Plasma Tocopherols and Risk of Prostate Cancer in the Selenium and Vitamin E Cancer Prevention Trial (SELECT)

Cancer Prevention Research
Q1
Jun 2014
Citations:69
Influential Citations:1
Observational Studies (Human)
81
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Enhanced Details

Methods
Design: randomized, double-blind, placebo-controlled SELECT trial; Participants: African American men aged ≥50 and non-African American men aged ≥55 at enrollment; 427 sites in the United States, Canada, and Puerto Rico; Eligibility: no evidence of prostate cancer at baseline (PSA ≤4 ng/mL and non-suspicious DRE); Case-cohort biomarker analysis included 1,746 prostate cancer cases and 3,211 subcohort members (combined n=4,754); median follow-up 5.5 years (range 0–7.9); Plasma tocopherol concentrations measured at randomization (2001–2004).
Intervention
Vitamin E: 400 IU daily of all-rac-alpha-tocopheryl acetate; Selenium: 200 mg elemental selenium daily as L-selenomethionine; duration through October 2008.
Results
Prerandomization plasma alpha-tocopherol was not associated with overall prostate cancer risk in the placebo arm or in the vitamin E–alone arm. A strong positive association emerged when higher alpha-tocopherol occurred with selenomethionine supplementation: Q5 vs Q1 HR 2.04 (95% CI 1.29–3.22; P-trend = 0.005) overall; and high-grade disease (Gleason 7–10) showed HR 2.12 (95% CI 1.32–3.40; P-trend = 0.0002) in the selenomethionine groups. Gamma-tocopherol showed no clear association. Findings suggest a biological interaction between alpha-tocopherol and selenium, potentially increasing high-grade prostate cancer risk, and imply caution with high-dose vitamin E supplementation, especially with selenium or in individuals with high baseline alpha-tocopherol; further study is needed to understand the mechanism.
Limitations
Short follow-up period largely during supplementation; limited power to assess interactions between tocopherol status and intervention arms; oversampling of African American participants; baseline eligibility favored early-stage tumors, limiting generalizability.

Abstract

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...