Genetic variability in N-acetyltransferase 2 gene determines susceptibility to childhood lymphoid or myeloid leukemia in Brazil

Abstract

Seven single nucleotide polymorphisms (SNPs) were genotyped in 535 Brazilian children (158 with acute lymphoblastic leukemia [ALL], 74 with acute myeloid leukemia [AML] and 303 controls). The subjects were classified as fast or slow acetylators based on their genotypic variants. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals. N-acetyltransferase 2 (NAT2) SNP 341T > C frequency was higher among both leukemia subtypes compared to controls. There was also a significant difference in the frequency of SNP 590G > A in AML (OR, 1.57, 1.07–2.30). The haplotypes *14A, *5A and *5C conferred an increased risk in cases of ALL, while *14E, *6B and *6F conferred an increased risk for AML. An age-dependent analysis demonstrated that the NAT2 slow-acetylators conferred an increased risk association with leukemia in children ≤ 1 year old (OR, 7.91, 3.87–16.16) and also in older children (1 ≥ 10 years old) (OR, 1.53, 1.01–2.31). However, in this latter group the magnitude was reduced. The results demonstrate that the different NAT2 haplotypes contribute to the risk of either ALL or AML.

Keywords::

• Acute lymphoblastic leukemia
• acute myeloid leukemia
• NAT2
• polymorphisms

Acknowledgements

This work was made possible due to the collaboration of physicians from different regions of Brazil who provided samples and clinical data. We are also grateful to the children and parents who agreed to participate in the study. The authors are currently supported by grants from the Brazilian National Research Council (CNPq) (CNPq-INCT#573806/20008-0) and FAPERJ (E26/170.026/2008). The funding body had no influence on the study design; the collection, analysis or interpretation of data; the writing of the manuscript; or the decision to submit the manuscript for publication.

Potential conflict of interest:

Disclosure forms provided by the authors are available with the full text of this article at www.informahealthcare.com/lal.