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Rosenberg P.S.,U.S. National Cancer Institute | Rosenberg P.S.,609 Medical Center Drive | Check D.P.,U.S. National Cancer Institute | Anderson W.F.,U.S. National Cancer Institute
Cancer Epidemiology Biomarkers and Prevention

Background: Age-period-cohort (APC) analysis can inform registry-based studies of cancer incidence and mortality, but concerns about statistical identifiability and interpretability, as well as the learning curves of statistical software packages, have limited its uptake. Methods: We implemented a panel of easy-to-interpret estimable APC functions and corresponding Wald tests in R code that can be accessed through a user-friendly Web tool. Results: Input data for the Web tool consist of age-specific numbers of events and person-years over time, in the form of a rate matrix of paired columns. Output functions include model-based estimators of cross-sectional and longitudinal age-specific rates, period and cohort rate ratios that incorporate the overall annual percentage change (net drift), and estimators of the age-specific annual percentage change (local drifts). The Web tool includes built-in examples for teaching and demonstration. User data can be input from a Microsoft Excel worksheet or by uploading a comma-separated-value file. Model outputs can be saved in a variety of formats, including R and Excel. Conclusions: APC methodology can now be carried out through a freely available user-friendly Web tool. The tool can be accessed at http://analysistools.nci.nih.gov/apc/. Impact: The Web tool can help cancer surveillance researchers make important discoveries about emerging cancer trends and patterns. ©2014 AACR. Source

Mondul A.M.,609 Medical Center Drive | Sampson J.N.,609 Medical Center Drive | Sampson J.N.,U.S. National Cancer Institute | Moore S.C.,609 Medical Center Drive | And 5 more authors.
American Journal of Clinical Nutrition

Background: Two chemoprevention trials found that supplementation with β-carotene increased the risk of lung cancer and overall mortality. The biologic basis of these findings remains poorly understood. Objective: The objective was to compare the on-study change in metabolomic profiles of men randomly assigned to receive or not receive β-carotene supplements in the Alpha-Tocopherol, Beta- Carotene Cancer Prevention (ATBC) Study. Design: The ATBC Study was a randomized, double-blind, placebo- controlled, primary cancer prevention trial; participants were Finnish male smokers assigned to 1 of 4 intervention groups: 1) a-tocopherol, 2) β-carotene, 3) both, or 4) placebo. Fifty participants with both baseline and follow-up fasting serum samples were randomly selected from each of these groups. Metabolomic profiling was conducted by mass spectrometry. The association between change in each metabolite over time and trial assignment (β-carotene or no β-carotene) was estimated by linear regression. Results: We measured 489 metabolites, and 17 changed significantly (P < 0.05) in response to β-carotene supplementation. More of these 17 metabolites were of xenobiotic origin than would be expected by chance (9 of 60, or 15%; P = 0.00004). We also found a suggestive association with 1,5-anhydroglucitol- A marker of glycemic control (β = 20.379, P = 0.0071). Conclusions: Male smokers supplemented with β-carotene developed metabolomic profiles consistent with the induction of cytochrome P450 enzymes, the primary metabolizers of xenobiotics in humans. These findings may shed light on the increased mortality associated with β-carotene supplementation in the ATBC Study and suggest the need to explore potential interactions between medication use and dietary supplements, particularly among smokers. This trial was registered at clinicaltrials.gov as NCT00342992. © 2013 American Society for Nutrition. Source

Felix A.S.,609 Medical Center Drive | Felix A.S.,U.S. National Institutes of Health | Brinton L.A.,609 Medical Center Drive | Scott McMeekin D.,609 Medical Center Drive | And 10 more authors.
Journal of the National Cancer Institute

Background: Stage is a critical determinant of treatment among endometrial carcinoma patients; understanding patterns of tumor spread may suggest approaches to improve staging. Specifically, the importance of exfoliation of endometrial carcinoma cells through the fallopian tubes into the peritoneum is ill defined. We assessed the hypothesis that tubal ligation (TL), which should impede transtubal passage of cells, is associated with lower endometrial carcinoma stage at presentation and, consequently, lower mortality. Methods: The NRG Oncology/Gynecologic Oncology Group (GOG) 210 Trial included 4489 endometrial carcinoma patients who completed a risk factor questionnaire that included TL history. Pathology data were derived from clinical reports and central review. We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between TL with stage and peritoneal metastasis, overall and by tumor subtype. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals for TL and mortality. All statistical tests were two-sided. Results: Compared with stage I, TL was inversely associated with stage III (OR = 0.63, 95% CI = 0.52 to 0.78) and stage IV carcinomas (OR = 0.14, 95% CI = 0.08 to 0.24) overall and among individual tumor subtypes. TL was inversely related to peritoneal metastasis overall (OR = 0.39, 95% CI = 0.22 to 0.68) and among serous carcinomas (OR = 0.28, 95% CI = 0.11 to 0.68). In multivariable models unadjusted for stage, TL was associated with lower endometrial carcinoma-specific mortality (HR = 0.74, 95% CI = 0.61 to 0.91); however, adjustment for stage eliminated the survival advantage. Similar relationships with all-cause mortality were observed. Conclusions: TL is associated with lower stage and mortality among women with aggressive endometrial carcinomas, suggesting transtubal spread is clinically important. Future studies should evaluate whether detection of intraluminal tumor cells is prognostically relevant. © 2015 The Author. Source

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