Association Studies of <i>ERCC1</i> Polymorphisms with Lung Cancer Susceptibility: A Systematic Review and Meta-Analysis

<div><p>Background</p><p>Excision repair cross-complimentary group 1 (ERCC1) is an essential component of the nucleotide excision repair system that is responsible for repairing damaged DNA. Functional genetic variations in the <i>ERCC1</i> gene may alter DNA repair capacity and modulate cancer risk. The putative roles of <i>ERCC1</i> gene polymorphisms in lung cancer susceptibility have been widely investigated. However, the results remain controversial.</p><p>Objectives</p><p>An updated meta-analysis was conducted to explore whether lung cancer risk could be attributed to the following <i>ERCC1</i> polymorphisms: rs11615 (T>C), rs3212986 (C>A), rs3212961 (A>C), rs3212948 (G>C), rs2298881 (C>A).</p><p>Methods</p><p>Several major databases (MEDLINE, EMBASE and Scopus) and the Chinese Biomedical database were searched for eligible studies. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to measure the strength of associations.</p><p>Results</p><p>Sixteen studies with 10,106 cases and 13,238 controls were included in this meta-analysis. Pooled ORs from 11 eligible studies (8,215 cases vs. 11,402 controls) suggested a significant association of <i>ERCC1</i> rs11615 with increased risk for lung cancer (homozygous: CC versus TT, OR = 1.24, 95% CI: 1.04–1.48, <i>P</i> = 0.02). However, such an association was disproportionately driven by a single study. Removal of that study led to null association. Moreover, initial analyses suggested that <i>ERCC1</i> rs11615 exerts a more profound effect on the susceptibility of non-smokers to lung cancer than that of smokers. Moreover, no statistically significant association was found between remaining <i>ERCC1</i> polymorphisms of interest and lung cancer risk, except for rs3212948 variation (heterozygous: CG vs.GG, OR = 0.78, 95% CI: 0.67–0.90, <i>P</i> = 0.001; dominant: CG/CC vs.GG, OR = 0.79, 95% CI: 0.69–0.91, <i>P = </i>0.001).</p><p>Conclusion</p><p>Overall, this meta-analysis suggests that <i>ERCC1</i> rs3212948 G>C, but not others, is a lung cancer risk-associated polymorphism. Carefully designed studies with large sample size involving different ethnicity, smoking status, and cancer types are needed to validate these findings.</p>