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A community-based study of nucleotide excision repair polymorphisms in relation to risk of non-melanoma skin cancer

Lee Wheless,E. Kistner‐Griffin,T. Jorgensen,I. Ruczinski,Y. Berthier-Schaad,B. Kessing,J. Hoffman-Bolton,Lesley Francis,Y. Shugart,P. Strickland,W. H. L. Kao,R. Alani,Michael W. Smith,A. Alberg,A. Alberg

Published 2012 in Journal of Investigative Dermatology

ABSTRACT

Nucleotide excision repair (NER) is responsible for protecting DNA in skin cells against ultraviolet radiation-induced damage. Using a candidate pathway approach, a matched case-control study nested within a prospective, community-based cohort was carried out to test the hypothesis that single nucleotide polymorphisms (SNPs) in NER genes are associated with susceptibility to non-melanoma skin cancer (NMSC). Histologically-confirmed cases of NMSC (n=900) were matched to controls (n=900) on age, gender, and skin type. Associations were measured between NMSC and 221 SNPs in 26 NER genes. Using the additive model, two tightly linked functional SNPs in ERCC6 were significantly associated with increased risk of NMSC: rs2228527 (odds ratio (OR) 1.57, 95% confidence interval (CI) 1.20 – 2.05), and rs2228529 (OR 1.57, 95% CI 1.20 – 2.05). These associations were confined to basal cell carcinoma of the skin (BCC) (rs2228529, OR 1.78, 95% CI 1.30 – 2.44; rs2228527 OR 1.78, 95% CI 1.31 – 2.43). These hypothesis-generating findings suggest functional variants in ERCC6 may be associated with an increased risk of NMSC that may be specific to BCC.

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