American Journal of Epidemiology Advance Access published online on March 1, 2007
American Journal of Epidemiology, doi:10.1093/aje/kwm022
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ORIGINAL CONTRIBUTION |
Excess Transmission of the NAD(P)H:Quinone Oxidoreductase 1 (NQO1) C609T Polymorphism in Families of Children with Acute Lymphoblastic Leukemia
1 Department of Epidemiology, Biostatistics and Occupational Health, Faculty of Medicine, McGill University, Montréal, Québec, Canada
2 Department of Methodology and Statistics, Faculty of Social and Behavioral Sciences, Tilburg University, Tilburg, the Netherlands
3 Biostatistics Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC
Correspondence to Dr. Claire Infante-Rivard, Department of Epidemiology, Biostatistics, and Occupational Health, Faculty of Medicine, McGill University, 1110 Pine Avenue West, Montréal, Québec H3A 1A3, Canada (e-mail: claire.infante-rivard{at}mcgill.ca).
Received for publication May 19, 2006. Accepted for publication November 13, 2006.
Topoisomerase II is a DNA-processing enzyme, and secondary acute myeloid leukemia has been associated with exposure to drugs that inhibit its action. Hence, prenatal exposure to chemicals that inhibit topoisomerase II could plausibly contribute to the incidence of childhood leukemia. The NAD(P)H:quinone oxidoreductase 1 (NQO1) enzyme is involved in the metabolism of topoisomerase II-inhibiting chemicals. A functional polymorphism (C609T) associated with reduced activity has been identified on the NQO1 gene. To assess its role in the etiology of childhood acute lymphoblastic leukemia, the authors studied transmission of the variant T allele in the families (parents and grandparents) of 657 affected children in Québec, Canada (1980–2000). Log-linear models that stratified on parental or grandparental mating types were used. Prenatal exposure to potential topoisomerase II inhibitors such as benzene and maternal smoking was studied, as well as interactions between the variant and these exposures. The variant allele was transmitted to cases more frequently than expected (for one or two copies of the allele vs. none, relative risk = 1.39, 95% confidence interval: 1.07, 1.79). There was no evidence of a maternally mediated genetic effect on risk, based on a log-linear assessment of genetic symmetry between mothers and fathers, nor was there evidence of interaction between the studied maternal exposures and the child or maternal variant.
association; child; infant; leukemia; linkage (genetics); models, genetic; NAD(P)H dehydrogenase (quinone); polymorphism, genetic
Abbreviations: ALL, acute lymphoblastic leukemia; CI, confidence interval; EDTA, ethylenediaminetetraacetic acid; MLL, mixed lineage leukemia; NQO1, NAD(P)H:quinone oxidoreductase 1; PCR, polymerase chain reaction
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