title: Role of the CYP2D6, EPHX1, MPO, and NQO1 genes in the susceptibility to acute lymphoblastic leukemia in Brazilian children.
abstract: Polymorphic variations of several genes associated with dietary effects and exposure to environmental carcinogens may influence susceptibility to leukemia development. The objective of the present study was to evaluate the effect of the polymorphisms of debrisoquine hydroxylase (CYP2D6), epoxide hydrolase (EPHX1), myeloperoxidase (MPO), and quinone-oxoreductase (NQO1), which have been implicated in xenobiotic metabolism, on the risk of childhood acute lymphoblastic leukemia (ALL). We evaluated the frequency of polymorphisms in the CYP2D6 (*3 and *4), EPHX1 (*2 and *3), MPO (*2), and NQO1 (*2) genes in 206 patients with childhood ALL and in 364 healthy individuals matched for age and gender from a Brazilian population separated by ethnicity (European ancestry and African ancestry), using the PCR-RFLP method. The CYP2D6 polymorphism variants were associated with an increased risk of ALL. The EPHX1, NQO1, and MPO variant genotypes were significantly associated with a reduced risk of childhood ALL. A significantly stronger protective effect is observed when the EPHX1, NQO1, and MPO variant genotypes are combined suggesting that, CYP2D6 polymorphisms may play a role in the susceptibility to pediatric ALL, whereas the EPHX1, NQO1, and MPO polymorphisms might have a protective function against leukemogenesis.
authors: Department of Genetics, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil. vssilveira@usp.br
authors: Vanessa da Silva
authors: Vda S
authors: Silveira
authors: Renata
authors: R
authors: Canalle
authors: Carlos Alberto
authors: CA
authors: Scrideli
authors: Rosane Gomes de Paula
authors: RG
authors: Queiroz
authors: Luiz Gonzaga
authors: LG
authors: Tone
mesh_terms: D000293:Adolescent; D001938:Brazil; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D004851:Epoxide Hydrolases / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D016179:Granulocyte Colony-Stimulating Factor / Q000235:genetics*; D006801:Humans; D007223:Infant; D007377:Interleukin-3 / Q000235:genetics*; D008297:Male; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000235:genetics*; D011994:Recombinant Proteins
chemical_list: D007377:Interleukin-3; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; C404145:myelopoietin; D016179:Granulocyte Colony-Stimulating Factor; D019389:Cytochrome P-450 CYP2D6; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; D004851:Epoxide Hydrolases; C522330:EPHX1 protein, human