Previous prospective studies assessing the relationship between circulating concentrations of vitamin D and prostate cancer risk have shown inconclusive results, particularly for risk of aggressive disease. In this study, we examine the association between pre-diagnostic concentrations of 25-hydroxyvitamin D (25(OH)D) and 1,25(OH)2D and the risk of prostate cancer overall and by tumor characteristics. Principal investigators of 19 prospective studies provided individual participant data on circulating 25(OH)D and 1,25(OH)2D for up to 13,462 men with incident prostate cancer and 20,261 control participants. Odds ratios (OR) for prostate cancer by study-specific fifths of season-standardized vitamin D concentration were estimated using multivariable-adjusted conditional logistic regression. 25(OH)D concentration was positively associated with risk for total prostate cancer (multivariable-adjusted OR comparing highest versus lowest study-specific fifth was 1.22, 95% CI 1.13-1.31; P trend<0.001). However, this association varied by disease aggressiveness (Pheterogeneity=0.014); higher circulating 25(OH)D was associated with a higher risk of non-aggressive disease (OR per 80 percentile increase=1.24, 1.13-1.36) but not with aggressive disease (defined as stage 4, metastases, or prostate cancer death, 0.95, 0.78-1.15). 1,25(OH)2D concentration was not associated with risk for prostate cancer overall or by tumor characteristics. The absence of an association of vitamin D with aggressive disease does not support the hypothesis that vitamin D deficiency increases prostate cancer risk. Rather, the association of high circulating 25(OH)D concentration with a higher risk of non-aggressive prostate cancer may be influenced by detection bias.
Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford.