Genetic Variation in XPD, Sun Exposure, and Risk of Skin Cancer
- 1Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School; 2Department of Epidemiology, 3Department of Biostatistics, 4Harvard Center for Cancer Prevention, and 5Program in Molecular and Genetic Epidemiology, Harvard School of Public Health, Boston, Massachusetts and 6Department of Statistics, Harvard University, Cambridge, Massachusetts
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Jiali Han, Channing Laboratory, Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115. Phone: 617-525-2098; Fax: 617-525-2008. E-mail: jiali.han{at}channing.harvard.edu
Abstract
The XPD gene is involved in the nucleotide excision repair pathway removing DNA photoproducts induced by UV radiation. Genetic variation in XPD may exert a subtle effect on DNA repair capacity. We assessed the associations between two common nonsynonymous polymorphisms (Asp312Asn and Lys751Gln) with skin cancer risk in a nested case-control study within the Nurses' Health Study (219 melanoma, 286 squamous cell carcinoma, 300 basal cell carcinoma, and 874 controls) along with exploratory analysis on the haplotype structure of the XPD gene. There were inverse associations between the Lys751Gln and Asp312Asn polymorphisms and the risks of melanoma and squamous cell carcinoma. No association was observed between these two polymorphisms and basal cell carcinoma risk. We also observed that the association of the 751Gln allele with melanoma risk was modified by lifetime severe sunburns, cumulative sun exposure with a bathing suit, and constitutional susceptibility score (P for interaction = 0.03, 0.04, and 0.02 respectively). Similar interactions were also observed for the Asp312Asn. Our data suggest these two XPD nonsynonymous polymorphisms may be associated with skin cancer risk, especially for melanoma.
Footnotes
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↵7 Han et al. Risk factors of skin cancer: a nested case-control study within the Nurses' Health Study, in preparation.
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Grant support: NIH grants CA97746 and CA87969 and Harvard Specialized Programs of Research Excellence in Skin Cancer.
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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 April 7, 2005.
- Received November 16, 2004.
- Revision received March 22, 2005.
