Association Of Single Nucleotide Polymorphisms And Outcome Of Patients With Advanced Colorectal Cancer Treated With First-Line FOLFOX Or XELOX Chemotherapy

Association of Single Nucleotide Polymorphisms And Outcome of Patients With Advanced Colorectal Cancer Treated With First-Line FOLFOX or XELOXChemotherapyPurpose:The object is to investigate whether germline single nucleotide polymorphisms within genes known or suspected to influence drug activity could predict the efficacy of first-line FOLFOX or XELOX regimens in patients with advanced colorectal cancer in Chinese population.Methods:A retrospective study of patients with advance colorectal cancer treated with first-line standard mFOLFOX6 or XELOX regimens was performed. Peripheral blood samples were used for genotyping 5 polymorphisms in methylenetetrahydrofolate reductase(MTHFR), glutathione S-transferases P1(GSTP1), excision repair cross complementing group 1 (ERCC1), x-ray cross complementing protein 1(XRCC1) genes. The primary end point of the study was to investigate the association between genotypes and response rate, as well as progression-free survival (PFS).Results:In 93 patients, ERCC1-118C/C and MTHFR-677C/C genotpyes were independently associated with adverse response rate. Clinical outcome was significantly improved with the number of favorable genotypes of MTHFR-677T,1298A and XRCC1-399G (response rate, P=0.013; PFS,P=0.0003). This profile also revealed prognostic values for PFS on both univariate analysis (P=0.001) and multivariate analysis (P=0.048).Conclusion:Single nucleotide polymorphisms are promising predictive markers for patients with advanced colorectal cancer and could be used for optimizing palliative chemotherapy.