Role of the CYP2D6, EPHX1, MPO, and NQO1 genes in the susceptibility to acute lymphoblastic leukemia in Brazilian children

• Published in: Environmental and molecular mutagenesis Vol. 51; no. 1; pp. 48 - 56
• Main Authors: Silveira, Vanessa da Silva, Canalle, Renata, Scrideli, Carlos Alberto, Queiroz, Rosane Gomes de Paula, Tone, Luiz Gonzaga
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 2010; Wiley-Liss
• Subjects: Adolescent; Biological and medical sciences; Brazil; childhood ALL; CYP2D6; Cytochrome P-450 CYP2D6 - genetics; EPHX1; Epoxide Hydrolases - genetics; Female; Fundamental and applied biological sciences. Psychology; genetic polymorphisms; Genetic Predisposition to Disease; Genetics of eukaryotes. Biological and molecular evolution; Granulocyte Colony-Stimulating Factor - genetics; Humans; Infant; Interleukin-3 - genetics; Male; Medical sciences; MPO; NAD(P)H Dehydrogenase (Quinone) - genetics; NQO1; Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics; Recombinant Fusion Proteins - genetics; Recombinant Proteins; Toxicology; South America; Brazil; America; Africa; Human; NQO1; EPHX1; Acute leukemia; genetic polymorphisms; MPO; Sensitivity; Toxicology; CYP2D6; Genetics; childhood ALL; Acute lymphocytic leukemia; Child; Polymorphism
• ISSN: 0893-6692; 1098-2280
• DOI: 10.1002/em.20510

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. Environ. Mol. Mutagen., 2010.