The role of the MTHFR C677T polymorphism in methotrexate-induced toxicity in pediatric osteosarcoma patients
Related Experiment Video
Updated: Mar 1, 2026

Author Spotlight: Genetic Profiling for Fluorouracil Response in Gastric Cancer
Published on: May 10, 2024
Loes Lambrecht1, Charlotte Sleurs2,3, Veerle Labarque4,3
1Department of Pediatrics, University Hospital Leuven, Leuven, Belgium.
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.
Related Concept Videos
Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
Mismatch Repair
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
Mismatch Repair
Pharmacokinetics in Pediatric Patients: Drug Metabolism

