title: NQO1 C609T polymorphism in distinct entities of pediatric hematologic neoplasms.
abstract: OBJECTIVE
  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.
  
  
  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).
  
  
  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.
authors.affiliation: Pediatric Hematology/Oncology, Medical School of Hannover, Germany.
authors.forename: Thorben
authors.initials: T
authors.lastname: Kracht
authors.forename: Martin
authors.initials: M
authors.lastname: Schrappe
authors.forename: Sabine
authors.initials: S
authors.lastname: Strehl
authors.forename: Alfred
authors.initials: A
authors.lastname: Reiter
authors.forename: Holger-Andreas
authors.initials: HA
authors.lastname: Elsner
authors.forename: Jan
authors.initials: J
authors.lastname: Trka
authors.forename: Gunnar
authors.initials: G
authors.lastname: Cario
authors.forename: Susanne
authors.initials: S
authors.lastname: Viehmann
authors.forename: Jochen
authors.initials: J
authors.lastname: Harbott
authors.forename: Arndt
authors.initials: A
authors.lastname: Borkhardt
authors.forename: Markus
authors.initials: M
authors.lastname: Metzler
authors.forename: Thorsten
authors.initials: T
authors.lastname: Langer
authors.forename: Reinald
authors.initials: R
authors.lastname: Repp
authors.forename: Rolf
authors.initials: R
authors.lastname: Marschalek
authors.forename: Karl
authors.initials: K
authors.lastname: Welte
authors.forename: Oskar A
authors.initials: OA
authors.lastname: Haas
authors.forename: Martin
authors.initials: M
authors.lastname: Stanulla
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D002051:Burkitt Lymphoma / Q000201:enzymology / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D003062:Codon / Q000235:genetics; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics* / Q000502:physiology; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D010575:Pesticides / Q000009:adverse effects; D020641:Polymorphism, Single Nucleotide; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000201:enzymology / Q000235:genetics*; D012306:Risk; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D003062:Codon; D050676:Core Binding Factor Alpha 2 Subunit; D016044:Fusion Proteins, bcr-abl; D051788:Myeloid-Lymphoid Leukemia Protein; D016660:NAD(P)H Dehydrogenase (Quinone); D015514:Oncogene Proteins, Fusion; D010575:Pesticides; C113855:MLL-AF4 fusion protein, human; C102421:TEL-AML1 fusion protein; D000097764:ETS Translocation Variant 6 Protein; C447479:NQO1 protein, human