Effects of MTHFR Genetic Polymorphisms on Toxicity and Clinical Response of Irinotecan-Based Chemotherapy in Patients with Colorectal Cancer

Abstract

This meta-analysis aims to evaluate the effects of common polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene on the toxicity and clinical responses of irinotecan-based chemotherapy in patients with colorectal cancer (CRC). The PubMed, CISCOM, CINAHL, Web of Science, Google Scholar, EBSCO, Cochrane Library, and CBM databases were searched from their inception through November 1st, 2013 without language restrictions. Meta-analysis was conducted with the use of the STATA 12.0 software. Crude odds ratios (ORs) and their 95% confidence intervals (95% CIs) were calculated. Seven clinical cohort studies with a total of 815 CRC patients met the inclusion criteria. Two common polymorphisms (677 C>T and 1298 A>C) in the MTHFR gene were assessed. The results from our meta-analysis suggested that MTHFR genetic polymorphisms might significantly decrease the rate of grade 3/4 toxicity of irinotecan-based chemotherapy in CRC patients (OR=0.53, 95% CI: 0.32-0.89, p=0.015). Furthermore, we also demonstrated that MTHFR genetic polymorphisms strongly correlated with good clinical responses (complete response+partial response) to irinotecan-based chemotherapy in CRC patients (OR=1.47, 95% CI: 1.05-2.04, p=0.024). Our findings provide empirical evidence that MTHFR genetic polymorphisms may decrease the toxicity of irinotecan-based chemotherapy and increase the clinical benefits for CRC patients. Thus, MTHFR genetic polymorphisms may be screened to predict the clinical responses to irinotecan-based chemotherapy in CRC patients.