title: Polymorphisms in nucleotide excision repair genes and risk of multiple primary melanoma: the Genes Environment and Melanoma Study.
abstract: Polymorphisms in six genes involved in nucleotide excision repair of DNA were examined in a large population-based case-control study of melanoma. Genotyping was conducted for 2485 patients with a single primary melanoma (controls) and 1238 patients with second or higher order primary melanomas (cases). Patients were ascertained from nine geographic regions in Australia, Canada, Italy and the United States. Positive associations were observed for XPD 312 Asn/Asn versus Asp/Asp [odds ratio (OR) = 1.5, 95% confidence interval (CI) 1.2-1.9] and XPD 751 Gln/Gln versus Lys/Lys (OR = 1.4, 95% CI 1.1-1.7) genotypes and melanoma. The combined XPD Asn (A) 312 + Gln (C) 751 haplotype was significantly more frequent in cases (32%) compared with controls (29%) (P = 0.003) and risk of melanoma increased significantly with one and two copies of the haplotype (ORs 1.2, 95% CI 1.0-1.4, and 1.6, 95% CI 1.2-2.0, trend P = 0.002). No significant associations were observed for HR23B codon 249, XPG codon 1104, XPC codon 939, XPF codon 415, XPF nt 2063, ERCC6 codon 1213 or ERCC6 codon 1230. ORs for XPD and XPC genotypes were stronger for melanoma diagnosed at an early age, but tests for interaction were not statistically significant. The results provide further evidence for a role of XPD in the etiology of melanoma.
authors.affiliation: Department of Epidemiology, CB #7435, School of Public Health, University of North Carolina, Chapel Hill, NC 27599, USA. millikan@email.unc.edu
authors.forename: Robert C
authors.initials: RC
authors.lastname: Millikan
authors.forename: Amanda
authors.initials: A
authors.lastname: Hummer
authors.forename: Colin
authors.initials: C
authors.lastname: Begg
authors.forename: Jon
authors.initials: J
authors.lastname: Player
authors.forename: Allan René
authors.initials: AR
authors.lastname: de Cotret
authors.forename: Scott
authors.initials: S
authors.lastname: Winkel
authors.forename: Harvey
authors.initials: H
authors.lastname: Mohrenweiser
authors.forename: Nancy
authors.initials: N
authors.lastname: Thomas
authors.forename: Bruce
authors.initials: B
authors.lastname: Armstrong
authors.forename: Anne
authors.initials: A
authors.lastname: Kricker
authors.forename: Loraine D
authors.initials: LD
authors.lastname: Marrett
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Gruber
authors.forename: Hoda Anton
authors.initials: HA
authors.lastname: Culver
authors.forename: Roberto
authors.initials: R
authors.lastname: Zanetti
authors.forename: Richard P
authors.initials: RP
authors.lastname: Gallagher
authors.forename: Terence
authors.initials: T
authors.lastname: Dwyer
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Rebbeck
authors.forename: Klaus
authors.initials: K
authors.lastname: Busam
authors.forename: Lynn
authors.initials: L
authors.lastname: From
authors.forename: Urvi
authors.initials: U
authors.lastname: Mujumdar
authors.forename: Marianne
authors.initials: M
authors.lastname: Berwick
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002648:Child; D004260:DNA Repair; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008545:Melanoma / Q000209:etiology / Q000235:genetics*; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012878:Skin Neoplasms / Q000209:etiology / Q000235:genetics*; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics*
chemical_list: D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human