Selenium- or vitamin E-related gene variants, interaction with supplementation, and risk of high-grade prostate cancer in SELECT
Menée aux Etats-Unis auprès de 1 434 participants, cette étude évalue l'effet d'une supplémentation en sélénium ou en vitamine E sur le risque de cancer de la prostate de haut grade (278 cas) en fonction de la présence de polymorphismes à simple nucléotide sur des gènes impliqués dans le métabolisme ou le transport de ces deux substances
Background : 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. 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 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. 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. Conclusions : 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. Impact : The effect of selenium or vitamin E supplementation on high-grade prostate cancer risk may vary by genotype.