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Prepublished online as a Blood First Edition Paper on August 1, 2002; DOI 10.1182/blood-2001-12-0264. This Article Full Text (PDF) All Versions of this Article: 2001-12-0264v1 100/13/4590    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Smith, M. T Articles by Felix, C. A Search for Related Content PubMed PubMed Citation Articles by Smith, M. T Articles by Felix, C. A Social Bookmarking                   What's this? Submitted December 18, 2001 Accepted July 17, 2002 Low NAD(P)H:quinone oxidoreductase (NQO1) activity is associated with increased risk of leukemia with MLL translocations in infants and children Martyn T Smith*, Yunxia Wang, Christine F Skibola, Diane J Slater, Luca Lo Nigro, Peter C Nowell, Beverly J Lange, and Carolyn A Felix Division of Environmental Health Sciences, University of California-Berkeley School of Public Health, Berkeley, CA, USA Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA; Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA * Corresponding author; email: martynts{at}uclink4.berkeley.edu. 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 (OR=2.77, 95% C.I. 1.17, 6.57; p=0.02), 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% C.I. 1.08, 5.68; p=0.033). 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=0.02). Infants <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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