Genetic Variants in the Vitamin D Receptor Gene and Prostate Cancer Risk
- Vanessa M. Hayes1,
- Gianluca Severi2,
- Emma J.D. Padilla1,
- Sarah A. Eggleton1,
- Melissa C. Southey3,
- Robert L. Sutherland1,
- John L. Hopper4 and
- Graham G. Giles2
- 1Cancer Research Program, Garvan Institute of Medical Research, St. Vincent's Hospital, Darlinghurst, Sydney, New South Wales; 2Cancer Epidemiology Centre, The Cancer Council Victoria, Carlton; and 3Department of Pathology and 4Centre for Genetic Epidemiology, University of Melbourne, Parkville, Melbourne, Victoria, Australia
- Requests for reprints:
Vanessa M. Hayes, Cancer Research Program, Garvan Institute of Medical Research, St. Vincent's Hospital, 384 Victoria Street, Darlinghurst, New South Wales 2010, Australia. Phone: 61-2-9295-8345; Fax: 61-2-9295-8321. E-mail: v.hayes{at}garvan.org.au
Abstract
Vitamin D receptor (VDR), a member of the steroid/thyroid hormone nuclear receptor family, is bound by the steroid hormone 1,25-dihydroxyvitamin D3, which is thought to play a role in the etiology and progression of prostate cancer. Polymorphisms in the VDR gene have been associated with prostate cancer risk, although findings are inconclusive. The purpose of this study was to determine if VDR polymorphisms were associated with prostate cancer risk using a large, Australian population–based study of 812 cases and 713 controls frequency-matched by age. As the 3′ region polymorphisms are in strong linkage disequilibrium, for joint effects, we only evaluated the common g.60890G > A polymorphism with the unlinked g.27823C > T (5′ region) polymorphism. Allele frequencies were similar in cases and controls (g.27823C > T, 36% versus 36%; g.60890 G>A, 41% versus 43%). No genotypes were individually associated with prostate cancer risk (all P > 0.3). All nine possible genotype combinations were evident, and although the g.27823CT/g.60890GA combination was nominally more prevalent in controls (24%) than in cases (19%, P = 0.03), there was no difference in the combined genotype distribution between cases and controls (P = 0.2). The associations of risk with genotype were between 0.91 and 1.03, all with 95% confidence intervals within 0.81 to 1.15. In conclusion, VDR polymorphisms either alone or in combination do not seem to contribute appreciably to prostate cancer risk.
Footnotes
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Grant support: Supported by grants from the National Health and Medical Research Council of Australia, The Cancer Councils of New South Wales and Victoria, Tattersall's and the Whitten Foundation, the Australian Cancer Research Foundation, and the Armati Family Fellowship, Australia. The study was approved by the Ethics Review Committee of the Cancer Council of Victoria (HREC 9500).
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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- Accepted December 7, 2004.
- Received September 7, 2004.
- Revision received November 15, 2004.
