Frontiers in Oncology (Sep 2020)

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

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

DOI
https://doi.org/10.3389/fonc.2020.571869
Journal volume & issue
Vol. 10

Abstract

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Background: 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 NQO1, CYP2E1, and NAT2 polymorphisms or some genotype-environmental interactions were associated with ALL risk in Mexican children.Methods: 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.Results: 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 NAT2 rs1799929 TT genotype confers high risk to ALL under exposure to fertilizers, insecticides, hydrocarbon derivatives, and parental tobacco smoking. No associations among NQO1, CYP2E1, and ALL were observed.Conclusion: Our study provides evidence for the association between NAT2 polymorphisms/gene-environment interactions, and the risk of childhood ALL in Mexican children.

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