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

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.

Association between ERCC1 and ERCC2 polymorphisms and breast cancer risk in a Chinese population

“…Many epidemiologic studies have investigated the impact of the ERCC1 rs3212986 polymorphism in the risk of several cancers including glioma, breast cancer, lung cancer, and colorectal cancer (Adel Fahmideh et al, 2014;Zhu et al, 2014;Hou et al, 2014). For example, Adel Fahmideh et al (2014) conducted a meta-analysis of 27 case-control studies and assessed the association between DNA repair gene polymorphisms and risk of glioma, and found that the ERCC1 rs3212986 polymorphism may significantly increase the risk of glioma.…”

“…For example, Adel Fahmideh et al (2014) conducted a meta-analysis of 27 case-control studies and assessed the association between DNA repair gene polymorphisms and risk of glioma, and found that the ERCC1 rs3212986 polymorphism may significantly increase the risk of glioma. Interestingly, Zhu et al (2014) conducted a meta-analysis of 16 case-control studies, which demonstrated that there was no association between the ERCC1 rs3212986 polymorphism and lung cancer. However, Hou et al (2014) conducted a 1:1 matched case-control study in a Chinese population, and found that the ERCC1 rs3212986 polymorphism was correlated with an increased risk of colorectal cancer.…”

Role of single nucleotide polymorphisms of DNA repair genes in susceptibility to pancreatic cancer in Chinese population

“…Hou et al (2014) conducted a study in a Chinese population, and reported that the ERCC1 rs3212986 polymorphism is associated with a risk of colorectal cancer. Zhu et al (2014) conducted a meta-analysis with 11 case-control studies, but they did not find any association between the ERCC1 rs3212986 polymorphism and development of lung cancer. Yuan et al (2014) also conducted a meta-analysis with seven studies, and reported that the ERCC1 rs3212986 polymorphism correlated with the risk of non-glioblastoma multiforme.…”

3018 Functional intronic ERCC1 polymorphism from RegulomeDB can predict survival in lung cancer after surgery

“…luc, luciferase. www.impactjournals.com/oncotarget in many types of cancer including NSCLC [6][7][8][9][10][11][12][13][14]. However, most of the studies have focused on only a few SNPs, such as ERCC1 rs11615T>C (N118N) and rs3212986C>A in 3′-UTR, and the results have not been consistent among studies.…”

“…The expression of ERCC1 by quantitative real-time polymerase chain reaction or immunohistochemistry has been correlated with the clinical outcomes of non-small cell lung cancer (NSCLC) [3][4][5]. Genetic polymorphism of ERCC1 has also been investigated for the association with the risk and clinical outcome of many types of cancer including NSCLC [6][7][8][9][10][11][12][13][14]. The most widely studied single nucleotide polymorphisms (SNPs) include rs11615T>C (N118N) which is the only SNP tested in the exon region of ERCC1, and rs3212986C>A in 3′-UTR of ERCC1 (Q504K for CD3EAP, antisense to ERCC1).…”