title: Polymorphisms in the DNA repair genes XPC, XPD, and XPG and risk of cutaneous melanoma: a case-control analysis.
abstract: Sunlight causes DNA damage, including bulky lesions that are removed effectively by the nucleotide-excision repair (NER) pathway. There are at least eight core NER proteins participating in the pathway, and genetic variations in their genes may alter NER functions. We hypothesized that some NER variants are associated with risk of cutaneous melanoma. In a hospital-based case-control study of 602 non-Hispanic White patients with cutaneous melanoma and 603 age- and sex-matched cancer-free controls, we genotyped five common non-synonymous single-nucleotide polymorphisms identified to date and assessed their associations with risk of cutaneous melanoma. We found that a significantly increased risk of cutaneous melanoma was associated with XPD 751Lys/Gln [adjusted odds ratio (OR), 1.55 and 95% confidence interval (95% CI), 1.12-2.16] and XPD 751Gln/Gln (OR, 1.66; 95% CI, 1.03-2.68) genotypes compared with the XPD 751Lys/Lys genotype as well as XPD312Asp/Asn (OR, 1.54; 95% CI, 1.11-2.12) and XPD312Asn/Asn (OR, 1.75; 95% CI, 1.05-2.90) genotypes compared with the XPD 312Asp/Asp genotype. This increased risk was not observed in the other three XPC and XPG single-nucleotide polymorphisms. Moreover, the number of the observed XPD at-risk genotypes (i.e., 312Asn/Asn+Asn/Asp and 751Gln/Gln+Lys/Gln) was associated with cutaneous melanoma risk in a dose-response manner (OR, 1.47; 95% CI, 0.97-2.23 for one at-risk genotype; OR, 1.83; 95% CI, 1.29-2.61 for two at-risk genotypes; P(trend) < 0.001). However, we found no evidence of any interaction between XPD genotypes with XPC and XPG genotypes or the known risk factors. We concluded that genetic variants of the XPD gene might serve as biomarkers for susceptibility to cutaneous melanoma.
authors.affiliation: Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Unit 1365, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
authors.forename: Chunying
authors.initials: C
authors.lastname: Li
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Hu
authors.forename: Zhensheng
authors.initials: Z
authors.lastname: Liu
authors.forename: Li-E
authors.initials: LE
authors.lastname: Wang
authors.forename: Sara S
authors.initials: SS
authors.lastname: Strom
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Gershenwald
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Lee
authors.forename: Merrick I
authors.initials: MI
authors.lastname: Ross
authors.forename: Paul F
authors.initials: PF
authors.lastname: Mansfield
authors.forename: Janice N
authors.initials: JN
authors.lastname: Cormier
authors.forename: Victor G
authors.initials: VG
authors.lastname: Prieto
authors.forename: Madeleine
authors.initials: M
authors.lastname: Duvic
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Grimm
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Wei
mesh_terms: D016022:Case-Control Studies; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics; D004720:Endonucleases / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008545:Melanoma / Q000453:epidemiology / Q000235:genetics*; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012878:Skin Neoplasms / Q000453:epidemiology / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics; D000099250:DNA Excision Repair Protein ERCC-5
chemical_list: D004268:DNA-Binding Proteins; D004720:Endonucleases; D009687:Nuclear Proteins; D014157:Transcription Factors; D051759:Xeroderma Pigmentosum Group D Protein; D000099250:DNA Excision Repair Protein ERCC-5; C086984:XPC protein, human; C497292:ERCC2 protein, human