Investigation of an NQO1 polymorphism as a possible risk and prognostic factor for chronic lymphocytic leukemia.
NAD(P)H:quinoneoxidoreductase 1 (NQO1) inhibits some cancers and increases p53 and apoptosis in cells. Due to an inactivating polymorphism, 10% of humans have no NQO1 activity. A case:control study suggested that chronic lymphocytic leukemia (CLL) patients may have an increased incidence of the NQO1 null genotype compared with controls. NQO1 genotype did not correlate with various CLL prognostic factors, but we observed a trend toward lower drug response in patients with the NQO1 null genotype. Inhibiting NQO1 activity decreased p53 levels and drug induced apoptosis in CLL cells. These results raise the possibility that the NQO1 polymorphism may be a risk factor for CLL and a predictor of response to chemotherapy.
Begleiter
Asher
A
Manitoba Institute of Cell Biology, CancerCare Manitoba, Winnipeg, Manitoba, Canada. begleit@cc.umanitoba.ca
Hewitt
Donna
D
Gibson
Spencer B
SB
Johnston
James B
JB
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics*; D011110:Polymorphism, Genetic; D011379:Prognosis; D012307:Risk Factors
D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human