Plasma Vitamin D and Prostate Cancer Risk: Results from the Selenium and Vitamin E Cancer Prevention Trial

BACKGROUND: In-vitro, animal and ecological studies suggest that inadequate vitamin D intake could increase prostate cancer risk, but results of biomarker-based longitudinal studies are inconsistent. METHODS: Data for this case (n=1,731)-cohort (n=3,203) analysis are from the Selenium and Vitamin E Cancer Prevention Trial. Cox proportional hazard models were used to test whether baseline plasma vitamin D (25-hydroxy) concentration, adjusted for season of blood collection, was associated with the risk of total and Gleason Score 2-6, 7-10 and 8-10 prostate cancer. RESULTS: There were U-shaped associations of vitamin D with total cancer risk: compared to the first quintile, hazard ratios were 0.83 (95% CI 0.66-1.03, p=0.092), 0.74 (95% CI 0.59-0.92, p=0.008), 0.86 (95% CI 0.69-1.07, p=0.181) and 0.98 (95% CI 0.78-1.21, p=0.823), for the 2nd through 5th quintiles, respectively. For Gleason 7-10 cancer, corresponding hazard ratios were 0.63 (95% CI 0.45-0.90, p=0.010), 0.66 (95% CI 0.47-0.92, p=0.016), 0.79 (95% CI 0.56-1.10, p=0.165) and 0.88 (95% CI 0.63-1.22, p=0.436). Among African American men (n=250 cases), higher vitamin D was associated with reduced risk of Gleason 7-10 cancer only: in the a posteriori contrast of quintiles 1-2 vs 3-5, the hazard ratio was 0.55 (95% CI 0.31-0.97, p=0.037), with no evidence of dose-response or a U-shaped association. CONCLUSIONS: Both low and high vitamin D concentrations were associated with increased risk of prostate cancer, and more strongly for high-grade disease