Grant Number:	5R01CA052689-14 Interpret this number
Primary Investigator:	Wrensch, Margaret
Organization:	University Of California, San Francisco
Project Title:	Genetic and Molecular Epidemiology of Adult Glioma
Fiscal Year:	2004

Malignant gliomas are debilitating and rapidly fatal. It is increasingly evident that substantial etiologic heterogeneity exists within major histologic types of glioma. This may partly explain why no dominant etiologic risk factors have emerged from the diverse factors previously implicated. The purpose of our research is to identify important risk factors for genetically defined subgroups of glioma. This competitive renewal evolved from our and others' results suggesting that standard glioma risk factors such as age, ethnicity, and gender, as well as history of certain infections and allergies, serologic factors, dietary carcinogens and antioxidants, and genetic variation in detoxification and DNA repair may differentially influence risk to specific histologic and genetically defined subgroups of glioma. We will build on our two population based series to further the understanding of genetic modulation of environmental and host factors influencing gliomagenesis. We will accrue another 700 glioma cases diagnosed from 11/1/01- 12/1/04 in six San Francisco area counties using rapid case ascertainment and Kaiser Permanente clinics and appropriate population based controls obtained through random-digit dialing. In-person interviews with our existing questionnaires elicit information on many relevant factors including family and personal medical histories, occupation, and dietary preferences. Blood and buccal specimens will be collected from all willing subjects and pathology reports, slides and tumor tissue will be collected from cases. Blood specimens will be collected prior to surgery for cases diagnosed at Kaiser Permanente. We will (1) categorize astrocytic tumors according to expression of p53, EGFR, and MDM2 and to p53 mutation, EGFR and MDM2 amplifications and p14arf and p16 deletions; (2) genotype subjects for pertinent detoxification, DNA repair and immune function genes (glutathione transferase mu and theta, epoxide hydrolase, ERCC1, ERCC2, XRCC1, and alkylguanine transferase, IL-4R, IL-13, IL-13R and RANTES); (3) assay subjects' antibodies to varicella zoster, other herpes viruses and certain allergens and determine T-cell proliferation to these antigenic challenges; (4) test several specific hypotheses based on preliminary data; (5) compare histologically or molecularly defined case subgroups with controls for genotypes, serologies, allergies, dietary and other risk factors with multiple logistic regressions; and (6) determine if short- term glioma survival is associated with study factors to refine inferences about effects of factors in gliomagenesis versus tumor progression.





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