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

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Abstract

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 patients, 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 meta-analysis 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.

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Authors and Affiliations

  1. Department of Pharmacy, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China

    Jian Chen, Qing-wei Zhao & Lin-run Wang

  2. Department of Medical Oncology, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China

    Jian Chen & Gen-ming Shi

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  1. Jian Chen
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  2. Qing-wei Zhao
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Correspondence to Lin-run Wang.

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Project supported by the Zhejiang Provincial Department of Education Research Program (No. Y201120237) and the Zhejiang Provincial Natural Science Foundation of China (No. Y2090447)

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Chen, J., Zhao, Qw., Shi, Gm. et al. XRCC1 Arg399Gln and clinical outcome of platinum-based treatment for advanced non-small cell lung cancer: a meta-analysis in 17 studies. J. Zhejiang Univ. Sci. B 13, 875–883 (2012). https://doi.org/10.1631/jzus.B1200083

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