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.
Clin Cancer Res
; 6(10): 4091-5, 2000 Oct.
Article
em En
| MEDLINE
| ID: mdl-11051261
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)Hquinone 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.
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Base de dados:
MEDLINE
Assunto principal:
Polimorfismo Genético
/
Síndromes Mielodisplásicas
/
Leucemia Mieloide Aguda
/
Leucemia
/
Sistema Enzimático do Citocromo P-450
/
Glutationa Transferase
/
Oxigenases de Função Mista
/
NADH NADPH Oxirredutases
País/Região como assunto:
Asia
Idioma:
En
Ano de publicação:
2000
Tipo de documento:
Article
País de afiliação:
Japão