The
Selenium and
Vitamin E Cancer Prevention Trial (SELECT) showed higher
prostate cancer incidence in men supplemented with high-dose α-
tocopherol. We, therefore, examined whether presupplementation plasma α-
tocopherol or γ-
tocopherol was associated with overall or high-grade
prostate cancer. A stratified case-cohort sample that included 1,746 incident
prostate cancer cases diagnosed through June 2009 and a subcohort of 3,211 men was derived from the SELECT trial of 35,533 men. Plasma was collected at entry from 2001 to 2004, and median follow-up was 5.5 years (range, 0-7.9 years). Incidence of
prostate cancer as a function of plasma α-
tocopherol, γ-
tocopherol, and supplementation with α-
tocopherol or
selenomethionine was estimated by the hazard ratio (HR). Plasma γ-
tocopherol was not associated with
prostate cancer. Men with higher α-
tocopherol concentrations seemed to have risk similar to that of men with lower concentrations [overall HR for fifth (Q5) vs. first quintile (Q1), 1.21; 95 % confidence interval (CI), 0.88-1.66; P-trend = 0.24; in the trial placebo arm, Q5 HR, 0.85; 95% CI, 0.44-1.62; P-trend = 0.66]. We found a strong positive plasma α-
tocopherol association among men receiving the trial
selenomethionine supplement [Q5 HR, 2.04; 95% CI, 1.29-3.22; P-trend = 0.005]. A positive plasma α-
tocopherol-
prostate cancer association also seemed limited to high-grade disease (Gleason grade, 7-10; overall Q5 HR, 1.59; 95% CI, 1.13-2.24; P-trend = 0.001; among men receiving
selenomethionine, Q5 HR, 2.12; 95% CI, 1.32-3.40; P-trend = 0.0002). Our findings indicate that higher plasma α-
tocopherol concentrations may interact with
selenomethionine supplements to increase high-grade
prostate cancer risk, suggesting a
biologic interaction between α-
tocopherol and
selenium itself or
selenomethionine.