At present, several studies have assessed the association between ERCC6 rs2228526 polymorphism and the risk of cancer. However, the association remained controversial. To provide a more accurate estimate on the association, we performed a meta-analysis search of case-control studies on the associations of ERCC6 rs2228526 with susceptibility to cancer. PubMed, Embase, Google Scholar, Wanfang database, and Chinese National Knowledge Infrastructure databases (CNKI) China Biological Medicine Database (CBM) (up to August 2021) were searched to identify eligible studies. The effect summary odds ratio (OR) with 95% confidence intervals (CI) was applied to assay the association between the ERCC6 rs2228526 polymorphism and the risk of cancer. 14 studies included 15 case-control studies which contained 5,856 cases, and 6,387 controls were finally determined as qualified studies for this meta-analysis. Overall, based on current studies, we found significant association between ERCC6 rs2228526 polymorphism and the risk of cancer in four genetic models [the allele model G vs. A: 1.10, (1.03-1.17); the homozygous model GG vs. AA: 1.27, (1.07-1.51); heterozygote model GA vs. AA: 1.08, (1.00-1.17); the dominant model GG + GA vs. AA: 1.10, (1.02-1.19); the recessive model GG vs. GA + AA: 1.22, (1.03-1.45)]. In the stratified analysis based on ethnicity, we found significant association in two genetic models in Asians. Further, significant genetic cancer susceptibility was found under PB control on subgroup analysis by source of control. In addition, no significant association was found in lung cancer and bladder cancer patients in subgroup analyses based on cancer style. This study suggests that the ERCC6 rs2228526 polymorphism may be associated with increased cancer risk.
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