Science.gov

Sample records for cancer pooled analysis

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

    PubMed Central

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

    2014-01-01

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

  2. Nonsteroidal antiinflammatory drugs and bladder cancer: a pooled analysis.

    PubMed

    Daugherty, Sarah E; Pfeiffer, Ruth M; Sigurdson, Alice J; Hayes, Richard B; Leitzmann, Michael; Schatzkin, Arthur; Hollenbeck, Albert R; Silverman, Debra T

    2011-04-01

    Case-control studies have shown that regular use of nonsteroidal antiinflammatory drugs (NSAIDs) decreases bladder cancer risk, but few cohort studies have evaluated this association. The authors investigated NSAID use and bladder cancer in 3 large prospective studies (NIH-AARP Diet and Health Study; Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial; and U.S. Radiologic Technologists Study). Frequency of aspirin and nonaspirin NSAID use 1 year prior to baseline was ascertained using self-administered questionnaires. Study-specific hazard ratios and 95% confidence intervals were estimated using Cox regression models and were combined using a fixed-effects meta-analytic model. Data from all studies were aggregated, and aggregated hazard ratios were estimated. The analysis included 508,842 individuals, with 2,489 incident cases of bladder cancer. A reduction in risk was observed for individuals who reported regular use (>2 times/week) of nonaspirin NSAIDs compared with those who reported no use (hazard ratio (HR) = 0.92, 95% confidence interval (CI): 0.81, 1.04). The risk reduction was limited to nonsmokers (HR = 0.58, 95% CI: 0.41, 0.83) (P(trend) = 0.008) (P(interaction) = 0.02). No association was observed between regular aspirin use and bladder cancer risk (HR = 1.04, 95% CI: 0.94, 1.15). Results suggest that nonaspirin NSAIDs, but not aspirin, are associated with a reduction in risk of bladder cancer, particularly for nonsmokers. PMID:21367875

  3. 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

  4. 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

  5. Age at last birth in relation to risk of endometrial cancer: pooled analysis in the epidemiology of endometrial cancer consortium.

    PubMed

    Setiawan, Veronica Wendy; Pike, Malcolm C; Karageorgi, Stalo; Deming, Sandra L; Anderson, Kristin; Bernstein, Leslie; Brinton, Louise A; Cai, Hui; Cerhan, James R; Cozen, Wendy; Chen, Chu; Doherty, Jennifer; Freudenheim, Jo L; Goodman, Marc T; Hankinson, Susan E; Lacey, James V; Liang, Xiaolin; Lissowska, Jolanta; Lu, Lingeng; Lurie, Galina; Mack, Thomas; Matsuno, Rayna K; McCann, Susan; Moysich, Kirsten B; Olson, Sara H; Rastogi, Radhai; Rebbeck, Timothy R; Risch, Harvey; Robien, Kim; Schairer, Catherine; Shu, Xiao-Ou; Spurdle, Amanda B; Strom, Brian L; Thompson, Pamela J; Ursin, Giske; Webb, Penelope M; Weiss, Noel S; Wentzensen, Nicolas; Xiang, Yong-Bing; Yang, Hannah P; Yu, Herbert; Horn-Ross, Pamela L; De Vivo, Immaculata

    2012-08-15

    Childbearing at an older age has been associated with a lower risk of endometrial cancer, but whether the association is independent of the number of births or other factors remains unclear. Individual-level data from 4 cohort and 13 case-control studies in the Epidemiology of Endometrial Cancer Consortium were pooled. A total of 8,671 cases of endometrial cancer and 16,562 controls were included in the analysis. After adjustment for known risk factors, endometrial cancer risk declined with increasing age at last birth (P(trend) < 0.0001). The pooled odds ratio per 5-year increase in age at last birth was 0.87 (95% confidence interval: 0.85, 0.90). Women who last gave birth at 40 years of age or older had a 44% decreased risk compared with women who had their last birth under the age of 25 years (95% confidence interval: 47, 66). The protective association was similar across the different age-at-diagnosis groups and for the 2 major tumor histologic subtypes (type I and type II). No effect modification was observed by body mass index, parity, or exogenous hormone use. In this large pooled analysis, late age at last birth was independently associated with a reduced risk of endometrial cancer, and the reduced risk persisted for many years. PMID:22831825

  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. 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

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

    PubMed Central

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

    2009-01-01

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

  10. 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

  11. Pooled analysis of the surgical treatment for colorectal cancer liver metastases.

    PubMed

    Veereman, G; Robays, J; Verleye, L; Leroy, R; Rolfo, C; Van Cutsem, E; Bielen, D; Ceelen, W; Danse, E; De Man, M; Demetter, P; Flamen, P; Hendlisz, A; Sinapi, I; Vanbeckevoort, D; Ysebaert, D; Peeters, M

    2015-04-01

    Liver metastases in colorectal cancer patients decreases the expected 5 year survival rates by a factor close to nine. It is generally accepted that resection of liver metastases should be attempted whenever feasible. This manuscript addresses the optimal therapeutic plan regarding timing of resection of synchronous liver metastases and the use of chemotherapy in combination with resection of synchronous metachronous liver metastases. The aim is to pool all published results in order to attribute a level of evidence to outcomes and identify lacking evidence areas. A systematic search of guidelines, reviews, randomised controlled, observational studies and updating a meta-analysis was performed. Data were extracted and analysed. Data failed to demonstrate an effect of timing of surgery or use of chemotherapy on overall survival. Concomitant resection of liver metastases and the primary tumour may result in lower postoperative morbidity. Systemic peri-operative chemotherapy may improve progression free survival compared to surgery alone. PMID:25666309

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. Telomere length in white blood cell DNA and lung cancer: a pooled analysis of three prospective cohorts.

    PubMed

    Seow, Wei Jie; Cawthon, Richard M; Purdue, Mark P; Hu, Wei; Gao, Yu-Tang; Huang, Wen-Yi; Weinstein, Stephanie J; Ji, Bu-Tian; Virtamo, Jarmo; Hosgood, H Dean; Bassig, Bryan A; Shu, Xiao-Ou; Cai, Qiuyin; Xiang, Yong-Bing; Min, Shen; Chow, Wong-Ho; Berndt, Sonja I; Kim, Christopher; Lim, Unhee; Albanes, Demetrius; Caporaso, Neil E; Chanock, Stephen; Zheng, Wei; Rothman, Nathaniel; Lan, Qing

    2014-08-01

    We investigated the relationship between telomere length and lung cancer in a pooled analysis from three prospective cohort studies: the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, conducted among men and women in the United States, and previously published data from the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Trial conducted among male smokers in Finland, and the Shanghai Women's Health Study (SWHS), which is comprised primarily of never-smokers. The pooled population included 847 cases and 847 controls matched by study, age, and sex. Leukocyte telomere length was measured by a monochrome multiplex qPCR assay. We used conditional logistic regression models to calculate ORs and their 95% confidence intervals (CI) for the association between telomere length and lung cancer risk, adjusted for age and pack-years of smoking. Longer telomere length was associated with increased lung cancer risk in the pooled analysis [OR (95% CI) by quartile: 1.00; 1.24 (0.90-1.71); 1.27 (0.91-1.78); and 1.86 (1.33-2.62); P trend = 0.000022]. Findings were consistent across the three cohorts and strongest for subjects with very long telomere length, i.e., lung cancer risks for telomere length [OR (95% CI)] in the upper half of the fourth quartile were 2.41 (1.28-4.52), 2.16 (1.11-4.23), and 3.02(1.39-6.58) for the PLCO trial, the ATBC trial, and the SWHS, respectively. In addition, the association persisted among cases diagnosed more than 6 years after blood collection and was particularly evident for female adenocarcinoma cases. Telomere length in white blood cell DNA may be a biomarker of future increased risk of lung cancer in diverse populations. PMID:24853549

  19. Circulating Leptin and Risk of Pancreatic Cancer: A Pooled Analysis From 3 Cohorts.

    PubMed

    Stolzenberg-Solomon, Rachael Z; Newton, Christina C; Silverman, Debra T; Pollak, Michael; Nogueira, Leticia M; Weinstein, Stephanie J; Albanes, Demetrius; Männistö, Satu; Jacobs, Eric J

    2015-08-01

    Adiposity is associated with pancreatic cancer; however, the underlying mechanism(s) is uncertain. Leptin is an adipokine involved in metabolic regulation, and obese individuals have higher concentrations. We conducted a pooled, nested case-control study of cohort participants from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, and the Cancer Prevention Study II Nutrition Cohort to investigate whether prediagnostic serum leptin was associated with pancreatic cancer. A total of 731 pancreatic adenocarcinoma cases that occurred between 1986 and 2010 were included (maximum follow-up, 23 years). Incidence density-selected controls (n = 909) were matched to cases by cohort, age, sex, race, and blood draw date. Conditional logistic regression was used to calculate odds ratios and 95% confidence intervals. Sex-specific quintiles were based on the distribution of the controls. Overall, serum leptin was not associated with pancreatic cancer (quintile 5 vs. quintile 1: odds ratio = 1.13, 95% confidence interval: 0.75, 1.71; Ptrend = 0.38). There was a significant interaction by follow-up time (P = 0.003), such that elevated risk was apparent only during follow-up of more than 10 years after blood draw (quintile 5 vs. quintile 1: odds ratio = 2.55, 95% confidence interval: 1.23, 5.27; Ptrend = 0.004). Our results support an association between increasing leptin concentration and pancreatic cancer; however, long follow-up is necessary to observe the relationship. Subclinical disease may explain the lack of association during early follow-up. PMID:26085045

  20. Dietary carotenoids and risk of lung cancer in a pooled analysis of seven cohort studies.

    PubMed

    Männistö, Satu; Smith-Warner, Stephanie A; Spiegelman, Donna; Albanes, Demetrius; Anderson, Kristin; van den Brandt, Piet A; Cerhan, James R; Colditz, Graham; Feskanich, Diane; Freudenheim, Jo L; Giovannucci, Edward; Goldbohm, R Alexandra; Graham, Saxon; Miller, Anthony B; Rohan, Thomas E; Virtamo, Jarmo; Willett, Walter C; Hunter, David J

    2004-01-01

    Intervention trials with supplemental beta-carotene have observed either no effect or a harmful effect on lung cancer risk. Because food composition databases for specific carotenoids have only become available recently, epidemiological evidence relating usual dietary levels of these carotenoids with lung cancer risk is limited. We analyzed the association between lung cancer risk and intakes of specific carotenoids using the primary data from seven cohort studies in North America and Europe. Carotenoid intakes were estimated from dietary questionnaires administered at baseline in each study. We calculated study-specific multivariate relative risks (RRs) and combined these using a random-effects model. The multivariate models included smoking history and other potential risk factors. During follow-up of up to 7-16 years across studies, 3,155 incident lung cancer cases were diagnosed among 399,765 participants. beta-Carotene intake was not associated with lung cancer risk (pooled multivariate RR = 0.98; 95% confidence interval, 0.87-1.11; highest versus lowest quintile). The RRs for alpha-carotene, lutein/zeaxanthin, and lycopene were also close to unity. beta-Cryptoxanthin intake was inversely associated with lung cancer risk (RR = 0.76; 95% confidence interval, 0.67-0.86; highest versus lowest quintile). These results did not change after adjustment for intakes of vitamin C (with or without supplements), folate (with or without supplements), and other carotenoids and multivitamin use. The associations generally were similar among never, past, or current smokers and by histological type. Although smoking is the strongest risk factor for lung cancer, greater intake of foods high in beta-cryptoxanthin, such as citrus fruit, may modestly lower the risk. PMID:14744731

  1. 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

  2. Red meat intake, NAT2, and risk of colorectal cancer: A pooled analysis of 11 studies

    PubMed Central

    Ananthakrishnan, Ashwin N.; Du, Mengmeng; Berndt, Sonja I.; Brenner, Hermann; Caan, Bette J.; Casey, Graham; Chang-Claude, Jenny; Duggan, David; Fuchs, Charles S.; Gallinger, Steven; Giovannucci, Edward L.; Harrison, Tabitha A.; Hayes, Richard B.; Hoffmeister, Michael; Hopper, John L.; Hou, Lifang; Hsu, Li; Jenkins, Mark A.; Kraft, Peter; Ma, Jing; Nan, Hongmei; Newcomb, Polly A.; Ogino, Shuji; Potter, John D.; Seminara, Daniela; Slattery, Martha L.; Thornquist, Mark; White, Emily; Wu, Kana; Peters, Ulrike; Chan, Andrew T.

    2014-01-01

    Background Red meat intake has been associated with risk of colorectal cancer (CRC), potentially mediated through heterocyclic amines. The metabolic efficiency of N-acetyltransferase 2 (NAT2) required for the metabolic activation of such amines is influenced by genetic variation. The interaction between red meat intake, NAT2 genotype, and CRC has been inconsistently reported. Methods We used pooled individual-level data from the Colon Cancer Family Registry (CCFR) and the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). Red meat intake was collected by each study. We inferred NAT2 phenotype based on polymorphism at rs1495741, highly predictive of enzyme activity. Interaction was assessed using multiplicative interaction terms in multivariate-adjusted models. Results From 11 studies, 8,290 CRC cases and 9,115 controls were included. The highest quartile of red meat intake was associated with increased risk of CRC compared to the lowest quartile (OR 1.41, 95%CI 1.29 – 1.55). However, a significant association was observed only for studies with retrospective diet data, not for studies with diet prospectively assessed before cancer diagnosis. Combining all studies, high red meat intake was similarly associated with CRC in those with a rapid/intermediate NAT2 genotype (OR 1.38, 95%CI 1.20 – 1.59) as with a slow genotype (OR 1.43, 95%CI 1.28 – 1.61) (p- interaction=0.9). Conclusion We found that high red meat intake was associated with increased risk of CRC only from retrospective case-control studies and not modified by NAT2 enzyme activity. Impact Our results suggest no interaction between NAT2 genotype and red-meat intake in mediating risk of CRC. PMID:25342387

  3. 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

  4. Pooled Analysis of Phosphatidylinositol 3-kinase Pathway Variants and Risk of Prostate Cancer

    PubMed Central

    Koutros, Stella; Schumacher, Fredrick R.; Hayes, Richard B.; Ma, Jing; Huang, Wen-Yi; Albanes, Demetrius; Canzian, Federico; Chanock, Stephen J.; Crawford, E. David; Diver, W. Ryan; Feigelson, Heather Spencer; Giovanucci, Edward; Haiman, Christopher A.; Henderson, Brian E.; Hunter, David J.; Kaaks, Rudolf; Kolonel, Laurence N.; Kraft, Peter; Le Marchand, Loïc; Riboli, Elio; Siddiq, Afshan; Stampfer, Mier J.; Stram, Daniel O.; Thomas, Gilles; Travis, Ruth C.; Thun, Michael J.; Yeager, Meredith; Berndt, Sonja I.

    2010-01-01

    The phosphatidylinositol 3-kinase (PI3K) pathway regulates various cellular processes, including cellular proliferation and intracellular trafficking and may impact prostate carcinogenesis. Thus, we explored the association between single nucleotide polymorphisms (SNPs) in PI3K genes and prostate cancer. Pooled data from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium were examined for associations between 89 SNPs in PI3K genes (PIK3C2B, PIK3AP1, PIK3C2A, PIK3CD, and PIK3R3) and prostate cancer risk in 8,309 cases and 9,286 controls. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression. SNP rs7556371 in PIK3C2B was significantly associated with prostate cancer risk (ORper allele=1.08 (95% CI: 1.03, 1.14), p-trend = 0.0017) after adjustment for multiple testing (Padj=0.024). Simultaneous adjustment of rs7556371 for nearby SNPs strengthened the association (ORper allele=1.21 (95% CI: 1.09, 1.34); p-trend =0.0003). The adjusted association was stronger for men who were diagnosed before 65 years (ORper allele= 1.47 (95% CI: 1.20, 1.79), p-trend = 0.0001) or had a family history (ORper allele= 1.57 (95% CI: 1.11, 2.23), p-trend = 0.0114), and was strongest in those with both characteristics (ORper allele= 2.31 (95% CI: 1.07, 5.07), p-interaction = 0.005). Increased risks were observed among men in the top tertile of circulating insulin like growth factor-1 (IGF-1) levels (ORper allele= 1.46 (95% CI: 1.04, 2.06), p-trend=0.075). No differences were observed with disease aggressiveness (≥8/stage T3/T4/fatal). In conclusion, we observed a significant association between PIK3C2B and prostate cancer risk, especially for familial, early onset disease, which may be attributable to IGF-dependent PI3K signaling. PMID:20197460

  5. Prophylactic cranial irradiation in small-cell lung cancer: Findings from a North Central Cancer Treatment Group Pooled Analysis

    PubMed Central

    Schild, S. E.; Foster, N. R.; Meyers, J. P.; Ross, H. J.; Stella, P. J.; Garces, Y. I.; Olivier, K. R.; Molina, J. R.; Past, L. R.; Adjei, A. A.

    2012-01-01

    Background This pooled analysis evaluated the outcomes of prophylactic cranial irradiation (PCI) in 739 small-cell lung cancer (SCLC patients with stable disease (SD) or better following chemotherapy ± thoracic radiation therapy (TRT) to examine the potential advantage of PCI in a wider spectrum of patients than generally participate in PCI trials. Patients and methods Three hundred eighteen patients with extensive SCLC (ESCLC) and 421 patients with limited SCLC (LSCLC) participated in four phase II or III trials. Four hundred fifty-nine patients received PCI (30 Gy/15 or 25 Gy/10) and 280 did not. Survival and adverse events (AEs) were compared. Results PCI patients survived significantly longer than non-PCI patients {hazard ratio [HR] = 0.61 [95% confidence interval (CI): 0.52–0.72]; P < 0.0001}. The 1- and 3-year survival rates were 56% and 18% for PCI patients versus 32% and 5% for non-PCI patients. PCI was still significant after adjusting for age, performance status, gender, stage, complete response, and number of metastatic sites (HR = 0.82, P = 0.04). PCI patients had significantly more grade 3+ AEs (64%) compared with non-PCI patients (50%) (P = 0.0004). AEs associated with PCI included alopecia and lethargy. Dose fractionation could be compared only for LSCLC patients and 25 Gy/10 was associated with significantly better survival compared with 30 Gy/15 (HR = 0.67, P = 0.018). Conclusions PCI was associated with a significant survival benefit for both ESCLC and LSCLC patients who had SD or a better response to chemotherapy ± TRT. Dose fractionation appears important. PCI was associated with an increase in overall and specific grade 3+ AE rates. PMID:22782333

  6. 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.

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

    PubMed Central

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

    2010-01-01

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

  8. Risk of second primary cancer after treatment for esophageal cancer: a pooled analysis of nine cancer registries.

    PubMed

    Zhu, G; Chen, Y; Zhu, Z; Lu, L; Bi, X; Deng, Q; Chen, X; Su, H; Liu, Y; Guo, H; Zheng, T; Yu, H; Zhang, Y

    2012-08-01

    The introduction of new treatments for esophageal cancer including surgery, chemotherapy, radiotherapy, or a combination of these modalities has not only improved patient survival, but may also increase the risk of the second primary cancers. The available evidence is conflicting with most risk estimates based on sparse numbers. Here we estimated standardized incidence ratios (SIRs) of second cancer among 24,557 esophageal cancer survivors (at least 2 months) in the Surveillance, Epidemiology, and End Results (SEER) Program between 1973 and 2007, who had been followed up for median 6.5 years (range 2 months-29.3 years). Second cancer risk was statistically significantly elevated (SIR = 1.34, 95% confidence interval [CI]= 1.25-1.42) among the survivors compared with the general population; the SIRs for cancers of oral and pharynx, stomach, small intestine, larynx, lung and bronchus, thyroid and prostate cancer were 8.64 (95% CI = 7.36-10.07), 2.87 (95% CI = 2.10-3.82), 3.80 (95% CI = 1.82-7.00), 3.19 (95% CI = 2.12-4.61), 1.68 (95% CI = 1.46-1.93), 2.50 (95% CI = 1.25-4.47), and 0.77 (95% CI = 0.65-0.90), respectively. Radiotherapy raised cancer risk of larynx (SIR = 3.98, 95% CI = 2.43-6.14) and thyroid (SIR = 3.57, 95% CI = 1.54-7.03) among all esophageal cancer survivors. For patients who had 5-9 years of follow up after radiotherapy, the SIR for lung cancer was 3.46 (95% CI = 2.41-4.82). Patients with esophageal cancer are at increased risks of second cancers of oral and pharynx, larynx, lung, and thyroid, while at a decreased risk for prostate cancer. These findings indicate that radiotherapy for esophageal cancer patients may increase risk of developing second cancers of larynx, lung, and thyroid. Thus, randomized clinical trials to address the association of radiotherapy and the risk of secondary cancer are warranted. PMID:22067063

  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. In-Home Coal and Wood Use and Lung Cancer Risk: A Pooled Analysis of the International Lung Cancer Consortium

    PubMed Central

    Hosgood, H. Dean; Boffetta, Paolo; Greenland, Sander; Lee, Yuan-Chin Amy; McLaughlin, John; Seow, Adeline; Duell, Eric J.; Andrew, Angeline S.; Zaridze, David; Szeszenia-Dabrowska, Neonila; Rudnai, Peter; Lissowska, Jolanta; Fabiánová, Eleonóra; Mates, Dana; Bencko, Vladimir; Foretova, Lenka; Janout, Vladimir; Morgenstern, Hal; Rothman, Nathaniel; Hung, Rayjean J.; Brennan, Paul; Lan, Qing

    2010-01-01

    Background Domestic fuel combustion from cooking and heating is an important public health issue because roughly 3 billion people are exposed worldwide. Recently, the International Agency for Research on Cancer classified indoor emissions from household coal combustion as a human carcinogen (group 1) and from biomass fuel (primarily wood) as a probable human carcinogen (group 2A). Objectives We pooled seven studies from the International Lung Cancer Consortium (5,105 cases and 6,535 controls) to provide further epidemiological evaluation of the association between in-home solid-fuel use, particularly wood, and lung cancer risk. Methods Using questionnaire data, we classified subjects as predominant solid-fuel users (e.g., coal, wood) or nonsolid-fuel users (e.g., oil, gas, electricity). Unconditional logistic regression was used to estimate the odds ratios (ORs) and to compute 95% confidence intervals (CIs), adjusting for age, sex, education, smoking status, race/ethnicity, and study center. Results Compared with nonsolid-fuel users, predominant coal users (OR = 1.64; 95% CI, 1.49–1.81), particularly coal users in Asia (OR = 4.93; 95% CI, 3.73–6.52), and predominant wood users in North American and European countries (OR = 1.21; 95% CI, 1.06–1.38) experienced higher risk of lung cancer. The results were similar in never-smoking women and other subgroups. Conclusions Our results are consistent with previous observations pertaining to in-home coal use and lung cancer risk, support the hypothesis of a carcinogenic potential of in-home wood use, and point to the need for more detailed study of factors affecting these associations. PMID:20846923

  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

  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. 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

  16. 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

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

    PubMed Central

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

    2014-01-01

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

  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

  19. 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

  20. Reduced NM23 Protein Level Correlates With Worse Clinicopathologic Features in Colorectal Cancers: A Meta-Analysis of Pooled Data.

    PubMed

    Yang, Tian; Chen, Bo-Zan; Li, Dan-Feng; Wang, Huai-Ming; Lin, Xiao-Sheng; Wei, Hong-Fa; Zeng, Yong-Ming

    2016-01-01

    The clinical value of a prominent metastasis suppressor, nonmetastatic protein 23 (NM23), remains controversial. In this study, we examined the correlation between NM23 protein levels and the clinicopathologic features of colorectal cancers (CRC), and assessed the overall prognostic value of NM23 for CRC. Embase, PubMed, Web of Science, and other scientific literature databases were exhaustively searched to identify relevant studies published prior to June 31, 2015. The methodological qualities of selected studies were scored based on the critical appraisal skills program (CASP) criteria, as independently assessed by 2 reviewers. NM23 protein levels in tumor tissues of CRC patients were examined in relation to Dukes stage, differentiation grade, T-stage, lymph node metastasis status, and overall survival (OS). STATA software version 12.0 (Stata Corp, College Station, TX) was used for statistical analysis of data pooled from selected studies. Nineteen cohort studies met the inclusion criteria for present study and contained a combined total of 2148 study subjects. Pooled odd ratios (ORs) for NM23 expression revealed that reduced NM23 protein levels in CRC tumor tissues correlated with Dukes stage C and D (OR = 1.89, 95% CI: 1.06-3.39, P = 0.032), poor differentiation grades (OR = 1.41, 95% CI: 1.03-1.94, P = 0.032), and positive lymph node metastasis status (OR = 3.21, 95% CI: 1.95-5.29, P < 0.001). On the other hand, no such correlations were evident with T-stage T3-4 (OR = 1.56, 95% CI: 0.60-4.06, P = 0.367) or OS (OR = 0.79, 95% CI: 0.58-1.08, P = 0.138). Our analysis of pooled data found that NM23 expression is reduced in CRC tissues and low NM23 levels tightly correlate with higher Dukes stages, poorer differentiation grade, and positive lymph node metastases. However, NM23 levels did not influence the OS in CRC patients. PMID:26825905

  1. Pooled Analysis of Clinical Outcomes with Neoadjuvant Cisplatin and Gemcitabine Chemotherapy for Muscle Invasive Bladder Cancer

    PubMed Central

    Yuh, Bertram E.; Ruel, Nora; Wilson, Timothy G.; Vogelzang, Nicholas; Pal§, Sumanta K.

    2014-01-01

    Purpose Neoadjuvant chemotherapy for muscle invasive bladder cancer has been shown to confer a survival advantage in phase III studies. Although cisplatin and gemcitabine are often used in this setting, a comprehensive evaluation of this regimen is lacking. In this review we summarize the efficacy of neoadjuvant cisplatin and gemcitabine chemotherapy for muscle invasive bladder cancer based on currently published studies. Materials and Methods A systematic literature review was conducted in April 2012 searching MEDLINE® databases. Articles were selected if they included patients with muscle invasive bladder cancer, evaluated the combination of cisplatin and gemcitabine as neoadjuvant treatment, and reported pathological data after cystectomy. Cisplatin and gemcitabine dosing regimens and clinical data were further summarized using weighted averages. Results Seven studies encompassing 164 patients were published between 2007 and 2012. The majority of patients (79%) received cisplatin and gemcitabine on a 21-day cycle. A weighted average of 19.2 lymph nodes was obtained at cystectomy, and 29.7% of patients were found to have pN1 disease. Pathological down staging to pT0 and less than pT2 occurred in 42 (25.6%) and 67 (46.5%) patients, respectively. Conclusions Neoadjuvant cisplatin and gemcitabine yield appreciable pathological response rates in patients with muscle invasive bladder cancer. Since pathological response has been implicated as a potential surrogate for survival in muscle invasive bladder cancer, these data suggest that neoadjuvant cisplatin and gemcitabine may warrant further prospective assessment. PMID:23123547

  2. 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 1.04–2.52), hormone-related cancers (OR, 1.87; 95%CI 1.07–3.26) and breast cancer (OR, 2.34; 95%CI 1.05–5.22) 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

  3. 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

  4. 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

  5. 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

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

    PubMed Central

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

    2010-01-01

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

  7. 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.

  8. Intrathecal chemotherapy as a treatment for leptomeningeal metastasis of non-small cell lung cancer: A pooled analysis

    PubMed Central

    Wu, Ya-Lan; Zhou, Lin; Lu, You

    2016-01-01

    Leptomeningeal metastasis (LM) is increasingly common in patients with non-small cell lung cancer (NSCLC) due to improved treatment, and ultimately, prolonged patient survival. The current study is a pooled analysis that evaluated intrathecal chemotherapy (ITC) as a treatment for NSCLC patients with LM. The PUBMED, OVID, EBSCO and Cochrane Library databases were searched for published studies involving ITC in NSCLC patients with LM. The primary outcomes of interest included response (symptomatic, radiographic and cytological) and survival. Overall, 4 prospective studies and 5 retrospective studies were included. In total, 37 patients received ITC only, and 552 patients received multiple interventions (ITC, whole-brain radiotherapy, epidermal growth factor receptor tyrosine kinase inhibitors, systemic chemotherapy and support care). In patients with available individual information, the reevaluated cytological, clinical and radiographic rates of response to ITC were 55% (53–60%; n=49), 64% (53–79%; n=58), and 53% (n=32), respectively, and the reevaluated median survival time (from the onset of treatment, n=50) was 6.0 months (95% CI, 5.2–6.8). In patients without available individual information, the reported cytological and clinical rates of response to ITC are 14–52% and 13–50%, respectively, and the reported median survival time (from the diagnosis of LM) was 3.0–4.3 months. The clinical response rates of patients only receiving ITC varied from 71 to 79% (100% if including stable disease). The median survival time of patients who only received ITC (7.5 months) was much longer than that of patients who received multiple interventions (3.0–5.0 months). Accordingly, in NSCLC patients with LM, ITC may offer a promising response rate and survival benefits under a suitable regimen. In addition, a suitable combination strategy of multidisciplinary therapy is extremely important for these particular patients. PMID:27446430

  9. Efficacy of erlotinib in patients with advanced non-small cell lung cancer: a pooled analysis of randomized trials.

    PubMed

    Gao, Hui; Ding, Xin; Wei, Dong; Cheng, Peng; Su, Xiaomei; Liu, Huanyi; Aziz, Fahad; Wang, Daoyuan; Zhang, Tao

    2011-10-01

    Erlotinib is a potent reversible HER1/epidermal growth factor receptor tyrosine kinase inhibitor with single-agent activity in patients with non-small cell lung cancer. The aim of this study was to evaluate the efficacy of erlotinib for treating advanced non-small cell lung cancer by carrying out a pooled analysis of randomized controlled trials that compared erlotinib-based regimens with other agent-based regimens between January 1997 and 2011. Outcomes analyzed were objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse events. Fourteen trials including 7974 patients were identified. As first-line therapy was compared with chemotherapy, there was a similar ORR [OR: 0.33; 95% confidence interval (CI): 0.64-17.36; P=0.15], but decreased PFS [hazard ratio (HR): 1.55; 95% CI: 1.24-1.93; P<0.01] and OS (HR: 1.39; 95% CI: 0.99-1.94; P=0.05). As maintenance therapy was compared with placebo, erlotinib-based regimens significantly increased ORR (OR: 0.47; 95% CI: 0.31-0.70; P<0.01), prolonged PFS (HR: 0.71; 95% CI: 0.60-0.83; P<0.01), but did not improve OS (HR: 0.87; 95% CI: 0.68-1.11; P=0.22). As second/third-line therapy was compared with placebo, erlotinib-based regimens also significantly increased ORR (OR: 0.10; 95% CI: 0.02-0.41; P<0.01), prolonged PFS (HR: 0.61; 95% CI: 0.51-0.73; P<0.01), and improved OS (HR: 0.70; 95% CI: 0.58-0.84; P<0.01). However, as second/third-line therapy was compared with chemotherapy, the outcomes were similar between the two arms. When compared with PF299804, there was a decreased ORR (OR: 3.87; 95% CI: 1.27-11.81; P=0.02), and shortened PFS (HR: 0.58; 95% CI: 0.49-0.95; P=0.02). Meanwhile, erlotinib-based regimens showed no significant difference in adverse events, except for diarrhea, rash, and anemia. Erlotinib-based regimens significantly increased ORR and improved PFS as a first-line maintenance therapy or as a second/third-line therapy when compared with placebo. PMID:21808188

  10. 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

  11. 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

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

    PubMed

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

    2015-11-10

    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

  13. Mediterranean diet and risk of endometrial cancer: a pooled analysis of three italian case-control studies

    PubMed Central

    Filomeno, M; Bosetti, C; Bidoli, E; Levi, F; Serraino, D; Montella, M; La Vecchia, C; Tavani, A

    2015-01-01

    Background: Some components of the Mediterranean diet have favourable effects on endometrial cancer, and the Mediterranean diet as a whole has been shown to have a beneficial role on various neoplasms. Methods: We analysed this issue pooling data from three case-control studies carried out between 1983 and 2006 in various Italian areas and in the Swiss Canton of Vaud. Cases were 1411 women with incident, histologically confirmed endometrial cancer, and controls were 3668 patients in hospital for acute diseases. We measured the adherence to the Mediterranean diet using a Mediterranean Diet Score (MDS), based on the nine dietary components characteristics of this diet, that is, high intake of vegetables, fruits/nuts, cereals, legumes, fish; low intake of dairy products and meat; high monounsaturated to saturated fatty acid ratio; and moderate alcohol intake. We estimated the odds ratios (OR) and the corresponding 95% confidence intervals (CI) for increasing levels of the MDS (varying from 0, no adherence, to 9, maximum adherence) using multiple logistic regression models, adjusted for major confounding factors. Results: The adjusted OR for a 6–9 components of the MDS (high adherence) compared with 0–3 (low adherence) was 0.43 (95% CI 0.34–0.56). The OR for an increment of one component of MDS diet was 0.84 (95% CI 0.80–0.88). The association was consistent in strata of various covariates, although somewhat stronger in older women, in never oral contraceptive users and in hormone-replacement therapy users. Conclusions: Our study provides evidence for a beneficial role of the Mediterranean diet on endometrial cancer risk, suggesting a favourable effect of a combination of foods rich in antioxidants, fibres, phytochemicals, and unsaturated fatty acids. PMID:26010500

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

    PubMed Central

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

    2015-01-01

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

  15. 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

  16. Efficacy of nonestrogenic hot flash therapies among women stratified by breast cancer history and tamoxifen use: a pooled analysis

    PubMed Central

    Bardia, Aditya; Novotny, Paul; Sloan, Jeff; Barton, Deb; Loprinzi, Charles

    2014-01-01

    Objective Various nonestrogenic therapies have been found to be effective in mitigating hot flashes, but it has been unclear whether the efficacy varies by whether women have had breast cancer and/or were taking tamoxifen. Methods This study used data from Mayo Clinic/North Central Cancer Treatment Group clinical trials that evaluated the efficacy of any nonestrogenic agent for hot flashes and had information on breast cancer history or tamoxifen use. Statistically significant changes from the fourth treatment week versus the baseline week, using individual patient data, were assessed using Student’s t test. Results A total of 1,396 women from 20 hot flash studies were eligible for analysis. Overall, women without breast cancer had a similar percentage of baseline hot flash score at week 4, as did those with breast cancer (53% vs 50%, P = 0.92). Women who were not taking tamoxifen had a significantly lower percentage of hot flash score at week 4 as compared with those who used tamoxifen (54% vs 61%, P = 0.01). However, this was due to a higher reduction in hot flash scores in the placebo arms among women not receiving tamoxifen; the percentage reduction in hot flash scores at week 4 from baseline in the active therapy arms of the randomized placebo-controlled trials (ie, excluding placebo arms) was similar among the tamoxifen users and nonusers (difference in mean percentage reduction, 5.7; 95% CI, −1.76 to 13.16). Conclusions Some nonestrogenic therapies seem to be useful for reducing hot flashes, irrespective of the etiology of hot flashes. PMID:19188850

  17. 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

  18. Natural vitamin C intake and the risk of head and neck cancer: a pooled analysis in the International Head and Neck Cancer Epidemiology consortiuma,b

    PubMed Central

    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; Lee, Yuan-Chin Amy; Chuang, Shu-Chun; La Vecchia, Carlo; Decarli, Adriano

    2014-01-01

    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 (5959 cases and 12248 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. Reinterpretation of the results of a pooled analysis of dietary carotenoid intake and breast cancer risk by using the interval collapsing method

    PubMed Central

    2016-01-01

    OBJECTIVES: A pooled analysis of 18 prospective cohort studies reported in 2012 for evaluating carotenoid intakes and breast cancer risk defined by estrogen receptor (ER) and progesterone receptor (PR) statuses by using the “highest versus lowest intake” method (HLM). By applying the interval collapsing method (ICM) to maximize the use of the estimated information, we reevaluated the results of the previous analysis in order to reinterpret the inferences made. METHODS: In order to estimate the summary effect size (sES) and its 95% confidence interval (CI), meta-analyses with the random-effects model were conducted for adjusted relative risks and their 95% CI from the second to the fifth interval according to five kinds of carotenoids and ER/PR status. RESULTS: The following new findings were identified: α-Carotene and β-cryptoxanthin have protective effects on overall breast cancer. All five kinds of carotenoids showed protective effects on ER− breast cancer. β-Carotene level increased the risk of ER+ or ER+/PR+ breast cancer. α-Carotene, β-carotene, lutein/zeaxanthin, and lycopene showed a protective effect on ER−/PR+ or ER−/PR− breast cancer. CONCLUSIONS: The new facts support the hypothesis that carotenoids that show anticancer effects with anti-oxygen function might reduce the risk of ER− breast cancer. Based on the new facts, the modification of the effects of α-carotene, β-carotene, and β-cryptoxanthin should be evaluated according to PR and ER statuses. PMID:27283141

  20. MC1R gene variants and non-melanoma skin cancer: a pooled-analysis from the M-SKIP project

    PubMed Central

    Tagliabue, E; Fargnoli, M C; Gandini, S; Maisonneuve, P; Liu, F; Kayser, M; Nijsten, T; Han, J; Kumar, R; Gruis, N A; Ferrucci, L; Branicki, W; Dwyer, T; Blizzard, L; Helsing, P; Autier, P; García-Borrón, J C; Kanetsky, P A; Landi, M T; Little, J; Newton-Bishop, J; Sera, F; Raimondi, S

    2015-01-01

    Background: The melanocortin-1-receptor (MC1R) gene regulates human pigmentation and is highly polymorphic in populations of European origins. The aims of this study were to evaluate the association between MC1R variants and the risk of non-melanoma skin cancer (NMSC), and to investigate whether risk estimates differed by phenotypic characteristics. Methods: Data on 3527 NMSC cases and 9391 controls were gathered through the M-SKIP Project, an international pooled-analysis on MC1R, skin cancer and phenotypic characteristics. We calculated summary odds ratios (SOR) with random-effect models, and performed stratified analyses. Results: Subjects carrying at least one MC1R variant had an increased risk of NMSC overall, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC): SOR (95%CI) were 1.48 (1.24–1.76), 1.39 (1.15–1.69) and 1.61 (1.35–1.91), respectively. All of the investigated variants showed positive associations with NMSC, with consistent significant results obtained for V60L, D84E, V92M, R151C, R160W, R163Q and D294H: SOR (95%CI) ranged from 1.42 (1.19–1.70) for V60L to 2.66 (1.06–6.65) for D84E variant. In stratified analysis, there was no consistent pattern of association between MC1R and NMSC by skin type, but we consistently observed higher SORs for subjects without red hair. Conclusions: Our pooled-analysis highlighted a role of MC1R variants in NMSC development and suggested an effect modification by red hair colour phenotype. PMID:26103569

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

    PubMed Central

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

    2013-01-01

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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. Decline in Tested and Self-Reported Cognitive Functioning Following Prophylactic Cranial Irradiation for Lung Cancer: Pooled Secondary Analysis of RTOG Randomized Trials 0212 and 0214

    PubMed Central

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

    2013-01-01

    Summary Prior studies have demonstrated an association between prophylactic cranial irradiation (PCI) and subsequent decline in the Hopkins Verbal Learning Test (HVLT). In this analysis, prophylactic cranial irradiation is also associated with a higher rate of decline in self-reported cognitive functioning (SRCF). This study provides novel observations regarding the absence of a close correlation between decline in HVLT and decline in SRCF, suggesting that they may represent distinct elements of the cognitive spectrum. Purpose Prophylactic cranial irradiation (PCI) has been associated with decline in tested cognitive functioning, using the Hopkins Verbal Learning Test (HVLT). The purpose of this study was to assess the impact of PCI on self-reported cognitive functioning (SRCF), a functional scale on EORTC QLQ-C30. Methods and Materials RTOG 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, HVLT-recall (R) and -delayed recall (DR) and SRCF were assessed at baseline (following locoregional therapy but before PCI or observation) and at 6 and 12 months (mos). Patients developing brain relapse prior to 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. PCI was associated with a higher risk of decline in SRCF at 6 mos (Odds Ratio (OR), 3.60, 95% confidence interval (95%CI), 2.34-6.37, p<0.0001) and 12 mos (OR 3.44, 95%CI 1.84-6.44, p<0.0001). HVLT-R decline at 6 and 12 mos was also associated with

  8. 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.

  9. 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

  10. Stereotactic ablative radiotherapy versus lobectomy for operable stage I non-small-cell lung cancer: a pooled analysis of two randomised trials

    PubMed Central

    Chang, Joe Y; Senan, Suresh; Paul, Marinus A; Mehran, Reza J; Louie, Alexander V; Balter, Peter; Groen, Harry J M; McRae, Stephen E; Widder, Joachim; Feng, Lei; van den Borne, Ben E E M; Munsell, Mark F; Hurkmans, Coen; Berry, Donald A; van Werkhoven, Erik; Kresl, John J; Dingemans, Anne-Marie; Dawood, Omar; Haasbeek, Cornelis J A; Carpenter, Larry S; De Jaeger, Katrien; Komaki, Ritsuko; Slotman, Ben J; Smit, Egbert F; Roth, Jack A

    2015-01-01

    Summary Background The standard of care for operable, stage I, non-small-cell lung cancer (NSCLC) is lobectomy with mediastinal lymph node dissection or sampling. Stereotactic ablative radiotherapy (SABR) for inoperable stage I NSCLC has shown promising results, but two independent, randomised, phase 3 trials of SABR in patients with operable stage I NSCLC (STARS and ROSEL) closed early due to slow accrual. We aimed to assess overall survival for SABR versus surgery by pooling data from these trials. Methods Eligible patients in the STARS and ROSEL studies were those with clinical T1–2a (<4 cm), N0M0, operable NSCLC. Patients were randomly assigned in a 1:1 ratio to SABR or lobectomy with mediastinal lymph node dissection or sampling. We did a pooled analysis in the intention-to-treat population using overall survival as the primary endpoint. Both trials are registered with ClinicalTrials.gov (STARS: NCT00840749; ROSEL: NCT00687986). Findings 58 patients were enrolled and randomly assigned (31 to SABR and 27 to surgery). Median follow-up was 40.2 months (IQR 23.0–47.3) for the SABR group and 35.4 months (18.9–40.7) for the surgery group. Six patients in the surgery group died compared with one patient in the SABR group. Estimated overall survival at 3 years was 95% (95% CI 85–100) in the SABR group compared with 79% (64–97) in the surgery group (hazard ratio [HR] 0.14 [95% CI 0.017–1.190], log-rank p=0.037). Recurrence-free survival at 3 years was 86% (95% CI 74–100) in the SABR group and 80% (65–97) in the surgery group (HR 0.69 [95% CI 0.21–2.29], log-rank p=0.54). In the surgery group, one patient had regional nodal recurrence and two had distant metastases; in the SABR group, one patient had local recurrence, four had regional nodal recurrence, and one had distant metastases. Three (10%) patients in the SABR group had grade 3 treatment-related adverse events (three [10%] chest wall pain, two [6%] dyspnoea or cough, and one [3%] fatigue and rib

  11. 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

  12. The SDF-1 rs1801157 Polymorphism is Associated with Cancer Risk: An Update Pooled Analysis and FPRP Test of 17,876 Participants

    PubMed Central

    Tong, Xiang; Ma, Yao; Deng, Huajiang; Wang, Xixi; Liu, Sitong; Yan, Zhipeng; Peng, Shifeng; Fan, Hong

    2016-01-01

    The stromal cell derived factor-1 (SDF-1) rs1801157 gene polymorphism has been implicated in susceptibility to cancer, but the results were inconclusive. The current study was to precisely investigate the association between SDF-1 rs1801157 polymorphism and cancer risk using meta-analysis and the false positive report probability (FPRP) test. All 17,876 participants were included in the study. The meta-analysis results indicated a significant association between the SDF-1 rs1801157 polymorphism and cancer risk. By subgroup analyses, the results detected that the SDF-1 rs1801157 polymorphism was associated with cancer susceptibility among Asians and Caucasians. Additionally, we also found significant associations between the SDF-1 rs1801157 polymorphism and susceptibility to different types of cancer. However, to avoid a “false positive report”, we further investigated the significant associations observed in the present meta-analysis using the FPRP test. Interestingly, the results of the FPRP test indicated that only 4 gene models were truly associated with cancer risk, especially in Asians. Moreover, we confirmed that the SDF-1 rs1801157 gene polymorphism was only associated with lung and urologic cancer risk. In summary, this study suggested that the SDF-1 rs1801157 polymorphism may serve as a risk factor for cancer development among Asians, especially an increased risk of urologic and lung cancers. PMID:27265091

  13. The SDF-1 rs1801157 Polymorphism is Associated with Cancer Risk: An Update Pooled Analysis and FPRP Test of 17,876 Participants.

    PubMed

    Tong, Xiang; Ma, Yao; Deng, Huajiang; Wang, Xixi; Liu, Sitong; Yan, Zhipeng; Peng, Shifeng; Fan, Hong

    2016-01-01

    The stromal cell derived factor-1 (SDF-1) rs1801157 gene polymorphism has been implicated in susceptibility to cancer, but the results were inconclusive. The current study was to precisely investigate the association between SDF-1 rs1801157 polymorphism and cancer risk using meta-analysis and the false positive report probability (FPRP) test. All 17,876 participants were included in the study. The meta-analysis results indicated a significant association between the SDF-1 rs1801157 polymorphism and cancer risk. By subgroup analyses, the results detected that the SDF-1 rs1801157 polymorphism was associated with cancer susceptibility among Asians and Caucasians. Additionally, we also found significant associations between the SDF-1 rs1801157 polymorphism and susceptibility to different types of cancer. However, to avoid a "false positive report", we further investigated the significant associations observed in the present meta-analysis using the FPRP test. Interestingly, the results of the FPRP test indicated that only 4 gene models were truly associated with cancer risk, especially in Asians. Moreover, we confirmed that the SDF-1 rs1801157 gene polymorphism was only associated with lung and urologic cancer risk. In summary, this study suggested that the SDF-1 rs1801157 polymorphism may serve as a risk factor for cancer development among Asians, especially an increased risk of urologic and lung cancers. PMID:27265091

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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)

  20. 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)

  1. Circulating 25-hydroxyvitamin D and risk of pancreatic cancer: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers.

    PubMed

    Stolzenberg-Solomon, Rachael Z; Jacobs, Eric J; Arslan, Alan A; Qi, Dai; Patel, Alpa V; Helzlsouer, Kathy J; Weinstein, Stephanie J; McCullough, Marjorie L; Purdue, Mark P; Shu, Xiao-Ou; Snyder, Kirk; Virtamo, Jarmo; Wilkins, Lynn R; Yu, Kai; Zeleniuch-Jacquotte, Anne; Zheng, Wei; Albanes, Demetrius; Cai, Qiuyin; Harvey, Chinonye; Hayes, Richard; Clipp, Sandra; Horst, Ronald L; Irish, Lonn; Koenig, Karen; Le Marchand, Loic; Kolonel, Laurence N

    2010-07-01

    Results from epidemiologic studies examining pancreatic cancer risk and vitamin D intake or 25-hydroxyvitamin D (25(OH)D) concentrations (the best indicator of vitamin D derived from diet and sun) have been inconsistent. Therefore, the authors conducted a pooled nested case-control study of participants from 8 cohorts within the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers (VDPP) (1974-2006) to evaluate whether prediagnostic circulating 25(OH)D concentrations were associated with the development of pancreatic cancer. In total, 952 incident pancreatic adenocarcinoma cases occurred among participants (median follow-up, 6.5 years). Controls (n = 1,333) were matched to each case by cohort, age, sex, race/ethnicity, date of blood draw, and follow-up time. Conditional logistic regression analysis was used to calculate smoking-, body mass index-, and diabetes-adjusted odds ratios and 95% confidence intervals for pancreatic cancer. Clinically relevant 25(OH)D cutpoints were compared with a referent category of 50-<75 nmol/L. No significant associations were observed for participants with lower 25(OH)D status. However, a high 25(OH)D concentration (> or =100 nmol/L) was associated with a statistically significant 2-fold increase in pancreatic cancer risk overall (odds ratio = 2.12, 95% confidence interval: 1.23, 3.64). Given this result, recommendations to increase vitamin D concentrations in healthy persons for the prevention of cancer should be carefully considered. PMID:20562185

  2. 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; 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.

  3. 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

  4. 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; 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

  5. 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

  6. Impact of Young Age on Treatment Efficacy and Safety in Advanced Colorectal Cancer: A Pooled Analysis of Patients From Nine First-Line Phase III Chemotherapy Trials

    PubMed Central

    Blanke, Charles D.; Bot, Brian M.; Thomas, David M.; Bleyer, Archie; Kohne, Claus-Henning; Seymour, Matthew T.; de Gramont, Aimery; Goldberg, Richard M.; Sargent, Daniel J.

    2011-01-01

    Purpose Colorectal cancer predominantly occurs in the elderly, but approximately 5% of patients are 50 years old or younger. We sought to determine whether young age is prognostic, or whether it influences efficacy/toxicity of chemotherapy, in patients with advanced disease. Methods We analyzed individual data on 6,284 patients from nine phase III trials of advanced colorectal cancer (aCRC) that used fluorouracil-based single-agent and combination chemotherapy. End points included progression-free survival (PFS), overall survival (OS), response rate (RR), and grade 3 or worse adverse events. Stratified Cox and adjusted logistic-regression models were used to test for age effects and age-treatment interactions. Results A total of 793 patients (13%) were younger than 50 years old; 188 of these patients (3% of total patients) were younger than 40 years old. Grade 3 or worse nausea (10% v 7%; P = .01) was more common, and severe diarrhea (11% v 14%; P = .001) and neutropenia (23% v 26%; P < .001) were less common in young (younger than 50 years) than in older (older than 50 years) patients. Age was prognostic for PFS, with poorer outcomes occurring in those younger than 50 years (median, 6.0 v 7.5 months; hazard ratio, 1.10; P = .02), but it did not affect RR or OS. In the subset of monotherapy versus combination chemotherapy trials, the relative benefits of multiagent chemotherapy were similar for young and older patients. Results were comparable when utilizing an age cut point of 40 years. Conclusion Young age is modestly associated with poorer PFS but not OS or RR in treated patients with aCRC, and young patients have more nausea but less diarrhea and neutropenia with chemotherapy in general. Young versus older patients derive the same benefits from combination chemotherapy. Absent results of a clinical trial, standard combination chemotherapy approaches are appropriate for young patients with aCRC. PMID:21646604

  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. 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

  9. 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.

  10. 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

  11. Induction of apoptosis in cancer cell lines by the Red Sea brine pool bacterial extracts

    PubMed Central

    2013-01-01

    Background Marine microorganisms are considered to be an important source of bioactive molecules against various diseases and have great potential to increase the number of lead molecules in clinical trials. Progress in novel microbial culturing techniques as well as greater accessibility to unique oceanic habitats has placed the marine environment as a new frontier in the field of natural product drug discovery. Methods A total of 24 microbial extracts from deep-sea brine pools in the Red Sea have been evaluated for their anticancer potential against three human cancer cell lines. Downstream analysis of these six most potent extracts was done using various biological assays, such as Caspase-3/7 activity, mitochondrial membrane potential (MMP), PARP-1 cleavage and expression of γH2Ax, Caspase-8 and -9 using western blotting. Results In general, most of the microbial extracts were found to be cytotoxic against one or more cancer cell lines with cell line specific activities. Out of the 13 most active microbial extracts, six extracts were able to induce significantly higher apoptosis (>70%) in cancer cells. Mechanism level studies revealed that extracts from Chromohalobacter salexigens (P3-86A and P3-86B(2)) followed the sequence of events of apoptotic pathway involving MMP disruption, caspase-3/7 activity, caspase-8 cleavage, PARP-1 cleavage and Phosphatidylserine (PS) exposure, whereas another Chromohalobacter salexigens extract (K30) induced caspase-9 mediated apoptosis. The extracts from Halomonas meridiana (P3-37B), Chromohalobacter israelensis (K18) and Idiomarina loihiensis (P3-37C) were unable to induce any change in MMP in HeLa cancer cells, and thus suggested mitochondria-independent apoptosis induction. However, further detection of a PARP-1 cleavage product, and the observed changes in caspase-8 and -9 suggested the involvement of caspase-mediated apoptotic pathways. Conclusion Altogether, the study offers novel findings regarding the anticancer

  12. Analysis of enterovirus and adenovirus presence in swimming pools in Cyprus from 2007-2008.

    PubMed

    Bashiardes, S; Koptides, D; Pavlidou, S; Richter, J; Stavrou, N; Kourtis, C; Papageorgiou, G T; Christodoulou, C G

    2011-01-01

    An analysis was carried out to determine the presence of enteroviruses and adenoviruses in public swimming pools in Cyprus. The effectiveness of the commonly implemented disinfection procedure of chlorination was confirmed by determination of bacteriological markers. Analysis of viral presence was carried out by sampling random swimming pools from the five major cities in Cyprus during a period of 21 months spanning from April 2007 to December 2008. A 10 I sample was taken from each swimming pool to be tested and was subsequently concentrated via membrane filtration using a new methodological approach for virus elution. Concentrated samples were analysed using of a Real Time Polymerase Chain Reaction (PCR) TaqMan probe based approach to detect the presence of enteroviruses and adenoviruses. Over the period of 21 months a total of 126 swimming pools were sampled and analysed. In four swimming pools enteroviruses were detected, in one pool echovirus 18 was identified, in two pools echovirus 30 was identified and in one other pool poliovirus Sabin 1 was identified. Similarly, in four swimming pools adenoviruses were detected, in all four adenovirus 41 was identified. Bacteriological marker analysis showed that 98% of pools complied with Cyprus regulations. PMID:22049764

  13. 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

  14. 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

  15. PD-L1 expression as predictive biomarker in patients with NSCLC: a pooled analysis

    PubMed Central

    Natoli, Clara; Rizzo, Sergio; Galvano, Antonio; Listì, Angela; Cicero, Giuseppe; Rolfo, Christian; Santini, Daniele; Russo, Antonio

    2016-01-01

    Background Clinical trials of immune checkpoints modulators, including both programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) inhibitors, have recently shown promising activity and tolerable toxicity in pre-treated NSCLC patients. However the predictive role of PD-L1 expression is still controversial. This pooled analysis aims to clarify the association of clinical objective responses to anti PD-1/PD-L1 monoclonal antibodies (MoAbs) and tumor PD-L1 expression in pre-treated NSCLC patients. Methods Data from published studies, that evaluated efficacy and safety of PD-1/PD-L1 inhibitors in pre-treated NSCLC patients, stratified by tumor PD-L1 expression status (immunohistochemistry, cut-off point 1%), were collected by searching in PubMed, Cochrane Library, American Society of Clinical Oncology, European Society of Medical Oncology and World Conference of Lung Cancer, meeting proceedings. Pooled Odds ratio (OR) and 95% confidence intervals (95% CIs) were calculated for the Overall Response Rate (ORR) (as evaluated by Response Evaluation Criteria in Solid Tumors, version 1.1), according to PD-L1 expression status. Results A total of seven studies, with 914 patients, were eligible. Pooled analysis showed that patients with PD-L1 positive tumors (PD-L1 tumor cell staining ≥1%), had a significantly higher ORR, compared to patients with PD-L1 negative tumors (OR: 2.44; 95% CIs: 1.61-3.68). Conclusions PD-L1 tumor over-expression seems to be associated with higher clinical activity of anti PD-1/PD-L1 MoAbs, in pre-treated NSCLC patients, suggesting a potential role of PD-L1 expression, IHC cut-off point 1%, as predictive biomarker for the selection of patients to treat with immune-checkpoint inhibitors. PMID:26918451

  16. Impact of postmenopausal hormone therapy on cardiovascular events and cancer: pooled data from clinical trials.

    PubMed Central

    Hemminki, E.; McPherson, K.

    1997-01-01

    OBJECTIVE: To examine the incidence of cardiovascular diseases and cancer from published clinical trials that studied other outcomes of postmenopausal hormone therapy as some surveys have suggested that it may decrease the incidence of cardiovascular diseases and increase the incidence of hormone dependent cancers. DESIGN: Trials that compared hormone therapy with placebo, no therapy, or vitamins and minerals in comparable groups of postmenopausal women and reported cardiovascular or cancer outcomes were searched from the literature. SUBJECTS: 22 trials with 4124 women were identified. In each group, the numbers of women with cardiovascular and cancer events were summed and divided by the numbers of women originally allocated to the groups. RESULTS: Data on cardiovascular events and cancer were usually given incidentally, either as a reason for dropping out of a study or in a list of adverse effects. The calculated odds ratios for women taking hormones versus those not taking hormones was 1.39 (95% confidence interval 0.48 to 3.95) for cardiovascular events without pulmonary embolus and deep vein thrombosis and 1.64 (0.55 to 4.18) with them. It is unlikely that such results would have occurred if the true odds ratio were 0.7 or less. For cancers, the numbers of reported events were too low for a useful conclusion. CONCLUSIONS: The results of these pooled data do not support the notion that postmenopausal hormone therapy prevents cardiovascular events. PMID:9251544

  17. 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.

  18. 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.

  19. 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.

  20. Monte Carlo Test Assembly for Item Pool Analysis and Extension

    ERIC Educational Resources Information Center

    Belov, Dmitry I.; Armstrong, Ronald D.

    2005-01-01

    A new test assembly algorithm based on a Monte Carlo random search is presented in this article. A major advantage of the Monte Carlo test assembly over other approaches (integer programming or enumerative heuristics) is that it performs a uniform sampling from the item pool, which provides every feasible item combination (test) with an equal…

  1. 76 FR 72923 - Pool Corporation; Analysis To Aid Public Comment

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-28

    ... Dentsply's teeth.''); In re Transitions Optical, Inc., 75 FR 10799 (Mar. 2010) (proposed complaint and... support a finding of monopoly power and competitive harm. PoolCorp's ``all or nothing'' threats acted as a... entry harms consumers by providing a greater opportunity for monopoly pricing.\\6\\ \\5\\ LePage's, Inc....

  2. Body mass index, effect modifiers, and risk of pancreatic cancer: a pooled study of seven prospective cohorts

    PubMed Central

    de Gonzalez, Amy Berrington; Hartge, Patricia; Pfeiffer, Ruth M.; Park, Yikyung; Freedman, D. Michal; Gail, Mitchell H.; Alavanja, Michael C. R.; Albanes, Demetrius; Beane Freeman, Laura E.; Chow, Wong-Ho; Huang, Wen-Yi; Hayes, Richard B.; Hoppin, Jane A.; Ji, Bu-tian; Leitzmann, Michael F.; Linet, Martha S.; Meinhold, Cari L.; Schairer, Catherine; Schatzkin, Arthur; Virtamo, Jarmo; Weinstein, Stephanie J.; Zheng, Wei; Stolzenberg-Solomon, Rachael Z.

    2010-01-01

    Objective To investigate whether the positive association of body mass index (BMI, kg/m2) with risk of pancreatic cancer is modified by age, sex, smoking status, physical activity, and history of diabetes. Methods In a pooled analysis of primary data of seven prospective cohorts including 458,070 men and 485,689 women, we identified 2,454 patients with incident pancreatic cancer during an average 6.9 years of follow-up. Cox proportional hazard regression models were used in data analysis. Results In a random-effects meta-analysis, for every 5 kg/m2 increment in BMI, the summary relative risk (RR) was 1.06 (95% confidence interval (CI) 0.99–1.13) for men and 1.12 (95% CI 1.05–1.19) for women. The aggregate analysis showed that compared with normal weight (BMI: 18.5 to <25), the adjusted RR was 1.13 (95% CI 1.03–1.23) for overweight (BMI: 25 to <30) and 1.19 (95% CI 1.05–1.35) for obesity class I (BMI: 30 to <35). Tests of interactions of BMI effects by other risk factors were not statistically significant. Every 5 kg/m2 increment in BMI was associated with an increased risk of pancreatic cancer among never and former smokers, but not among current smokers (P-interaction = 0.08). Conclusion The present evidence suggests that a high BMI is an independent risk factor of pancreatic cancer. PMID:20383573

  3. 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

  4. 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

  5. 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

  6. Pooled Analysis of the Prognostic and Predictive Effects of KRAS Mutation Status and KRAS Mutation Subtype in Early-Stage Resected Non–Small-Cell Lung Cancer in Four Trials of Adjuvant Chemotherapy

    PubMed Central

    Shepherd, Frances A.; Domerg, Caroline; Hainaut, Pierre; Jänne, Pasi A.; Pignon, Jean-Pierre; Graziano, Stephen; Douillard, Jean-Yves; Brambilla, Elizabeth; Le Chevalier, Thierry; Seymour, Lesley; Bourredjem, Abderrahmane; Teuff, Gwénaël Le; Pirker, Robert; Filipits, Martin; Rosell, Rafael; Kratzke, Robert; Bandarchi, Bizhan; Ma, Xiaoli; Capelletti, Marzia; Soria, Jean-Charles; Tsao, Ming-Sound

    2013-01-01

    Purpose We undertook this analysis of KRAS mutation in four trials of adjuvant chemotherapy (ACT) versus observation (OBS) to clarify the prognostic/predictive roles of KRAS in non–small-cell lung cancer (NSCLC). Methods KRAS mutation was determined in blinded fashion. Exploratory analyses were performed to characterize relationships between mutation status and subtype and survival outcomes using a multivariable Cox model. Results Among 1,543 patients (763 OBS, 780 ACT), 300 had KRAS mutations (codon 12, n = 275; codon 13, n = 24; codon 14, n = 1). In OBS patients, there was no prognostic difference for overall survival for codon-12 (mutation v wild type [WT] hazard ratio [HR] = 1.04; 95% CI, 0.77 to 1.40) or codon-13 (HR = 1.01; 95% CI, 0.47 to 2.17) mutations. No significant benefit from ACT was observed for WT-KRAS (ACT v OBS HR = 0.89; 95% CI, 0.76 to 1.04; P = .15) or codon-12 mutations (HR = 0.95; 95% CI, 0.67 to 1.35; P = .77); with codon-13 mutations, ACT was deleterious (HR = 5.78; 95% CI, 2.06 to 16.2; P < .001; interaction P = .002). There was no prognostic effect for specific codon-12 amino acid substitution. The effect of ACT was variable among patients with codon-12 mutations: G12A or G12R (HR = 0.66; P = .48), G12C or G12V (HR = 0.94; P = .77) and G12D or G12S (HR = 1.39; P = .48; comparison of four HRs, including WT, interaction P = .76). OBS patients with KRAS-mutated tumors were more likely to develop second primary cancers (HR = 2.76, 95% CI, 1.34 to 5.70; P = .005) but not ACT patients (HR = 0.66; 95% CI, 0.25 to 1.75; P = .40; interaction, P = .02). Conclusion KRAS mutation status is not significantly prognostic. The potential interaction in patients with codon-13 mutations requires validation. At this time, KRAS status cannot be recommended to select patients with NSCLC for ACT. PMID:23630215

  7. Calculation notes for surface leak resulting in pool, TWRS FSAR accident analysis

    SciTech Connect

    Hall, B.W.

    1996-09-25

    This document includes the calculations performed to quantify the risk associated with the unmitigated and mitigated accident scenarios described in the TWRS FSAR for the accident analysis titled: Surface Leaks Resulting in Pool.

  8. Calculation Notes for Subsurface Leak Resulting in Pool, TWRS FSAR Accident Analysis

    SciTech Connect

    Hall, B.W.

    1996-09-25

    This document includes the calculations performed to quantify the risk associated with the unmitigated and mitigated accident scenarios described in the TWRS FSAR for the accident analysis titled: Subsurface Leaks Resulting in Pool.

  9. Pooled analysis of clinical outcome for EGFR TKI-treated patients with EGFR mutation-positive NSCLC

    PubMed Central

    Paz-Ares, Luis; Soulières, Denis; Moecks, Joachim; Bara, Ilze; Mok, Tony; Klughammer, Barbara

    2014-01-01

    Patients with non-small-cell lung cancer (NSCLC) appear to gain particular benefit from treatment with epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitors (TKI) if their disease tests positive for EGFR activating mutations. Recently, several large, controlled, phase III studies have been published in NSCLC patients with EGFR mutation-positive tumours. Given the increased patient dataset now available, a comprehensive literature search for EGFR TKIs or chemotherapy in EGFR mutation-positive NSCLC was undertaken to update the results of a previously published pooled analysis. Pooling eligible progression-free survival (PFS) data from 27 erlotinib studies (n = 731), 54 gefitinib studies (n = 1802) and 20 chemotherapy studies (n = 984) provided median PFS values for each treatment. The pooled median PFS was: 12.4 months (95% accuracy intervals [AI] 11.6–13.4) for erlotinib-treated patients; 9.4 months (95% AI 9.0–9.8) for gefitinib-treated patients; and 5.6 months (95% AI 5.3–6.0) for chemotherapy. Both erlotinib and gefitinib resulted in significantly longer PFS than chemotherapy (permutation testing; P = 0.000 and P = 0.000, respectively). Data on more recent TKIs (afatinib, dacomitinib and icotinib) were insufficient at this time-point to carry out a pooled PFS analysis on these compounds. The results of this updated pooled analysis suggest a substantial clear PFS benefit of treating patients with EGFR mutation-positive NSCLC with erlotinib or gefitinib compared with chemotherapy. PMID:25100284

  10. 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

  11. 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

  12. 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

  13. 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

  14. Meta- and pooled analyses of the methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and gastric cancer risk: a huge-GSEC review.

    PubMed

    Boccia, Stefania; Hung, Rayjean; Ricciardi, Gualtiero; Gianfagna, Francesco; Ebert, Matthias P A; Fang, Jing-Yuan; Gao, Chang-Ming; Götze, Tobias; Graziano, Francesco; Lacasaña-Navarro, Marina; Lin, Dongxin; López-Carrillo, Lizbeth; Qiao, You-Lin; Shen, Hongbing; Stolzenberg-Solomon, Rachael; Takezaki, Toshiro; Weng, Yu-Rong; Zhang, Fang Fang; van Duijn, Cornelia M; Boffetta, Paolo; Taioli, Emanuela

    2008-03-01

    Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in the metabolism of folate, whose role in gastric carcinogenesis is controversial. The authors performed a meta-analysis and individual data pooled analysis of case-control studies that examined the association between C677T and A1298C polymorphisms (the former being associated with low folate serum levels) and gastric cancer (meta-analyses: 16 studies, 2,727 cases and 4,640 controls for C677T and seven studies, 1,223 cases and 2,015 controls for A1298C; pooled analyses: nine studies, 1,540 cases and 2,577 controls for C677T and five studies, 1,146 cases and 1,549 controls for A1298C). An increased risk was found for MTHFR 677 TT in the meta-analysis (odds ratio (OR) = 1.52, 95% confidence interval (CI): 1.31, 1.77) and pooled analysis (OR = 1.49, 95% CI: 1.14, 1.95). No association resulted for MTHFR 1298 CC (meta-OR = 0.94, 95% CI: 0.65, 1.35; pooled OR = 0.90, 95% CI: 0.69, 1.34). Results from the pooled analysis of four studies on C677T stratified according to folate levels showed an increased risk for individuals with low (OR = 2.05, 95% CI: 1.13, 3.72) versus high (OR = 0.95, 95% CI: 0.54, 1.67) folate levels. Overall, these findings support the hypothesis that folate plays a role in gastric carcinogenesis. PMID:18162478

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

    PubMed

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

    2010-07-01

    Low vitamin D status is common globally and is associated with multiple disease outcomes. Understanding the correlates of vitamin D status will help guide clinical practice, research, and interpretation of studies. Correlates of circulating 25-hydroxyvitamin D (25(OH)D) concentrations measured in a single laboratory were examined in 4,723 cancer-free men and women from 10 cohorts participating in the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers, which covers a worldwide geographic area. Demographic and lifestyle characteristics were examined in relation to 25(OH)D using stepwise linear regression and polytomous logistic regression. The prevalence of 25(OH)D concentrations less than 25 nmol/L ranged from 3% to 36% across cohorts, and the prevalence of 25(OH)D concentrations less than 50 nmol/L ranged from 29% to 82%. Seasonal differences in circulating 25(OH)D were most marked among whites from northern latitudes. Statistically significant positive correlates of 25(OH)D included male sex, summer blood draw, vigorous physical activity, vitamin D intake, fish intake, multivitamin use, and calcium supplement use. Significant inverse correlates were body mass index, winter and spring blood draw, history of diabetes, sedentary behavior, smoking, and black race/ethnicity. Correlates varied somewhat within season, race/ethnicity, and sex. These findings help identify persons at risk for low vitamin D status for both clinical and research purposes. PMID:20562191

  16. 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

  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

  19. Assessment of the site of ventricular activation by Fourier analysis of gated blood-pool studies

    SciTech Connect

    Links, J.M.; Raichlen, J.S.; Wagner, H.N. Jr.; Reid, P.R.

    1985-01-01

    The authors studied the use of first-harmonic Fourier analysis of gated blood-pool images to assess the site of ventricular activation in a group of 12 patients undergoing electrophysiologic pacing studies. They acquired gated blood-pool studies during pacing at up to four sites at each of two different rates. A total of 50 studies were made. At a pacing rate of 100 beats/min, when the pacing electrode was the right-ventricular outflow tract, 7/8; at the anterolateral left-ventricular wall, 4/4. When the Fourier activation site was at the right-ventricular apex, 9/9 times the pacing electrode was there; at the right-ventricular outflow tract, 7/10; in the left ventricle, 4/4. Fourier analysis of gated blood-pool studies can help identify the site of ventricular activation but is not sufficiently accurate to fully replace endocardial mapping.

  20. Pooled analyses of eribulin in metastatic breast cancer patients with at least one prior chemotherapy

    PubMed Central

    Pivot, X.; Marmé, F.; Koenigsberg, R.; Guo, M.; Berrak, E.; Wolfer, A.

    2016-01-01

    Background Based on data from two multicenter, phase III clinical trials (Studies 301 and 305), eribulin (a microtubule dynamics inhibitor) is indicated in the European Union (EU) for patients with locally advanced or metastatic breast cancer (MBC) after ≥1 prior chemotherapy for advanced disease, including an anthracycline and a taxane in either the adjuvant or metastatic setting. Data from Studies 305 and 301 were pooled to investigate the efficacy of eribulin in various subgroups of patients who matched the EU label, including those with human epidermal growth factor receptor 2 (HER2)-negative and triple-negative disease. Patients and methods In Study 305 (NCT00388726), patients were randomized 2:1 to eribulin mesylate 1.4 mg/m2 (equivalent to eribulin 1.23 mg/m2 [expressed as free base]) intravenously on days 1 and 8 every 21 days] or treatment of physician's choice after 2–5 prior chemotherapies (≥2 for advanced disease), including an anthracycline and a taxane (in early/advanced setting). In Study 301 (NCT00337103), patients were randomized 1:1 to eribulin (as above) or capecitabine (1.25 g/m2 orally twice daily on days 1–14 every 21 days) following ≤3 prior chemotherapies (≤2 for advanced disease), including an anthracycline and a taxane. Efficacy end points were investigated in the intent-to-treat population and subgroups, pooled as discussed above. Results Overall, 1644 patients were included (eribulin: 946; control: 698); baseline characteristics were well matched. Overall survival was significantly longer with eribulin versus control (P < 0.01), as were progression-free survival and clinical benefit rate (both P < 0.05). Significant survival benefits with eribulin versus control were observed in a wide range of patient subgroups, including HER2-negative or triple-negative disease (all P < 0.05). Conclusion Our findings underline the survival benefit achieved by eribulin used according to EU label in the overall MBC population and in various

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

    SciTech Connect

    Lee, Percy; Eppinga, Wietse; Lagerwaard, Frank; Cloughesy, Timothy; Slotman, Benjamin; Nghiemphu, Phioanh L.; Wang, Pin-Chieh; Kupelian, Patrick; Agazaryan, Nzhde; Demarco, John; Selch, Michael T.; Steinberg, Michael; 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.

  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. Leisure Time Physical Activity of Moderate to Vigorous Intensity and Mortality: A Large Pooled Cohort Analysis

    PubMed Central

    Moore, Steven C.; Patel, Alpa V.; Matthews, Charles E.; Berrington de Gonzalez, Amy; Park, Yikyung; Katki, Hormuzd A.; Linet, Martha S.; Weiderpass, Elisabete; Visvanathan, Kala; Helzlsouer, Kathy J.; Thun, Michael; Gapstur, Susan M.; Hartge, Patricia; Lee, I-Min

    2012-01-01

    Background Leisure time physical activity reduces the risk of premature mortality, but the years of life expectancy gained at different levels remains unclear. Our objective was to determine the years of life gained after age 40 associated with various levels of physical activity, both overall and according to body mass index (BMI) groups, in a large pooled analysis. Methods and Findings We examined the association of leisure time physical activity with mortality during follow-up in pooled data from six prospective cohort studies in the National Cancer Institute Cohort Consortium, comprising 654,827 individuals, 21–90 y of age. Physical activity was categorized by metabolic equivalent hours per week (MET-h/wk). Life expectancies and years of life gained/lost were calculated using direct adjusted survival curves (for participants 40+ years of age), with 95% confidence intervals (CIs) derived by bootstrap. The study includes a median 10 y of follow-up and 82,465 deaths. A physical activity level of 0.1–3.74 MET-h/wk, equivalent to brisk walking for up to 75 min/wk, was associated with a gain of 1.8 (95% CI: 1.6–2.0) y in life expectancy relative to no leisure time activity (0 MET-h/wk). Higher levels of physical activity were associated with greater gains in life expectancy, with a gain of 4.5 (95% CI: 4.3–4.7) y at the highest level (22.5+ MET-h/wk, equivalent to brisk walking for 450+ min/wk). Substantial gains were also observed in each BMI group. In joint analyses, being active (7.5+ MET-h/wk) and normal weight (BMI 18.5–24.9) was associated with a gain of 7.2 (95% CI: 6.5–7.9) y of life compared to being inactive (0 MET-h/wk) and obese (BMI 35.0+). A limitation was that physical activity and BMI were ascertained by self report. Conclusions More leisure time physical activity was associated with longer life expectancy across a range of activity levels and BMI groups. Please see later in the article for the Editors' Summary PMID:23139642

  4. 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

  5. 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

  6. Elucidation and Structural Analysis of Conserved Pools for Genome-Scale Metabolic Reconstructions

    PubMed Central

    Nikolaev, Evgeni V.; Burgard, Anthony P.; Maranas, Costas D.

    2005-01-01

    In this article, we introduce metabolite concentration coupling analysis (MCCA) to study conservation relationships for metabolite concentrations in genome-scale metabolic networks. The analysis allows the global identification of subsets of metabolites whose concentrations are always coupled within common conserved pools. Also, the minimal conserved pool identification (MCPI) procedure is developed for elucidating conserved pools for targeted metabolites without computing the entire basis conservation relationships. The approaches are demonstrated on genome-scale metabolic reconstructions of Helicobacter pylori, Escherichia coli, and Saccharomyces cerevisiae. Despite significant differences in the size and complexity of the examined organism's models, we find that the concentrations of nearly all metabolites are coupled within a relatively small number of subsets. These correspond to the overall exchange of carbon molecules into and out of the networks, interconversion of energy and redox cofactors, and the transfer of nitrogen, sulfur, phosphate, coenzyme A, and acyl carrier protein moieties among metabolites. The presence of large conserved pools can be viewed as global biophysical barriers protecting cellular systems from stresses, maintaining coordinated interconversions between key metabolites, and providing an additional mode of global metabolic regulation. The developed approaches thus provide novel and versatile tools for elucidating coupling relationships between metabolite concentrations with implications in biotechnological and medical applications. PMID:15489308

  7. 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

  8. Safety and tolerability of dienogest in endometriosis: pooled analysis from the European clinical study program

    PubMed Central

    Strowitzki, Thomas; Faustmann, Thomas; Gerlinger, Christoph; Schumacher, Ulrike; Ahlers, Christiane; Seitz, Christian

    2015-01-01

    Background In four randomized, controlled, European trials, dienogest 2 mg once daily demonstrated significant efficacy for lesion reduction and reduction in pain intensity in endometriosis. We describe a pooled analysis of the safety and tolerability data from these trials to confirm and further characterize the safety profile of dienogest in the treatment of endometriosis. Methods All 332 women treated with dienogest 2 mg who participated in the four clinical trials were included in the pooled analyses for safety assessments, including adverse events, laboratory tests, vital signs, body weight, and bleeding patterns. Safety variables were analyzed using descriptive statistics. Results Pooled analyses of this large patient population confirmed that dienogest 2 mg is well tolerated, with a favorable safety profile extending over a period up to 65 weeks in women with endometriosis. The most common adverse drug reactions were headache, breast discomfort, depressed mood, and acne, each occurring in <10% of women. All these adverse events were generally of mild-to-moderate intensity and associated with low discontinuation rates. The bleeding pattern associated with dienogest 2 mg was well tolerated, and only two women (0.6%) reported bleeding events as the primary reason for premature discontinuation. Laboratory and vital sign assessments indicated no safety concerns for dienogest. Estradiol levels were maintained within the low-physiological range, in support of previous evidence indicating that dienogest 2 mg demonstrates therapeutic efficacy without inducing estradiol deficiency. Conclusion In this pooled analysis of 332 women with endometriosis, dienogest was well tolerated with a favorable safety profile extending over a period of up to 65 weeks. There is a paucity of randomized trial evidence to support the use of many treatments in endometriosis. These pooled analyses from four clinical trials of dienogest 2 mg represent a contribution to evidence-based medicine

  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. A Systematic Review and Pooled Analysis of CPR-Associated Cardiovascular and Thoracic Injuries

    PubMed Central

    Miller, Andrew C.; Rosati, Shannon F.; Suffredini, Anthony F.; Schrump, David S.

    2014-01-01

    OBJECTIVE The incidence of thoracic injuries resulting from cardiopulmonary resuscitation (CPR) is not well characterized. We describe a case in which a CPR-associated atrial rupture was identified with ultrasound and successfully managed in the intensive care unit with a bedside thoracotomy and atrial repair. We then describe a systematic review with pooled data analysis of CPR-associated cardiovascular, pulmonary, pleural, and thoracic wall injuries. DATA SOURCES PubMed, Scopus, EMBASE, and Web of Science were searched to identify relevant published studies. Unpublished studies were identified by searching the Australian and New Zealand Clinical Trials Registry, World Health Organization International Clinical Trials Registry Platform, Cochrane Library, ClinicalTrials.gov, Current Controlled Trials, and Google. STUDY SELECTION Inclusion criteria for the pooled analysis were any clinical or autopsy study in which a) patients underwent cardiopulmonary resuscitation, b) chest compressions were administered either manually or with the assistance of active compression-decompression devices, and c) autopsy or dedicated imaging assessments were conducted to identify complications. Exclusion criteria for the pooled analysis were pre-clinical studies, case reports and abstracts. DATA EXTRACTION Nine-hundred twenty-eight potentially relevant references were identified. Twenty-seven references met inclusion criteria. DATA SYNTHESIS A systematic review of the literature is provided with pooled data analysis. CONCLUSIONS The incidence of reported CPR-associated cardiovascular and thoracic wall injuries varies widely. CPR with active compression-decompression devices has a higher reported incidence of cardiopulmonary injuries. Bedside ultrasound may be a useful adjunct to assess and risk-stratify patients to identify serious or life-threatening CPR-associated injuries. PMID:24525116

  11. The science of pooling

    SciTech Connect

    Gilbert, E.

    1995-10-01

    The pooling of data from radon studies is described. Pooling refers to the analysis of original data from several studies, not meta-analysis in which summary measures from published data are analyzed. A main objective for pooling is to reduce uncertainty and to obtain more precise estimates of risk than would be available from any single study.

  12. 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

  13. 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

  14. Autophagy provides metabolic substrates to maintain energy charge and nucleotide pools in Ras-driven lung cancer cells.

    PubMed

    Guo, Jessie Yanxiang; Teng, Xin; Laddha, Saurabh V; Ma, Sirui; Van Nostrand, Stephen C; Yang, Yang; Khor, Sinan; Chan, Chang S; Rabinowitz, Joshua D; White, Eileen

    2016-08-01

    Autophagy degrades and is thought to recycle proteins, other macromolecules, and organelles. In genetically engineered mouse models (GEMMs) for Kras-driven lung cancer, autophagy prevents the accumulation of defective mitochondria and promotes malignancy. Autophagy-deficient tumor-derived cell lines are respiration-impaired and starvation-sensitive. However, to what extent their sensitivity to starvation arises from defective mitochondria or an impaired supply of metabolic substrates remains unclear. Here, we sequenced the mitochondrial genomes of wild-type or autophagy-deficient (Atg7(-/-)) Kras-driven lung tumors. Although Atg7 deletion resulted in increased mitochondrial mutations, there were too few nonsynonymous mutations to cause generalized mitochondrial dysfunction. In contrast, pulse-chase studies with isotope-labeled nutrients revealed impaired mitochondrial substrate supply during starvation of the autophagy-deficient cells. This was associated with increased reactive oxygen species (ROS), lower energy charge, and a dramatic drop in total nucleotide pools. While starvation survival of the autophagy-deficient cells was not rescued by the general antioxidant N-acetyl-cysteine, it was fully rescued by glutamine or glutamate (both amino acids that feed the TCA cycle and nucleotide synthesis) or nucleosides. Thus, maintenance of nucleotide pools is a critical challenge for starving Kras-driven tumor cells. By providing bioenergetic and biosynthetic substrates, autophagy supports nucleotide pools and thereby starvation survival. PMID:27516533

  15. 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

  16. Analysis of linear and mildly nonlinear relationships using pooled subject data.

    PubMed

    Poon, C S

    1988-02-01

    The detection of mild nonlinearities and/or state-dependent variability in otherwise linear physiological relationships is generally difficult in the presence of significant measurement errors. Conventional approaches using pooled subject data to increase the degree of freedom for statistical inference are enervated by the resultant introduction of intersubject variability. This paper proposes a new, simple method of pooling multiple subject data for linearity analysis. With the use of a special standardization procedure for the individual response curves, this method allows sensitive detection of occult nonlinearities as well as any state-dependent variability in the underlying relationship. Application of this analytic approach to reported hypercapnic exercise-response data in eight healthy subjects showed that 1) the hypercapnic ventilation-CO2 output relationship is nonlinear with a downward concavity; and 2) the ventilation-tidal volume relationship, which is linear at low tidal volume values, is similar in hypercapnic exercise as in resting hypercapnia or eucapnic exercise. PMID:3372442

  17. Dietary intake and urinary level of cadmium and breast cancer risk: A meta-analysis.

    PubMed

    Lin, Jinbo; Zhang, Fang; Lei, Yixiong

    2016-06-01

    Cadmium, a human carcinogenic heavy metal, has been reported to be associated with breast cancer risk; however, the results from the epidemiological studies are not always consistent. The objective of this study was to quantitatively summarize the current evidence for the relationship between cadmium exposure and breast cancer risk using meta-analysis methods. Six studies determining the dietary cadmium intake level and five studies evaluating the urinary cadmium level were identified in a systematic search of MEDLINE and PubMed databases, and the associations between these levels and breast cancer risk were analysed. The pooled estimates under the random-effects model suggested that higher urinary cadmium levels were associated with an increased risk for breast cancer (highest versus lowest quantile, pooled odds ratio [OR]=2.24, 95% confidence interval [95%CI]=1.49-3.35) and a 1μg/g creatinine increase in urinary cadmium led to a 1.02-fold increment of breast cancer (pooled OR=2.02, 95%CI=1.34-3.03); however, pooled estimates for dietary cadmium intake found no significant association between cadmium exposure and breast cancer risk (highest versus lowest quantile, pooled relative risk [RR]=1.01, 95%CI=0.89-1.15). These results suggest that cadmium exposure may lead to an increased risk of breast cancer, and urinary cadmium levels can serve as a reliable biomarker for long-term cadmium exposure and may predict the breast cancer risk. PMID:27085960

  18. 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.

  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. 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; Wöckel, 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

  1. Sample distillation/graphitization system for carbon pool analysis by accelerator mass spectrometry (AMS)

    NASA Astrophysics Data System (ADS)

    Pohlman, J. W.; Knies, D. L.; Grabowski, K. S.; DeTurck, T. M.; Treacy, D. J.; Coffin, R. B.

    2000-10-01

    A facility at the Naval Research Laboratory (NRL), Washington, DC, has been developed to extract, trap, cryogenically distill and graphitize carbon from a suite of organic and inorganic carbon pools for analysis by accelerator mass spectrometry (AMS). The system was developed to investigate carbon pools associated with the formation and stability of methane hydrates. However, since the carbon compounds found in hydrate fields are ubiquitous in aquatic ecosystems, this apparatus is applicable to a number of oceanographic and environmental sample types. Targeted pools are dissolved methane, dissolved organic carbon (DOC), dissolved inorganic carbon (DIC), solid organic matrices (e.g., seston, tissue and sediments), biomarkers and short chained (C 1-C 5) hydrocarbons from methane hydrates. In most instances, the extraction, distillation and graphitization events are continuous within the system, thus, minimizing the possibility of fractionation or contamination during sample processing. A variety of methods are employed to extract carbon compounds and convert them to CO 2 for graphitization. Dissolved methane and DIC from the same sample are sparged and cryogenically separated before the methane is oxidized in a high temperature oxygen stream. DOC is oxidized to CO 2 by 1200 W ultraviolet photo-oxidation lamp, and solids oxidized in sealed, evacuated tubes. Hydrocarbons liberated from the disassociation of gas hydrates are cryogenically separated with a cryogenic temperature control unit, and biomarkers separated and concentrated by preparative capillary gas chromatography (PCGC). With this system, up to 20 samples, standards or blanks can be processed per day.

  2. Cryptococcal meningitis in systemic lupus erythematosus patients: pooled analysis and systematic review.

    PubMed

    Fang, Wenjie; Chen, Min; Liu, Jia; Hagen, Ferry; Ms, Abdullah; Al-Hatmi; Zhang, Peilian; Guo, Yun; Boekhout, Teun; Deng, Danqi; Xu, Jianping; Pan, Weihua; Liao, Wanqing

    2016-01-01

    Cryptococcal meningitis is an important fungal infection among systemic lupus erythematosus patients. We conducted a pooled analysis and systematic review to describe the epidemiological and clinical profile of cryptococcal meningitis in systemic lupus erythematosus patients. From two hospitals in China and nine literature databases, cases and prevalence data were collected for pooled analysis and meta-analysis, respectively. Categorical variables of cases were compared using a χ(2)-test on the statistical program of SAS. A multiple regression analysis was performed to ascertain independent predictors significantly correlated with prognosis. Meta-analysis was conducted by the statistical program of R. The prevalence of cryptococcal meningitis in systemic lupus erythematosus patients was 0.5%. Patients were predominantly females and adults. A prednisone equivalent of more than 30 mg/day before infection was associated with higher mortality (odds ratio (OR)=9.69 (1.54, 60.73)). In all, 36.8-38.9% patients showed low lupus activity when they developed the crytococcal infection. Moreover, 38.2% of the patients were misdiagnosed. The estimated case-fatality rate was 23.6%. Our results suggest that more emphasis should be placed to further understand lupus-related cryptococcal meningitis and to develop better prophylaxis and management strategies to combat this condition. PMID:27599471

  3. Plasma prolactin and breast cancer risk: a meta- analysis.

    PubMed

    Wang, Minghao; Wu, Xiujuan; Chai, Fan; Zhang, Yi; Jiang, Jun

    2016-01-01

    Breast cancer is the most common cancer among women, and its incidence is on a constant rise. Previous studies suggest that higher levels of plasma prolactin are associated with escalated risk of breast cancer, however, these results are contradictory and inconclusive. PubMed and Medline were used to search and identify published observational studies that assessed the relationship between plasma prolactin levels and the risk of breast cancer. The pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated using a fixed-effects or random-effects model. A total of 7 studies were included in our analysis. For the highest versus lowest levels of plasma prolactin, the pooled RR (95% CI) of breast cancer were 1.16 (1.04, 1.29). In subgroup analyses, we found a positive association between plasma prolactin levels and the risk of breast cancer among the patients who were postmenopausal, ER(+)/PR(+) or in situ and invasive carcinoma. However, this positive association was not detected in the premenopausal and ER(-)/PR(-) patients. In conclusion, the present study provides evidence supporting a significantly positive association between plasma prolactin levels and the risk of breast cancer. PMID:27184120

  4. Plasma prolactin and breast cancer risk: a meta- analysis

    PubMed Central

    Wang, Minghao; Wu, Xiujuan; Chai, Fan; Zhang, Yi; Jiang, Jun

    2016-01-01

    Breast cancer is the most common cancer among women, and its incidence is on a constant rise. Previous studies suggest that higher levels of plasma prolactin are associated with escalated risk of breast cancer, however, these results are contradictory and inconclusive. PubMed and Medline were used to search and identify published observational studies that assessed the relationship between plasma prolactin levels and the risk of breast cancer. The pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated using a fixed-effects or random-effects model. A total of 7 studies were included in our analysis. For the highest versus lowest levels of plasma prolactin, the pooled RR (95% CI) of breast cancer were 1.16 (1.04, 1.29). In subgroup analyses, we found a positive association between plasma prolactin levels and the risk of breast cancer among the patients who were postmenopausal, ER+/PR+ or in situ and invasive carcinoma. However, this positive association was not detected in the premenopausal and ER-/PR- patients. In conclusion, the present study provides evidence supporting a significantly positive association between plasma prolactin levels and the risk of breast cancer. PMID:27184120

  5. Coffee consumption and risk of hepatocellular carcinoma and intrahepatic cholangiocarcinoma by sex: The Liver Cancer Pooling Project

    PubMed Central

    Petrick, Jessica L.; Freedman, Neal D.; Graubard, Barry I.; Sahasrabuddhe, Vikrant V.; Lai, Gabriel Y.; Alavanja, Michael C.; Beane-Freeman, Laura E.; Boggs, Deborah A.; Buring, Julie E.; Chan, Andrew T.; Chong, Dawn Q.; Fuchs, Charles S.; Gapstur, Susan M.; Gaziano, John Michael; Giovannucci, Edward L.; Hollenbeck, Albert R.; King, Lindsay Y.; Koshiol, Jill; Lee, I-Min; Linet, Martha S.; Palmer, Julie R.; Poynter, Jenny N.; Purdue, Mark P.; Robien, Kim; Schairer, Catherine; Sesso, Howard D.; Sigurdson, Alice J.; Zeleniuch-Jacquotte, Anne; Wactawski-Wende, Jean; Campbell, Peter T.; McGlynn, Katherine A.

    2015-01-01

    Background Coffee consumption has been reported to be inversely associated with hepatocellular carcinoma (HCC), the most common type of liver cancer. Caffeine has chemopreventive properties, but whether caffeine is responsible for the coffee-HCC association is not well studied. In addition, few studies have examined the relationship by sex, and no studies have examined whether there is an association between coffee and intrahepatic cholangiocarcinoma (ICC), the second most common type of liver cancer. Methods In the Liver Cancer Pooling Project, a consortium of U.S.-based cohort studies, data from 1,212,893 individuals (HCC n=860, ICC n=260) in nine cohorts were pooled. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CI) were estimated using proportional hazards regression. Results Higher coffee consumption was associated with lower risk of HCC (HR>3 cups/day vs. non-drinker, 0.73; 95% CI, 0.53-0.99; ptrend cups/day=<0.0001). More notable reduced risk was seen among women than men (pinteraction=0.07). Women who consumed more than three cups of coffee per day were at a 54% lower risk of HCC (HR, 0.46; 95% CI, 0.26-0.81), whereas men had more modest reduced risk of HCC (HR, 0.93; 95% CI, 0.63-1.37). The associations were stronger for caffeinated coffee (HR>3 cups/day vs. non-drinker, 0.71, 95% CI, 0.50-1.01) than decaffeinated coffee (HR, 0.92; 95% CI, 0.55-1.54). There was no relationship between coffee consumption and ICC. Conclusions These findings suggest that, in a U.S. population, coffee consumption is associated with reduced risk of HCC. Impact Further research into specific coffee compounds and mechanisms that may account for these associations is needed. PMID:26126626

  6. 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 μM, 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

  7. 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

  8. Pooling data from multiple longitudinal studies: the role of item response theory in integrative data analysis.

    PubMed

    Curran, Patrick J; Hussong, Andrea M; Cai, Li; Huang, Wenjing; Chassin, Laurie; Sher, Kenneth J; Zucker, Robert A

    2008-03-01

    There are a number of significant challenges researchers encounter when studying development over an extended period of time, including subject attrition, the changing of measurement structures across groups and developmental periods, and the need to invest substantial time and money. Integrative data analysis is an emerging set of methodologies that allows researchers to overcome many of the challenges of single-sample designs through the pooling of data drawn from multiple existing developmental studies. This approach is characterized by a host of advantages, but this also introduces several new complexities that must be addressed prior to broad adoption by developmental researchers. In this article, the authors focus on methods for fitting measurement models and creating scale scores using data drawn from multiple longitudinal studies. The authors present findings from the analysis of repeated measures of internalizing symptomatology that were pooled from three existing developmental studies. The authors describe and demonstrate each step in the analysis and conclude with a discussion of potential limitations and directions for future research. PMID:18331129

  9. Age-specific risk factor profiles of adenocarcinomas of the esophagus: A pooled analysis from the international BEACON consortium.

    PubMed

    Drahos, Jennifer; Xiao, Qian; Risch, Harvey A; Freedman, Neal D; Abnet, Christian C; Anderson, Lesley A; Bernstein, Leslie; Brown, Linda; Chow, Wong-Ho; Gammon, Marilie D; Kamangar, Farin; Liao, Linda M; Murray, Liam J; Ward, Mary H; Ye, Weimin; Wu, Anna H; Vaughan, Thomas L; Whiteman, David C; Cook, Michael B

    2016-01-01

    Esophageal (EA) and esophagogastric junction (EGJA) adenocarcinoma have been steadily increasing in frequency in younger people; however, the etiology of these cancers is poorly understood. We therefore investigated associations of body mass index (BMI), cigarette smoking, alcohol consumption, gastroesophageal reflux and use of nonsteroidal anti-inflammatory drugs (NSAIDs) in relation to age-specific risks of EA and EGJA. We pooled individual participant data from eight population-based, case-control studies within the international Barrett's and Esophageal Adenocarcinoma Consortium (BEACON). The analysis included 1,363 EA patients, 1,472 EGJA patients and 5,728 control participants. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for age-specific (<50, 50-59, 60-69, ≥70 years) cancer outcomes, as well as interactions by age. BMI, smoking status and pack-years, recurrent gastroesophageal reflux and frequency of gastroesophageal reflux were positively associated with EA and EGJA in each age group. Early-onset EA (<50 years) had stronger associations with recurrent gastroesophageal reflux (OR = 8.06, 95% CI: 4.52, 14.37; peffect modification  = 0.01) and BMI (ORBMI ≥ 30 vs . <25  = 4.19, 95% CI: 2.23, 7.87; peffect modification  = 0.04), relative to older age groups. In contrast, inverse associations of NSAID use were strongest in the oldest age group (≥70 years), although this apparent difference was not statistically significant. Age-specific associations with EGJA showed similar, but slightly weaker patterns and no statistically significant differences by age were observed. Our study provides evidence that associations between obesity and gastroesophageal reflux are stronger among earlier onset EA cancers. PMID:26175109

  10. Biochip analysis of prostate cancer.

    PubMed

    Fan, M Q; Wang, P X; Feng, J Y; Xiao, Y; Huang, C B

    2014-01-01

    Microarray expression analysis was used to forecast the roles of differentially co-expressed genes (DCG) and DCG and links in the pathogenesis of prostate cancer. In addition, we demonstrate that the relationship between transcriptional factors (TFs) and their targets can be considered a key factor in determining the difference between primary and metastatic prostate cancer. Regulatory impact factors were adopted to calculate the impact of TF. We identified 5 TFs and 29 target genes important in the transition between normal prostate and primary prostate cancer and 2 TFs and 7 target genes important in the transition between primary and metastatic prostate cancer. These results suggest that it may be possible to predict the clinical behavior of prostate cancer based on gene expression analysis. PMID:24446298

  11. Effects of Serum Triglycerides on Prostate Cancer and Breast Cancer Risk: A Meta-Analysis of Prospective Studies.

    PubMed

    Ma, Hong-Qun; Cui, Lian-Hua; Li, Cheng-Cheng; Yu, Zhuang; Piao, Jin-Mei

    2016-10-01

    Epidemiological studies show conflicting results regarding the link between serum triglyceride and the risk of prostate cancer and breast cancer. Therefore, we performed a meta-analysis of prospective studies to clarify this association. We searched PubMed, EMBASE, the Chinese Biomedical Database (CBM), and the China National Knowledge Infrastructure (CNKI) database to identify relevant prospective studies of the relationship between serum triglyceride and prostate cancer and breast cancer risk. Study-specific estimates adjusting for potential confounders were combined to evaluate a summary relative risks (RRs) and 95% confidence intervals (95% CIs) using a fixed- or random-effects model. A total of 11 prospective studies (619,410 subjects and 15,691 incident prostate cancer patients) and 8 prospective studies (590,878 subjects and 12,177 incident breast cancer patients) were respectively included in our meta-analysis to assess the associations of serum triglyceride with prostate cancer and breast cancer risk. The pooled adjusted RR estimates for prostate cancer and breast cancer for the highest versus the lowest exposure levels of serum triglycerides were 0.95 (95% CI: 0.87-1.04) and 0.94 (95% CI: 0.87-1.00), respectively. Additionally, a dose-response analysis revealed that serum levels of triglycerides were not associated with the risk of prostate cancer and breast cancer. We found that serum triglyceride was not related to the risk of prostate cancer and breast cancer. PMID:27618148

  12. 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

  13. 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.

  14. Efficacy of RTS,S malaria vaccines: individual-participant pooled analysis of phase 2 data

    PubMed Central

    Bejon, Philip; White, Michael T; Olotu, Ally; Bojang, Kalifa; Lusingu, John PA; Salim, Nahya; Otsyula, Nekoye N; Agnandji, Selidji T; Asante, Kwaku Poku; Owusu-Agyei, Seth; Abdulla, Salim; Ghani, Azra C

    2013-01-01

    Summary Background The efficacy of RTS,S/AS01 as a vaccine for malaria is being tested in a phase 3 clinical trial. Early results show significant, albeit partial, protection against clinical malaria and severe malaria. To ascertain variations in vaccine efficacy according to covariates such as transmission intensity, choice of adjuvant, age at vaccination, and bednet use, we did an individual-participant pooled analysis of phase 2 clinical data. Methods We analysed data from 11 different sites in Africa, including 4453 participants. We measured heterogeneity in vaccine efficacy by estimating the interactions between covariates and vaccination in pooled multivariable Cox regression and Poisson regression analyses. Endpoints for measurement of vaccine efficacy were infection, clinical malaria, severe malaria, and death. We defined transmission intensity levels according to the estimated local parasite prevalence in children aged 2–10 years (PrP2–10), ranging from 5% to 80%. Choice of adjuvant was either AS01 or AS02. Findings Vaccine efficacy against all episodes of clinical malaria varied by transmission intensity (p=0·001). At low transmission (PrP2–10 10%) vaccine efficacy was 60% (95% CI 54 to 67), at moderate transmission (PrP2–10 20%) it was 41% (21 to 57), and at high transmission (PrP2–10 70%) the efficacy was 4% (−10 to 22). Vaccine efficacy also varied by adjuvant choice (p<0·0001)—eg, at low transmission (PrP2–10 10%), efficacy varied from 60% (95% CI 54 to 67) for AS01 to 47% (14 to 75) for AS02. Variations in efficacy by age at vaccination were of borderline significance (p=0·038), and bednet use and sex were not significant covariates. Vaccine efficacy (pooled across adjuvant choice and transmission intensity) varied significantly (p<0·0001) according to time since vaccination, from 36% efficacy (95% CI 24 to 45) at time of vaccination to 0% (−38 to 38) after 3 years. Interpretation Vaccine efficacy against clinical disease was of

  15. 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)

  16. 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

  17. 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

  18. A Pooled Analysis of the Effect of Condoms in Preventing HSV-2 Acquisition

    PubMed Central

    Martin, Emily T.; Krantz, Elizabeth; Gottlieb, Sami L.; Magaret, Amalia S.; Langenberg, Andria; Stanberry, Lawrence; Kamb, Mary; Wald, Anna

    2010-01-01

    Background The degree of effectiveness of condoms in preventing the transmission of herpes simplex virus 2 (HSV-2), is uncertain. We performed a large pooled analysis to address this question. Methods We identified prospective studies with individual-level condom use data and laboratory-defined HSV-2 acquisition. Six studies were identified through a review of publications through 2007: three candidate HSV-2 vaccine studies, an HSV-2 drug study, an observational STD incidence study and a behavioral STD intervention study. Study investigators provided us individual-level data to perform a pooled analysis. Effect of condom use was modeled using a continuous percent of sex acts during which a condom was used and, alternatively, using absolute number of unprotected sex acts. Results A total of 5384 people who were HSV-2 negative at baseline contributed 2,040,894 follow-up days. 415 persons acquired laboratory-documented HSV-2 during follow-up. Consistent (100%) condom users had a 30% lower risk of HSV-2 acquisition compared to those who never used condoms (hazard ratio: 0.70; 95 percent confidence interval: 0.40, 0.94; p = 0.01). Risk for HSV-2 acquisition increased steadily and significantly with each unprotected sex act (hazard ratio: 1.16; 95 percent confidence interval: 1.08, 1.25); p < 0.001). Condom effectiveness did not vary by gender. Conclusions This is the largest analysis using prospective data to assess the effect of condoms in preventing HSV-2 acquisition. Although the magnitude of protection was not as large as has been observed with other STIs, we found that condoms offer moderate protection against HSV-2 acquisition in men and women. PMID:19597073

  19. 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

  20. [Comparative Estimate of the Sheep Breed Gene Pools using ISSR Analysis].

    PubMed

    Nesteruk, L V; Makarova, N N; Evsyukov, A N; Svishcheva, G R; Lhasaranov, B B; Stolpovsky, Yu A

    2016-03-01

    Using the ISSR-PCR technique, the genetic structure of nine sheep breeds (Ovis aries) bred on the territories of Russia and Mongolia was examined. Species-specific and breed-specific DNA fragments were identified. For the first time, data on the genetic diversity of Telengit and Buubey sheep breeds were obtained. The main parameters of the genetic diversity and the breed structure were assessed, and the phylogenetic relationships and genetic distances between the studied breeds were determined. Using the method of hierarchical frequency averaging, the prototypal sheep gene pool was reconstructed. The three-tiered analysis of diversity based on the ISSR fingerprinting data showed that 15.8% of variability was found between the breeds, 31.4% of variability was found between the populations within the breeds, and the diversity among the individuals within the populations constituted 52.8%. PMID:27281855

  1. System seismic analysis of an innovative primary system for a large pool type LMFBR plant

    SciTech Connect

    Pan, Y.C.; Wu, T.S.; Cha, B.K.; Burelbach, J.; Seidensticker, R.

    1984-01-01

    The system seismic analysis of an innovative primary system for a large pool type liquid metal fast breeder reactor (LMFBR) plant is presented. In this primary system, the reactor core is supported in a way which differs significantly from that used in previous designs. The analytical model developed for this study is a three-dimensional finite element model including one-half of the primary system cut along the plane of symmetry. The model includes the deck and deck mounted components,the reactor vessel, the core support structure, the core barrel, the radial neutron shield, the redan, and the conical support skirt. The sodium contained in the primary system is treated as a lumped mass appropriately distributed among various components. The significant seismic behavior as well as the advantages of this primary system design are discussed in detail.

  2. 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.

  3. 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

  4. 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

  5. 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

  6. Cardiovascular safety of sitagliptin in patients with type 2 diabetes mellitus: a pooled analysis

    PubMed Central

    2013-01-01

    Objective To compare the incidence of cardiovascular events and mortality in patients with type 2 diabetes mellitus treated with sitagliptin or non-sitagliptin comparators. Methods A post hoc assessment of cardiovascular safety in 14,611 patients was performed by pooling data from 25 double-blind studies, which randomised patients at baseline to sitagliptin 100 mg/day or a non-sitagliptin comparator (i.e., non-exposed). Included studies were limited to those at least 12 weeks in duration (range: 12 to 104 weeks). Patient-level data were used in this analysis of major adverse cardiovascular events (MACE) including ischaemic events and cardiovascular deaths. Analyses were performed in three cohorts: the entire 25-study cohort, the cohort from placebo-controlled portions of studies (n=19), and the cohort from studies comparing sitagliptin to a sulphonylurea (n=3). Results In the entire cohort analysis, 78 patients had at least 1 reported MACE-related event, with 40 in the sitagliptin group and 38 in the non-exposed group. The exposure-adjusted incidence rate was 0.65 per 100 patient-years in the sitagliptin group and 0.74 in the non-exposed group (incidence rate ratio = 0.83 [95% confidence interval (CI): 0.53, 1.30]). In the analysis comparing sitagliptin to placebo, the exposure-adjusted incidence rate was 0.80 per 100-patient-years with sitagliptin and 0.76 with placebo (incidence rate ratio = 1.01 [95% CI: 0.55, 1.86]). In the analysis comparing sitagliptin to sulphonylurea, the exposure-adjusted incidence rate was 0.00 per 100 patient-years with sitagliptin and 0.86 with sulphonylurea (incidence rate ratio = 0.00 [95% CI: 0.00, 0.31]). Conclusion A pooled analysis of 25 randomised clinical trials does not indicate that treatment with sitagliptin increases cardiovascular risk in patients with type 2 diabetes mellitus. In a subanalysis, a higher rate of cardiovascular-related events was associated with sulphonylurea relative to sitagliptin. PMID:23286208

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

    SciTech Connect

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

    2014-10-16

    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 paper, 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. Finally, independent of substrate, Caloramator was enriched at lower (<65 °C) temperatures while highly active cellulolytic bacteria Caldicellulosiruptor were dominant at high (>65 °C) temperatures.

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

    DOE PAGESBeta

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

    2014-10-16

    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 paper, 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 diversitymore » 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. Finally, independent of substrate, Caloramator was enriched at lower (<65 °C) temperatures while highly active cellulolytic bacteria Caldicellulosiruptor were dominant at high (>65 °C) temperatures.« less

  9. 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

  10. 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

  11. Comparison of the RECIST 1.0 and RECIST 1.1 in patients treated with targeted agents: a pooled analysis and review

    PubMed Central

    Kim, Jung Han

    2016-01-01

    Patients treated with targeted agents were not included in the data warehouse when the RECIST 1.1 was revised in 2009. We conducted this pooled analysis to investigate the impact of the RECIST 1.1 on the assessment of tumor response in cancer patients treated with targeted agents. We surveyed MEDLINE, EMBASE and PubMed for articles with terms of the RECIST 1.0 or RECIST 1.1. We searched for all the references of relevant articles and reviews using the ‘related articles’ feature in the PubMed. There were six articles in the literature comparing the clinical impacts of the RECIST 1.0 and RECIST 1.1 in patients treated with targeted agents for advanced or metastatic cancer. A total of 322 patients were recruited from the six trials; 217 with non-small cell lung cancer, 23 with thyroid cancer, 20 with gastrointestinal stromal tumor, and 62 with renal cell carcinoma. Because of new lymph node criteria, eight patients (2.5%) had no target lesions when adopting the RECIST 1.1. The number of target lesions by the RECIST 1.1 was significantly lower than that by the RECIST 1.0 (P < 0.001). However, the RECIST 1.1 showed high concordance with the RECIST 1.0 in the assessment of best tumor responses (k = 0.908). Seventeen patients (5.6%) showed discrepancy in the best tumor response between the RECIST 1.0 and RECIST 1.1. This pooled study demonstrates that the RECIST 1.1 shows the highly concordant response assessment with the RECIST 1.0 in patients treated with targeted agents. PMID:26885610

  12. Comparison of the RECIST 1.0 and RECIST 1.1 in patients treated with targeted agents: a pooled analysis and review.

    PubMed

    Kim, Jung Han

    2016-03-22

    Patients treated with targeted agents were not included in the data warehouse when the RECIST 1.1 was revised in 2009. We conducted this pooled analysis to investigate the impact of the RECIST 1.1 on the assessment of tumor response in cancer patients treated with targeted agents. We surveyed MEDLINE, EMBASE and PubMed for articles with terms of the RECIST 1.0 or RECIST 1.1. We searched for all the references of relevant articles and reviews using the 'related articles' feature in the PubMed. There were six articles in the literature comparing the clinical impacts of the RECIST 1.0 and RECIST 1.1 in patients treated with targeted agents for advanced or metastatic cancer. A total of 322 patients were recruited from the six trials; 217 with non-small cell lung cancer, 23 with thyroid cancer, 20 with gastrointestinal stromal tumor, and 62 with renal cell carcinoma. Because of new lymph node criteria, eight patients (2.5%) had no target lesions when adopting the RECIST 1.1. The number of target lesions by the RECIST 1.1 was significantly lower than that by the RECIST 1.0 (P < 0.001). However, the RECIST 1.1 showed high concordance with the RECIST 1.0 in the assessment of best tumor responses (k = 0.908). Seventeen patients (5.6%) showed discrepancy in the best tumor response between the RECIST 1.0 and RECIST 1.1. This pooled study demonstrates that the RECIST 1.1 shows the highly concordant response assessment with the RECIST 1.0 in patients treated with targeted agents. PMID:26885610

  13. 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

  14. 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.

  15. 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

  16. Pesticide exposures and the risk of multiple myeloma in men: An analysis of the North American Pooled Project.

    PubMed

    Presutti, Roseanna; Harris, Shelley A; Kachuri, Linda; Spinelli, John J; Pahwa, Manisha; Blair, Aaron; Zahm, Shelia Hoar; Cantor, Kenneth P; Weisenburger, Dennis D; Pahwa, Punam; McLaughlin, John R; Dosman, James A; Freeman, Laura Beane

    2016-10-15

    Multiple myeloma (MM) has been consistently linked with agricultural activities, including farming and pesticide exposures. Three case-control studies in the United States and Canada were pooled to create the North American Pooled Project (NAPP) to investigate associations between pesticide use and haematological cancer risk. This analysis used data from 547 MM cases and 2700 controls. Pesticide use was evaluated as follows: ever/never use; duration of use (years); and cumulative lifetime-days (LD) (days/year handled × years of use). Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression adjusted for age, province/state of residence, use of proxy respondents and selected medical conditions. Increased MM risk was observed for ever use of carbaryl (OR = 2.02, 95% CI = 1.28-3.21), captan (OR = 1.98, 95% CI = 1.04-3.77) and DDT (OR = 1.44, 95% CI = 1.05-1.97). Using the Canadian subset of NAPP data, we observed a more than threefold increase in MM risk (OR = 3.18, 95% CI = 1.40-7.23) for ≤10 cumulative LD of carbaryl use. The association was attenuated but remained significant for >10 LD of carbaryl use (OR = 2.44; 95% CI = 1.05-5.64; ptrend  = 0.01). For captan, ≤17.5 LD of exposure was also associated with a more than threefold increase in risk (OR = 3.52, 95% CI = 1.32-9.34), but this association was attenuated in the highest exposure category of >17.5 LD (OR = 2.29, 95% CI = 0.81-6.43; ptrend  = 0.01). An increasing trend (ptrend  = 0.04) was observed for LD of DDT use (LD > 22; OR = 1.92, 95% CI = 0.95-3.88). In this large North American study of MM and pesticide use, we observed significant increases in MM risk for use of carbaryl, captan and DDT. PMID:27261772

  17. 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

  18. 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

  19. 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

  20. 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 ...

  1. 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...

  2. Essential Indicators Identifying Chronic Inorganic Mercury Intoxication: Pooled Analysis across Multiple Cross-Sectional Studies

    PubMed Central

    Doering, Stefan

    2016-01-01

    Background The continuous exposure to inorganic mercury vapour in artisanal small-scale gold mining (ASGM) areas leads to chronic health problems. It is therefore essential to have a quick, but reliable risk assessing tool to diagnose chronic inorganic mercury intoxication. This study re-evaluates the state-of-the-art toolkit to diagnose chronic inorganic mercury intoxication by analysing data from multiple pooled cross-sectional studies. The primary research question aims to reduce the currently used set of indicators without affecting essentially the capability to diagnose chronic inorganic mercury intoxication. In addition, a sensitivity analysis is performed on established biomonitoring exposure limits for mercury in blood, hair, urine and urine adjusted by creatinine, where the biomonitoring exposure limits are compared to thresholds most associated with chronic inorganic mercury intoxication in artisanal small-scale gold mining. Methods Health data from miners and community members in Indonesia, Tanzania and Zimbabwe were obtained as part of the Global Mercury Project and pooled into one dataset together with their biomarkers mercury in urine, blood and hair. The individual prognostic impact of the indicators on the diagnosis of mercury intoxication is quantified using logistic regression models. The selection is performed by a stepwise forward/backward selection. Different models are compared based on the Bayesian information criterion (BIC) and Cohen`s kappa is used to evaluate the level of agreement between the diagnosis of mercury intoxication based on the currently used set of indicators and the result based on our reduced set of indicators. The sensitivity analysis of biomarker exposure limits of mercury is based on a sequence of chi square tests. Results The variable selection in logistic regression reduced the number of medical indicators from thirteen to ten in addition to the biomarkers. The estimated level of agreement using ten of thirteen medical

  3. Pooled Analysis of Six Pharmacologic and Nonpharmacologic Interventions for Vasomotor Symptoms

    PubMed Central

    Guthrie, Katherine A.; LaCroix, Andrea Z.; Ensrud, Kristine E.; Joffe, Hadine; Newton, Katherine M.; Reed, Susan D.; Caan, Bette; Carpenter, Janet S.; Cohen, Lee S.; Freeman, Ellen W.; Larson, Joseph C.; Manson, JoAnn E.; Rexrode, Kathy; Skaar, Todd C.; Sternfeld, Barbara; Anderson, Garnet L.

    2015-01-01

    Objective To describe the effects of six interventions for menopausal vasomotor symptoms relative to control in a pooled analysis, facilitating translation of the results for clinicians and symptomatic women. The MsFLASH (Menopause Strategies: Finding Lasting Answers for Symptoms and Health) network tested these interventions in three randomized clinical trials (RCTs). Methods An analysis of pooled individual-level data from three RCTs is presented. Participants were 899 peri- and postmenopausal women with at least 14 bothersome vasomotor symptoms/week. Interventions included escitalopram 10–20 mg/day, non-aerobic yoga, aerobic exercise, 1.8 g/day omega-3 fatty acid supplementation, low-dose oral 17-beta-estradiol 0.5-mg/day, and low-dose venlafaxine XR 75-mg/day. The main outcome measures were changes from baseline in mean daily vasomotor symptoms frequency and bother during 8–12 weeks of treatment. Linear regression models estimated differences in outcomes between each intervention and corresponding control group, adjusted for baseline characteristics. Models included trial-specific intercepts, effects of the baseline outcome measure, and time. Results The 8-week reduction in vasomotor symptoms frequency from baseline relative to placebo was similar for escitalopram at −1.4/day (95% CI: −2.7 to −0.2), low-dose estradiol at −2.4 (95% CI: −3.4 to −1.3), and venlafaxine at −1.8 (95% CI: −2.8 to −0.8); vasomotor symptoms bother reduction was minimal and did not vary across these three pharmacologic interventions (means −0.2 to −0.3 relative to placebo). No effects on vasomotor symptoms frequency or bother were seen with aerobic exercise, yoga or omega-3 supplements. Conclusions These analyses suggest that escitalopram, low-dose estradiol, and venlafaxine provide comparable, modest reductions in vasomotor symptoms frequency and bother among women with moderate hot flushes. Clinical Trial Registration ClinicalTrials.gov, www

  4. 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.

  5. A meta-analysis on depression and subsequent cancer risk

    PubMed Central

    2007-01-01

    Background The authors tested the hypothesis that depression is a possible factor influencing the course of cancer by reviewing prospective epidemiological studies and calculating summary relative risks. Methods Studies were identified by computerized searches of Medline, Embase and PsycINFO. as well as manual searches of reference lists of selected publications. Inclusion criteria were cohort design, population-based sample, structured measurement of depression and outcome of cancer known for depressed and non-depressed subjects Results Thirteen eligible studies were identified. Based on eight studies with complete crude data on overall cancer, our summary relative risk (95% confidence interval) was 1.19 (1.06–1.32). After adjustment for confounders we pooled a summary relative risk of 1.12 (0.99–1.26). No significant association was found between depression and subsequent breast cancer risk, based on seven heterogeneous studies, with or without adjustment for possible confounders. Subgroup analysis of studies with a follow-up of ten years or more, however, resulted in a statistically significant summary relative risk of 2.50 (1.06–5.91). No significant associations were found for lung, colon or prostate cancer. Conclusion This review suggests a tendency towards a small and marginally significant association between depression and subsequent overall cancer risk and towards a stronger increase of breast cancer risk emerging many years after a previous depression. PMID:18053168

  6. 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

  7. 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.

  8. Artificial neural network ensembles and their application in pooled flood frequency analysis

    NASA Astrophysics Data System (ADS)

    Shu, Chang; Burn, Donald H.

    2004-09-01

    Recent theoretical and empirical studies show that the generalization ability of artificial neural networks can be improved by combining several artificial neural networks in redundant ensembles. In this paper, a review is given of popular ensemble methods. Six approaches for creating artificial neural network ensembles are applied in pooled flood frequency analysis for estimating the index flood and the 10-year flood quantile. The results show that artificial neural network ensembles generate improved flood estimates and are less sensitive to the choice of initial parameters when compared with a single artificial neural network. Factors that may affect the generalization of an artificial neural network ensemble are analyzed. In terms of the methods for creating ensemble members, the model diversity introduced by varying the initial conditions of the base artificial neural networks to reduce the prediction error is comparable with more sophisticated methods, such as bagging and boosting. When the same method for creating ensemble members is used, combining member networks using stacking is generally better than using simple averaging. An ensemble size of at least 10 artificial neural networks is suggested to achieve sufficient generalization ability. In comparison with parametric regression methods, properly designed artificial neural network ensembles can significantly reduce the prediction error.

  9. 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

  10. 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

  11. Assessing coal-mine safety regulation: A pooled time-series analysis

    SciTech Connect

    Chun Youngpyoung.

    1991-01-01

    This study attempts to assess the independent, relative, and conjoint effects of four types of variables on coal-mine safety: administrative (mine inspections, mine investigations, and mine safety grants); political (state party competition, gubernatorial party affiliation, and deregulation); economic (state per-capita income and unemployment rates); task-related (mine size, technology, and type of mining), and state dummy variables. Trend, Pearson correlation, and pooled time-series analyses are performed on fatal and nonfatal injury rates reported in 25 coal-producing states during the 1975-1985 time period. These are then interpreted in light of three competing theories of regulation: capture, nonmarket failure, and threshold. Analysis reveals: (1) distinctions in the total explanatory power of the model across different types of injuries, as well as across presidential administrations; (2) a consistently more powerful impact on safety of informational implementation tools (safety education grants) over command-and-control approaches (inspections and investigations) or political variables; and (3) limited, albeit conjectural, support for a threshold theory of regulation in the coal mine safety arena.

  12. 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

  13. 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

  14. 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

  15. 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

  16. Prognostic value of ALDH1 expression in lung cancer: a meta-analysis

    PubMed Central

    Huo, Wei; Du, Min; Pan, Xinyan; Zhu, Xiaomin; Li, Zhimin

    2015-01-01

    Objective: ALDH1 has recently been reported as a marker of cancer stem-like cells in lung cancer. However, the predictive value of ALDH1 in lung cancer remains controversial. In this study, we aimed to evaluate the association of ALDH1 expression with the clinicopathological features and outcomes of lung cancer patients through a meta-analysis. Methods: Publications that assessed the clinical or prognostic significance of ALDH1 in lung cancer up to October 2014 were identified. A meta-analysis was performed to clarify the association between ALDH1 expression and clinical outcomes. Results: Ten eligible publications with 1836 patients were included. The analysis of these data showed that ALDH1 expression was highly correlated with lymph node metastasis (pooled OR = 1.45, 95% CI: 1.04-2.02, P = 0.027), decreased overall survival (pooled RR: 2.25, 95% CI: 1.15-4.41, P = 0.019), and decreased disease-free survival (pooled RR: 1.63, 95% CI: 1.01-2.64, P = 0.047). Conclusion: Patients with ALDH1-positive lung cancer had poor prognosis, which was associated with common clinicopathological poor prognostic factors. PMID:25932135

  17. 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

  18. 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

  19. 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

  20. 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

  1. The Oncological Safety of Nipple-Sparing Mastectomy: A Systematic Review of the Literature with a Pooled Analysis of 12,358 Procedures

    PubMed Central

    Headon, Hannah Louise; Kasem, Abdul

    2016-01-01

    Nipple-sparing mastectomy (NSM) is increasingly popular as a procedure for the treatment of breast cancer and as a prophylactic procedure for those at high risk of developing the disease. However, it remains a controversial option due to questions regarding its oncological safety and concerns regarding locoregional recurrence. This systematic review with a pooled analysis examines the current literature regarding NSM, including locoregional recurrence and complication rates. Systematic electronic searches were conducted using the PubMed database and the Ovid database for studies reporting the indications for NSM and the subsequent outcomes. Studies between January 1970 and January 2015 (inclusive) were analysed if they met the inclusion criteria. Pooled descriptive statistics were performed. Seventy-three studies that met the inclusion criteria were included in the analysis, yielding 12,358 procedures. After a mean follow up of 38 months (range, 7.4–156 months), the overall pooled locoregional recurrence rate was 2.38%, the overall complication rate was 22.3%, and the overall incidence of nipple necrosis, either partial or total, was 5.9%. Significant heterogeneity was found among the published studies and patient selection was affected by tumour characteristics. We concluded that NSM appears to be an oncologically safe option for appropriately selected patients, with low rates of locoregional recurrence. For NSM to be performed, tumours should be peripherally located, smaller than 5 cm in diameter, located more than 2 cm away from the nipple margin, and human epidermal growth factor 2-negative. A separate histopathological examination of the subareolar tissue and exclusion of malignancy at this site is essential for safe oncological practice. Long-term follow-up studies and prospective cohort studies are required in order to determine the best reconstructive methods. PMID:27462565

  2. 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

  3. 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.

  4. Experimental analysis of nanofluid pool boiling heat transfer in copper bead packed porous layers

    NASA Astrophysics Data System (ADS)

    Chen, Wei; Wang, Ji

    2016-07-01

    Coupling the nanofluid as working fluid and the copper beads packed porous structure on heating surface were employed to enhance the pool boiling heat transfer by changing the fluid properties with the adjunction of nanoparticles in liquid and altering the heating surface with a bead porous layer. Due to the higher thermal conductivity, the copper beads served as an extended heating surface and the boiling nucleation sites rose, but the flow resistance increased. The CuO-water and SiO2-water nanofluids as well as the pure water were respectively employed as working fluids in the pool boiling experiments. Comparing with the base fluid of water, the higher thermal conductivity and lower surface tension occur in the nanofluids and those favor the boiling heat transfer, but the higher viscosity and density of nanofluids serve as deteriorative factors. So, the concentration region of the nanofluids should be chosen properly. The maximum relative error between the collected experimental data of the pure water on a flat surface and the theoretical prediction of pool boiling using the Rohsenow correlation was less than 12 %. The comparisons of the pool boiling heat transfer characteristics were also conducted between the pure water and the nanofluids respectively on the horizontal flat surface and on the heating surface packed with a copper bead porous layer. Besides, the boiling bubble generation, integration and departure have a great affect on the pool boiling and were recorded with a camera in the bead stacked porous structures at different heat flux.

  5. 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.

  6. Synoptic climatological analysis of persistent cold air pools over the Carpathian Basin

    NASA Astrophysics Data System (ADS)

    Szabóné André, Karolina; Bartholy, Judit; Pongrácz, Rita

    2016-04-01

    A persistent cold air pool (PCAP) is a winter-time, anticyclone-related weather event over a relatively large basin. During this time the air is colder near the surface than aloft. This inversion near the surface can last even for weeks. As the cold air cools down, relative humidity increases and fog forms. The entire life cycle of a PCAP depends on the large scale circulation pattern. PCAP usually appears when an anticyclone builds up after a cold front passed over the examined basin, and it is usually destructed by a coming strong cold front of another midlatitude cyclone. Moreover, the intensity of the anticyclone affects the intensity of the PCAP. PCAP may result in different hazards for the population: (1) Temperature inversion in the surface layers together with weak wind may lead to severe air pollution causing health problems for many people, especially, elderly and children. (2) The fog and/or smog during chilly weather conditions often results in freezing rain. Both fog and freezing rain can distract transportation and electricity supply. Unfortunately, the numerical weather prediction models have difficulties to predict PCAP formation and destruction. One of the reasons is that PCAP is not defined objectively with a simple formula, which could be easily applied to the numerical output data. However, according to some recommendations from the synoptic literature, the shallow convective potential energy (SCPE) can be used to mathematically describe PCAP. In this study, we used the ERA-Interim reanalysis datasets to examine this very specific weather event (i.e., PCAP) over the Carpathian Basin. The connection between the mean sea level pressure and some PCAP measures (e.g., SCPE, energy deficit, etc.) is evaluated. For instance, we used logistic regression to identify PCAP periods over the Carpathian Basin. Then, further statistical analysis includes the evaluation of the length and intensity of these PCAP periods.

  7. Coffee and gastric cancer: systematic review and meta-analysis.

    PubMed

    Botelho, Francisco; Lunet, Nuno; Barros, Henrique

    2006-05-01

    We systematically reviewed the literature on the association between coffee consumption and gastric cancer and performed a meta-analysis of the results. Published cohort and case-control studies were identified in PubMed and reference lists. Random effects meta-analysis was used to pool effects from 23 studies, and heterogeneity was explored by stratification and meta-regression. The odds ratio (OR) for the overall association between coffee and gastric cancer (highest vs. lowest category of exposure) was 0.97 (95%CI: 0.86-1.09), similar for cohort (OR = 1.02; 95%CI: 0.76-1.37) and case-control studies (population-based: OR = 0.90; 95%CI: 0.70-1.15; hospital-based: OR = 0.97; 95%CI: 0.83-1.13). The OR was 1.26 (95%CI: 1.02-1.57) when considering five studies conducted in the USA, 0.97 (95%CI: 0.82-1.14) for the five Japanese studies, 0.98 (95%CI: 0.81-1.17) for the six studies from Europe, and 0.64 (95%CI: 0.47-0.86) for the two studies from South America. In this meta-analysis we found no adverse effect of coffee associated with gastric cancer. Knowledge on the level of exposure to different coffee constituents may provide a deeper understanding of this reassuring result and the real role of coffee on cancer risk. PMID:16680342

  8. NaK pool-boiler bench-scale receiver durability test: Test results and materials analysis

    SciTech Connect

    Andraka, C.E.; Goods, S.H.; Bradshaw, R.W.; Moreno, J.B.; Moss, T.A.; Jones, S.A.

    1994-06-01

    Pool-boiler reflux receivers have been considered as an alternative to heat pipes for the input of concentrated solar energy to Stirling-cycle engines in dish-Stirling electric generation systems. Pool boilers offer simplicity in design and fabrication. The operation of a full-scale pool-boiler receiver has been demonstrated for short periods of time. However, to generate cost-effective electricity, the receiver must operate Without significant maintenance for the entire system life, as much as 20 to 30 years. Long-term liquid-metal boiling stability and materials compatibility with refluxing NaK-78 is not known and must be determined for the pool boiler receiver. No boiling system has been demonstrated for a significant duration with the current porous boiling enhancement surface and materials. Therefore, it is necessary to simulate the full-scale pool boiler design as much as possible, including flux levels, materials, and operating cycles. On-sun testing is impractical because of the limited test time available. A test vessel was constructed with a porous boiling enhancement surface. The boiling surface consisted of a brazed stainless steel powder with about 50% porosity. The vessel was heated with a quartz lamp array providing about go W/CM2 peak incident thermal flux. The vessel was charged with NaK-78. This allows the elimination of costly electric preheating, both on this test and on fullscale receivers. The vessel was fabricated from Haynes 230 alloy. The vessel operated at 750{degrees}C around the clock, with a 1/2-hour shutdown cycle to ambient every 8 hours. The test completed 7500 hours of lamp-on operation time, and over 1000 startups from ambient. The test was terminated when a small leak in an Inconel 600 thermowell was detected. The test design and data are presented here. Metallurgical analysis of virgin and tested materials has begun, and initial results are also presented.

  9. 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...

  10. [Cancer Genome Atlas Pan-cancer Analysis Project].

    PubMed

    Zhang, Kun; Wang, Hong

    2015-04-01

    Cancer can exhibit different forms depending on the site of origin, cell types, the different forms of genetic mutations which also affect cancer therapeutic effect. Although many genes have been demonstrated to change a direct result of the change in phenotype, however, many cancers lineage complex molecular mechanisms are still not fully elucidated. Therefore, The Cancer Genome Atlas (TCGA) Research Network analyzed a large human tumors, in order to find the molecular changes in DNA, RNA, protein and epigenetic level, The results contain a wealth of data provides us with an opportunity for common, personality and new ideas throughout the cancer lineages form a whole description. Pan-cancer genome program first compares the 12 kinds of cancer types. Analysis of different tumor molecular changes and their functions, will tell us how effective treatment method is applied to a similar phenotype of the tumor. PMID:25936886

  11. Prognostic Value and Clinicopathological Differences of Bmi1 in Gastric Cancer: A Meta-analysis.

    PubMed

    Yuan, Bin; Zhao, Hong; Xue, Xiaofeng; Zhou, Jin; Wang, Xu; Han, Ye; Zhang, Lifeng; Guo, Xiaobo; Zhi, Qiaoming

    2016-01-01

    B cell-specific Moloney murine leukemia virus integration site 1 (Bmi1) was identified as a biomarker of cancer stem cells, and over-expression of Bmi1 might enhance tumor aggressive clinical behavior in gastric cancer (GC). Our aim of this meta-analysis is to investigate the prognostic role and clinicopathological differences of Bmi1 in GC patients. A total of 6 studies up to September 2014 were included in our study. Our results showed that there were no relationships between Bmi1 expression and the gender (pooled OR=0.87, 95%CI=0.66-1.14, P=0.319, fixed effect), age (pooled OR=1.22, 95%CI=0.95-1.59, P=0.126, fixed effect) and differentiation (pooled OR=1.15, 95%CI=0.71-1.86, P=0.582, random effect) in GC patients. But high Bmi1 expression was significantly correlated with the clinical stage (pooled OR=3.04, 95%CI=1.31-7.07, P=0.010, random effect), tumor size (pooled OR=2.01, 95%CI=1.14-3.55, P=0.016, random effect), T classification (pooled OR=2.79, 95%CI=1.94-4.03, P<0.001, fixed effect), lymph node metastasis (pooled OR=2.24, 95%CI=1.47-3.39, P<0.001, random effect) and distant metastasis (pooled OR=5.05, 95%CI=1.29-19.70, P=0.020, random effect), and led to a poor overall survival (OS) in GC patients (RR=3.38, 95%CI=2.43-4.69, P<0.001, fixed effect). These findings suggested that Bmi1 might serve as a novel and effective prognostic biomarker in GC, and could be a promising emerging molecular target in GC therapy. PMID:25968877

  12. Characterizing sexual function in patients with generalized anxiety disorder: a pooled analysis of three vilazodone studies

    PubMed Central

    Clayton, Anita H; Durgam, Suresh; Tang, Xiongwen; Chen, Changzheng; Ruth, Adam; Gommoll, Carl

    2016-01-01

    Background Vilazodone has been shown to reduce core symptoms of generalized anxiety disorder (GAD) in three randomized, double-blind, placebo-controlled trials. Since sexual dysfunction (SD) is not well characterized in GAD, a post hoc analysis of these trials was conducted to evaluate the effects of vilazodone on sexual functioning in GAD patients. Materials and methods Data were pooled from one fixed-dose trial of vilazodone 20 and 40 mg/day (NCT01629966) and two flexible-dose studies of vilazodone 20–40 mg/day (NCT01766401, NCT01844115) in adults with GAD. Sexual functioning was assessed using the Changes in Sexual Functioning Questionnaire (CSFQ). Outcomes included mean change from baseline to end of treatment (EOT) in CSFQ total score and percentage of patients shifting from SD at baseline (CSFQ total score ≤47 for males, ≤41 for females) to normal functioning at EOT. Treatment-emergent adverse events related to sexual functioning were also analyzed. Results A total of 1,373 patients were included in the analyses. SD at baseline was more common in females (placebo, 46.4%; vilazodone, 49%) than in males (placebo, 35.1%; vilazodone, 40.9%). CSFQ total score improvement was found in both females (placebo, +1.2; vilazodone, +1.6) and males (placebo, +2.1; vilazodone, +1.0), with no statistically significant differences between treatment groups. The percentage of patients who shifted from SD at baseline to normal sexual functioning at EOT was higher in males (placebo, 40.6%; vilazodone, 35.7%) than in females (placebo, 24.9%; vilazodone, 34.9%); no statistical testing was performed. Except for erectile dysfunction and delayed ejaculation in vilazodone-treated males (2.4% and 2.1%, respectively), no treatment-emergent adverse events related to sexual functioning occurred in ≥2% of patients in either treatment group. Conclusion Approximately 35%–50% of patients in the vilazodone GAD studies had SD at baseline. Vilazodone and placebo had similar effects on

  13. 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.

  14. Three-Dimensional Ignition and Flame Propagation Above Liquid Fuel Pools: Computational Analysis

    NASA Technical Reports Server (NTRS)

    Cai, Jinsheng; Sirignano, William A.

    2001-01-01

    A three-dimensional unsteady reactive Navier-Stokes code is developed to study the ignition and flame spread above liquid fuels initially below the flashpoint temperature. Opposed air flow to the flame spread due to forced and/or natural convection is considered. Pools of finite width and length are studied in air channels of prescribed height and width. Three-dimensional effects of the flame front near the edge of the pool are captured in the computation. The formation of a recirculation zone in the gas phase similar to that found in two-dimensional calculations is also present in the three-dimensional calculations. Both uniform spread and pulsating spread modes are found in the calculated results.

  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

    SciTech Connect

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

    1995-01-01

    The principal materials used in the construction of a NaKbased pool-boiler were analyzed. The device, operated for 7500 hours, accumulated 1000 thermal cycles to a peak temperature of 750{degrees}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 (> 30 {mu}m) pits and cavities. A zirconium metal foil used to getter oxygen from the NaK became extremely brittle.

  19. 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.

  20. 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

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

    PubMed Central

    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

  2. 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

  3. Vasectomy and prostate cancer risk: a meta-analysis of cohort studies.

    PubMed

    Shang, Yonggang; Han, Guangwei; Li, Jia; Zhao, Jiang; Cui, Dong; Liu, Chengcheng; Yi, Shanhong

    2015-01-01

    Some studies have suggested that vasectomy is associated with the increased risk of prostate cancer, however, this conclusion is not supported by all the published studies. In order to examine the relationship between vasectomy and prostate cancer risk, we conducted a meta-analysis of cohort studies to clarify this controversial association. PubMed and Medline were used to identify the cohort studies that reported the association of vasectomy with prostate cancer risk from 1980 to January 2015. Based on a random effects model, the RR and 95% CI were used to assess the combined risk. In total, 10 cohort studies involving more than 7027 cases and 429914 participants were included. There was no significant relationship between vasectomy and prostate cancer risk, the pooled RR (95%CI) was 1.11[0.98, 1.27] (P = 0.109). In subgroup-analysis, the relationship between vasectomy and prostate cancer risk was not significantly modified by the length of follow-up and population distribution except Americans. Omission of any single study had little effect on the pooled risk estimate. Little evidence of publication bias was found. In conclusion, our meta-analysis suggests that vasectomy is not associated with the increased risk of prostate cancer. More studies based on other populations including the Chinese are needed. PMID:25927401

  4. Association between Alcohol Consumption and Cancers in the Chinese Population—A Systematic Review and Meta-Analysis

    PubMed Central

    Li, Ying; Yang, Huan; Cao, Jia

    2011-01-01

    Background Alcohol consumption is increasing worldwide and is associated with numerous cancers. This systematic review examined the role of alcohol in the incidence of cancer in the Chinese population. Methods Medline/PubMed, EMBASE, CNKI and VIP were searched to identify relevant studies. Cohort and case-control studies on the effect of alcohol use on cancers in Chinese were included. Study quality was evaluated using the Newcastle-Ottawa Scale. Data were independently abstracted by two reviewers. Odds ratios (OR) or relative risks (RR) were pooled using RevMan 5.0. Heterogeneity was evaluated using the Q test and I-squared statistic. P<.01 was considered statistically significant. Results Pooled results from cohort studies indicated that alcohol consumption was not associated with gastric cancer, esophageal cancers (EC) or lung cancer. Meta-analysis of case-control studies showed that alcohol consumption was a significant risk factor for five cancers; the pooled ORs were 1.79 (99% CI, 1.47–2.17) EC, 1.40 (99% CI, 1.19–1.64) gastric cancer, 1.56 (99% CI, 1.16–2.09) hepatocellular carcinoma, 1.21 (99% CI, 1.00–1.46) nasopharyngeal cancer and 1.71 (99% CI, 1.20–2.44) oral cancer. Pooled ORs of the case-control studies showed that alcohol consumption was protective for female breast cancer and gallbladder cancer: OR 0.76 (99% CI, 0.60–0.97) and 0.70 (99% CI, 0.49–1.00) respectively. There was no significant correlation between alcohol consumption and lung cancer, colorectal cancer, pancreatic cancer, cancer of the ampulla of Vater, prostate cancer or extrahepatic cholangiocarcinoma. Combined results of case-control and cohort studies showed that alcohol consumption was associated with 1.78- and 1.40-fold higher risks of EC and gastric cancer but was not significantly associated with lung cancer. Conclusions Health programs focused on limiting alcohol intake may be important for cancer control in China. Further studies are needed to examine the

  5. Circulating adiponectin levels and risk of endometrial cancer: Systematic review and meta-analysis

    PubMed Central

    LI, ZHI-JUN; YANG, XUE-LING; YAO, YAN; HAN, WEI-QING; LI, BO

    2016-01-01

    Previous epidemiological studies have presented conflicting results regarding associations between circulating adiponectin (APN) levels and the risk of endometrial cancer. Thus a meta-analysis was performed to investigate the association between these factors. Multiple electronic sources, including PubMed, SpringerLink and Google Scholar databases were searched to identify relevant studies for the present meta-analysis. All of the selected studies examined the correlation between circulating APN levels and endometrial cancer. The standardized mean difference (SMD) and 95% confidence intervals (CIs) were estimated and pooled using meta-analysis methods. Overall, 18 case-control studies met the inclusion criteria. A total of 5,692 participants and 2,337 cases of endometrial cancer were included in this meta-analysis. The SMD of the pooled analysis (95% CI) were −1.96 (−2.60, −1.31), P=0.000. When the cancer grades were compared, the APN values were not significantly different between the grades of endometrial cancer [G1 vs. G3, 1.02 (−0.68, 2.72), P>0.05; G1 vs. G2, 0.34 (−0.86, 1.54), P>0.05]. However, there was a significant association between high APN levels and postmenopausal endometrial cancer cases with an SMD (95% CI) of −2.27 (−4.36, −0.18) and P<0.05, however, no association was observed in premenopausal endometrial cancer cases with an SMD (95% CI) of −1.52 (−3.49, 0.45) and P>0.05. The low circulating APN level increases the risk of endometrial cancer, whereas the high APN level decreases this risk in postmenopausal women. Circulating APN as simple biomarkers may be a promising tool for the prevention, early diagnosis and disease monitoring of endometrial cancer. PMID:27284314

  6. Reflux pool-boiler as a heat-transport device for Stirling engines - Postmortem analysis and next-generation design

    NASA Astrophysics Data System (ADS)

    Moreno, J. B.; Andraka, C. E.; Diver, R. B.; Moss, T. A.; Hoffman, E. L.; Stone, C. M.

    In a prior study, operation of a 75-kWt sodium reflux pool-boiler solar receiver was demonstrated and its performance characterized at Sandia National Laboratories. Subsequently, during the final testing phase, the receiver developed a leak, releasing part of the sodium inventory to the atmosphere. The possible causes of the leak are examined, including materials selection, thermal stresses, fatigue, high local solar flux, film boiling, and flooding limits. The results of the failure analysis are applied to the next-generation receiver design, which is presented. Plans for bench-scale testing of some design modifications are also presented.

  7. GSTM1 polymorphism contribute to colorectal cancer in Asian populations: a prospective meta-analysis

    PubMed Central

    Li, Jing; Xu, Wen; Liu, Fang; Huang, Silin; He, Meirong

    2015-01-01

    Glutathione S-transferases (GSTs) are enzymes which expressed in many tissues and play important roles in neutralization of toxic compounds, and protecting hosts against cancer. Among several GSTs, Glutathione S-transferases mu (GSTM) has been drawn attention upon the association with the genetic risk for many types of cancers. But whether the GSTM1 polymorphisms confer the susceptibility to colorectal cancer in Asians has not been well established. We searched the PubMed database with GSTM1, polymorphism and colorectal cancer, attempting to identify the eligible studies. In total, 33 case-control studies in Asian populations with 8502 colorectal cancer patients and 13699 controls were included in the current meta-analysis. The association between the polymorphism and susceptibility to colorectal cancer was evaluated by the odds ratio (OR) and 95% confidence intervals (CI). The pooled meta-analysis suggested that GSTM1 null variant was correlated to the colorectal cancer risk in Asians. There was a marginal heterogeneity among these eligible studies. Nevertheless, cumulative meta-analysis observed a trend of an obvious association between the GSTM1 null genotype and colorectal cancer risk in Asians. In summary, the meta-analysis suggested that GSTM1 null polymorphism confer the susceptibility to colorectal cancer in Asians, especially in Chinese populations. PMID:26219826

  8. 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

  9. 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

  10. 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

  11. 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

  12. Cancer risk in patients receiving renal replacement therapy: A meta-analysis of cohort studies

    PubMed Central

    Shang, Weifeng; Huang, Liu; Li, Li; Li, Xiaojuan; Zeng, Rui; Ge, Shuwang; Xu, Gang

    2016-01-01

    It has been reported that patients receiving renal replacement therapy (RRT), including dialysis and kidney transplantation, tend to have an increased risk of cancer; however, studies on the degree of this risk have remained inconclusive. The present meta-analysis was therefore performed to quantify the cancer risk in patients with RRT. Cohort studies assessing overall cancer risk in RRT patients published before May 29, 2015 were included following systematic searches with of PubMed, EMBASE and the reference lists of the studies retrieved. Random-effects meta-analyses were used to pool standardized incidence rates (SIRs) with 95% confidence intervals (CIs). Heterogeneity tests, sensitivity analyses and publication bias assessment were performed. A total of 18 studies including 22 cohort studies were eventually identified, which comprised a total of 1,528,719 patients. In comparison with the general population, the pooled SIR for patients with dialysis including non-melanoma skin cancer (NMSC), dialysis excluding NMSC, transplantation including NMSC, transplantation excluding NMSC and RRT were 1.40 (95% CI, 1.36–1.45), 1.35 (95% CI, 1.23–1.50), 3.26 (95% CI, 2.29–4.63), 2.08 (95% CI, 1.73–2.50) and 2.01 (95% CI, 1.70–2.38), respectively. The cancer risk was particularly high in subgroups of large sample size trials, female patients, younger patients (age at first dialysis, 0–34 years; age at transplantation, 0–20 years), the first year of RRT and non-Asian transplant patients. A significant association was also found between RRT and the majority of organ-specific cancers. However, neither dialysis nor transplantation was associated with breast, body of uterus, colorectal or prostate cancer. Significant heterogeneity was found regarding the association between RRT and overall cancer as well as the majority of site-specific cancer types. However, this heterogeneity had no substantial influence on the pooled SIR for overall cancer in RRT according to the

  13. 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.

  14. '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.

  15. 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)

  16. 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.

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

    NASA Astrophysics Data System (ADS)

    Coniglio, N.; Mathieu, A.; Aubreton, O.; Stolz, C.

    2014-03-01

    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.

  18. 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

  19. Incidence and Mortality of Solid Cancers in People Exposed In Utero to Ionizing Radiation: Pooled Analyses of Two Cohorts from the Southern Urals, Russia

    PubMed Central

    Deltour, Isabelle; Krestinina, Lyudmila; Sokolnikov, Mikhail; Tsareva, Yulia; Tolstykh, Evgenia; Schüz, Joachim

    2016-01-01

    Background Previous studies have shown that acute external in utero exposure to ionizing radiation can increase cancer risk. It is not known whether chronic exposure at low dose rates, including due to radionuclide intake, influences the lifetime risk of solid cancers in the offspring. The objective of this study was to investigate solid cancer risk after in utero irradiation. Methods Cancer incidence and mortality over a 60-year period (from January 1950 to December 2009) were analyzed in the Urals Prenatally Exposed Cohort (UPEC). The cohort comprised in utero exposed offspring of Mayak Production Association female workers and of female residents of Techa River villages. Some of the offspring also received postnatal exposure, either due to becoming radiation workers themselves or due to continuing to live in the contaminated areas of the Techa River. The mortality analyses comprised 16,821 subjects (601,372 person-years), and the incidence analyses comprised 15,813 subjects (554,411 person-years). Poisson regression was used to quantify the relative risk as a function of the in utero soft tissue dose (with cumulative doses up to 944.9 mGy, mean dose of 14.1 mGy in the pooled cohort) and the postnatal stomach dose for solid cancer incidence and mortality. Results When a log-linear model was used, relative risk of cancer per 10 mGy of in utero dose was 0.99 (95% confidence interval (CI) = 0.96 to 1.01) based on incidence data and 0.98 (CI = 0.94 to 1.01) based on mortality data. Postnatal exposure to ionizing radiation was positively associated with the solid cancer risk in members of the UPEC, with a relative risk of 1.02 per 10mGy CI = 1.00 to 1.04). Conclusions No strong evidence was found that chronic low-dose-rate exposure of the embryo and fetus increased the risk of solid cancers in childhood or in adulthood. For both incidence and mortality, a tendency towards a decreased relative risk was noted with increasing doses to soft tissues of the fetus. Further

  20. 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

  1. 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

  2. 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

  3. MGMT Leu84Phe gene polymorphism and lung cancer risk: a meta-analysis.

    PubMed

    Qiu, Zhi-xiong; Xue, Fei; Shi, Xuan-feng; He, Xiao; Ma, Hui-ni; Chen, Lan; Chen, Pin-zhong

    2014-05-01

    Many studies have examined the association between the MGMT Leu84Phe polymorphism gene polymorphisms and lung cancer risk in various populations, but their results have been inconsistent. To assess this relationship more precisely, a meta-analysis was performed. The PubMed and CNKI database was searched for case-control studies published up to Nov. 2013. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated. Ultimately, 7 studies, comprising 3,094 lung cancer cases and 4,216 controls, were included. Overall, for (Phe/Phe+Phe/Leu) versus Leu/Leu, the pooled OR for all studies was 1.08 (95% CI = 0.97-1.21 P = 0.518 for heterogeneity); for Phe/Phe versus Leu/Leu and Phe versus Leu, the pooled OR was 1.10 (95% CI = 0.99-1.21 P = 0.445 for heterogeneity) and 1.46 (95% CI = 1.05-2.02 P = 0.352 for heterogeneity), respectively. In the stratified analysis by ethnicity, significantly risks were found among Caucasians not in Asians. This meta-analysis suggests that the MGMT Leu84Phe polymorphisms are associated with lung cancer risk among Caucasians not in Asians. PMID:24390665

  4. 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

  5. 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

  6. Analysis of the Endogenous Deoxynucleoside Triphosphate Pool in HIV-Positive and -Negative Individuals Receiving Tenofovir-Emtricitabine.

    PubMed

    Chen, Xinhui; Castillo-Mancilla, Jose R; Seifert, Sharon M; McAllister, Kevin B; Zheng, Jia-Hua; Bushman, Lane R; MaWhinney, Samantha; Anderson, Peter L

    2016-09-01

    Tenofovir (TFV) disoproxil fumarate (TDF) and emtricitabine (FTC), two nucleos(t)ide analogs (NA), are coformulated as an anti-HIV combination tablet for treatment and preexposure prophylaxis (PrEP). TDF/FTC may have effects on the deoxynucleoside triphosphate (dNTP) pool due to their similar structures and similar metabolic pathways. We carried out a comprehensive clinical study to characterize the effects of TDF/FTC on the endogenous dNTP pool, from baseline to 30 days of TDF/FTC therapy, in both treatment-naive HIV-positive and HIV-negative individuals. dATP, dCTP, dGTP, and TTP were quantified in peripheral blood mononuclear cells (PBMC) with a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) methodology. Forty individuals (19 HIV-positive) were enrolled and underwent a baseline visit and then received TDF/FTC for at least 30 days. Longitudinal measurements were analyzed using mixed-model segmented linear regression analysis. The dNTPs were reduced by 14% to 37% relative to the baseline level within 3 days in both HIV-negative and HIV-positive individuals (P ≤ 0.003). These reductions persisted to various degrees at day 30. These findings indicate that dNTP pools are influenced by TDF/FTC therapy. This may alter cellular homeostasis and could increase the antiviral effect through a more favorable analog/dNTP ratio. Further work is needed to elucidate mechanisms, to evaluate the clinical significance of these findings, and to further probe differences between HIV-negative and HIV-positive individuals. (This study has been registered at ClinicalTrials.gov under identifier NCT01040091.). PMID:27353267

  7. 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

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

    PubMed

    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

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

    NASA Astrophysics Data System (ADS)

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

    2016-05-01

    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.

  10. Systematic review and meta-analysis suggest that dietary cholesterol intake increases risk of breast cancer.

    PubMed

    Li, Changkun; Yang, Li; Zhang, Dongfeng; Jiang, Wenjie

    2016-07-01

    Several epidemiological investigations have been conducted to evaluate the relationship between dietary cholesterol intake and risk of breast cancer, but the results are inconsistent. This meta-analysis was performed to summarize the evidence from observational studies to test the hypothesis that dietary cholesterol intake increases the risk of breast cancer. PubMed, EMBASE, Web of Science, and China National Knowledge Infrastructure were searched for relevant articles published up to July 2015. Pooled relative risks were calculated with random effects model. Dose-response relationship was assessed by restricted cubic spline model. Overall, 9 articles involving 6 cohort studies and 3 case-control studies were included in this study. The pooled relative risk with 95% confidence intervals of breast cancer for the highest vs lowest category of dietary cholesterol intake was 1.29 (1.06-1.56). For dose-response analysis, a nonlinear relationship was found between dietary cholesterol and breast cancer, and the association became statistically significant when the cholesterol intake was greater than 370 mg/d. Results from this meta-analysis indicated that dietary cholesterol was associated with an increased risk of breast cancer. PMID:27333953