TY - JOUR
T1 - NQO1 C609T polymorphism in distinct entities of pediatric hematologic neoplasms
AU - Kracht, Thorben
AU - Schrappe, Martin
AU - Strehl, Sabine
AU - Reiter, Alfred
AU - Elsner, Holger Andreas
AU - Trka, Jan
AU - Cario, Gunnar
AU - Viehmann, Susanne
AU - Harbott, Jochen
AU - Borkhardt, Arnot
AU - Metzler, Markus
AU - Langer, Thorsten
AU - Repp, Reinald
AU - Marschalek, Rolf
AU - Welte, Karl
AU - Haas, Oskar A.
AU - Stanulla, Martin
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2004/12
Y1 - 2004/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=10444228837&partnerID=8YFLogxK
M3 - Journal articles
C2 - 15590400
AN - SCOPUS:10444228837
SN - 0390-6078
VL - 89
SP - 1492
EP - 1497
JO - Haematologica
JF - Haematologica
IS - 12
ER -