Prediagnostic Plasma Vitamin D Metabolites and Mortality among Patients with Prostate Cancer

Background: Laboratory evidence suggests that vitamin D might influence prostate cancer prognosis. Methodology/Principal Findings: We examined the associations between prediagnostic plasma levels of 25(OH) vitamin D [25(OH)D] and 1,25(OH)(2)vitamin D [1,25(OH)(2)D] and mortality among 1822 participants of the Health Professionals Follow-up Study and Physicians' Health Study who were diagnosed with prostate cancer. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of total mortality (n = 595) and lethal prostate cancer (death from prostate cancer or development of bone metastases; n = 202). In models adjusted for age at diagnosis, BMI, physical activity, and smoking, we observed a HR of 1.22 (95% CI: 0.97, 1.54) for total mortality, comparing men in the lowest to the highest quartile of 25(OH) D. There was no association between 1,25(OH) 2D and total mortality. Men with the lowest 25(OH) D quartile were more likely to die of their cancer (HR: 1.59; 95% CI: 1.06, 2.39) compared to those in the highest quartile (P-trend = 0.006). This association was largely explained by the association between low 25(OH) D levels and advanced cancer stage and higher Gleason score, suggesting that these variables may mediate the influence of 25(OH) D on prognosis. The association also tended to be stronger among patients with samples collected within five years of cancer diagnosis. 1,25(OH)(2)D levels were not associated with lethal prostate cancer. Conclusions/Significance: Although potential bias of less advanced disease due to more screening activity among men with high 25(OH) D levels cannot be ruled out, higher prediagnostic plasma 25(OH) D might be associated with improved prostate cancer prognosis.