title: NQO1 rs1800566 (C609T), PON1 rs662 (Q192R), and PON1 rs854560 (L55M) polymorphisms segregate the risk of childhood acute leukemias according to age range distribution.
abstract: OBJECTIVE
  The risk of developing childhood leukemia has been associated with gene polymorphisms that decrease the activity of detoxifying metabolic enzymes and enzymes involved in systemic oxidative stress. We investigated the NQO1 and PON1 polymorphisms for associations with susceptibility to childhood leukemia.
  
  
  METHODS
  Samples from 1,027 Brazilian children (519 acute lymphoblastic leukemia, ALL; 107 acute myeloid leukemia, AML; 401 controls) were analyzed. TaqMAN real-time assays were used to determine the NQO1 rs1800566 (C609T), PON1 rs662 (Q192R), and PON1 rs854560 (L55M) frequencies. Logistic regression was used to evaluate the association of polymorphisms with cases and controls, with age and somatic fusion genes (MLL-r and ETV6-RUNX1) as covariables.
  
  
  RESULTS
  Children with at least one NQO1 variant allele were at lower risk for developing infant AML (odds ratio (OR) 0.26, 95 % confidence interval (CI) 0.10-0.68); no association was detected for ALL. PON1 rs854560 (L55M) was associated with an increased risk of developing childhood leukemia (LM + MM, OR 1.93, 95 % CI 1.32-2.81). The PON1 rs662 R192R genotype had a statistically significant decreased frequency in ALL (OR 0.64, 95 % CI 0.43-0.93). Infant ALL cases were more likely to harbor homozygous PON1 rs854560 alleles than controls (OR 1.72, 95 % CI 1.03-2.89); at least one M allele was associated with an increased risk of ALL in children older than 1 year (OR 1.99, 95 % CI 1.17-3.3).
  
  
  CONCLUSIONS
  The NQO1 rs1800566 (C609T), PON1 rs854560 (L55M), and PON1 rs662 (Q192R) polymorphisms modified risk depending on leukemia subtype (decreased in AML, increased and decreased in ALL, respectively), age strata, and variant genotype combinations.
authors.affiliation: Pediatric Hematology-Oncology Program, Research Center, Instituto Nacional de Câncer, Rua André Cavalcanti 37, Rio de Janeiro, RJ 20231050, Brazil.
authors.forename: Bruno Alves
authors.initials: BA
authors.lastname: de Aguiar Gonçalves
authors.forename: Gisele M
authors.initials: GM
authors.lastname: Vasconcelos
authors.forename: Luiz Claudio Santos
authors.initials: LC
authors.lastname: Thuler
authors.forename: Camilla
authors.initials: C
authors.lastname: Andrade
authors.forename: Alessandra
authors.initials: A
authors.lastname: Faro
authors.forename: Maria S
authors.initials: MS
authors.lastname: Pombo-de-Oliveira
authors.forename: Mariana
authors.initials: M
authors.lastname: Emerenciano
authors.forename: Beatriz
authors.initials: B
authors.lastname: de Camargo
authors.forename: Luna
authors.initials: L
authors.lastname: Bernstain
authors.forename: Cynthia Curvello
authors.initials: CC
authors.lastname: Neves
authors.forename: Jozina Maria de Andrade
authors.initials: JM
authors.lastname: Agareno
authors.forename: Lilian Maria Burlacchini
authors.initials: LM
authors.lastname: de Carvalho
authors.forename: Flávia Nogueira Serafim
authors.initials: FN
authors.lastname: Araújo
authors.forename: Nilma Pimentel
authors.initials: NP
authors.lastname: de Brito
authors.forename: Isis Q
authors.initials: IQ
authors.lastname: Magalhães
authors.forename: José Carlos
authors.initials: JC
authors.lastname: Cordoba
authors.forename: Flávia
authors.initials: F
authors.lastname: Pimenta
authors.forename: Andreia
authors.initials: A
authors.lastname: Gadelha
authors.forename: Eloísa
authors.initials: E
authors.lastname: Cartaxo
authors.forename: Rosania Maria
authors.initials: RM
authors.lastname: Basegio
authors.forename: Atalla
authors.initials: A
authors.lastname: Mnayarji
authors.forename: Marcelo S
authors.initials: MS
authors.lastname: Souza
authors.forename: Alejandro
authors.initials: A
authors.lastname: Arencibia
authors.forename: Renato
authors.initials: R
authors.lastname: Melaragno
authors.forename: Virgínia Maria
authors.initials: VM
authors.lastname: Cóser
authors.forename: Thereza Christina
authors.initials: TC
authors.lastname: Lafayete
authors.forename: Sergio
authors.initials: S
authors.lastname: Koifman
mesh_terms: D017677:Age Distribution; D000483:Alleles; D043303:Aryldialkylphosphatase / Q000235:genetics* / Q000378:metabolism; D001938:Brazil / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D005838:Genotype; D006801:Humans; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000201:enzymology* / Q000453:epidemiology / Q000235:genetics*; D012307:Risk Factors
chemical_list: D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human