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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
2R01CA052689-11
Application #
6326317
Study Section
Special Emphasis Panel (ZRG1-EDC-2 (05))
Program Officer
Seminara, Daniela
Project Start
1991-05-15
Project End
2006-04-30
Budget Start
2001-09-28
Budget End
2002-04-30
Support Year
11
Fiscal Year
2001
Total Cost
$1,081,007
Indirect Cost
Name
University of California San Francisco
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Ostrom, Quinn T; Kinnersley, Ben; Armstrong, Georgina et al. (2018) Age-specific genome-wide association study in glioblastoma identifies increased proportion of 'lower grade glioma'-like features associated with younger age. Int J Cancer 143:2359-2366
Kinnersley, Ben; Houlston, Richard S; Bondy, Melissa L (2018) Genome-Wide Association Studies in Glioma. Cancer Epidemiol Biomarkers Prev 27:418-428
Disney-Hogg, Linden; Sud, Amit; Law, Philip J et al. (2018) Influence of obesity-related risk factors in the aetiology of glioma. Br J Cancer 118:1020-1027
Takahashi, Hannah; Cornish, Alex J; Sud, Amit et al. (2018) Mendelian randomisation study of the relationship between vitamin D and risk of glioma. Sci Rep 8:2339
Amirian, E Susan; Ostrom, Quinn T; Armstrong, Georgina N et al. (2018) Aspirin, Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), and Glioma Risk: Original Data from the Glioma International Case-Control Study and a Meta-Analysis. Cancer Epidemiol Biomarkers Prev :
Disney-Hogg, Linden; Cornish, Alex J; Sud, Amit et al. (2018) Impact of atopy on risk of glioma: a Mendelian randomisation study. BMC Med 16:42
Salas, Lucas A; Wiencke, John K; Koestler, Devin C et al. (2018) Tracing human stem cell lineage during development using DNA methylation. Genome Res 28:1285-1295
Ostrom, Quinn T; Kinnersley, Ben; Wrensch, Margaret R et al. (2018) Sex-specific glioma genome-wide association study identifies new risk locus at 3p21.31 in females, and finds sex-differences in risk at 8q24.21. Sci Rep 8:7352
Salas, Lucas A; Koestler, Devin C; Butler, Rondi A et al. (2018) An optimized library for reference-based deconvolution of whole-blood biospecimens assayed using the Illumina HumanMethylationEPIC BeadArray. Genome Biol 19:64
Jacobs, Daniel I; Liu, Yanhong; Gabrusiewicz, Konrad et al. (2018) Germline polymorphisms in myeloid-associated genes are not associated with survival in glioma patients. J Neurooncol 136:33-39

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