title: Pharmacogenetic role of XRCC1 polymorphisms on the clinical outcome of gastric cancer patients with platinum-based chemotherapy: a systematic review and meta-analysis.
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.
authors.affiliation: Department of Molecular Cell Biology and Toxicology, Jiangsu Key Lab of Cancer Biomarkers, Prevention & Treatment, Cancer Center, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: J
authors.initials: J
authors.lastname: Xu
authors.affiliation: The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: J
authors.initials: J
authors.lastname: Ma
authors.affiliation: The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: H T
authors.initials: HT
authors.lastname: Zong
authors.affiliation: Department of Molecular Cell Biology and Toxicology, Jiangsu Key Lab of Cancer Biomarkers, Prevention & Treatment, Cancer Center, School of Public Health, Nanjing Medical University, Nanjing, China sywang@njmu.edu.cn.
authors.forename: S Y
authors.initials: SY
authors.lastname: Wang
authors.affiliation: Department of Molecular Cell Biology and Toxicology, Jiangsu Key Lab of Cancer Biomarkers, Prevention & Treatment, Cancer Center, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: J W
authors.initials: JW
authors.lastname: Zhou
mesh_terms: D000483:Alleles; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005838:Genotype; D006801:Humans; D016017:Odds Ratio; D010984:Platinum / Q000627:therapeutic use*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D016896:Treatment Outcome; D000076105:X-ray Repair Cross Complementing Protein 1
chemical_list: D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; D010984:Platinum