Methylenetetrahydrofolate reductase C677T and A1298C gene polymorphisms and therapy-related toxicity in children treated for acute lymphoblastic leukemia and non-Hodgkin lymphoma

Mehmet Kantar; Buket Kosova; Nazan Cetingul; Sevinc Gumus; Ertug Toroslu; Nur Zafer; Nejat Topcuoglu; Serap Aksoylar; Mehtap Cinar; Asli Tetik; Zuhal Eroglu

doi:10.1080/10428190902893819

Methylenetetrahydrofolate reductase C677T and A1298C gene polymorphisms and therapy-related toxicity in children treated for acute lymphoblastic leukemia and non-Hodgkin lymphoma

Leuk Lymphoma. 2009 Jun;50(6):912-7. doi: 10.1080/10428190902893819.

Authors

Mehmet Kantar¹, Buket Kosova, Nazan Cetingul, Sevinc Gumus, Ertug Toroslu, Nur Zafer, Nejat Topcuoglu, Serap Aksoylar, Mehtap Cinar, Asli Tetik, Zuhal Eroglu

Affiliation

¹ Pediatric Oncology Department and Pediatric BMT Center, Ege University School of Medicine, Bornova, Izmir, Turkey.

PMID: 19391036
DOI: 10.1080/10428190902893819

Abstract

This study aimed to investigate the association of the methylenetetrahydrofolate reductase (MTHFR) gene C677T and A1298C polymorphisms with serum drug levels and toxicities after high-dose methotrexate (MTX) infusion. The study included 37 children with acute lymphoblastic leukemia or non-Hodgkin lymphoma. Serum MTX levels and toxicities of bone marrow, liver and kidney were analysed. Genotype analysis of the C677T and A1298C gene polymorphisms from genomic DNA of the subjects was performed by real-time PCR. Subjects with MTHFR polymorphism for C677T (CT, TT) had significantly higher MTX levels at 24 h (p = 0.009), and these genotypes did not seem to cause toxicity. Subjects with MTHFR polymorphism for A1298C (AC, CC) had significantly higher MTX levels at 48 h (p = 0.02), and had more grade III/IV anemia (p = 0.02), thrombocytopenia (p = 0.0001), elevated AST levels (p = 0.04) and frequent febrile neutropenic episodes (p = 0.004). The present study suggests that A1298C gene, but not C677T polymorphism is associated with MTX-related toxicity.

MeSH terms

Adolescent
Alleles
Anemia / chemically induced
Antimetabolites, Antineoplastic / administration & dosage
Antimetabolites, Antineoplastic / adverse effects
Antimetabolites, Antineoplastic / therapeutic use
Bone Marrow / drug effects
Bone Marrow / pathology
Child
Child, Preschool
Dose-Response Relationship, Drug
Drug Administration Schedule
Drug-Related Side Effects and Adverse Reactions / chemically induced
Drug-Related Side Effects and Adverse Reactions / genetics
Female
Gene Frequency
Genotype
Humans
Kidney / drug effects
Kidney / pathology
Liver / drug effects
Liver / pathology
Lymphoma, Non-Hodgkin / drug therapy*
Lymphoma, Non-Hodgkin / genetics
Male
Methotrexate / adverse effects
Methotrexate / blood
Methotrexate / therapeutic use*
Methylenetetrahydrofolate Reductase (NADPH2) / genetics*
Polymorphism, Single Nucleotide*
Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics
Thrombocytopenia / chemically induced
Time Factors

Substances

Antimetabolites, Antineoplastic
Methylenetetrahydrofolate Reductase (NADPH2)
Methotrexate