Vitamin D–Related Genetic Variation, Plasma Vitamin D, and Risk of Lethal Prostate Cancer: A Prospective Nested Case–Control Study

There is abundant laboratory evidence that vitamin D may have anticancer properties. In prostate cancer cell lines, vitamin D has been reported to promote differentiation and apoptosis and to inhibit cell proliferation, cell adhesion, and angiogenesis (1–4). In contrast, results from most epidemiological studies have not sup-ported an association of circulating plasma 25-hydroxyvitamin D [25(OH)D], the biomarker of vitamin D status, with overall pros-tate cancer risk (5). Fewer studies have investigated whether 25(OH)D levels are related to a lower risk of lethal prostate cancer, the most clinically relevant outcome. In a previous publication (6), we examined plasma 25(OH)D levels and prostate cancer risk in the Health Professionals Follow-up Study (HPFS). During follow-up through the year 2000, 692 men developed prostate cancer. We found no statistically significant association of plasma 25(OH)D levels with the incidence of overall prostate cancer, but we di