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.