title: Methylenetetrahydrofolate reductase C677T and A1298C gene polymorphisms and therapy-related toxicity in children treated for acute lymphoblastic leukemia and non-Hodgkin lymphoma.
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.
authors.affiliation: Pediatric Oncology Department and Pediatric BMT Center, Ege University School of Medicine, Bornova, Izmir, Turkey.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Kantar
authors.forename: Buket
authors.initials: B
authors.lastname: Kosova
authors.forename: Nazan
authors.initials: N
authors.lastname: Cetingul
authors.forename: Sevinc
authors.initials: S
authors.lastname: Gumus
authors.forename: Ertug
authors.initials: E
authors.lastname: Toroslu
authors.forename: Nur
authors.initials: N
authors.lastname: Zafer
authors.forename: Nejat
authors.initials: N
authors.lastname: Topcuoglu
authors.forename: Serap
authors.initials: S
authors.lastname: Aksoylar
authors.forename: Mehtap
authors.initials: M
authors.lastname: Cinar
authors.forename: Asli
authors.initials: A
authors.lastname: Tetik
authors.forename: Zuhal
authors.initials: Z
authors.lastname: Eroglu
mesh_terms: D000293:Adolescent; D000483:Alleles; D000740:Anemia / Q000139:chemically induced; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D064420:Drug-Related Side Effects and Adverse Reactions / Q000139:chemically induced / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008727:Methotrexate / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics; D013921:Thrombocytopenia / Q000139:chemically induced; D013997:Time Factors
chemical_list: D000964:Antimetabolites, Antineoplastic; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008727:Methotrexate