Carcinogenesis Advance Access published online on March 2, 2006
Carcinogenesis, doi:10.1093/carcin/bgi376
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1 Department of Environmental Health, Harvard School of Public Health, Boston, MA; Department of Environmental Health, Harvard School of Public Health, Boston, MA
* To whom correspondence should be addressed. Nucleotide excision repair (NER) is instrumental in removing DNA lesions caused by ultraviolet (UV) radiation, the dominant risk factor for keratinocyte carcinomas, including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). We evaluated whether BCC or SCC risk was influenced by the A23G single nucleotide polymorphism (SNP) in Xeroderma pigmentosum group A (XPA), which codes for an essential protein in NER. We also investigated whether haplotypes of XPA, determined by seven haplotype-tagging SNPs, better define susceptibility to keratinocyte carcinomas. Incident cases of BCC and SCC from New Hampshire were identified through dermatologists and pathology laboratories. Population-based controls were frequency-matched to cases by gender and age. 886 cases of BCC and 682 cases of SCC were compared to 796 controls. Models controlled for age, gender, pigmentation factors, and severe sunburns and were restricted to Caucasians. Using GG as the reference, the A allele was less frequent among cases of BCC (ORAG = 0.82, 95% CI (0.66, 1.01); ORAA = 0.74, 95% CI (0.53, 1.03); trend test p = 0.03) and SCC (ORAG = 0.85, 95% CI (0.67, 1.07); ORAA = 0.74, 95% CI (0.52, 1.05); trend test p = 0.05) than controls. Risk from
Received December 19, 2005
Revised February 8, 2006
Accepted February 14, 2006
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
XPA, haplotypes, and risk of basal and squamous cell carcinoma
Katie L. Miller 1 *,
Margaret R. Karagas 2,
Peter Kraft 3,
David J. Hunter 3,
Paul J. Catalano 4,
Steven H. Byler 5,
and
Heather H. Nelson 6
2 Section of Biostatistics and Epidemiology, Department of Community and Family Medicine, and the Norris Cotton Cancer Center, Dartmouth Medical School, Lebanon, NH
3 Department of Environmental Health, Harvard School of Public Health, Boston, MA; Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA
4 Department of Biostatistics, Harvard School of Public Health, Boston, MA; Department of Biostatistics and Computational Biology, Dana Farber Cancer Institute, Boston, MA
5 Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, MA
6 Department of Environmental Health, Harvard School of Public Health, Boston, MA
Katie L. Miller, E-mail: kmiller{at}hsph.harvard.edu
Abstract 
3 severe sunburns was elevated for those with the GG genotype only, and this interaction was nearly significant for BCC (p = 0.07). XPA genotype also modified a relationship between SCC and the amount of pigmentation (p = 0.02). Using a haplotype analysis identifying seven common XPA haplotypes indicated that the A23G polymorphism alone captured the differences in susceptibility to keratinocyte carcinomas. The common G allele of the A23G polymorphism was associated with an increased risk of BCC and SCC and this polymorphism appeared to be the determining polymorphism in XPA that alters cancer susceptibility.
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