Role Of ERCC2/XPD Polymorphisms And Interaction With Tobacco Smoking In Lung Cancer Susceptibility: A Systemic Review And Meta-analysis

Objective: Given the present studies, the association of the two ERCC polymorphisms, Asp312Asn and Lys751Gln, with lung cancer risk remains controversial and inconclusive. To better evaluate the potential role of these two ERCC2 polymorphisms and their interaction with tobacco smoking in lung cancer susceptibility presented in diverse populations, we have conducted this systemic review and meta-analysis.Methods:With proposed inclusion criteria, the literatures eligible from Pubmed, Medline, Embase databases and the Google Scholar were enrolled in the meta-analysis. By the aid of Rev-Man 5.0 and STATA 10.0 software, heterogeneity among combined studies was assessed, the pooled OR and 95%CI were calculated, and the sensitivity analysis and the publication bias were evaluated. What's more, to explore the possible heterogeneity, additional subgroup analyses were performed based on ethnicity and smoking status if relevant data were available.Results:This meta-analysis based on 26 studies from 24 publications included analyses in relation to Asp312Asn (7121 cases,8962 controls) and Lys751Gln (8396 cases,10510 controls) polymorphisms. Overall, significantly elevated lung cancer risk was associated with ERCC2 Asp312Asn (homozygous model:OR=1.20[1.05,1.36], P=0.006; recessive model: OR=1.20[1.06,1.35], P=0.004) and Lys751Gln (homozygous model: OR=1.31[1.17,1.46], P<0.00001; heterozygous model:OR=1.11[1.04,1.19], P=0.003; recessive model:OR=1.23[1.11,1.37], P<0.0001; dominant model: OR=1.15[1.08,1.23], P<0.0001). In ethnic subgroup analyses, significantly increased risk was associated with ERCC2 Asp312Asn for both Caucasians and Asians, and Lys751Gln for both Caucasians and Latino-Americans. When stratified by smoking status, significantly elevated risk of both polymorphisms for never-smokers was detected (dominant model:OR=1.46[1.09,1.95] and 1.57[1.19,2.08], P=0.01 and 0.002, respectively).Conclusions:The two well-characterized polymorphisms of ERCC2, Asp312Asn and Lys751Gln, may contribute to lung cancer susceptibility serving as low-penetrance risk factors.