title: Polymorphism G80A in the reduced folate carrier gene and its relationship to methotrexate plasma levels and outcome of childhood acute lymphoblastic leukemia.
abstract: Methotrexate (MTX) is a key compound of chemotherapeutic regimens used in the treatment of childhood acute lymphoblastic leukemia (ALL). Resistance to this drug may arise by, among other factors, altered cellular uptake that may hamper the efficacy of the treatment. Recently, a G(80)A polymorphism has been described in the reduced folate carrier gene (RFC1), which encodes the major MTX transporter. Here, we assessed the association between the genetic polymorphisms G(80)A and both MTX plasma levels and childhood ALL outcome. Children with the A(80) variant had worse prognoses than patients with the GG genotype (P =.04), as shown by event-free survival estimates. Patients homozygous for A(80) had higher levels of MTX (P =.004) than the other genotype groups. Possible explanations for observed associations are discussed; however, additional experiments are required to achieve understanding of the underlying mechanism.
authors.affiliation: Centre de Recherche, Hôpital Sainte-Justine, Montréal, QC, Canada.
authors.forename: Caroline
authors.initials: C
authors.lastname: Laverdière
authors.forename: Sonia
authors.initials: S
authors.lastname: Chiasson
authors.forename: Irina
authors.initials: I
authors.lastname: Costea
authors.forename: Albert
authors.initials: A
authors.lastname: Moghrabi
authors.forename: Maja
authors.initials: M
authors.lastname: Krajinovic
mesh_terms: D000293:Adolescent; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000097:blood*; D002352:Carrier Proteins / Q000235:genetics* / Q000502:physiology; D002648:Child; D002675:Child, Preschool; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D058973:Folate Receptors, GPI-Anchored; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000097:blood*; D020641:Polymorphism, Single Nucleotide; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000235:genetics*; D011956:Receptors, Cell Surface; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D002352:Carrier Proteins; D058973:Folate Receptors, GPI-Anchored; D011956:Receptors, Cell Surface; D008727:Methotrexate