Association between Polymorphisms of X-Ray Repair Cross Complementing Group 1 Gene and Pancreatic Cancer Risk: a Systematic Review with Meta-Analysis

X射线修复交叉互补组1基因多态性与胰腺癌风险的关联:系统评价和荟萃分析

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Abstract

Emerging evidences have shown that common genetic polymorphisms in X-ray repair cross complementing group 1 (XRCC1) gene may be associated with the development of pancreatic cancer, but individually published studies and previous meta-analyses revealed inconclusive results. The aim of our study was to investigate the association between polymorphisms in XRCC1 gene and pancreatic cancer risk. We conducted a search of PubMed, Embase, the Cochrane Library and Web of Science databases. Odds ratios (ORs) with 95% confidence intervals (CIs) were determined as measures of the strength of association between polymorphisms of XRCC1 and pancreatic cancer risk. Sensitivity analysis and publication bias were evaluated. All analyses were undertaken using the STATA 13.0. A total of 10 studies were included in this systematic review. Five common functional single-nucleotide polymorphisms (SNPs) in XRCC1 gene were found, including Arg399Gln G > A (rs25487), Arg194Trp C > T (rs1799782), Arg280His G > A (rs25489), c.1517G > C, c.1471G > A. Results from our stratified analysis based on Hardy-Weinberg equilibrium (HWE) showed that there was a robust significant association between Arg280His polymorphism and pancreatic cancer risk (allelic model, OR 0.743, 95% CI 0.576-0.958, P = 0.022; heterozygous model, OR 0.701, 95% CI 0.525-0.936, P = 0.016; dominant model, OR 0.710, 95% CI 0.537-0.939, P = 0.016). We also found a statistically significant association between c.1517G > C polymorphism and pancreatic cancer risk (Allelic model, OR 1.252, 95% CI 1.064-1.473, P = 0.007). No significant results were obtained for Arg399Gln, Arg194Trp and c.1471G > A polymorphisms. The present meta-analysis suggested that Arg280His and c.1517G > C polymorphisms in XRCC1 gene were associated with pancreatic cancer risk.

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