title: Polymorphisms of MTHFR Associated with Higher Relapse/Death Ratio and Delayed Weekly MTX Administration in Pediatric Lymphoid Malignancies.
abstract: Backgrounds. Outcome of childhood malignancy has been improved mostly due to the advances in diagnostic techniques and treatment strategies. While methotrexate (MTX) related polymorphisms have been under investigation in childhood malignancies, many controversial results have been offered. Objectives. To evaluate associations of polymorphisms related MTX metabolisms and clinical course in childhood lymphoid malignancies. Method. Eighty-two acute lymphoblastic leukemia and 21 non-Hodgkin's lymphoma children were enrolled in this study. Four single nucleotide polymorphisms in 2 genes (MTHFR (rs1801133/c.677C>T/p.Ala222Val and rs1801131/c.1298A>C/p.Glu429Ala) and SLCO1B1 (rs4149056/c.521T>C/p.V174A and rs11045879/c.1865+4846T>C)) were genotyped by Taqman PCR method or direct sequencing. Clinical courses were reviewed retrospectively. Results. No patient who had the AC/CC genotype of rs1801131 (MTHFR) had relapsed or died, in which distribution was statistically different among the AA genotype of rs1801131 (P = 0.004). Polymorphisms of SLCO1B1 (rs11045879 and rs4149056) were not correlated with MTX concentrations, adverse events, or disease outcome. Conclusions. Polymorphisms of MTHFR (rs1801131) could be the plausive candidate for prognostic predictor in childhood lymphoid malignancies.
authors.affiliation: Department of Child Health, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Fukushima
authors.affiliation: Department of Child Health, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Fukushima
authors.affiliation: Department of Pediatrics, University of Tsukuba Hospital, Japan.
authors.forename: Aiko
authors.initials: A
authors.lastname: Sakai
authors.affiliation: Department of Pediatrics, University of Tsukuba Hospital, Japan.
authors.forename: Ryoko
authors.initials: R
authors.lastname: Suzuki
authors.affiliation: Department of Pediatrics, University of Tsukuba Hospital, Japan.
authors.forename: Ryoko
authors.initials: R
authors.lastname: Nakajima-Yamaguchi
authors.affiliation: Department of Child Health, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Chie
authors.initials: C
authors.lastname: Kobayashi
authors.affiliation: Department of Pediatrics, University of Tsukuba Hospital, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Iwabuchi
authors.affiliation: Department of Child Health, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Saito
authors.affiliation: Department of Hematology/Oncology, Ibaraki Children's Hospital, Japan.
authors.forename: Ai
authors.initials: A
authors.lastname: Yoshimi
authors.affiliation: Department of Hematology/Oncology, Ibaraki Children's Hospital, Japan.
authors.forename: Tomohei
authors.initials: T
authors.lastname: Nakao
authors.affiliation: Department of Hematology/Oncology, Ibaraki Children's Hospital, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Kato
authors.affiliation: Department of Hematology/Oncology, Ibaraki Children's Hospital, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tsuchida
authors.affiliation: Department of Epidemiology, Faculty of Medicine, University of Tsukuba, Japan.
authors.forename: Hideto
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: Department of Hematology/Oncology, Ibaraki Children's Hospital, Japan.
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Koike
authors.affiliation: Department of Pediatric Hematology and Oncology Research, National Research Institute for Child Health and Development, Japan.
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Kiyokawa
authors.affiliation: Department of Genetics, Faculty of Medicine, University of Tsukuba, Japan.
authors.forename: Emiko
authors.initials: E
authors.lastname: Noguchi
authors.affiliation: Department of Child Health, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Sumazaki