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

• Published in: Genetics and molecular research 2014-03, Vol.13 (1), p.1438-1446
• Main Authors: Xu, J, Ma, J, Zong, H T, Wang, S Y, Zhou, J W
• Format: Article
• Language: English
• Subjects: Alleles; Antineoplastic Agents - therapeutic use; DNA-Binding Proteins - genetics; Genotype; Humans; Odds Ratio; Platinum - therapeutic use; Polymorphism, Genetic; Polymorphism, Single Nucleotide; Prognosis; Stomach Neoplasms - drug therapy; Stomach Neoplasms - genetics; Stomach Neoplasms - mortality; Treatment Outcome; X-ray Repair Cross Complementing Protein 1
• ISSN: 1676-5680; 1676-5680
• DOI: 10.4238/2014.March.6.2

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.