Journal
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
Volume 16, Issue 10, Pages 1990-1999Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1055-9965.EPI-07-0487
Keywords
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Funding
- Intramural NIH HHS Funding Source: Medline
- NCI NIH HHS [P50 CA97186, K22 CA118421, CA94880, R01 CA56678] Funding Source: Medline
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Genetic variation in vitamin D-related genes has not been investigated comprehensively and findings are equivocal. We studied the association between polymorphisms across the entire vitamin D receptor (VDR) gene and genes encoding for vitamin D activating enzyme 1-alpha-hydroxylase (CYP27B1) and deactivating enzyme 24-hyroxylase (CYP24A1) and prostate cancer risk among middle-aged men using a population-based case-control study design. DNA samples and survey data were obtained from incident cases (n = 630), 40 to 64 years old, identified through the Seattle-Puget Sound Surveillance, Epidemiology, and End Results cancer registry from 1993 to 1996 and from random controls (n = 565) of similar age without a history of prostate cancer. We selected and genotyped tag single-nucleotide polymorphisms to predict common variants across VDR (n = 22), CYP27B1 (n = 2), and CYP24A1 (n = 14). Haplotypes of VDR and CYP24A1 were not associated with prostate cancer risk. In the genotype analysis, homozygotes at two VDR loci (rs2107301 and rs2238135) were associated with a 2- to 2.5-fold higher risk of prostate cancer compared with the homozygote common allele [odds ratio, 2.47 (95% confidence interval, 1.52-4.00; P = 0.002) and 1.95 (95% confidence interval, 1.17-3.26; P = 0.007), respectively, P value corrected for multiple comparisons for VDR = 0.002]. We found no evidence that the two associated VDR single-nucleotide polymorphisms were modified by age at diagnosis, prostate cancer aggressiveness, first-degree family history of prostate cancer, or vitamin D intake. Genotypes of CYP27B1 and CYP24A1 were not associated with prostate cancer risk. Our findings suggest that polymorphisms, in the VDR gene may be associated with prostate cancer risk and, therefore, that the vitamin D pathway might have an etiologic role in the development of prostate cancer.
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