Serum 25-Hydroxy Vitamin D and Prostate Cancer Risk in a Large Nested Case-Control Study

Background: Vitamin D compounds inhibit prostate tumorigenesis experimentally, but epidemiologic data are inconsistent with respect to prostate cancer risk, with some studies suggesting nonsignificant positive associations. Methods: The 25-hydroxy vitamin D [25(OH)D]-prostate cancer relation was examined in a nested case-control study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study of 50- to 69-year-old Finnish men. We matched 1,000 controls to 1,000 cases diagnosed during up to 20 years of follow-up on the basis of age (+/- 1 year) and fasting blood collection date (+/- 30 days). Conditional multivariate logistic regression models estimated ORs and 95% CIs. All statistical significance testing was 2-sided. Results: Cases had nonsignificantly 3% higher serum 25(OH)D levels (P = 0.19). ORs (95% CIs) for increasing season-specific quintiles of 25(OH)D concentrations were 1.00 (reference), 1.29 (0.95-1.74), 1.34 (1.00-1.80), 1.26 (0.93-1.72), and 1.56 (1.15-2.12), with P-trend = 0.01. Analyses based on prespecified clinical categories and season-adjusted values yielded similar results. These findings seemed stronger for aggressive disease [OR (95% CI) for fifth quintile of serum 25(OH)D [1.70 (1.05-2.76), P-trend = 0.02], among men with greater physical activity [1.85 (1.26-2.72), P-trend = 0.002], higher concentrations of serum total cholesterol [2.09 (1.36-3.21), P-trend = 0.003] or alpha-tocopherol [2.00 (1.30-3.07), P-trend = 0.01] and higher intakes of total calcium [1.82 (1.20-2.76), P-trend = 0.01] or vitamin D [1.69 (1.04-2.75), P-trend = 0.08], or among those who had received the trial a-tocopherol supplements [1.74 (1.15-2.64), P-trend = 0.006]. Conclusion: Our findings indicate that men with higher vitamin D blood levels are at increased risk of developing prostate cancer. Impact: Greater caution is warranted with respect to recommendations for high-dose vitamin D supplementation and higher population target blood levels. Cancer Epidemiol Biomarkers Prev; 20(9); 1850-60. (C)2011 AACR.