NQO1 C609T polymorphism in distinct entities of pediatric hematologic neoplasms.
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.
Kracht
Thorben
T
Pediatric Hematology/Oncology, Medical School of Hannover, Germany.
Schrappe
Martin
M
Strehl
Sabine
S
Reiter
Alfred
A
Elsner
Holger-Andreas
HA
Trka
Jan
J
Cario
Gunnar
G
Viehmann
Susanne
S
Harbott
Jochen
J
Borkhardt
Arndt
A
Metzler
Markus
M
Langer
Thorsten
T
Repp
Reinald
R
Marschalek
Rolf
R
Welte
Karl
K
Haas
Oskar A
OA
Stanulla
Martin
M
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
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