Vitamin D and the epidemiology of prostate cancer.

Mortality rates from prostate cancer are significantly higher among African Americans than Caucasian Americans and are inversely related to the availability of ultraviolet (UV) radiation. These findings support the hypothesis, originally proposed in 1990, that prostate cancer may be caused by vitamin D deficiency. In 1992, specific receptors for 1,25-dihydroxyvitamin D [1,25(OH)2D] were demonstrated in human prostate cells. We and others have shown that 1,25(OH)2D exerts prodifferentiating, antiproliferative, and antimetastatic effects on these cells. In 1998 we demonstrated that normal prostate cells express 1alpha-hydroxylase and synthesize their own 1,25(OH)2D. Thus, 1,25(OH)2D is an autocrine hormone in the prostate. The consensus emerging from analytic epidemiologic studies is that low levels of UV radiation/vitamin D are indeed associated with an increased risk of prostate cancer in individual men. The evolution of our understanding of the role of vitamin D in the epidemiology of prostate cancer parallels our understanding of the role of vitamin D in the epidemiology of rickets. In both diseases, ecologic observations about UV radiation preceded experimental observations and were subsequently validated by them.