Selenium- or vitamin E-related gene variants, interaction with supplementation, and risk of high-grade prostate cancer in SELECT

June M. Chan, Amy K. Darke, Kathryn L. Penney, Catherine M. Tangen, Phyllis J. Goodman, Gwo Shu Mary Lee, Tong Sun, Sam Peisch, Alex M. Tinianow, James M. Rae, Eric A. Klein, Ian M. Thompson, Philip W. Kantoff, Lorelei A. Mucci

Research output: Contribution to journalArticlepeer-review

36 Scopus citations


Background: Epidemiologic 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. Methods: We 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 highgrade 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. Results: We 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. Conclusion: Variants 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 seleniumsupplementation with regards to these risks. Impact: The effect of selenium or vitamin E supplementation on high-grade prostate cancer risk may vary by genotype.

Original languageEnglish (US)
Pages (from-to)1050-1058
Number of pages9
JournalCancer Epidemiology Biomarkers and Prevention
Issue number7
StatePublished - Jul 2016

ASJC Scopus subject areas

  • Epidemiology
  • Oncology


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