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Grant Details

Grant Number: 5R01CA052689-22 Interpret this number
Primary Investigator: Wrensch, Margaret
Organization: University Of California, San Francisco
Project Title: Genetic and Molecular Epidemiology of Adult Glioma
Fiscal Year: 2012
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Abstract

DESCRIPTION (provided by applicant): Glioma is a debilitating, often rapidly fatal cancer. Two recent genome wide association studies including one by our group discovered and confirmed three regions associated with risk of glioblastoma and other high grade glioma, and two additional regions that are likely to be associated with risk of lower grade glioma. Two of the glioma risk genes, TERT and RTEL1, are related to telomere maintenance. Polymorphisms (SNPs) in a third risk region in chromosome 9p21 (commonly deleted in glioblastoma) suggest a role for variation in the cell cycle gene CDKN2B in gliomagenesis. These represent the first consistent and highly significant genetic risk factors for glioma which provide a completely new perspective on glioma epidemiology and form a basis for this fifth grant cycle of our San Francisco Bay Area Glioma Study. In this application, we build on our extensive data and biospecimen repository and continuing recruitment at our site of adult glioma cases and controls supported through the Glioma International Case Control Study (R01CA139020). The Specific Aims are to: (1) Examine associations of patients' genotypic risk profile with meaningful histologic and molecular subtypes of glioma including IDH1 and IDH2 mutations, P53 and EGFR mutation status, and the ontological status of brain tumors related to gene expression. (2) Perform functional genomic experiments for glioma risk SNPs in CDKN2B (9p21), TERT, RTEL1, in vitro or model systems and in cell culture isolates (lymphocytes) derived from our epidemiologic recruitment and use bioinformatic analyses to discover effects of SNPs on transcription factor binding or disruption of gene function. (3) Conduct a thorough examination of the association of inherited variation in all known telomere-related genes with glioma risk through genotyping and analysis of a comprehensive set of candidate SNPs in telomere related genes in astrocytic glioma cases and controls. In addition to being part of the recently funded Glioma International Case Control study and the brain tumor SPORE program, our existing biorepository and data from this grant's previous 20 years of studies reduce costs for this proposed study. Our ongoing active collaborations with other glioma researchers ensure coordination and harmonization of results and maximize opportunities for rapid translation.

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Publications

Rare and uncommon genetic variants may hold key to the 'missing heritability' in glioma.
Authors: Egan KM, Wrensch MR, Jenkins RB
Source: CNS Oncol, 2012 Nov;1(2), p. 109-12.
PMID: 25057857
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Decreased NK cells in patients with head and neck cancer determined in archival DNA.
Authors: Accomando WP, Wiencke JK, Houseman EA, Butler RA, Zheng S, Nelson HH, Kelsey KT
Source: Clin Cancer Res, 2012 Nov 15;18(22), p. 6147-54.
EPub date: 2012 Sep 26.
PMID: 23014525
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A variable age of onset segregation model for linkage analysis, with correction for ascertainment, applied to glioma.
Authors: Sun X, Vengoechea J, Elston R, Chen Y, Amos CI, Armstrong G, Bernstein JL, Claus E, Davis F, Houlston RS, Il'yasova D, Jenkins RB, Johansen C, Lai R, Lau CC, Liu Y, McCarthy BJ, Olson SH, Sadetzki S, Schildkraut J, Shete S, Yu R, Vick NA, Merrell R, Wrensch M, Yang P, Melin B, Bondy ML, Barnholtz-Sloan JS, Gliogene Consortium
Source: Cancer Epidemiol Biomarkers Prev, 2012 Dec;21(12), p. 2242-51.
EPub date: 2012 Sep 7.
PMID: 22962404
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Peripheral blood immune cell methylation profiles are associated with nonhematopoietic cancers.
Authors: Koestler DC, Marsit CJ, Christensen BC, Accomando W, Langevin SM, Houseman EA, Nelson HH, Karagas MR, Wiencke JK, Kelsey KT
Source: Cancer Epidemiol Biomarkers Prev, 2012 Aug;21(8), p. 1293-302.
EPub date: 2012 Jun 19.
PMID: 22714737
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Distinct germ line polymorphisms underlie glioma morphologic heterogeneity.
Authors: Jenkins RB, Wrensch MR, Johnson D, Fridley BL, Decker PA, Xiao Y, Kollmeyer TM, Rynearson AL, Fink S, Rice T, McCoy LS, Halder C, Kosel ML, Giannini C, Tihan T, O'Neill BP, Lachance DH, Yang P, Wiemels J, Wiencke JK
Source: Cancer Genet, 2011 Jan;204(1), p. 13-8.
PMID: 21356187
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Risk factors for oligodendroglial tumors: a pooled international study.
Authors: McCarthy BJ, Rankin KM, Aldape K, Bondy ML, Brännström T, Broholm H, Feychting M, Il'yasova D, Inskip PD, Johansen C, Melin BS, Ruder AM, Butler MA, Scheurer ME, Schüz J, Schwartzbaum JA, Wrensch MR, Davis FG
Source: Neuro Oncol, 2011 Feb;13(2), p. 242-50.
EPub date: 2010 Dec 10.
PMID: 21149253
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Association between body mass index and mortality in patients with glioblastoma mutliforme.
Authors: Jones LW, Ali-Osman F, Lipp E, Marcello JE, McCarthy B, McCoy L, Rice T, Wrensch M, Il'yasova D
Source: Cancer Causes Control, 2010 Dec;21(12), p. 2195-201.
EPub date: 2010 Sep 14.
PMID: 20838873
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Epidemiology and etiology of meningioma.
Authors: Wiemels J, Wrensch M, Claus EB
Source: J Neurooncol, 2010 Sep;99(3), p. 307-14.
EPub date: 2010 Sep 7.
PMID: 20821343
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Aging and environmental exposures alter tissue-specific DNA methylation dependent upon CpG island context.
Authors: Christensen BC, Houseman EA, Marsit CJ, Zheng S, Wrensch MR, Wiemels JL, Nelson HH, Karagas MR, Padbury JF, Bueno R, Sugarbaker DJ, Yeh RF, Wiencke JK, Kelsey KT
Source: PLoS Genet, 2009 Aug;5(8), p. e1000602.
EPub date: 2009 Aug 14.
PMID: 19680444
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IgE, allergy, and risk of glioma: update from the San Francisco Bay Area Adult Glioma Study in the temozolomide era.
Authors: Wiemels JL, Wilson D, Patil C, Patoka J, McCoy L, Rice T, Schwartzbaum J, Heimberger A, Sampson JH, Chang S, Prados M, Wiencke JK, Wrensch M
Source: Int J Cancer, 2009 Aug 1;125(3), p. 680-7.
PMID: 19408307
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Total dietary antioxidant index and survival in patients with glioblastoma multiforme.
Authors: Il'yasova D, Marcello JE, McCoy L, Rice T, Wrensch M
Source: Cancer Causes Control, 2009 Oct;20(8), p. 1255-60.
EPub date: 2009 Apr 12.
PMID: 19363672
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Reproductive factors and hormone use and risk of adult gliomas.
Authors: Felini MJ, Olshan AF, Schroeder JC, Carozza SE, Miike R, Rice T, Wrensch M
Source: Cancer Causes Control, 2009 Feb;20(1), p. 87-96.
EPub date: 2008 Sep 3.
PMID: 18766447
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Pathway analysis of single-nucleotide polymorphisms potentially associated with glioblastoma multiforme susceptibility using random forests.
Authors: Chang JS, Yeh RF, Wiencke JK, Wiemels JL, Smirnov I, Pico AR, Tihan T, Patoka J, Miike R, Sison JD, Rice T, Wrensch MR
Source: Cancer Epidemiol Biomarkers Prev, 2008 Jun;17(6), p. 1368-73.
PMID: 18559551
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Allergy-related polymorphisms influence glioma status and serum IgE levels.
Authors: Wiemels JL, Wiencke JK, Kelsey KT, Moghadassi M, Rice T, Urayama KY, Miike R, Wrensch M
Source: Cancer Epidemiol Biomarkers Prev, 2007 Jun;16(6), p. 1229-35.
PMID: 17548690
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Methylation of the PTEN promoter defines low-grade gliomas and secondary glioblastoma.
Authors: Wiencke JK, Zheng S, Jelluma N, Tihan T, Vandenberg S, Tamgüney T, Baumber R, Parsons R, Lamborn KR, Berger MS, Wrensch MR, Haas-Kogan DA, Stokoe D
Source: Neuro Oncol, 2007 Jul;9(3), p. 271-9.
EPub date: 2007 May 15.
PMID: 17504928
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Nonsynonymous coding single-nucleotide polymorphisms spanning the genome in relation to glioblastoma survival and age at diagnosis.
Authors: Wrensch M, McMillan A, Wiencke J, Wiemels J, Kelsey K, Patoka J, Jones H, Carlton V, Miike R, Sison J, Moghadassi M, Prados M
Source: Clin Cancer Res, 2007 Jan 1;13(1), p. 197-205.
PMID: 17200355
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Serum IgE, tumor epidermal growth factor receptor expression, and inherited polymorphisms associated with glioma survival.
Authors: Wrensch M, Wiencke JK, Wiemels J, Miike R, Patoka J, Moghadassi M, McMillan A, Kelsey KT, Aldape K, Lamborn KR, Parsa AT, Sison JD, Prados MD
Source: Cancer Res, 2006 Apr 15;66(8), p. 4531-41.
PMID: 16618782
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Diagnostic, treatment, and demographic factors influencing survival in a population-based study of adult glioma patients in the San Francisco Bay Area.
Authors: Wrensch M, Rice T, Miike R, McMillan A, Lamborn KR, Aldape K, Prados MD
Source: Neuro Oncol, 2006 Jan;8(1), p. 12-26.
PMID: 16443944
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Epidemiology of intracranial meningioma.
Authors: Claus EB, Bondy ML, Schildkraut JM, Wiemels JL, Wrensch M, Black PM
Source: Neurosurgery, 2005 Dec;57(6), p. 1088-95; discussion 1088-95.
PMID: 16331155
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Positive and negative associations of human leukocyte antigen variants with the onset and prognosis of adult glioblastoma multiforme.
Authors: Tang J, Shao W, Dorak MT, Li Y, Miike R, Lobashevsky E, Wiencke JK, Wrensch M, Kaslow RA, Cobbs CS
Source: Cancer Epidemiol Biomarkers Prev, 2005 Aug;14(8), p. 2040-4.
PMID: 16103458
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Reduced immunoglobulin E and allergy among adults with glioma compared with controls.
Authors: Wiemels JL, Wiencke JK, Patoka J, Moghadassi M, Chew T, McMillan A, Miike R, Barger G, Wrensch M
Source: Cancer Res, 2004 Nov 15;64(22), p. 8468-73.
PMID: 15548720
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Associations between ERCC2 polymorphisms and gliomas.
Authors: Caggana M, Kilgallen J, Conroy JM, Wiencke JK, Kelsey KT, Miike R, Chen P, Wrensch MR
Source: Cancer Epidemiol Biomarkers Prev, 2001 Apr;10(4), p. 355-60.
PMID: 11319176
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Lack of association of rare alleles in the HRAS variable number of tandem repeats (VNTR) region with adult glioma.
Authors: Chen P, Wiencke JK, Conway K, Edmiston SN, Miike R, Wrensch M
Source: Neuro Oncol, 2000 Apr;2(2), p. 120-4.
PMID: 11303621
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Association of an ERCC1 polymorphism with adult-onset glioma.
Authors: Chen P, Wiencke J, Aldape K, Kesler-Diaz A, Miike R, Kelsey K, Lee M, Liu J, Wrensch M
Source: Cancer Epidemiol Biomarkers Prev, 2000 Aug;9(8), p. 843-7.
PMID: 10952103
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Adult glioma in relation to residential power frequency electromagnetic field exposures in the San Francisco Bay area.
Authors: Wrensch M, Yost M, Miike R, Lee G, Touchstone J
Source: Epidemiology, 1999 Sep;10(5), p. 523-7.
PMID: 10468425
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Gliomas in families: chromosomal analysis by comparative genomic hybridization.
Authors: Patel A, van Meyel DJ, Mohapatra G, Bollen A, Wrensch M, Cairncross JG, Feuerstein BG
Source: Cancer Genet Cytogenet, 1998 Jan 1;100(1), p. 77-83.
PMID: 9406586
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Identifying genetic markers to assess the presence of gene-environment interactions.
Authors: Seillier-Moiseiwitsch F, Pinheiro H, Li H, Newman B
Source: Genet Epidemiol, 1997;14(6), p. 1041-6.
PMID: 9433621
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