Association of DNA repair gene XRCC1 and lung cancer susceptibility among nonsmoking Chinese women.
Nonsmokers who develop lung cancer provide a good model for investigating the effect of genetic polymorphisms. XRCC1 is one of the major DNA repair proteins involved in the base-excision repair pathway. XRCC1 gene variations may lead to lower DNA repair capacity and thus confer inherited predisposition to cancer risk. To address this question in more detail, we conducted a hospital-based case-control study consisting of 55 lung cancer cases and 74 cancer-free controls matched on age and ethnicity among nonsmoking Chinese women. We analyzed five coding single-nucleotide polymorphisms in the XRCC1 gene: Agr194Trp, Arg280His, Arg399Gln, Pro206Pro, and Gln632Gln. Polymerase chain reaction-restriction fragment length polymorphism was used for genotyping. Carriers of the variant T-allele of Arg194Trp had a lower lung cancer risk than carriers of CC genotypes [odds ratio (OR)=0.46, 95% confidence interval (CI)=0.22-0.96, P=0.04], and carriers of the variant G-allele of Pro206Pro were at almost fourfold (OR=3.93, 95%CI=1.47-10.52, P=0.004) higher risk of lung cancer than carriers of the AA genotype. Furthermore, we observed that individuals with haplotype 1(194(T)-206(A)-280(G)-399(G)-632(G)) had decreased risk of lung cancer (OR=0.51, 95%CI= 0.27-0.97, P=0.04) and subjects with haplotype 2 (194(C)-206(G)280(G)-399(G)- 632(A)) had almost a threefold increased risk of lung cancer (OR=3.01, 95%CI=1.01-8.92, P=0.04). These findings further suggest that the polymorphisms XRCC1 Arg194Trp and Pro206Pro or the haplotype encompassing the variant alleles may contribute to susceptibility of lung cancer in a Chinese population.
Yin
Jiaoyang
J
Key Laboratory of Environment and Population Health of University in Liaoning Province, Shenyang Medical College, Shenyang 110034, Liaoning Province, PR China. yinjyf@yahoo.com.cn
Vogel
Ulla
U
Ma
Yegang
Y
Qi
Rong
R
Wang
Huiwen
H
D000368:Aged; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002681:China; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D015810:Linkage Disequilibrium; D008175:Lung Neoplasms / Q000453:epidemiology / Q000235:genetics*; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012907:Smoking; D000076105:X-ray Repair Cross Complementing Protein 1
D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human