ASSOCIATION OF PROSTATE-CANCER WITH VITAMIN-D-RECEPTOR GENE POLYMORPHISM

The incidence of prostate cancer in the United States is second only t o skin cancers, and the disease kills almost the same number of men as breast cancer does women, Relatively few risk factors are known for p rostate cancer, although several lines of evidence suggest that vitami n D may be an important determinant of prostate cancer risk, A series of common polymorphisms in the vitamin D receptor gene were recently r eported to be associated with bone density and risk of osteoporosis (M orrison et al., Nature (Lond.), 367: 284-287, 1994), These genetic var iants have been correlated with both circulating levels of active vita min D hormone and in vitro measures of gene expression (Morrison et al ., Nature (Lond.), 367: 284-287, 1994). We tested the hypothesis that vitamin D receptor gene polymorphisms are associated with prostate can cer risk using a case-control study of 108 men undergoing radical pros tatectomy and 170 male urology clinic controls with no history of canc er, Among the white control group, 22% were homozygous for the presenc e of a TaqI RFLP at codon 352 (genotype tt), but only 8% of cases had this genotype (P < 0.01), A similar trend mas seen among the small num ber of blacks in this study (13% for controls, 8% for cases), although the difference was not statistically significant, Race-adjusted combi ned analysis suggests that men who are homozygous for the t allele (sh own to correlate with higher serum levels of the active form of vitami n D) have one-third the risk of developing prostate cancer requiring p rostatectomy compared to men who are heterozygotes or homozygous for t he T allele (odds ratio(MH) = 0.34; 95% confidence interval, 0.16-0.76 ; P < 0.01), These results support recent ecological, population, and in vitro studies suggesting that vitamin D is an important determinant of prostate cancer risk and, if confirmed, suggest strategies for che moprevention of this common cancer.