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American Journal of Epidemiology Advance Access published online on October 22, 2008
American Journal of Epidemiology, doi:10.1093/aje/kwn246
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American Journal of Epidemiology © The Author 2008. Published by the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org.

NQO1 Polymorphisms and De Novo Childhood Leukemia: A HuGE Review and Meta-Analysis

Neela Guha, Jeffrey S. Chang, Anand P. Chokkalingam, Joseph L. Wiemels, Martyn T. Smith and Patricia A. Buffler

Correspondence to Neela Guha, University of California at Berkeley, Northern California Childhood Leukemia Study, 2150 Shattuck Avenue, Suite 500, Berkeley, CA 94704 (e-mail: neela{at}berkeley.edu).

Received for publication September 27, 2007. Accepted for publication July 16, 2008.

Polymorphisms in NQO1, a gene coding for the phase II enzyme involved in the detoxification of quinone carcinogens, have been associated with childhood leukemia in some studies, although the observed direction and magnitude of effects have been inconsistent. Therefore, the authors systematically reviewed all published reports describing the effect of NQO1 in de novo childhood leukemia and conducted a meta-analysis of 7 case-control studies that examined the association between NQO1*2 and childhood leukemia. Although a family-based study previously demonstrated overtransmission of this allele among childhood acute lymphoblastic leukemia cases, the meta-analysis showed that the presence of a NQO1*2 variant allele, which reduces the activity of the enzyme NAD(P)H:quinone oxidoreductase 1 (NQO1), had no significant effect on childhood leukemia. However, there was an increased risk associated with having at least 1 copy of the NQO1*2 allele in a subset of cases with MLL translocations (summary odds ratio = 1.39, 95% confidence interval: 0.98, 1.97). Heterogeneity between studies may be due to differences in population exposures to NQO1 substrates and small sample sizes, as well as potential population stratification in non-family-based studies. Therefore, further research is warranted on the role of NQO1 polymorphisms in the etiology of childhood leukemia, especially among MLL-positive leukemias.

epidemiology; leukemia; meta-analysis; NAD(P)H dehydrogenase (quinone); NQO1 ; polymorphism, single nucleotide; systematic review

Abbreviations: ALL, acute lymphoblastic leukemia; AML, acute myeloid leukemia; CI, confidence interval; NQO1, NAD(P)H:quinone oxidoreductase 1; OR, odds ratio; SNP, single nucleotide polymorphism

Editor's note: This paper is also available on the website of the Human Genome Epidemiology Network (http://www.cdc.gov/genomics/hugenet/).


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RE: "NQO1 POLYMORPHISMS AND DE NOVO CHILDHOOD LEUKEMIA: A HUGE REVIEW AND META-ANALYSIS"
Am. J. Epidemiol., May 15, 2009; 169(10): 1280 - 1280.
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 Am J EpidemiolHome page
N. Guha, J. S. Chang, A. P. Chokkalingam, J. L. Wiemels, M. T. Smith, and P. A. Buffler
THE AUTHORS REPLY
Am. J. Epidemiol., May 15, 2009; 169(10): 1279 - 1279.
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 Am J EpidemiolHome page
M. Lanciotti and C. Dufour
Re: "NQO1 POLYMORPHISMS AND DE NOVO CHILDHOOD LEUKEMIA: A HUGE REVIEW AND META-ANALYSIS"
Am. J. Epidemiol., May 15, 2009; 169(10): 1278 - 1279.
[Full Text] [PDF]


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