A 28-Year Prospective Analysis of Serum Vitamin E, Vitamin E-Related Genetic Variation and Risk of Prostate Cancer

OBJECTIVE: Investigate the relationship between serum α-tocopherol concentration and long-term risk of prostate cancer, and evaluate the interaction with vitamin E–related genetic variants and their polygenic risk score (PRS). METHODS: We conducted a biochemical analysis of 29 102 male Finnish smokers in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Serum α-tocopherol was measured at baseline using high-performance liquid chromatography, and 2 724 prostate cancer cases were identified during 28 years of follow-up. Cox proportional hazards models examined whether serum α-tocopherol concentrations were associated with prostate cancer risk. Among 8 383 participants, three SNPs related to vitamin E status (rs964184, rs2108622, and rs11057830) were examined to determine whether they modified the relationship between serum α-tocopherol concentrations and prostate cancer risk, both individually and as a PRS using logistic regression models. RESULTS: No association was observed between serum α-tocopherol and prostate cancer risk (fifth quintile (Q5) versus Q1 hazard ratio (HR)=0.87, 95% confidence interval (95% CI) 0.75, 1.02; p-trend=0.57). Though no interactions were seen by population characteristics, high α-tocopherol concentration was associated with reduced prostate cancer risk among the trial α-tocopherol supplementation group (Q5 quintile versus Q1 HR=0.79, 95% CI 0.64, 0.99). Finally, no associated interaction between the three SNPs or their PRS and prostate cancer risk was observed. CONCLUSION: Although there was a weak inverse association between α-tocopherol concentration and prostate cancer risk over nearly three decades, our findings suggest that men receiving the trial α-tocopherol supplementation who had higher baseline serum α-tocopherol concentration experienced reduced prostate cancer risk. Vitamin E–related genotypes did not modify the serum α-tocopherol-prostate cancer risk association.