Exploring Gene-Environment Factors in Child Brain Tumors

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DESCRIPTION (provided by applicant): The causes of childhood brain tumors (CBT) are largely unknown. Environmental exposures are thought to play a role due to the vulnerability of fetal and early childhood brain to environmental toxins. This project would improve our limited understanding of the relationships of environmental and genetic factors in CBT occurrence by providing necessary preliminary data about the frequency of selected polymorphisms in CBT cases and controls, and demonstrating the feasibility of measuring polymorphisms in dried blood spots (DBS) from newborn screening archives for population-based epidemiologic studies of CBT, thus positioning us for larger CBT studies examining genes and environment. We have an opportunity to gain this information efficiently and economically, as specimens and exposure data already have been obtained. We propose to measure polymorphisms for genes which code for enzymes that metabolize chemicals potentially related to CBT occurrence, in DBS collected from 66 CBT cases and 237 controls. We will compare polymorphisms for the following genes: 1) Cytochrome P-450 (CYP) 2E1 and CYP 2D6, coding Phase I enzymes that activate nitrosamines and other chemicals into cancer-causing intermediates; 2) Glutathione S-transferase (GST) (GSTP1, GSTT1, and GSTM1), which code for Phase II enzymes that detoxify organochlorine pesticides, nitrosoureas, CYP-activated nitrosamines, polycyclic aromatic hydrocarbons (PAH); 3) Microsomal epoxide hydrolase, relevant to activation of PAHs into cancer-causing intermediates; 4) Paraoxonase (PON1), potentially important in detoxifying metabolites of the common organophosphate (OP) insecticides chlorpyrifos and diazinon. To the extent possible with these data, we will describe polymorphisms within histologic categories and by age at diagnosis, and examine their relationship with relevant environmental exposures among a subset of subjects with exposure data for the prenatal and early childhood periods.