NQO1 rs1800566 (C609T), PON1 rs662 (Q192R), and PON1 rs854560 (L55M) polymorphisms segregate the risk of childhood acute leukemias according to age range distribution
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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.
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.
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).
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.
KeywordsInfant leukemia Acute lymphoblastic leukemia NQO1 PON1 Polymorphisms
This investigation was supported by the Brazilian National Research Council (CNPq), Instituto Nacional de Câncer and Fundação do Cancer Ary Frauzino. MSPO is supported by CNPq research scholarship #309091/2007. The project was granted by INCT-Controle do Cancer; CNPq #573806/2008-0 and FAPERJ E026/2008. We thank Dr. Davy Rapozo for helping with the setup of the technical procedures. We are grateful to Dr. Joseph L. Wiemels for helpful comments and reviewing the manuscript.
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