Methylene tetrahydrofolate reductase (MTHFR) gene rs1801133 C>T polymorphisms and response to 5-FU based chemotherapy in patients with colorectal cancer: A meta-analysis

Abstract

Background: Methylene tetrahydrofolate reductase (MTHFR) catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a cosubstrate for homocysteine remethylation to methionine. Single nucleotide polymorphisms (SNP) of MTHF rs1801133 C>T can influence susceptibility to colorectal cancer. However, an association between MTHFR rs1801133 C>T polymorphisms and response to 5-Fluorouracil (5-FU) based chemotherapy in patients with colorectal cancer was not clear. Methods: Studies relevant to MTHFR rs1801133 C>T polymorphisms and response to 5-FU based chemotherapy in patients with colorectal cancer were systematic searched in the electronic databases of PubMed, Web of Science, Embase, and China National Knowledge Infrastructure (CNKI). The genotypes of CC, CT, and TT were extracted from each included publication. The genotypes CC, CT, and TT distribution in 5-FU based chemotherapy response and resistance groups were calculated and pooled through random or fixed effect model by the effect size of odds ratio (OR) and 95% confidence interval (95% CI). The publication bias was evaluated through Begg's funnel plot and Egger's line regression test. Results: After searching the electronic databases, 16 studies related to MTHFR gene rs1801133 C>T polymorphisms and a response to 5-FU based chemotherapy in patients with colorectal cancer were included in the present meta-analysis. The pooled data showed no statistical difference in tumor response rate between CT+TT and CC groups in the dominant genetic model CT+CC vs CC (OR=1.21, 95% CI: 0.93~1.59, p>0.05) and recessive model TT vs CT+CC (OR=1.37, 95% CI: 0.91~2.06, p>0.05). The grade 3-4 adverse reaction rate between CT+TT and CC groups also had no statistical difference in the dominant genetic model CT+CC vs CC (OR=0.90, 95% CI: 0.76~1.07, p>0.05) and recessive model TT vs CT+CC (OR=1.12, 95% CI: 0.84~1.50, p>0.05). The Begg's funnel plot and Egger's line regression test demonstrated no publication bias. Conclusion: The response and adverse reaction of 5-FU based chemotherapy in colorectal patients were not different in terms of MTHFR rs1801133 C>T polymorphisms.