Research Article

Pharmacogenetic role of XRCC1 polymorphisms on the clinical outcome of gastric cancer patients with platinum-based chemotherapy: a systematic review and meta-analysis

Published: March 06, 2014
Genet. Mol. Res. 13 (1) : 1438-1446 DOI: 10.4238/2014.March.6.2

Abstract

It is still controversial whether X-ray repair cross-complementing group (XRCC1) gene polymorphisms (Arg194Trp and Arg399Gln) are associated with the clinical outcome of platinum-based chemotherapy in gastric cancer patients based on published studies. Meta-analysis was performed to provide a systematic review of the findings. Eligible articles from the PubMed, SinoMed, and CNKI databases before September 1, 2012, were selected. Objective response (complete response + partial response vs progressive disease + stable disease), progress-free survival (PFS) and overall survival (OS) were applied to evaluate clinical outcomes. We calculated the odds ratio or hazard risk (HR) with 95% confidence interval (CI) using the STATA software. Eleven eligible articles including 1274 gastric cancer patients with platinum-based treatment were enrolled in our meta-analysis. The results indicated that the A allele of the XRCC1 Arg399Gln polymorphism was significantly associated with poor OS (HR = 1.40; 95%CI = 1.04-1.90) of gastric cancer but not for platinum-based chemotherapy response or PFS. No significant associations were observed between XRCC1 Arg194Trp and objective response. The data suggest that the XRCC1 Arg399Gln polymorphism may be a prognostic biomarker of OS for platinum-based gastric cancer treatment. However, further cohorts with larger sample sizes from different ethnic backgrounds and with improved experimental design are needed to confirm these findings.

It is still controversial whether X-ray repair cross-complementing group (XRCC1) gene polymorphisms (Arg194Trp and Arg399Gln) are associated with the clinical outcome of platinum-based chemotherapy in gastric cancer patients based on published studies. Meta-analysis was performed to provide a systematic review of the findings. Eligible articles from the PubMed, SinoMed, and CNKI databases before September 1, 2012, were selected. Objective response (complete response + partial response vs progressive disease + stable disease), progress-free survival (PFS) and overall survival (OS) were applied to evaluate clinical outcomes. We calculated the odds ratio or hazard risk (HR) with 95% confidence interval (CI) using the STATA software. Eleven eligible articles including 1274 gastric cancer patients with platinum-based treatment were enrolled in our meta-analysis. The results indicated that the A allele of the XRCC1 Arg399Gln polymorphism was significantly associated with poor OS (HR = 1.40; 95%CI = 1.04-1.90) of gastric cancer but not for platinum-based chemotherapy response or PFS. No significant associations were observed between XRCC1 Arg194Trp and objective response. The data suggest that the XRCC1 Arg399Gln polymorphism may be a prognostic biomarker of OS for platinum-based gastric cancer treatment. However, further cohorts with larger sample sizes from different ethnic backgrounds and with improved experimental design are needed to confirm these findings.