Association between polymorphisms in XRCC1 gene and treatment outcomes of patients with advanced gastric cancer: a systematic review and meta-analysis.
BACKGROUND
Many reports have shown inconsistent results on the relationship between single nucleotide polymorphisms (SNPs) of X-ray repair cross complementing protein (XRCC1) gene and platinum-based chemotherapeutic efficacy. This meta-analysis aimed to summarize published data about the association between two SNPs of XRCC1 (Arg194Trp and Arg399Gln) and treatment outcomes of patients with advanced gastric cancer.


RESULTS
We retrieved the relevant articles from MEDLINE, Web of Knowledge, and the China National Knowledge Infrastructure (CNKI) databases. Studies were selected according to specific inclusion and exclusion criteria. Study quality was assessed according to the guidelines outlined by Hayden, et al. and PRISMA guidelines. We estimated the odds ratio (OR) for response rate versus no response after platinum-based chemotherapy. Progression-free survival (PFS) and overall survival (OS) were evaluated by pooled Cox proportional hazard ratios (HRs) and 95% confidence intervals (CIs). We found that none of the XRCC1 Arg194Trp and Arg399Gln polymorphisms was significantly associated with tumor response. Stratified analysis by ethnicity or sensitivity analysis also showed that XRCC1 SNPs were not related with chemotherapy response. Patients with minor variant A allele were likely to have poorer 2-year survival rate than those with G/G genotype. However, in the group of 5-year follow up, there was no significant association between the A allele and OS yet.


CONCLUSIONS
There is no evidence to support the use of XRCC1 Arg194Trp and Arg399Gln polymorphisms as prognostic predictors of TR and PFS in gastric patients treated with platinum-based chemotherapy. The relationship between minor variant A allele and OS requires further verification.
Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, PR China.
Zhuo
Z
Cao
Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, PR China.
Jia
J
Song
Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, PR China.
Jun
J
Wang
Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, PR China.
Xufeng
X
Guo
Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, PR China.
Shijie
S
Yu
Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, PR China.
Weiguo
W
Dong
D000328:Adult; D000368:Aged; D000483:Alleles; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002945:Cisplatin / Q000627:therapeutic use; D004268:DNA-Binding Proteins / Q000235:genetics*; D016206:Databases, Bibliographic; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D016019:Survival Analysis; D016896:Treatment Outcome; D000076105:X-ray Repair Cross Complementing Protein 1
D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; D002945:Cisplatin