The role of the MTHFR C677T polymorphism in methotrexate-induced toxicity in pediatric osteosarcoma patients

Abstract

Aim: Osteosarcoma patients receive high doses of methotrexate (MTX). However, pharmacogenetic information remains limited and has mainly been investigated in leukemia so far. Patients & methods: We investigated the link between the MTHFR C677T genotype, toxicity levels (mucositis, MTX plasma level, hematological toxicity and hepatotoxicity) and survival of 48 pediatric osteosarcoma patients. Results: The TT genotype did not show more toxicity compared with the CC/CT genotype. However, plasma MTX levels were related with mucositis, but not with hematological toxicity, nor hepatotoxicity. Survival rates did not differ between homozygous and non-homozygous patients. Yet, homozygous patients had higher relapse risk. Conclusion: The MTHFR C667T polymorphism is not predictive for toxicity or overall survival, but could be used for relapse risk stratification.