XPA polymorphism associated with reduced lung cancer risk and a modulating effect on nucleotide excision repair capacity.
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.
Wu
Xifeng
X
Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA. xwu@mail.mdanderson.org
Zhao
Hua
H
Wei
Qingyi
Q
Amos
Christopher I
CI
Zhang
Kerang
K
Guo
Zhaozheng
Z
Qiao
Yawei
Y
Hong
Waun K
WK
Spitz
Margaret R
MR
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
D017931:DNA Primers; D004268:DNA-Binding Proteins; C497314:XPA protein, human; D051760:Xeroderma Pigmentosum Group A Protein