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We conducted a population-based case-control study of childhood acute lymphoblastic leukemia (ALL) to evaluate the risk posed by reported exposure to pesticides used in and around the home. We compared 491 cases 0–9 years of age to as many controls. We also conducted a case-only study on a sub sample of 123 cases to evaluate gene-environment interaction between child genotype and maternal exposure during pregnancy as well as child exposure after birth. We used the polymerase chain reaction (PCR) approach to analyze polymorphisms in CYP1A1, CYP2D6, GSTT1, and GSTM1 genes, which en code enzymes involved in carcinogen metabolism. Indoor use of some insecticides by the owners and pesticide use in the garden and on interior plants, in particular frequent prenatal use, was associated with increased risks up to several fold in magnitude. Interaction odds ratios were increased among carriers of the CYP1A1m1 and CYP1a1m2 mutations when mother during pregnancy or the child had been exposed to certain indoor insecticides. No such effects were observed in the presence of other tested polymorphisms.