title: A community-based study of nucleotide excision repair polymorphisms in relation to the risk of non-melanoma skin cancer.
abstract: Nucleotide excision repair (NER) is responsible for protecting DNA in skin cells against UVR-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 the basis of 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 (BCC) of the skin (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 that functional variants in ERCC6 may be associated with an increased risk of NMSC that may be specific to BCC.
authors.affiliation: Department of Medicine, Division of Epidemiology and Biostatistics, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
authors.forename: Lee
authors.initials: L
authors.lastname: Wheless
authors.forename: Emily
authors.initials: E
authors.lastname: Kistner-Griffin
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Jorgensen
authors.forename: Ingo
authors.initials: I
authors.lastname: Ruczinski
authors.forename: Yvette
authors.initials: Y
authors.lastname: Berthier-Schaad
authors.forename: Bailey
authors.initials: B
authors.lastname: Kessing
authors.forename: Judith
authors.initials: J
authors.lastname: Hoffman-Bolton
authors.forename: Lesley
authors.initials: L
authors.lastname: Francis
authors.forename: Yin Yao
authors.initials: YY
authors.lastname: Shugart
authors.forename: Paul T
authors.initials: PT
authors.lastname: Strickland
authors.forename: W H Linda
authors.initials: WH
authors.lastname: Kao
authors.forename: Rhoda M
authors.initials: RM
authors.lastname: Alani
authors.forename: Michael W
authors.initials: MW
authors.lastname: Smith
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Alberg
mesh_terms: D000328:Adult; D000368:Aged; D002280:Basal Cell Carcinoma / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D016022:Case-Control Studies; D016001:Confidence Intervals; D004265:DNA Helicases / Q000235:genetics*; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D000075223:Poly-ADP-Ribose Binding Proteins; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012878:Skin Neoplasms / Q000235:genetics*
chemical_list: D000075223:Poly-ADP-Ribose Binding Proteins; D004265:DNA Helicases; C078673:ERCC6 protein, human; D045643:DNA Repair Enzymes