AUTHOR=Medina-Sanson Aurora , Núñez-Enríquez Juan Carlos , Hurtado-Cordova Eduardo , Pérez-Saldivar María Luisa , Martínez-García Anayeli , Jiménez-Hernández Elva , Fernández-López Juan Carlos , Martín-Trejo Jorge Alfonso , Pérez-Lorenzana Héctor , Flores-Lujano Janet , Amador-Sánchez Raquel , Mora-Ríos Felix Gustavo , Peñaloza-González José Gabriel , Duarte-Rodríguez David Aldebarán , Torres-Nava José Refugio , Flores-Bautista Juan Eduardo , Espinosa-Elizondo Rosa Martha , Román-Zepeda Pedro Francisco , Flores-Villegas Luz Victoria , González-Ulivarri Juana Esther , Martínez-Silva Sofía Irene , Espinoza-Anrubio Gilberto , Almeida-Hernández Carolina , Ramírez-Colorado Rosario , Hernández-Mora Luis , García-López Luis Ramiro , Cruz-Ojeda Gabriela Adriana , Godoy-Esquivel Arturo Emilio , Contreras-Hernández Iris , Medina-Hernández Abraham , López-Caballero María Guadalupe , Hernández-Pineda Norma Angélica , Granados-Kraulles Jorge , Rodríguez-Vázquez María Adriana , Torres-Valle Delfino , Cortés-Reyes Carlos , Medrano-López Francisco , Pérez-Gómez Jessica Arleet , Martínez-Ríos Annel , Aguilar-De los Santos Antonio , Serafin-Díaz Berenice , Bekker-Méndez Vilma Carolina , Mata-Rocha Minerva , Morales-Castillo Blanca Angélica , Sepúlveda-Robles Omar Alejandro , Ramírez-Bello Julián , Rosas-Vargas Haydeé , Hidalgo-Miranda Alfredo , Mejía-Aranguré Juan Manuel , Jiménez-Morales Silvia 

TITLE=Genotype-Environment Interaction Analysis of NQO1, CYP2E1, and NAT2 Polymorphisms and the Risk of Childhood Acute Lymphoblastic Leukemia: A Report From the Mexican Interinstitutional Group for the Identification of the Causes of Childhood Leukemia

JOURNAL=Frontiers in Oncology

VOLUME=10

YEAR=2020

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.571869

DOI=10.3389/fonc.2020.571869

ISSN=2234-943X

ABSTRACT=<p><bold>Background:</bold> Acute lymphoblastic leukemia (ALL) is the main type of cancer in children. In Mexico and other Hispanic populations, the incidence of this neoplasm is one of the highest reported worldwide. Functional polymorphisms of various enzymes involved in the metabolism of xenobiotics have been associated with an increased risk of developing ALL, and the risk is different by ethnicity. The aims of the present study were to identify whether <italic>NQO1, CYP2E1</italic>, and <italic>NAT2</italic> polymorphisms or some genotype-environmental interactions were associated with ALL risk in Mexican children.</p><p><bold>Methods:</bold> We conducted a case-control study including 478 pediatric patients diagnosed with ALL and 284 controls (children without leukemia). Ancestry composition of a subset of cases and controls was assessed using 32 ancestry informative markers. Genetic-environmental interactions for the exposure to hydrocarbons were assessed by logistic regression analysis.</p><p><bold>Results:</bold> The polymorphisms rs1801280 (OR 1.54, 95% CI 1.21–1.93), rs1799929 (OR 1.96, 95% CI 1.55–2.49), and rs1208 (OR 1.44, 95% CI 1.14–1.81) were found to increase the risk of ALL; being the risks higher under a recessive model (OR 2.20, 95% CI 1.30–1.71, OR 3.87, 95% CI 2.20–6.80, and OR 2.26, 95% CI 1.32–3.87, respectively). Gene-environment interaction analysis showed that <italic>NAT2</italic> rs1799929 TT genotype confers high risk to ALL under exposure to fertilizers, insecticides, hydrocarbon derivatives, and parental tobacco smoking. No associations among <italic>NQO1, CYP2E1</italic>, and ALL were observed.</p><p><bold>Conclusion:</bold> Our study provides evidence for the association between <italic>NAT2</italic> polymorphisms/gene-environment interactions, and the risk of childhood ALL in Mexican children.</p>