Abstract
BackgroundExcision 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 ERCC1 gene may alter DNA repair capacity and modulate cancer risk. The putative roles of ERCC1 gene polymorphisms in lung cancer susceptibility have been widely investigated. However, the results remain controversial.ObjectivesAn updated meta-analysis was conducted to explore whether lung cancer risk could be attributed to the following ERCC1 polymorphisms: rs11615 (T>C), rs3212986 (C>A), rs3212961 (A>C), rs3212948 (G>C), rs2298881 (C>A).MethodsSeveral 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.ResultsSixteen 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 ERCC1 rs11615 with increased risk for lung cancer (homozygous: CC versus TT, OR = 1.24, 95% CI: 1.04–1.48, P = 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 ERCC1 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 ERCC1 polymorphisms of interest and lung cancer risk, except for rs3212948 variation (heterozygous: CG vs.GG, OR = 0.78, 95% CI: 0.67–0.90, P = 0.001; dominant: CG/CC vs.GG, OR = 0.79, 95% CI: 0.69–0.91, P = 0.001).ConclusionOverall, this meta-analysis suggests that ERCC1 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.
Highlights
It has become clear that the susceptibility to disease varies from one individual to another
Pooled odds ratios (ORs) from 11 eligible studies (8,215 cases vs. 11,402 controls) suggested a significant association of Excision repair cross-complimentary group 1 (ERCC1) rs11615 with increased risk for lung cancer
No statistically significant association was found between remaining ERCC1 polymorphisms of interest and lung cancer risk, except for rs3212948 variation. Overall, this meta-analysis suggests that ERCC1 rs3212948 G.C, but not others, is a lung cancer risk-associated polymorphism
Summary
It has become clear that the susceptibility to disease varies from one individual to another. Due to lack of non-synonymous single nucleotide polymorphism (SNP) in the coding region of the ERCC1 gene, most studies have focused on the rs3212986 (39UTR C8092A) and synonymous rs11615 (exon 4 T19007C) polymorphisms, which are believed to influence transcript stability and mRNA levels [4,5], respectively Numerous studies on such topics have been conducted over the past decades, but the results remain controversial. More case-control studies regarding these topics have emerged Apart from those two common ERCC1 variants, associations of three other ERCC1 polymorphisms (rs3212961 (17677A.C), rs3212948 G.C, and rs2298881 C.A) with lung cancer risk have gained increasing attentions.
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