ERCC1 Polymorphisms Predict Clinical Outcomes Of Oxaliplatin-Based Chemotherapies Colorectal Cancer:A Systemic Review And Meta-Analysis

OBJECTIVE:ERCC1 gene is an important gene for DNA repairing. Although the predictive value of the excision repair cross-complementing group 1 (ERCC1)C118T polymorphism in clinical outcomes of patients with colorectal cancer (CRC) receiving oxaliplatin-based chemotherapy has been evaluated in numerous published studies, the conclusions are conflicting. Therefore, we performed the present meta-analysis to determine the precise role of the ERCC1 C118T polymorphism in this clinical situation and help optimize individual chemotherapy..METHODS:Qualified studies published in English and Chinese retrieving from databases such as PubMed, Embase, PML, Springer Link, Ebsco, CBM, VIP, Wanfang and CNKI Database until January 31st,2015 were selected for meta-analysis. Data retrieved from these articles included study ID, title, author, publication year, ethnicity, country, numbers of cases and controls. Pooled odds ratios (ORs) and their 95% confidence intervals (CIs) were used to estimate objective response with hazard ratios(HRs) with 95%CIs for progression-free survival (PFS) and overall survival (OS). Statistical analysis was performed by employing Stata version 11.0.RESULTS:206 of records were serached through database. After 193 articles were eliminated due to the exclusion criteria,13 articles were included in the meta-analysis as a consequence. Overall, no significant correlation was found between the ERCC1 C118T polymorphism and objective response (OR=0.78 95%CI为0.29-2.07) to oxaliplatin-based chemotherapy, neither of PFS (HR=1.7095%CI为0.92-3.14) and OS (HR=1.6995%CI%0.91-3.14). On stratified analysis by ethnicity, no significant correlation was found between the ERCC1 C118T polymorphism and objective response (OR=2.03 VS 0.40; 95%CI为0.62-6.68 VS 0.12-1.30). However, the pooled analysis showed that the PFS and OS were significantly shorter in patients who carried T/T or T/C genotypes of ERCC1 C118T as compared to the C/C genotype. On stratified analysis by ethnicity, the ERCC1 118T allele was associated with an unfavorable prognosis in Asians (HR=2.41,95%CI:1.86-3.11, HR=2.36,95%CI: 1.76-3.16) but a favorable prognosis in Caucasians (HR=1.43,95%CI: 0.57-3.59; OS, HR=1.17,95%CI:0.32-4.30) based on a dominant model.CONLUSIONS:In patients with advanced colorectal cancer undergoing oxaliplatin-based chemotherapy have no correlation with ERCC1 Asn118Asn (C/T) gene polymorphism, but among Asian patients with T allele has shorter PFS and OS.