The ERCC1 C118T Polymorphism Predicts Clinical Outcomes of Colorectal Cancer Patients Receiving Oxaliplatin-Based Chemotherapy: a Meta-analysis Based on 22 Studies

Abstract

Background: 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. Materials and Methods: 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). Results: 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. Conclusions: The ERCC1 C118T polymorphism may have prognostic value in patients with CRC undergoing oxaliplatin-based chemotherapy.

ERCC1 polymorphism predicts clinical outcomes of oxaliplatin-based chemotherapies in advanced colorectal cancer: A systemic review and metaanalysis

“…The Caucasian populations showed the opposite results, with significantly longer PFS and OS in patients carrying the T allele. The results of subgroup analyses were consistent with the results of previous studies [31].…”

“…The meta-analysis results showed no correlation between Asn118Asn polymorphism and chemotherapy efficiency, PFS or OS of advanced CRC patients, which was consistent with the results of one previous meta-analysis [30]. However, recently a metaanalysis has reported correlations of ERCC1 Asn118Asn polymorphism with PFS and OS [31], and our results did not confirm it. In fact, our study also contains some advantages.…”

Genetic variability of ERCC1 and ERCC2 genes involved in the nucleotide excision repair pathway influences the treatment outcome of gastric cancer

“…The ERCC1 enzyme is involved in recognizing and removing platinum-induced intrastrand adducts in DNA; previous studies have reported that ERCC1 gene polymorphisms are associated with the response to platinum-based chemotherapy in patients with osteosarcoma, breast cancer, non-small cell lung cancer, and colorectal cancer (Bewick et al, 2011;Qian et al, 2014;Ji and He, 2015;Shi et al, 2015). Guo et al (2015) conducted a study in a Canadian population, and found that the ERCC1 rs3212986 polymorphism was not associated with the survival outcome of patients with breast cancer.…”

“…Shi et al (2015) also conducted a study in a Chinese population, and found that the ERCC1 rs11615 polymorphism influences the chemotherapy and survival of patients with non-small cell lung cancer. Qian et al (2014) reported that the ERCC1 rs11615 polymorphism is associated with prognosis in colorectal cancer patients. The studies mentioned above suggest that ERCC1 gene polymorphisms are associated with prognosis in cancer.…”

A functional single‐nucleotide polymorphism in the ERCC 1 gene alters the efficacy of narrowband ultraviolet B therapy in patients with active vitiligo in a Chinese population

“…Studies on the ERCC1 C118T SNP have focused mainly on nonsmall‐cell lung cancer and colorectal cancer . According to stratified analysis by ethnicity in a meta‐analysis, the ERCC1 118T allele was associated with a favourable prognosis in colorectal cancer in white patients, but with an unfavourable prognosis in Asian patients …”