Analysis of genetic polymorphism in NQO1, GST-M1, GST-T1, and CYP3A4 in 469 Japanese patients with therapy-related leukemia/myelodysplastic syndrome and de …
T Naoe, K Takeyama, T Yokozawa, H Kiyoi, M Seto… - Clinical Cancer …, 2000 - AACR
T Naoe, K Takeyama, T Yokozawa, H Kiyoi, M Seto, N Uike, T Ino, A Utsunomiya, A Maruta…
Clinical Cancer Research, 2000•AACRSeveral genetic polymorphisms in metabolic activation or detoxification enzymes have been
associated with susceptibility to therapy-related leukemia and myelodysplastic leukemia
(TRL/MDS). We analyzed gene polymorphisms of NAD (P) H: quinone oxidoreductase
(NQO1), glutathione S-tranferase (GST)-M1 and-T1, 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 NQO1 at …
associated with susceptibility to therapy-related leukemia and myelodysplastic leukemia
(TRL/MDS). We analyzed gene polymorphisms of NAD (P) H: quinone oxidoreductase
(NQO1), glutathione S-tranferase (GST)-M1 and-T1, 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 NQO1 at …
Abstract
Several genetic polymorphisms in metabolic activation or detoxification enzymes have been associated with susceptibility to therapy-related leukemia and myelodysplastic leukemia (TRL/MDS). We analyzed gene polymorphisms of NAD(P)H:quinone oxidoreductase (NQO1), glutathione S-tranferase (GST)-M1 and -T1, and CYP3A4, the enzymes of which are capable of metabolizing anticancer drugs, in 58 patients with TRL/MDS and in 411 patients with de novoacute myeloid leukemia (AML). Homozygous Ser/Ser genotype of NQO1 at codon 187, causing loss of function, was more frequent in the patients with TRL/MDS (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 NQO1 were different between TRL/MDS and de novo AML (P =0.01). In GST-M1 and -T1, 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 NQO1 polymorphism is significantly associated with the genetic risk of TRL/MDS.
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