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

Abstract

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) and 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 with the first quintile, HRs were 0.83 [95% confidence interval (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 second through fifth quintiles, respectively. For Gleason 7–10 cancer, corresponding HRs 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 versus 3–5, the HR 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.

Impact: The optimal range of circulating vitamin D for prostate cancer prevention may be narrow. Supplementation of men with adequate levels may be harmful. Cancer Epidemiol Biomarkers Prev; 23(8); 1494–504. ©2014 AACR.