MTHFR gene polymorphisms and methotrexate toxicity in adult patients with hematological malignancies: a meta-analysis

Abstract

Background: MTHFR gene polymorphisms has been shown to be associated with methotrexate (MTX) toxicity in adult hematological malignancies; however, the results remain inconclusive. Materials & methods: To examine the role of common MTHFR variants in MTX toxicity prediction, we performed a meta-analysis via identifying relevant studies for quantitative data pooling. Results: Our results showed a significant association between MTHFR C677T polymorphism and increased risk of MTX-induced all-grade (grade 1–4) and severe (grade 3–4) hepatic and gastrointestinal toxicities in Caucasian independent of MTX dosage. MTHFR 677T allele increased risk of severe mucositis and all-grade hematological toxicity. MTHFR A1298C polymorphism was not significantly associated with hepatic and hematological toxicity, whereas perhaps having a protective effect on mucositis and gastrointestinal toxicity. Conclusion: MTHFR C677T polymorphism may be a good predictor for MTX toxicity in adult hematological malignancies.