. This is the second submission for the continuation of a case-control study of gliomas. The originally funded study focussed on questionnaire risk factors and segregation analysis, and the current plan is to continue case and control recruitment, and to broaden the work to include metabolic susceptibility polymorphisms. Although diverse familial and environmental risk factors have been implicated in this cancer, no dominant factors have yet emerged. Recent studies suggest etiologic heterogeneity, even within histologic types. The application builds on the assumption that tumor status for p53 may be used to define a more homogeneous subset of glioma. The application proposes to enroll 400 additional adult cases in 6 San Francisco counties, and 400 population-based controls obtained through random digit dialing, frequency matched to the cases on age, sex, and race. In-person interviews with an abbreviated version of the original questionnaire will request information on family and personal medical history, occupation, smoking, and other factors. Dietary assessment with food models with emphasize antioxidant consumption and potential carcinogenicity of foods. Blood will be collected from all willing subjects. Polymorphisms for glutathione sulfotransferases mu (GSTM1) and theta (GSTT), cytochromes p450 1A1 (CYP1A1) and 2D6 (CYP2D6), N-acetyl-transferase 2 (NAT2), and epoxide hydrolase (EPHX) will be determined for all new and 357 original subjects with blood specimens. Immunohistochemistry of astrocytic tumors will detect unusual accumulation of 53 kDa protein (p53); molecular methods will determine mutations in a defined subset. Analysis will address 4 aims: to 1) replicated preliminary findings of an association of GSTM1 deletion in women with an early onset; 2) test hypotheses that p53+ cases will be more likely than p53- cases to consume highly carcinogenic foods and less likely to consume antioxidants or be homozygously deleted for GSTM1; 3) compare frequencies of polymorphisms in other genes between p53+ and p53- cases; and 4) conduct exploratory analyses of other risk factors stratifying by genotype and p53 status of case tumors. High risk families will be ascertained to facilitate future linkage studies.
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