Selenium- or Vitamin E-Related Gene Variants, Interaction with Supplementation, and Risk of High-Grade Prostate Cancer in SELECT
| Autor: | Chan, June M, Darke, Amy K, Penney, Kathryn L, Tangen, Catherine M, Goodman, Phyllis J, Lee, Gwo-Shu Mary, Sun, Tong, Peisch, Sam, Tinianow, Alex M, Rae, James M, Klein, Eric A, Thompson, Ian M, Kantoff, Philip W, Mucci, Lorelei A |
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| Rok vydání: | 2016 |
| Předmět: |
Male
Urologic Diseases Aging and promotion of well-being Pharmacogenomic Variants Epidemiology Clinical Trials and Supportive Activities Medical and Health Sciences Cohort Studies Selenium Risk Factors Clinical Research Complementary and Integrative Health Genetics Humans Vitamin E 2.1 Biological and endogenous factors Polymorphism Aetiology 3.3 Nutrition and chemoprevention Proportional Hazards Models Aged Nutrition Cancer Tumor Prevention Prostate Cancer Prostatic Neoplasms Genetic Variation Biological Transport Single Nucleotide Middle Aged Prevention of disease and conditions Good Health and Well Being Patient Safety Neoplasm Grading Biomarkers |
| Zdroj: | Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, vol 25, iss 7 |
| Popis: | BackgroundEpidemiologic studies and secondary analyses of randomized trials supported the hypothesis that selenium and vitamin E lower prostate cancer risk. However, the Selenium and Vitamin E Cancer Prevention Trial (SELECT) showed no benefit of either supplement. Genetic variants involved in selenium or vitamin E metabolism or transport may underlie the complex associations of selenium and vitamin E.MethodsWe undertook a case-cohort study of SELECT participants randomized to placebo, selenium, or vitamin E. The subcohort included 1,434 men; our primary outcome was high-grade prostate cancer (N = 278 cases, Gleason 7 or higher cancer). We used weighted Cox regression to examine the association between SNPs and high-grade prostate cancer risk. To assess effect modification, we created interaction terms between randomization arm and genotype and calculated log likelihood statistics.ResultsWe noted statistically significant (P < 0.05) interactions between selenium assignment, SNPs in CAT, SOD2, PRDX6, SOD3, and TXNRD2, and high-grade prostate cancer risk. Statistically significant SNPs that modified the association of vitamin E assignment and high-grade prostate cancer included SEC14L2, SOD1, and TTPA In the placebo arm, several SNPs, hypothesized to interact with supplement assignment and risk of high-grade prostate cancer, were also directly associated with outcome.ConclusionVariants in selenium and vitamin E metabolism/transport genes may influence risk of overall and high-grade prostate cancer, and may modify an individual man's response to vitamin E or selenium supplementation with regards to these risks.ImpactThe effect of selenium or vitamin E supplementation on high-grade prostate cancer risk may vary by genotype. Cancer Epidemiol Biomarkers Prev; 25(7); 1050-8. ©2016 AACR. |
| Databáze: | OpenAIRE |
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