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首页> 外文期刊>PLoS One >Association Studies of ERCC1 Polymorphisms with Lung Cancer Susceptibility: A Systematic Review and Meta-Analysis
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Association Studies of ERCC1 Polymorphisms with Lung Cancer Susceptibility: A Systematic Review and Meta-Analysis

机译：ERCC1基因多态性与肺癌易感性的关联研究：系统评价和Meta分析。

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Background 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 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. Objectives An updated meta-analysis was conducted to explore whether lung cancer risk could be attributed to the following ERCC1 polymorphisms: rs11615 (TC), rs3212986 (CA), rs3212961 (AC), rs3212948 (GC), rs2298881 (CA). Methods 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. Results 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 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). Conclusion Overall, this meta-analysis suggests that ERCC1 rs3212948 GC, 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.
机译：背景技术切除修复交叉互补组1（ERCC1）是核苷酸切除修复系统的重要组成部分，负责修复受损的DNA。 ERCC1基因的功能遗传变异可能会改变DNA修复能力并调节癌症风险。 ERCC1基因多态性在肺癌易感性中的假定作用已得到广泛研究。但是，结果仍然存在争议。目的进行了最新的荟萃分析，以探讨肺癌风险是否可归因于以下ERCC1多态性：rs11615（T> C），rs3212986（C> A），rs3212961（A> C），rs3212948（G> C） ，rs2298881（C> A）。方法检索几个主要数据库（MEDLINE，EMBASE和Scopus）和中国生物医学数据库以进行符合条件的研究。使用具有95％置信区间（CI）的原始比值比（OR）来衡量关联强度。结果该荟萃分析包括16项研究，共10106例患者和13238例对照者。来自11项合格研究的汇总OR（8,215例患者与11,402例对照）表明ERCC1 rs11615与肺癌风险增加显着相关（纯合子：CC与TT，OR = 1.24，95％CI：1.04-1.48，P = 0.02） 。但是，这种关联是由一项单独研究驱动的。删除该研究导致无效关联。此外，初步分析表明，ERCC1 rs11615对不吸烟者的肺癌敏感性比吸烟者更深远。此外，除rs3212948变异外，其他感兴趣的ERCC1多态性与肺癌风险之间均无统计学意义的关联（杂合子：CG vs.GG，OR = 0.78，95％CI：0.67–0.90，P = 0.001;显性：CG / CC对GG，OR = 0.79，95％CI：0.69-0.91，P = 0.001）。结论总体而言，这项荟萃分析表明ERCC1 rs3212948 G> C是肺癌风险相关的多态性，而非其他。需要仔细设计的，涉及不同种族，吸烟状况和癌症类型的大样本研究才能验证这些发现。

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