Relevance of methylenetetrahydrofolate reductase gene variants C677T and A1298C with response to fluoropyrimidine-based chemotherapy in colorectal cancer: a systematic review and meta-analysis

// Lei Zhong 1 , Xia He 1 , Yuan Zhang 1 , Jun-Lan Chuan 1 , Min Chen 1 , Shao-Min Zhu 2 and Qian Peng 3 1 Personalized Drug Therapy Key Laboratory of Sichuan Province, Hospital of the University of Electronic Science and Technology of China and Sichuan Provincial People’s Hospital, Sichuan 610072, China 2 Department of Anesthesiology, East Ward, Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital, Sichuan 610072, China 3 Cancer Center, Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital, Sichuan 610072, China Correspondence to: Qian Peng, email: pengqian0522@163.com Shao-Min Zhu, email: 541300362@qq.com Keywords: MTHFR; fluoropyrimidine; chemotherapy response; meta-analysis; polymorphism Received: January 21, 2017 Accepted: March 06, 2018 Published: July 27, 2018 ABSTRACT Methylenetetrahydrofolate reductase (MTHFR) is a critical enzyme influencing the metabolism of fluoropyrimidines. The relevance of MTHFR polymorphisms with the clinical response to fluoropyrimidine-based chemotherapy has been explored, but the results remain controversial. Thus, a meta-analysis was performed to provide a comprehensive estimate in this account. Relevant studies were identified through PubMed, Embase and Web of Science databases from inception up to May 2017. Odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were applied to assess the strength of association. A total of 2118 colorectal cancer patients from 21 studies were included in the meta-analysis. Overall, there was no significant association between MTHFR C677T (rs1801133) or A1298C (rs1801131) polymorphisms and the clinical response to fluoropyrimidine-based chemotherapy under all of the three genetic models (allele model, dominant model, and recessive model) and stratification analysis, except for the retrospective study subgroup in the dominant model of MTHFR C677T and the “5-Fu + FA” treatment group in the allele contrast of MTHFR A1298C. No or moderate heterogeneity was observed in all genetic models. This meta-analysis suggested that MTHFR polymorphisms could not be considered as reliable factors for predicting the clinical response to fluoropyrimidine-based chemotherapy in colorectal cancer patients.