title: Influence of MTHFR and RFC1 polymorphisms on toxicities during maintenance chemotherapy for childhood acute lymphoblastic leukemia or lymphoma.
abstract: We investigated preliminarily whether methylenetetrahydrofolate reductase (MTHFR) 677C/T or reduced folate carrier 1 (RFC1) 80G/A polymorphisms were associated with toxicities during maintenance chemotherapy with mercaptopurine (6MP) and methotrexate (MTX) in children with acute lymphoblastic leukemia or lymphoblastic lymphoma. The clinical records of 20 children (2 to 15-y old) who had received maintenance chemotherapy were reviewed retrospectively and their genomic DNA was genotyped to identify polymorphisms at MTHFR 677C/T, RFC1 80G/A, and thiopurine methyltransferase 719A/G. Maintenance chemotherapy with 6MP and MTX was repeated on a weekly basis, and any week during which 6MP and/or MTX dosing was withheld was counted as an interrupted episode. Associations between the risk of interruptions and polymorphisms were studied using a generalized estimating equation analysis. Patients with an increasing number of T alleles at MTHFR 677C/T experienced interruptions in both 6MP (P<0.01) and MTX (P=0.03) more frequently. Patients with an increasing number of A alleles at RFC1 80G/A experienced interruptions in 6MP (P=0.04) more frequently. This preliminary study does not prove but suggests that MTHFR 677C/T and RFC1 80G/A polymorphisms may serve as predictors of toxicity during maintenance chemotherapy.
authors.affiliation: Department of Pediatrics, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan. noriko-s@sc.itc.keio.ac.jp
authors.forename: Noriko
authors.initials: N
authors.lastname: Shimasaki
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Mori
authors.forename: Chiharu
authors.initials: C
authors.lastname: Torii
authors.forename: Reiko
authors.initials: R
authors.lastname: Sato
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Shimada
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Tanigawara
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Kosaki
authors.forename: Takao
authors.initials: T
authors.lastname: Takahashi
mesh_terms: D000293:Adolescent; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D019731:Carbon-Nitrogen Ligases / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005838:Genotype; D006801:Humans; D015122:Mercaptopurine / Q000627:therapeutic use; D008727:Methotrexate / Q000627:therapeutic use; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics*; D058978:Reduced Folate Carrier Protein / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D058978:Reduced Folate Carrier Protein; C548699:SLC19A1 protein, human; D015122:Mercaptopurine; D019731:Carbon-Nitrogen Ligases; C021557:5,10-methenyltetrahydrofolate synthetase; D008727:Methotrexate