XRCC1 Arg399Gln and clinical outcome of platinum-based treatment for advanced non-small cell lung cancer:a meta-analysis in 17 studies

Objective:XRCC1 polymorphism is a research hotpot in individual treatment for non-small cell lung cancer (NSCLC). To obtain the association between XRCC1 polymorphism and clinical outcome of platinum-based treatment for NSCLC, a meta-analysis was conducted. Methods:Databases including PubMed, Embase, Cochrane, and Chinese National Knowledge Infrastructure (CNKI) were searched for publications that met the inclusion criteria. A fixed effect model was used to estimate pooled odds ratio (OR) and hazard ratio (HR) with 95% confidence interval (CI) for the association between XRCC1 Arg399Gln and response or survival of platinum-based treatment for advanced NSCLC. A chi-squared-based Q-test was used to test the heterogeneity hypothesis. Egger’s test was used to check publication bias. Results:Seventeen published case-control studies that focus on the association between XRCC1 Arg399Gln and response or survival of platinum-based treatment for advanced NSCLC in 2 256 subjects were included in this meta-analysis, of whom 522 were AA genotypes (23.2% frequency), 916 AG genotypes (40.6% frequency), and 818 GG genotypes (36.2% frequency). The overall response rate (ORR) was 45.2% (110/243) for AA genotype pa- tients, 29.9% for AG genotype (73/244), and 30.7% for GG genotype (124/403). The heterogeneity test did not show any heterogeneity and the Egger’s test did not reveal an obvious publication bias among the included studies. The metaanalysis indicated that AA genotype patients presented higher response rates toward platinum drug treatment compared with G model (GG+GA) patients (GG vs. AA model:OR=0.489, 95% CI 0.266-0.900, P=0.021; AG vs. AA model: OR=0.608, 95% CI 0.392-0.941, P=0.026; GA+AA vs. GG model: OR=1.259, 95% CI 0.931-1.701, P=0.135; GG+GA vs. AA model: OR=0.455, 95% CI 0.313-0.663, P=0.0001). However, no evidence validates XRCC1 associates with the survival following platinum drug therapy. Conclusions:Our meta-analysis suggested that XRCC1 Arg399Gln is related with the sensitivity of NSCLC patients to platinum-based treatment. AA genotype patients present more desirable curative effectiveness compared with other patients.