Excess transmission of the NAD(P)H:quinone oxidoreductase 1 (NQO1) C609T polymorphism in families of children with acute lymphoblastic leukemia.
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.
Infante-Rivard
Claire
C
Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montréal, Québec, Canada. claire.infante-rivard@mcgill.ca
Vermunt
Jeroen K
JK
Weinberg
Clarice R
CR
D000293:Adolescent; D001554:Benzene / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D005192:Family Health; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D040582:Inheritance Patterns; D016013:Likelihood Functions; D016014:Linear Models; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics*; D016273:Occupational Exposure / Q000009:adverse effects; D011110:Polymorphism, Genetic; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000453:epidemiology* / Q000235:genetics*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000453:epidemiology / Q000235:genetics; D011792:Quebec / Q000453:epidemiology; D012306:Risk; D012907:Smoking / Q000009:adverse effects
D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; D001554:Benzene