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Blood, 1 March 2001, Vol. 97, No. 5, pp. 1422-1426
NEOPLASIA
Low NAD(P)H:quinone oxidoreductase 1 activity is
associated with increased risk of acute leukemia in adults
Martyn T. Smith,
Yunxia Wang,
Eleanor Kane,
Sara Rollinson,
Joseph L. Wiemels,
Eve Roman,
Philippa Roddam,
Raymond Cartwright, and
Gareth Morgan
From the Division of Environmental Health Sciences,
School of Public Health, University of California, Berkeley, CA;
Leukaemia Research Fund Centre for Clinical Epidemiology, Leeds, United
Kingdom; and Department of Haematology, University of Leeds, Leeds,
United Kingdom.
NAD(P)H:quinone oxidoreductase 1 (NQO1) is an
enzyme that detoxifies quinones and reduces oxidative stress. A
cysteine-to-threonine (C  T) substitution polymorphism at
nucleotide 609 of the NQO1 complementary DNA (NQO1
C609T) results in a lowering of NQO1 activity. Individuals homozygous for this mutation have no NQO1 activity, and
heterozygotes have low to intermediate activity compared with people
with wild type. DNA samples from 493 adult de novo acute leukemia patients and 838 matched controls were genotyped for NQO1 C609T. The majority of cases were diagnosed as acute
myeloid leukemia (AML) (n = 420); 67 as acute lymphoblastic leukemia
(ALL); and 6 as other forms of acute leukemia. The frequency of cases with low or null NQO1 activity (heterozygote + homozygous mutant) was significantly higher among total acute leukemia case subjects compared with their matched controls (odds ratio [OR] = 1.49; 95%
confidence interval [CI], 1.17-1.89). Both ALL (OR = 1.93; 95% CI,
0.96-3.87) and AML case subjects (OR = 1.47; 95% CI, 1.13-1.90) exhibited a higher frequency of low or null NQO1
genotypes than controls. For de novo AML, the most significant effect
of low or null NQO1 activity was observed among the 88 cases harboring translocations and inversions (OR = 2.39; 95% CI, 1.34-4.27)
and was especially high for those harboring inv(16) (OR = 8.13; 95% CI, 1.43-46.42). These findings were confirmed in a second group of 217 de novo AML cases with known cytogenetics. Thus, inheritance of
NQO1 C609T confers an increased risk of de novo acute
leukemia in adults, implicating quinones and related compounds that
generate oxidative stress in producing acute leukemia.
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