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

Epidemiological 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 epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2016 May 06 [Epub ahead of print]

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

Epidemiology & Biostatistics and Urology, University of California, San Francisco ., Fred Hutchinson Cancer Research Center., Channing Division of Network Medicine, Department of Epidemiology, Brigham and Women's Hospital/Harvard Medical School, Harvard T.H. Chan School of Public Health., Southwest Oncology Group Statistical Center, Fred Hutchinson Cancer Research Center., Southwest Oncology Group Statistical Center., Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School., Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School., Brigham and Women's Hospital/Harvard Medical School., Epidemiology, Harvard T.H. Chan School of Public Health., University of Michigan Cancer Center., Glickman Urological and Kidney Institute, Cleveland Clinic., Department of Urology, University of Texas Health Sciences Center San Antonio., Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School., Epidemiology, Harvard T.H. Chan School of Public Health.