Abstract
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. A multiple search strategy was used to identify eligible studies. Pooled odds ratios (ORs) and their 95% confidence intervals (CIs) were used to estimate objective response and oxaliplatin-induced toxicity, with hazard ratios (HRs) with 95%CIs for progression-free survival (PFS) and overall survival (OS). A total of 22 studies including 2,846 CRC patients were eligible in the analysis. Overall, no significant correlation was found between the ERCC1 C118T polymorphism and objective response to oxaliplatin-based chemotherapy, in all patients or in the Asian and Caucasian subgroups. 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 a favorable prognosis in Caucasians (PFS, HR=0.58, 95%CI: 0.24-1.44; OS, HR=0.38, 95%CI: 0.22-0.64) but an unfavorable prognosis in Asians (PFS, HR=2.49, 95%CI: 1.87-3.33; OS, HR=2.63, 95%CI: 1.87-3.69) based on a dominant model. In addition, we failed to find a statistically significant impact of ERCC1 C118T polymorphism on oxaliplatin-induced toxicity. The ERCC1 C118T polymorphism may have prognostic value in patients with CRC undergoing oxaliplatin-based chemotherapy.
Highlights
Colorectal cancer (CRC) is the third most commonly diagnosed cancer and is the fourth main cause of cancerrelated mortality worldwide, with 1.2 million new cases and over 600, 000 deaths estimated in 2008 (Jemal et al, 2011)
Search results and study selection We identified related 1378 records through a primary search of databases and reference lists according to the searching criteria
No statistical evidence of a publication bias among studies was identified either from the results of Egger’s test or Harbord’s test (Table 2, 3). In this meta-analysis, we included 22 studies containing 2846 colorectal cancer (CRC) patients treated with oxaliplatinbased regiments
Summary
Colorectal cancer (CRC) is the third most commonly diagnosed cancer and is the fourth main cause of cancerrelated mortality worldwide, with 1.2 million new cases and over 600, 000 deaths estimated in 2008 (Jemal et al, 2011). Oxaliplatin has been approved as first-line therapy for metastatic CRC (mCRC), with an object response rate >50% and a median survival time approaching 2 years (Alberts et al, 2005; Cassidy et al, 2008) Despite this demonstrated efficacy, virtually a large part of patients developed varying levels of resistance to oxaliplatin. 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. No significant correlation was found between the ERCC1 C118T polymorphism and objective response to oxaliplatin-based chemotherapy, in all patients or in the Asian and Caucasian subgroups. Conclusions: The ERCC1 C118T polymorphism may have prognostic value in patients with CRC undergoing oxaliplatin-based chemotherapy
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