Vitamin D receptor polymorphisms, circulating vitamin D metabolites, and risk of prostate cancer in United States physicians.
Prostatic cells express vitamin D receptor (VDR), which mediates the functions of 1,25-dihydroxyvitamin D. Two recent case-control studies suggested strong inverse associations between two VDR polymorphisms, TaqI and poly(A), and risk of prostate cancer. These two and a third polymorphism, BsmI, are closely linked. In a case-control study nested in the Physicians' Health Study, a randomized double-blind trial of aspirin and beta-carotene among 22,071 United States male physicians, we examined the associations between BsmI and TaqI and prostate cancer risk and whether the associations varied according to age and vitamin D metabolite levels among 372 incident cases and 591 controls. Among controls, the BB genotype was significantly associated with higher 1,25-dihydroxyvitamin D (median = 36.2 pg/ml for the BB versus 33.9 pg/ml for the bb genotype; P = 0.02), suggesting an association of the VDR polymorphisms with VDR function. Overall, we observed no significant associations of these VDR polymorphisms with prostate cancer risk: relative risk (RR) = 0.86 [95% confidence interval (CI) = 0.57-1.29] for the BB genotype and RR = 0.92 (95% CI = 0.69-1.22) for the Bb genotype, compared with the bb genotype (results were similar for the TaqI polymorphism). Stratification by age (< or = 61 and > 61 years) and tumor aggressiveness showed no significant associations. However, in an analysis restricted to men with plasma 25-hydroxyvitamin D below the median, we observed a 57% reduction (RR = 0.43, 95% CI = 0.19-0.98) in risk for those with the BB versus the bb genotype; the risk reduction was particularly marked among older men (RR = 0.18, 95% CI = 0.05-0.68). We did not observe this inverse association among men with 25-hydroxyvitamin D levels above the median, nor did we observe it among younger men.
Ma
J
J
Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Stampfer
M J
MJ
Gann
P H
PH
Hough
H L
HL
Giovannucci
E
E
Kelsey
K T
KT
Hennekens
C H
CH
Hunter
D J
DJ
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D015252:Deoxyribonucleases, Type II Site-Specific / Q000235:genetics; D004311:Double-Blind Method; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010820:Physicians / Q000706:statistics & numerical data; D011110:Polymorphism, Genetic / Q000235:genetics*; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D018167:Receptors, Calcitriol / Q000235:genetics*; D012307:Risk Factors; D014481:United States; D014807:Vitamin D / Q000097:blood / Q000378:metabolism*
D018167:Receptors, Calcitriol; D014807:Vitamin D; C053864:endodeoxyribonuclease BsmI; D015252:Deoxyribonucleases, Type II Site-Specific; C027046:TCGA-specific type II deoxyribonucleases