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 alpha-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 alpha-tocopherol was measured at baseline using high-performance liquid chromatography, and 2724 prostate cancer cases were identified during 28 years of follow-up. Cox proportional hazards models examined whether serum alpha-tocopherol concentrations were associated with prostate cancer risk. Among 8383 participants, three SNPs related to vitamin E status (rs964184, rs2108622, and rs11057830) were examined to determine whether they modified the relationship between serum alpha-tocopherol concentrations and prostate cancer risk, both individually and as a PRS using logistic regression models. Results No association was observed between serum alpha-tocopherol and prostate cancer risk (fifth quintile (Q5) vs. 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 alpha-tocopherol concentration was associated with reduced prostate cancer risk among the trial alpha-tocopherol supplementation group (Q5 quintile vs. 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 alpha-tocopherol concentration and prostate cancer risk over nearly three decades, our findings suggest that men receiving the trial alpha-tocopherol supplementation who had higher baseline serum alpha-tocopherol concentration experienced reduced prostate cancer risk. Vitamin E-related genotypes did not modify the serum alpha-tocopherol-prostate cancer risk association.

Automated summary

The study found no significant relationship between serum alpha-tocopherol concentration and prostate cancer risk. However, higher baseline alpha-tocopherol concentration in men receiving alpha-tocopherol supplementation was associated with reduced risk of prostate cancer. Vitamin E-related genotypes did not modify the association between serum alpha-tocopherol and prostate cancer risk.