title: Analysis of genetic polymorphism in NQO1, GST-M1, GST-T1, and CYP3A4 in 469 Japanese patients with therapy-related leukemia/ myelodysplastic syndrome and de novo acute myeloid leukemia.
abstract: Several genetic polymorphisms in metabolic activation or detoxification enzymes have been associated with susceptibility to therapy-related leukemia and myelodysplastic leukemia (TRLIMDS). We analyzed gene polymorphisms of NAD(P)H:quinone oxidoreductase (NQOl), glutathione S-tranferase (GST)-MI and -TI, and CYP3A4, the enzymes of which are capable of metabolizing anticancer drugs, in 58 patients with TRL/MDS and in 411 patients with de novo acute myeloid leukemia (AML). Homozygous Ser/Ser genotype of NQOl at codon 187, causing loss of function, was more frequent in the patients with TRLIMDS (14 of 58, 24.1%; OR = 2.62) than in those with de novo AML (64 of 411, 15.6%), and control (16 of 150, 10.6%; P = 0.002). Allelic frequencies of NQOJ were different between TRL/ MDS and de novo AML (P = 0.01). In GST-MJ and -Ti, the incidence of homologous deletion was similar among the three groups. The polymorphism of the 5' promoter region of CYP3A4 was not found in persons of Japanese ethnicity. These results suggest that the NQOJ polymorphism is significantly associated with the genetic risk of TRLIMDS.
authors.affiliation: Department of Infectious Diseases, The First Nagoya University School of Medicine, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Naoe
authors.forename: K
authors.initials: K
authors.lastname: Takeyama
authors.forename: T
authors.initials: T
authors.lastname: Yokozawa
authors.forename: H
authors.initials: H
authors.lastname: Kiyoi
authors.forename: M
authors.initials: M
authors.lastname: Seto
authors.forename: N
authors.initials: N
authors.lastname: Uike
authors.forename: T
authors.initials: T
authors.lastname: Ino
authors.forename: A
authors.initials: A
authors.lastname: Utsunomiya
authors.forename: A
authors.initials: A
authors.lastname: Maruta
authors.forename: I
authors.initials: I
authors.lastname: Jin-nai
authors.forename: N
authors.initials: N
authors.lastname: Kamada
authors.forename: Y
authors.initials: Y
authors.lastname: Kubota
authors.forename: H
authors.initials: H
authors.lastname: Nakamura
authors.forename: C
authors.initials: C
authors.lastname: Shimazaki
authors.forename: S
authors.initials: S
authors.lastname: Horiike
authors.forename: Y
authors.initials: Y
authors.lastname: Kodera
authors.forename: H
authors.initials: H
authors.lastname: Saito
authors.forename: R
authors.initials: R
authors.lastname: Ueda
authors.forename: J
authors.initials: J
authors.lastname: Wiemels
authors.forename: R
authors.initials: R
authors.lastname: Ohno
mesh_terms: D000328:Adult; D000483:Alleles; D003062:Codon; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D042967:Electron Transport Complex I; D005260:Female; D017353:Gene Deletion; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007564:Japan; D007938:Leukemia / Q000139:chemically induced* / Q000235:genetics*; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics*; D009190:Myelodysplastic Syndromes / Q000139:chemically induced* / Q000235:genetics*; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics*; D011110:Polymorphism, Genetic; D012306:Risk
chemical_list: D003062:Codon; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System; D042967:Electron Transport Complex I; D005982:Glutathione Transferase; D006899:Mixed Function Oxygenases; D009247:NADH, NADPH Oxidoreductases; C104464:CYP3A protein, human; C510163:CYP3A4 protein, human; C413545:glutathione S-transferase T1