XRCC1 gene polymorphisms and lung cancer susceptibility: a meta-analysis of 44 case-control studies.
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.
Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, 100 Science Avenue, Zhengzhou 450001, China. lpdai@zzu.edu.cn
Liping
L
Dai
Fujiao
F
Duan
Peng
P
Wang
Chunhua
C
Song
Kaijuan
K
Wang
Jianying
J
Zhang
D016022:Case-Control Studies; D003062:Codon; D004268:DNA-Binding Proteins / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D000076105:X-ray Repair Cross Complementing Protein 1
D003062:Codon; D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human