CIRCULATING VITAMIN-D METABOLITES IN RELATION TO SUBSEQUENT DEVELOPMENT OF PROSTATE-CANCER

An emerging hypothesis suggests that vitamin D metabolites suppress th e development of prostate cancer. In a recent epidemiological study, e levated levels of 1,25-dihydroxyvitamin D (1,25-D) in blood were assoc iated with a greatly reduced risk, particularly in older men. We condu cted a nested case-control study to evaluate the relationship between plasma levels of the two major vitamin D metabolites, 1,25-D and 25-hy droxyvitamin D (25-D), and subsequent diagnosis of prostate cancer. We also measured vitamin D-binding protein to investigate the influence of free metabolite levels on risk. Plasma samples from 14,916 particip ants in the Physicians' Health Study were collected and frozen in 1982 -1983. This analysis included 232 cases diagnosed up to 1992 and 414 a ge-matched control participants. Vitamin D metabolite and vitamin D-bi nding protein assays were conducted without knowledge of case-control status, Median levels of 25-D, 1,25-D, and vitamin D-binding protein w ere indistinguishable between cases and controls. Analysis of risk for increasing quartiles of total or free metabolites did not reveal a pa ttern of decreasing risk. For 1,25-D, men in the highest quartile had an odds ratio of 0.88 (95% confidence interval = 0.53-1.45) compared t o those in the lowest quartile, Significant reductions in risk were no t seen in analyses restricted to older men, to cases occurring > 3 yea rs from blood collection, or to cases presenting as aggressive prostat e cancer. Nonsignificant inverse associations for 1,25-D appeared for some groups according to 25-D level, particularly when the cutoff for defining low 25-D was reduced, These results do not support the hypoth esis that high circulating levels of vitamin D metabolites reduce pros tate cancer risk, although small to moderate effects cannot be exclude d.