Abstract

<div>Abstract<p><b>Background:</b> 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.</p><p><b>Methods:</b> 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 high-grade prostate cancer (<i>N</i> = 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.</p><p><b>Results:</b> We noted statistically significant (<i>P</i> < 0.05) interactions between selenium assignment, SNPs in <i>CAT, SOD2, PRDX6, SOD3</i>, and <i>TXNRD2</i>, and high-grade prostate cancer risk. Statistically significant SNPs that modified the association of vitamin E assignment and high-grade prostate cancer included <i>SEC14L2, SOD1</i>, and <i>TTPA</i>. 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.</p><p><b>Conclusion:</b> 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 selenium supplementation with regards to these risks.</p><p><b>Impact:</b> The effect of selenium or vitamin E supplementation on high-grade prostate cancer risk may vary by genotype. <i>Cancer Epidemiol Biomarkers Prev; 25(7); 1050–8. ©2016 AACR</i>.</p></div>

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