Selenium- or Vitamin E-Related Gene Variants, Interaction with Supplementation, and Risk of High-Grade Prostate Cancer in SELECT

• Published in: Cancer epidemiology, biomarkers & prevention biomarkers & prevention, 2016-07, Vol.25 (7), p.1050-1058
• Main Authors: 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, Jr, Ian M, Kantoff, Philip W, Mucci, Lorelei A
• Format: Article
• Language: English
• Subjects: Aged; Biological Transport - genetics; Biomarkers, Tumor - blood; Cohort Studies; Genetic Variation; Humans; Male; Middle Aged; Neoplasm Grading; Pharmacogenomic Variants; Polymorphism, Single Nucleotide; Proportional Hazards Models; Prostatic Neoplasms - blood; Prostatic Neoplasms - genetics; Prostatic Neoplasms - pathology; Risk Factors; Selenium - metabolism; Vitamin E - genetics; Vitamin E - metabolism
• ISSN: 1055-9965; 1538-7755
• DOI: 10.1158/1055-9965.EPI-16-0104

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. 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 (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. 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. 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. The 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.