Methylenetetrahydrofolate reductase C677T polymorphism and toxicity to 5-FU-based chemotherapy in colorectal cancer

Xiong-wei Xie,Yong-lian Zhang

doi:10.4314/tjpr.v19i1.30

Abstract

Purpose: To investigate the toxicity of methylenetetrahydrofolate reductase (MTHFR) polymorphism in colorectal cancer patients treated with 5-fluorouracil (5-FU).Methods: A total of 105 patients with colorectal cancer who underwent 5-FU therapy were included in this study. MTHFR C677T polymorphisms were determined using direct sequencing. Physical examination and the results of blood and urine tests were used to evaluate the toxicities, including gastrointestinal toxicity, hematopoietic toxicity, hair-skin toxicity and hand-foot syndrome.Results: In 90.5 % of all patients, 5-FU toxicity was observed. With regard to MTHFR C677T mutation, 45.7 % heterozygote mutants and 19.0 % homozygote mutants were observed. MTHFR C677T polymorphism was statistically related to 5-FU toxicity (p = 0.000). In addition, MTHFR C677T mutation was closely related to hematopoietic toxicity (p = 0.005).Conclusion: MTHFR C677T can be used for the prediction of 5-FU toxicity, and can also predict hematopoietic toxicity in patients with colorectal cancer. Keywords: MTHFR genes, Polymorphism, Colorectal cancer, Biomarker, Toxicity

Highlights

Gene polymorphism was associated with 5FU toxicity
Afzal et al reported that the Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism was closely related to fluoropyrimidine-related toxicity in colorectal cancer (CRC) patients, no specific types of toxicity were mentioned [16]
Noor et al found that MTHFR C677T polymorphism increased the tumor response to 5-FU and increased gastrointestinal toxicity in CRC patients [17]

Summary

Introduction

Methylenetetrahydrofolate reductase (MTHFR) is the most critical enzyme in the metabolism of folate and 5-FU [3]. The MTHFR activity may predict the clinical responses and toxicity to 5-FU. The grade and type of toxicities primarily depend on demographic factors including gender, age, dose of 5-FU and different methods of administration [4]. Individual differences in fluoropyrimidine-related toxicity are partly explained by genetic factors. One of the most common functional mutations in the MTHFR, C677T (rs1801133, A222V) has been identified the main variants in reducing the activity of this enzyme [6].

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