk. Two authors independently assessed eligibility and extracted data. Summary RRs was calculated using fixed-effects model or random-effects model. Heterogeneity among studies was examined using Q and I2 statistics. Results: We included six cohort studies and four case-control studies in the present meta-analysis, comprising 863,769 participants and 39,073 prostate cancer cases. The pooled RR of prostate cancer in relation to metformin therapy was 0.92 (95% CI: 0.84-1.02, P = 0.112). When we stratified the various studies by study type, we found that metformin therapy was associated with a significant reduced risk of prostate cancer among cohort studies (RR = 0.92, 95% CI [0.87, 0.96], P<0.001); however, no significant association was detected among case-control studies (RR = 0.95, 95% CI [0.78, 1.16], P = 0.632). There was also no indication of publication bias as suggested by Begg’s test (P = 0.421) and Egger’s test (P = 0.627). Conclusion: Our findings indicate that metformin therapy is not significantly associated with lower prostate cancer risk. PMID:26550231

  15. The therapy of amblyopia: an analysis of the results of amblyopia therapy utilizing the pooled data of published studies.

    PubMed Central

    Flynn, J T; Schiffman, J; Feuer, W; Corona, A

    1998-01-01

    CONTEXT: Although the treatment of amblyopia with occlusion has changed little over the past 3 centuries, there is little agreement about which regimes are most effective and for what reasons. OBJECTIVE: To determine the outcome of occlusion therapy in patients with anisometropic, strabismic, and strabismic-anisometropic amblyopia employing the raw data from 961 patients reported in 23 studies published between 1965 and 1994. DESIGN: Analysis of the published literature on amblyopia therapy results during the above interval, utilizing primary data obtained from the authors of these articles or tables published in the articles detailing individual patient outcomes. PARTICIPANTS: 961 amblyopic patients, participants in 23 studies, undergoing patching therapy for amblyopia from 1965 to 1994 with anisometropia, strabismus, or anisometropia-strabismus. MAIN OUTCOMES: In the pooled data set, success of occlusion therapy was defined as visual acuity of 20/40 at the end of treatment. RESULTS: Success by the 20/40 criteria was achieved in 512 of 689 (74.3%) patients. By category, 312 of 402 (77.6%) were successful in strabismic amblyopia, 44 of 75 (58.7%) in strabismic-anisometropic amblyopia, and 72 of 108 (66.7%) in anisometropic amblyopia. Success was not related to the duration of occlusion therapy, type of occlusion used, accompanying refractive error, patient's sex, or eye. Univariate analyses showed that success was related to the age at which therapy was initiated; the type of amblyopia; the depth of visual loss before treatment for the anisometropic patients and the strabismic patients, but not for the anisometropic-strabismic patients; and the difference in spherical equivalents between eyes, for the anisometropic patients. Logistic/linear regression revealed that 3 were independent predictors of a successful outcome of amblyopia therapy. CONCLUSIONS: Factors that appear most closely related to a successful outcome are age, type of amblyopia, and depth of visual loss before treatment. These may be related to factors, as yet undetermined in the pathogenesis of amblyopia. With present emphasis on the value of screening and prevention and the development of new screening tools, such a look at the results of amblyopia therapy in a large population seems indicated. Images FIGURE 4 PMID:10360300

  16. Efficacy and Safety of Moxifloxacin in Hospitalized Patients with Secondary Peritonitis: Pooled Analysis of Four Randomized Phase III Trials

    PubMed Central

    Tellado, Jose M.; Weiss, Günter; Alder, Jeffrey; Kruesmann, Frank; Arvis, Pierre; Hussain, Tajamul; Solomkin, Joseph S.

    2014-01-01

    Abstract Background: Secondary peritonitis is an advanced form of complicated intra-abdominal infection (cIAI) requiring hospitalization, surgical source control, and empiric antibiotic therapy against causative aerobic and anaerobic bacteria. Methods: This pooled analysis of four prospective, active-controlled randomized clinical trials compared the efficacy and safety of moxifloxacin with that of comparator antibiotics in patients with confirmed secondary peritonitis. The primary efficacy endpoint was clinical success rate at test-of-cure (TOC) between day 10 and 45 post-therapy in the per-protocol (PP) population. Safety and clinical efficacy were assessed also in the intent-to-treat population (ITT). Bacteriological success was assessed at TOC in the microbiologically-valid population as a secondary efficacy endpoint. Results: Overall clinical success rates at TOC were 85.3% (431 of 505 patients) in the moxifloxacin and 88.4% (459 of 519 patients) in the comparator treatment groups (PP population, point estimate for the difference in success rates: −3.0%; 95% CI −7.06%, 1.05%), respectively. Similar clinical success rates between moxifloxacin and comparators were observed by anatomical site of infection, and ranged from 80.6% to 100% for moxifloxacin and from 71.4% to 96.6% for comparators, respectively. Bacteriologic success rates were similar with moxifloxacin (82.4%) and comparators (86.8%), respectively. The proportion of patients experiencing any treatment-emergent adverse events was slightly higher with moxifloxacin (67.3%) versus comparators (59.8%). Rates of drug-related adverse events (20.9% versus 20.0%) and deaths (4.3% versus 3.4%) were similar in moxifloxacin and comparator groups; none of the deaths were drug-related. Conclusions: The data suggests that once-daily IV (or IV/PO) moxifloxacin has a comparable efficacy and safety profile to antibiotic regimens approved previously in the subgroup of patients with secondary peritonitis of mild-to-moderate severity. PMID:24833256

  17. The Effect of Dosing Regimens on the Antimalarial Efficacy of Dihydroartemisinin-Piperaquine: A Pooled Analysis of Individual Patient Data

    PubMed Central

    2013-01-01

    Background Dihydroartemisinin-piperaquine (DP) is increasingly recommended for antimalarial treatment in many endemic countries; however, concerns have been raised over its potential under dosing in young children. We investigated the influence of different dosing schedules on DP's clinical efficacy. Methods and Findings A systematic search of the literature was conducted to identify all studies published between 1960 and February 2013, in which patients were enrolled and treated with DP. Principal investigators were approached and invited to share individual patient data with the WorldWide Antimalarial Resistance Network (WWARN). Data were pooled using a standardised methodology. Univariable and multivariable risk factors for parasite recrudescence were identified using a Cox's regression model with shared frailty across the study sites. Twenty-four published and two unpublished studies (n = 7,072 patients) were included in the analysis. After correcting for reinfection by parasite genotyping, Kaplan–Meier survival estimates were 97.7% (95% CI 97.3%–98.1%) at day 42 and 97.2% (95% CI 96.7%–97.7%) at day 63. Overall 28.6% (979/3,429) of children aged 1 to 5 years received a total dose of piperaquine below 48 mg/kg (the lower limit recommended by WHO); this risk was 2.3–2.9-fold greater compared to that in the other age groups and was associated with reduced efficacy at day 63 (94.4% [95% CI 92.6%–96.2%], p<0.001). After adjusting for confounding factors, the mg/kg dose of piperaquine was found to be a significant predictor for recrudescence, the risk increasing by 13% (95% CI 5.0%–21%) for every 5 mg/kg decrease in dose; p = 0.002. In a multivariable model increasing the target minimum total dose of piperaquine in children aged 1 to 5 years old from 48 mg/kg to 59 mg/kg would halve the risk of treatment failure and cure at least 95% of patients; such an increment was not associated with gastrointestinal toxicity in the ten studies in which this could be assessed. Conclusions DP demonstrates excellent efficacy in a wide range of transmission settings; however, treatment failure is associated with a lower dose of piperaquine, particularly in young children, suggesting potential for further dose optimisation. Please see later in the article for the Editors' Summary PMID:24311989

  18. Fasting plasma glucose 6–12 weeks after starting insulin glargine predicts likelihood of treatment success: a pooled analysis

    PubMed Central

    Karl, D; Zhou, R; Vlajnic, A; Riddle, M

    2012-01-01

    Aims To evaluate whether fasting plasma glucose values measured early during insulin therapy can identify patients with Type 2 diabetes who may not achieve adequate glycaemic control after 6 months and will require additional treatment. Methods Patient-level data from seven prospective, randomized, controlled studies using treat-to-target methods were pooled to evaluate the efficacy of insulin glargine. Fasting plasma glucose was measured at baseline, week 6 or 8 (6/8) and week 12. HbA1c was measured at week 24 to assess glycaemic control. Results One thousand and thirty-six patients (56% male, 81% white) were included in the analysis (mean age 56.3 years; duration of diabetes 8.4 years). Baseline mean fasting plasma glucose was 11.2 mmol/l and mean HbA1c was 73 mmol/mol (8.8%). After 24 weeks of treatment, mean HbA1c decreased to 53 mmol/mol (7.0%); 56% of patients reached a target HbA1c≤ 53 mmol/mol (7.0%). Significant correlations with week 24 HbA1c were obtained for fasting plasma glucose measured at week 6/8 and week 12 (r = 0.32; P < 0.0001 for both). Patients with fasting plasma glucose > 10 mmol/l at week 6/8 or week 12 were significantly less likely to achieve the HbA1c target at the end of treatment than patients with fasting plasma glucose < 8.9 mmol/l (P < 0.0001 for both). If fasting plasma glucose was > 10 mmol/l at week 6/8 or week 12, patients had only a 27% chance of reaching the HbA1c goal. Conclusions Fasting plasma glucose remaining > 10 mmol/l after 6–12 weeks of glargine therapy indicates that reaching target HbA1c≤ 53 mmol/mol (7.0%) is unlikely and calls for individualized attention to consider further therapeutic options. PMID:22413808

  19. Innovative technology for cancer risk analysis.

    PubMed

    Tommasi, S; Tommas, S; Danza, K; Pilato, B; De Summa, S

    2011-01-01

    After completion of the Human Genome Project, analysis of genetic and genomic variations in different pathological states became possible. The capillary system based on Sanger methods is still very expensive in terms of time, cost and professionalism required. For this reason, the National Human Genome Institute proposed an 'advanced sequencing technology development' project with the aim of sequencing a genome in 1 day for $1000. Three validated platforms are commercially available and single molecule sequencing methods have been recently introduced, which are not only competitive in time and costs, but display greater accuracy than 'past generation' sequencing. Next generation technology allows, in a single experiment, the identification of copy number variation and large rearrangements, or detection of fusion transcripts analysis thus permitting the evaluation of cancer risk at multiple levels (genomic, transcriptomic, proteomic, epigenetic). PMID:21285149

  20. Methylenetetrahydrofolate reductase gene polymorphisms and skin cancer risk: a meta-analysis.

    PubMed

    Deng, Feng; Gao, Ying; L V, Ju-hong; Gao, Jian-min

    2014-01-01

    We sought to determine whether the methylenetetrahydrofolate reductase (MTHFR) A1298C and C677T polymorphisms are associated with increased skin cancer risk. We performed literature searches of the PubMed, BIOSIS Previews, and Web of Science databases to identify eligible articles published through September 15, 2013. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using fixed-effects or random-effects models. Publication bias and subgroup analyses were also performed. Eight articles, which consisted of 10,066 subjects (2,672 patients and 7,394 controls), were included in the meta-analysis. Homozygous MTHFR 1298C individuals were 1.29 times more likely to develop skin cancer (95% CI, 1.04-1.61) compared with A1298C allele (AA or AC) carriers. There was an increased risk for C allele homozygotes compared with the 1,298 AA+AC carriers (OR, 1.45; 95% CI, 1.08-1.96) when restricted to basal cell carcinomas (BCC). The 1298C homozygote carriers increased the odds of BCC by 1.47 times (95% CI, 1.07-2.01) compared with those who were 1298A homozygote carriers. ORs for all genetic models yielded a null association. The data obtained from this meta-analysis suggest that the MTHFR 1298C allele is associated with increased skin cancer risk, particularly BCC; however, no association was observed between the MTHFR C677T polymorphism and skin cancer. PMID:25306137