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Prepublished online as a Blood First Edition Paper on August 1, 2002; DOI 10.1182/blood-2001-12-0264.
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Blood, 15 December 2002, Vol. 100, No. 13, pp. 4590-4593
NEOPLASIA
Low NAD(P)H:quinone oxidoreductase activity is associated
with increased risk of leukemia with MLL translocations in
infants and children
Martyn T. Smith,
Yunxia Wang,
Christine F. Skibola,
Diana J. Slater,
Luca Lo Nigro,
Peter C. Nowell,
Beverly J. Lange, and
Carolyn A. Felix
From the Division of Environmental Health Sciences,
School of Public Health, University of California, Berkeley; the
Division of Oncology, The Children's Hospital of Philadelphia, and the
Department of Pathology and Laboratory Medicine and the Department of
Pediatrics, University of Pennsylvania School of Medicine,
Philadelphia, PA.
An inactivating polymorphism at position 609 in the NAD(P)H:quinone
oxidoreductase 1 gene (NQO1 C609T) is associated with an
increased risk of adult leukemia. A small British study suggested that
NQO1 C609T was associated with an increased risk of infant leukemias with MLL translocations, especially infant acute
lymphoblastic leukemia (ALL) with t(4;11). We explored NQO1 C609T
as a genetic risk factor in 39 pediatric de novo and 18 pediatric
treatment-related leukemias with MLL translocations in the
United States. Children with de novo B-lineage ALL without
MLL translocations and a calculation of the expected
genotype distribution in an ethnically matched population of
disease-free subjects served as the comparison groups. Patients with de
novo leukemias with MLL translocations were significantly more likely to be heterozygous at NQO1 C609T (odds ratio
[OR] = 2.77, 95% confidence intervals [CI] 1.17-6.57;
P = .02), and significantly more likely to have low/null
NQO1 activity than patients with de novo B-lineage ALL without
MLL translocations (OR = 2.47, 95% CI 1.08-5.68;
P = .033). They were also significantly more likely to
have low/null NQO1 activity than expected in an ethnically matched
population of disease-free subjects (OR = 2.50, P = .02). Infants younger than 12 months old at diagnosis
of leukemia with t(4;11) were most likely to have low/null NQO1
activity (OR > 10.0). Conversely, the distribution of
NQO1 genotypes among patients with treatment-related
leukemias with MLL translocations was not statistically
different than in the comparison groups. The inactivating NQO1
polymorphism is associated with an increased risk of de novo
leukemia with MLL translocations in infants and children.
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