1. Selenium- or Vitamin E–Related Gene Variants, Interaction with Supplementation, and Risk of High-Grade Prostate Cancer in SELECT
- Author
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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, and Mucci, Lorelei A
- Subjects
Biomedical and Clinical Sciences ,Health Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Aging ,Complementary and Integrative Health ,Urologic Diseases ,Genetics ,Clinical Trials and Supportive Activities ,Prevention ,Prostate Cancer ,Nutrition ,Cancer ,Patient Safety ,Clinical Research ,3.3 Nutrition and chemoprevention ,Aetiology ,Prevention of disease and conditions ,and promotion of well-being ,2.1 Biological and endogenous factors ,Good Health and Well Being ,Aged ,Biological Transport ,Biomarkers ,Tumor ,Cohort Studies ,Genetic Variation ,Humans ,Male ,Middle Aged ,Neoplasm Grading ,Pharmacogenomic Variants ,Polymorphism ,Single Nucleotide ,Proportional Hazards Models ,Prostatic Neoplasms ,Risk Factors ,Selenium ,Vitamin E ,Medical and Health Sciences ,Epidemiology ,Biomedical and clinical sciences ,Health sciences - Abstract
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.
- Published
- 2016