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- Title
Polymorphisms of MTHFR Associated with Higher Relapse/Death Ratio and Delayed Weekly MTX Administration in Pediatric Lymphoid Malignancies.
- Authors
Hiroko Fukushima; Takashi Fukushima; Aiko Sakai; Ryoko Suzuki; Nakajima-Yamaguchi, Ryoko; Chie Kobayashi; Atsushi Iwabuchi; Makoto Saito; Ai Yoshimi; Tomohei Nakao; Keisuke Kato; Masahiro Tsuchida; Hideto Takahashi; Kazutoshi Koike; Nobutaka Kiyokawa; Emiko Noguchi; Ryo Sumazaki
- 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 patientwho had the AC/CCgenotype 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.
- Subjects
METHYLENETETRAHYDROFOLATE reductase; LYMPHOCYTIC leukemia; GENETIC polymorphisms; CANCER relapse; CHILDHOOD cancer; METHOTREXATE; HEALTH outcome assessment; LEUKEMIA treatment
- Publication
Leukemia Research & Treatment, 2013, p1
- ISSN
2090-3219
- Publication type
Article
- DOI
10.1155/2013/238528