Vitamin D-related genes, serum vitamin D concentrations and prostate cancer risk

被引：130

作者：

Ahn, Jiyoung ^{[1
]}

Albanes, Demetrius ^{[1
]}

Berndt, Sonja I. ^{[1
]}

Peters, Ulrike ^{[2
,3
]}

Chatterjee, Nilanjan ^{[1
]}

Freedman, Neal D. ^{[1
]}

Abnet, Christian C. ^{[1
]}

Huang, Wen-Yi ^{[1
]}

Kibel, Adam S. ^{[4
]}

Crawford, E. David ^{[5
]}

Weinstein, Stephanie J. ^{[1
]}

Chanock, Stephen J. ^{[1
]}

Schatzkin, Arthur ^{[1
]}

Hayes, Richard B.

机构：

[1] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA

[2] Univ Washington, Canc Prevent Program, Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA

[3] Univ Washington, Dept Epidemiol, Sch Publ Hlth, Seattle, WA 98109 USA

[4] Washington Univ, Sch Med, Div Urol Surg, St Louis, MO 63110 USA

[5] Anschutz Canc Pavil Univ Colorado, Aurora, CO 80014 USA

来源：

CARCINOGENESIS | 2009年 / 30卷 / 05期

基金：

美国国家卫生研究院;

关键词：

D-RECEPTOR GENE; 1,25-DIHYDROXYVITAMIN D-3; MESSENGER-RNA; SUBSEQUENT DEVELOPMENT; SIGNALING PATHWAYS; UNITED-STATES; D METABOLITES; POLYMORPHISMS; 25-HYDROXYVITAMIN-D; ASSOCIATION;

D O I：

10.1093/carcin/bgp055

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：769 / 776

页数：8

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