Vitamin D receptor (VDR) gene polymorphisms and haplotypes, interactions with plasma 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D, and prostate cancer risk.
BACKGROUND
The vitamin D receptor (VDR) is required for actions of vitamin D. The binding of 1,25-dihydroxyvitamin D to the VDR on prostatic epithelial cells prompts the regulation of cancer-related genes.


METHODS
We conducted a nested case-control study in the Health Professionals Follow-up Study to investigate the role of the VDR Cdx2, Fok1, and Bsm1 gene polymorphisms and associated haplotypes and their interaction with plasma vitamin D metabolites in relation to prostate cancer (PC) risk.


RESULTS
No association was found between these SNPs or their associated haplotypes and all PC subtypes except that haplotype 2 (A-f-b) with Cdx2 A, Fok1 f, and Bsm1 b alleles and haplotype 3 (A-F-B) with Cdx2 A, Fok1 F and Bsm1 B alleles compared to the most common haplotype (A-F-b), were associated with reduced risk of aggressive PC (high stage or Gleason sum > or =7; P = 0.02), both with two alleles suspected of being low risk. Carriers of the variant Cdx2 A allele who were deficient in plasma 25-hydroxyvitamin D (< or =15 ng/ml) compared to non-carriers with normal 25-hydroxyvitamin D, had a lower risk of total and poorly differentiated PCs (Gleason sum > or =7) (P for interaction = 0.02 and 0.04, respectively). Plasma 1,25-dihydroxyvitamin D deficiency (< or =26 pg/ml) was associated with a threefold risk of poorly differentiated PC (P for interaction = 0.01) when comparing carriers of the Cdx2 A allele to non-carriers with normal 1,25-dihydroxyvitamin D.


CONCLUSIONS
In this population of men, none of the VDR polymorphisms studied was associated with susceptibility to PC.
Mikhak
Bahar
B
Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA.
Hunter
David J
DJ
Spiegelman
Donna
D
Platz
Elizabeth A
EA
Hollis
Bruce W
BW
Giovannucci
Edward
E
D000071616:CDX2 Transcription Factor; D002112:Calcifediol / Q000097:blood / Q000378:metabolism*; D002117:Calcitriol / Q000097:blood / Q000378:metabolism*; D016022:Case-Control Studies; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D011471:Prostatic Neoplasms / Q000453:epidemiology*; D018167:Receptors, Calcitriol / Q000235:genetics* / Q000378:metabolism; D018570:Risk Assessment; D014808:Vitamin D Deficiency / Q000235:genetics
D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D018398:Homeodomain Proteins; D018167:Receptors, Calcitriol; D002117:Calcitriol; D002112:Calcifediol