Vitamin D-related genes, serum vitamin D concentrations and prostate cancer risk.
We systematically investigated the association of 48 SNPS in four vitamin D metabolizing genes [CYP27A1, GC, CYP27B1 and CYP24A1] with serum 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)(2)D] levels and the association of these SNPS and an additional 164 SNPS in eight downstream mediators of vitamin D signaling [VDR, RXRA, RXRB, PPAR, NCOA1, NCOA2, NCOA3 and SMAD3] with prostate cancer risk in the 749 incident prostate cancer cases and 781 controls of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. 25(OH)D (all cases and controls) and 1,25(OH)(2)D (a subset of 150 controls) levels were measured by radioimmunoassay and SNP data were genotyped as part of a genome-wide scan. Among investigated SNPS, only four tag SNPS in GC, the major serum 25(OH)D carrier, were associated with 25(OH)D levels; no SNPS were associated with 1,25(OH)(2)D levels. None of the 212 SNPS examined were associated with cancer risk overall. Among men in the lowest tertile of serum 25(OH)D (<48.9 nmol/l), however, prostate cancer risk was related to tag SNPS in or near the 3' untranslated region (UTR) of VDR, with the strongest association for rs11574143 [odds ratio (95% confidence interval) for risk allele carriers versus wild-type: 2.49 (1.51-4.11), P = 0.0007]; the genotype associations were null among men in tertile 2 and tertile 3. Results from the most comprehensive evaluation of serum vitamin D and its related genes to date suggest that tag SNPS in the 3' UTR of VDR may be associated with risk of prostate cancer in men with low vitamin D status.
Ahn
Jiyoung
J
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, 6120 Executive Boulevard, Bethesda, MD 20892, USA. ahnj@mail.nih.gov
Albanes
Demetrius
D
Berndt
Sonja I
SI
Peters
Ulrike
U
Chatterjee
Nilanjan
N
Freedman
Neal D
ND
Abnet
Christian C
CC
Huang
Wen-Yi
WY
Kibel
Adam S
AS
Crawford
E David
ED
Weinstein
Stephanie J
SJ
Chanock
Stephen J
SJ
Schatzkin
Arthur
A
Hayes
Richard B
RB
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics*; D002112:Calcifediol / Q000097:blood*; D002117:Calcitriol / Q000097:blood*; D053493:Cholestanetriol 26-Monooxygenase / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000097:blood / Q000201:enzymology / Q000453:epidemiology* / Q000235:genetics; D018570:Risk Assessment; D012307:Risk Factors; D013250:Steroid Hydroxylases / Q000235:genetics*; D014481:United States / Q000453:epidemiology; D014807:Vitamin D / Q000097:blood*; D065668:Vitamin D3 24-Hydroxylase
D014807:Vitamin D; D013250:Steroid Hydroxylases; C506831:CYP27A1 protein, human; D053493:Cholestanetriol 26-Monooxygenase; C585549:CYP24A1 protein, human; D065668:Vitamin D3 24-Hydroxylase; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D002117:Calcitriol; D002112:Calcifediol