title: XPA polymorphism associated with reduced lung cancer risk and a modulating effect on nucleotide excision repair capacity.
abstract: XPA, a DNA binding protein in the nucleotide excision repair (NER) pathway, modulates damage recognition. Recently, a common single-nucleotide polymorphism (A --> G) of unknown function was identified in the 5' non-coding region of the XPA gene. Because a deficiency in NER is associated with an increased risk of lung cancer, we evaluated the role of this polymorphism in 695 lung cancer case patients and 695 age-, sex-, ethnicity- and smoking-matched control subjects. We also studied the effect of this polymorphism on NER capacity in a subset sample for whom the host cell reactivation data were available. The presence of one or two copies of the G allele was associated with a reduced lung cancer risk for Caucasians [adjusted odds ratio (ORadj) = 0.69 [95% confidence interval (CI) = 0.53-0.90]], Mexican-Americans [ORadj = 0.32 (95% CI = 0.12-0.83)] and African-Americans [ORadj = 0.45 (95% CI = 0.16-1.22)]. In Caucasians, ever smokers with one or more copies of the G allele were observed to have a significantly reduced risk of lung cancer. Control subjects with one or two copies of the G allele demonstrated more efficient DRC than did those with the homozygous A allele. Our data suggest that the XPA 5' non-coding region polymorphism modulates NER capacity and is associated with decreased lung cancer risk, especially in the presence of exposure to tobacco carcinogens.
authors.affiliation: Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA. xwu@mail.mdanderson.org
authors.forename: Xifeng
authors.initials: X
authors.lastname: Wu
authors.forename: Hua
authors.initials: H
authors.lastname: Zhao
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Wei
authors.forename: Christopher I
authors.initials: CI
authors.lastname: Amos
authors.forename: Kerang
authors.initials: K
authors.lastname: Zhang
authors.forename: Zhaozheng
authors.initials: Z
authors.lastname: Guo
authors.forename: Yawei
authors.initials: Y
authors.lastname: Qiao
authors.forename: Waun K
authors.initials: WK
authors.lastname: Hong
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Spitz
mesh_terms: D001483:Base Sequence; D016022:Case-Control Studies; D017931:DNA Primers; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics*; D005006:Ethnicity; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000208:ethnology / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012907:Smoking; D051760:Xeroderma Pigmentosum Group A Protein
chemical_list: D017931:DNA Primers; D004268:DNA-Binding Proteins; C497314:XPA protein, human; D051760:Xeroderma Pigmentosum Group A Protein