Abstract
X-ray repair cross-complementing group 1 gene (XRCC1) has been implicated in risk for lung cancer. However, the results from different studies remain controversial. In this meta-analysis, we have assessed 44 published case–control studies regarding associations of lung cancer risk with three common polymorphisms, codon 194, codon 280 and codon 399, and −77 T > C in the promoter region of XRCC1. The results in total population showed that the risk for lung cancer was increased among the variant homozygote Trp/Trp of codon 194 polymorphism, compared with the wild type Arg/Arg (OR: 1.19; 95 % CI 1.01–1.39), and the variant genotype CC of −77 T > C polymorphism showed a significantly increased risk of developing lung cancer, compared to wild-type genotype TT (OR: 1.91; 95 % CI 1.24–2.94). However, no associations were found between lung cancer risk and codon 280, codon 399. In the subgroup analyses by ethnicity, the OR for the variant homozygote Trp/Trp of codon 194 was 1.21(95 % CI 1.02–1.43) for Asian. When stratified by source of control, we found a protective effect of codon 194 Arg/Trp genotype (OR: 0.87; 95 % CI 0.77–0.98) and risk effect of codon 399 combined Arg/Gln + Gln/Gln variant genotype (OR: 1.09; 95 % CI 1.01–1.18) for lung cancer on the basis of hospital control. Subgroup analyses by histological types of lung cancer indicated that the heterozygote Arg/Trp in codon 194 could decrease and the combined variant genotype Arg/Gln + Gln/Gln in codon 399 could increase the risk of non-small cell lung cancer (OR: 0.69; 95 % CI 0.57–0.85 and OR: 1.14; 95 % CI 1.04–1.24). In conclusion, this meta-analysis has demonstrated that codon 194, codon 399 and −77 T > C polymorphisms of XRCC1 gene might have contributed to individual susceptibility to lung cancer. To further evaluate effect of XRCC1 polymorphisms, gene–gene interaction and gene-environment interaction on lung cancer risk, a single large sample size study with thousands of subjects is required to get conclusive results.
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This research was supported by People’s Republic of China (National Natural Science Foundation of China, No. 30872181, 81072360).
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Dai, L., Duan, F., Wang, P. et al. XRCC1 gene polymorphisms and lung cancer susceptibility: a meta-analysis of 44 case–control studies. Mol Biol Rep 39, 9535–9547 (2012). https://doi.org/10.1007/s11033-012-1818-2
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DOI: https://doi.org/10.1007/s11033-012-1818-2