XPA, haplotypes, and risk of basal and squamous cell carcinoma

Carcinogenesis
Katie L MillerHeather H Nelson

Abstract

Nucleotide excision repair (NER) is instrumental in removing DNA lesions caused by ultraviolet (UV) radiation, the dominant risk factor for keratinocyte carcinoma, 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 carcinoma. 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. Cases of BCC (886) and of SCC (682) were compared with controls (796). 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 (OR(AG) = 0.82, 95% CI (0.66, 1.01); OR(AA)= 0.74, 95% CI (0.53, 1.03); trend test P = 0.03) and SCC (OR(AG) = 0.85, 95% CI (0.67, 1.07); OR(AA) = 0.74, 95% CI (0.52, 1.05); trend test P = 0.05) than controls. Risk from > or ...Continue Reading

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