NQO1 C609T polymorphism in distinct entities of pediatric hematologic neoplasms

Thorben Kracht, Martin Schrappe, Sabine Strehl, Alfred Reiter, Holger Andreas Elsner, Jan Trka, Gunnar Cario, Susanne Viehmann, Jochen Harbott, Arnot Borkhardt, Markus Metzler, Thorsten Langer, Reinald Repp, Rolf Marschalek, Karl Welte, Oskar A. Haas, Martin Stanulla*

*Corresponding author for this work
36 Citations (Scopus)

Abstract

Background and Objectives. NAD(P)H:quinone oxidoreductase 1 (NQO1) is an enzyme that protects cells against mutagenicity from free radicals and toxic oxygen metabolites. The gene coding for NQO1 is subject to a genetic polymorphism at nucleotide position 609 (C→T) of the human NQO1 cDNA. Heterozygous individuals (C/T) have intermediate activity and homozygotes for the variant allele (T/T) are deficient in NQO1 activity. In previous studies, genotypes conferring lower NQO1 activity have been associated with an increased risk of acute leukemia, particularly infant leukemia carrying MLL/AF4 fusion genes. In the present study, we investigated this association in our population and extended the analysis to other subgroups of pediatric hematologic neoplasms characterized by specific fusion genes. Design and Methods. We genotyped 138 patients with childhood acute lymphoblastic leukemia (ALL) carrying distinct fusion genes (MLL/AF4=35; BCR/ABL=31; TEL/AML1=72), 71 cases of pediatric sporadic Burkitt's lymphoma and 190 healthy control individuals for the NQO1 C609T polymorphism. Results: When compared to the healthy control group, only children with Burkitt's lymphoma significantly more often had NQO1 genotypes associated with lower NQO1 activity (odds ratio, 1.81; p=0.036), predominantly at a younger age (< 9 years at diagnosis: odds ratio, 3.02; p=0.003). Interpretation and Conclusions. Our results suggest that in our population the NQO1 C609T polymorphism does not confer an increased risk of the investigated entities of childhood ALL However, there may be a modulating role for NQO1 in the pathogenesis of pediatric sporadic Burkitt's lymphoma.

Original languageEnglish
JournalHaematologica
Volume89
Issue number12
Pages (from-to)1492-1497
Number of pages6
ISSN0390-6078
Publication statusPublished - 12.2004

Research Areas and Centers

  • Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)

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