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Grant Details

Grant Number: 5R01CA139020-06 Interpret this number
Primary Investigator: Bondy, Melissa
Organization: Baylor College Of Medicine
Project Title: International Case Control Study of Malignant Glioma
Fiscal Year: 2015
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Abstract

DESCRIPTION (provided by applicant): Glioma comprises about 40% of all primary brain tumors accounting for as many as 26,000 U.S. and European deaths annually. Inherited susceptibility plays a role with 2-fold increased risk of glioma among first-degree relatives of glioma cases. We initiated a multi-center, international linkage study: "Genetic Epidemiology of Glioma International Consortium" in 2007 to address the role of inherited susceptibility. Since this study does not allow us currently to address the role of genetic susceptibility in sporadic cases, we propose this case- control study to address this gap. Members of the consortium have conducted genome wide association studies (GWAS) that will be the discovery phase (phase I). While of high value for discovery, we propose to recruit 6,000 newly diagnosed glioma cases and 6,000 age-gender-ethnicity-matched controls, and collect detailed epidemiologic data and biologic samples from the 13 participating Gliogene sites. We hypothesize that novel inherited variation influencing the susceptibility to glioma can be identified by high density SNP analysis, and propose the following specific aims: SA1: Identify common genetic variants contributing to the risk of glioma. We plan to conduct phases 2 and 3 of the 3 phase approach, specifically we will: (SA1a) Validate GWAS findings from the discovery sets, and replicate the top hits (~23,000 SNPs) with lowest p- values from the two phase GWA studies in a series of 2,000 cases and 2,000 controls (phase 2, validation). Validate the top hits from the test set (aim 1a). From stage 2, genes with SNPs displaying an association at pd10-4 (including the complete haplotype tagging - approximately 100 SNPs) will then be genotyped in a further series of 4,000 cases and 4,000 controls (stage 3, validation). SNPs significant at 10-7 or better will be considered in the final analyses. (SA1b). Using an a priori hypothesis that DNA repair in inflammation contribute to glioma risk, we will selectively interrogate DNA repair and inflammation pathway genes using data for select genes derived from the high-density array. We will conduct a hypothesis driven genetic association in DNA repair and in inflammation/immune function related genes with glioma risk using functional genomic and bioinformatic tools to interrogate available databases. (SA2): Evaluate gene-gene (G-G) and gene- environmental (G-E) interactions with strong biologic relevance to identify G-G and G-E interactions for glioma risk using machine-learning tools (MDR, FITF, and CART) in these exploratory analyses. There are no existing glioma case-control studies with sufficient numbers of biological samples and common epidemiologic data to conduct a comprehensive validation and replication study, or to address the issues of tumor heterogeneity as we will in this study.

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Publications

Age-specific genome-wide association study in glioblastoma identifies increased proportion of 'lower grade glioma'-like features associated with younger age.
Authors: Ostrom Q.T. , Kinnersley B. , Armstrong G. , Rice T. , Chen Y. , Wiencke J.K. , McCoy L.S. , Hansen H.M. , Amos C.I. , Bernstein J.L. , et al. .
Source: International Journal Of Cancer, 2018-08-27 00:00:00.0; , .
EPub date: 2018-08-27 00:00:00.0.
PMID: 30152087
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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.
Authors: Ostrom Q.T. , Kinnersley B. , Wrensch M.R. , Eckel-Passow J.E. , Armstrong G. , Rice T. , Chen Y. , Wiencke J.K. , McCoy L.S. , Hansen H.M. , et al. .
Source: Scientific Reports, 2018-05-09 00:00:00.0; 8(1), p. 7352.
EPub date: 2018-05-09 00:00:00.0.
PMID: 29743610
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Glioma-related seizures in relation to histopathological subtypes: a report from the glioma international case-control study.
Authors: Berntsson S.G. , Merrell R.T. , Amirian E.S. , Armstrong G.N. , Lachance D. , Smits A. , Zhou R. , Jacobs D.I. , Wrensch M.R. , Olson S.H. , et al. .
Source: Journal Of Neurology, 2018-04-23 00:00:00.0; , .
EPub date: 2018-04-23 00:00:00.0.
PMID: 29687214
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Influence of obesity-related risk factors in the aetiology of glioma.
Authors: Disney-Hogg L. , Sud A. , Law P.J. , Cornish A.J. , Kinnersley B. , Ostrom Q.T. , Labreche K. , Eckel-Passow J.E. , Armstrong G.N. , Claus E.B. , et al. .
Source: British Journal Of Cancer, 2018 Apr; 118(7), p. 1020-1027.
EPub date: 2018-03-13 00:00:00.0.
PMID: 29531326
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Impact of atopy on risk of glioma: a Mendelian randomisation study.
Authors: Disney-Hogg L. , Cornish A.J. , Sud A. , Law P.J. , Kinnersley B. , Jacobs D.I. , Ostrom Q.T. , Labreche K. , Eckel-Passow J.E. , Armstrong G.N. , et al. .
Source: Bmc Medicine, 2018-03-15 00:00:00.0; 16(1), p. 42.
EPub date: 2018-03-15 00:00:00.0.
PMID: 29540232
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Mendelian randomisation study of the relationship between vitamin D and risk of glioma.
Authors: Takahashi H. , Cornish A.J. , Sud A. , Law P.J. , Kinnersley B. , Ostrom Q.T. , Labreche K. , Eckel-Passow J.E. , Armstrong G.N. , Claus E.B. , et al. .
Source: Scientific Reports, 2018-02-05 00:00:00.0; 8(1), p. 2339.
EPub date: 2018-02-05 00:00:00.0.
PMID: 29402980
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Genome-wide association studies in glioma.
Authors: Kinnersley B. , Houlston R.S. , Bondy M.L. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2018-01-30 00:00:00.0; , .
EPub date: 2018-01-30 00:00:00.0.
PMID: 29382702
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Combined Proteomic-Molecular Epidemiology Approach to Identify Precision Targets in Brain Cancer.
Authors: Mostovenko E. , Liu Y. , Amirian E.S. , Tsavachidis S. , Armstrong G.N. , Bondy M.L. , Nilsson C.L. .
Source: Acs Chemical Neuroscience, 2018-01-17 00:00:00.0; 9(1), p. 80-84.
EPub date: 2017-07-11 00:00:00.0.
PMID: 28657708
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Germline polymorphisms in myeloid-associated genes are not associated with survival in glioma patients.
Authors: Jacobs D.I. , Liu Y. , Gabrusiewicz K. , Tsavachidis S. , Armstrong G.N. , Zhou R. , Wei J. , Ivan C. , Calin G. , Molinaro A.M. , et al. .
Source: Journal Of Neuro-oncology, 2017-09-30 00:00:00.0; , .
EPub date: 2017-09-30 00:00:00.0.
PMID: 28965162
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Genome-wide association study of glioma subtypes identifies specific differences in genetic susceptibility to glioblastoma and non-glioblastoma tumors.
Authors: Melin B.S. , Barnholtz-Sloan J.S. , Wrensch M.R. , Johansen C. , Il'yasova D. , Kinnersley B. , Ostrom Q.T. , Labreche K. , Chen Y. , Armstrong G. , et al. .
Source: Nature Genetics, 2017 May; 49(5), p. 789-794.
EPub date: 2017-03-27 00:00:00.0.
PMID: 28346443
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Adult Infiltrating Gliomas With Who 2016 Integrated Diagnosis: Additional Prognostic Roles Of Atrx And Tert
Authors: Pekmezci M. , Rice T. , Molinaro A.M. , Walsh K.M. , Decker P.A. , Hansen H. , Sicotte H. , Kollmeyer T.M. , McCoy L.S. , Sarkar G. , et al. .
Source: Acta Neuropathologica, 2017-03-02 00:00:00.0; , .
PMID: 28255664
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Immunomethylomic approach to explore the blood neutrophil lymphocyte ratio (NLR) in glioma survival.
Authors: Wiencke J.K. , Koestler D.C. , Salas L.A. , Wiemels J.L. , Roy R.P. , Hansen H.M. , Rice T. , McCoy L.S. , Bracci P.M. , Molinaro A.M. , et al. .
Source: Clinical Epigenetics, 2017; 9, p. 10.
EPub date: 2017-02-02 00:00:00.0.
PMID: 28184256
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Genetic Variation Associated with Longer Telomere Length Increases Risk of Chronic Lymphocytic Leukemia.
Authors: Ojha J. , Codd V. , Nelson C.P. , Samani N.J. , Smirnov I.V. , Madsen N.R. , Hansen H.M. , de Smith A.J. , Bracci P.M. , Wiencke J.K. , et al. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2016 Jul; 25(7), p. 1043-9.
PMID: 27197291
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Approaching a Scientific Consensus on the Association between Allergies and Glioma Risk: A Report from the Glioma International Case-Control Study.
Authors: Amirian E.S. , Zhou R. , Wrensch M.R. , Olson S.H. , Scheurer M.E. , Il'yasova D. , Lachance D. , Armstrong G.N. , McCoy L.S. , Lau C.C. , et al. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2016 Feb; 25(2), p. 282-90.
PMID: 26908595
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The Glioma International Case-Control Study: A Report From the Genetic Epidemiology of Glioma International Consortium.
Authors: Amirian E.S. , Armstrong G.N. , Zhou R. , Lau C.C. , Claus E.B. , Barnholtz-Sloan J.S. , Il'yasova D. , Schildkraut J. , Ali-Osman F. , Sadetzki S. , et al. .
Source: American Journal Of Epidemiology, 2016-01-15 00:00:00.0; 183(2), p. 85-91.
EPub date: 2016-01-15 00:00:00.0.
PMID: 26656478
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Melin and Bondy Respond to "E Pluribus Unum for Epidemiology".
Authors: Melin B.S. , Bondy M.L. , Genetic Epidemiology of Glioma International Consortium .
Source: American Journal Of Epidemiology, 2016-01-15 00:00:00.0; 183(2), p. 95.
EPub date: 2015-12-10 00:00:00.0.
PMID: 26656479
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Longer genotypically-estimated leukocyte telomere length is associated with increased adult glioma risk.
Authors: Walsh K.M. , Codd V. , Rice T. , Nelson C.P. , Smirnov I.V. , McCoy L.S. , Hansen H.M. , Elhauge E. , Ojha J. , Francis S.S. , et al. .
Source: Oncotarget, 2015-12-15 00:00:00.0; 6(40), p. 42468-77.
PMID: 26646793
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Genome-wide association study identifies multiple susceptibility loci for glioma.
Authors: Kinnersley B. , Labussière M. , Holroyd A. , Di Stefano A.L. , Broderick P. , Vijayakrishnan J. , Mokhtari K. , Delattre J.Y. , Gousias K. , Schramm J. , et al. .
Source: Nature Communications, 2015-10-01 00:00:00.0; 6, p. 8559.
EPub date: 2015-10-01 00:00:00.0.
PMID: 26424050
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Serum macrophage-derived chemokine/CCL22 levels are associated with glioma risk, CD4 T cell lymphopenia and survival time.
Authors: Zhou M. , Bracci P.M. , McCoy L.S. , Hsuang G. , Wiemels J.L. , Rice T. , Zheng S. , Kelsey K.T. , Wrensch M.R. , Wiencke J.K. .
Source: International Journal Of Cancer, 2015-08-15 00:00:00.0; 137(4), p. 826-36.
EPub date: 2015-08-15 00:00:00.0.
PMID: 25604093
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Genetic Modulation of Neurocognitive Function in Glioma Patients.
Authors: Liu Y. , Zhou R. , Sulman E.P. , Scheurer M.E. , Boehling N. , Armstrong G.N. , Tsavachidis S. , Liang F.W. , Etzel C.J. , Conrad C.A. , et al. .
Source: Clinical Cancer Research : An Official Journal Of The American Association For Cancer Research, 2015-07-15 00:00:00.0; 21(14), p. 3340-6.
EPub date: 2015-07-15 00:00:00.0.
PMID: 25904748
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Glioma Groups Based on 1p/19q, IDH, and TERT Promoter Mutations in Tumors.
Authors: Eckel-Passow J.E. , Lachance D.H. , Molinaro A.M. , Walsh K.M. , Decker P.A. , Sicotte H. , Pekmezci M. , Rice T. , Kosel M.L. , Smirnov I.V. , et al. .
Source: The New England Journal Of Medicine, 2015-06-25 00:00:00.0; 372(26), p. 2499-508.
EPub date: 2015-06-25 00:00:00.0.
PMID: 26061753
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CDKN2A loss is associated with shortened overall survival in lower-grade (World Health Organization Grades II-III) astrocytomas.
Authors: Reis G.F. , Pekmezci M. , Hansen H.M. , Rice T. , Marshall R.E. , Molinaro A.M. , Phillips J.J. , Vogel H. , Wiencke J.K. , Wrensch M.R. , et al. .
Source: Journal Of Neuropathology And Experimental Neurology, 2015 May; 74(5), p. 442-52.
PMID: 25853694
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A Pooled Multisite Analysis Of The Effects Of Atopic Medical Conditions In Glioma Risk In Different Ethnic Groups
Authors: Krishnamachari B. , Il'yasova D. , Scheurer M.E. , Bondy M. , Zhou R. , Wrensch M. , Davis F. .
Source: Annals Of Epidemiology, 2015 Apr; 25(4), p. 270-4.
PMID: 25691445
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Quantifying The Heritability Of Glioma Using Genome-wide Complex Trait Analysis
Authors: Kinnersley B. , Mitchell J.S. , Gousias K. , Schramm J. , Idbaih A. , Labussière M. , Marie Y. , Rahimian A. , Wichmann H.E. , Schreiber S. , et al. .
Source: Scientific Reports, 2015; 5, p. 17267.
PMID: 26625949
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A comparison of DNA methylation specific droplet digital PCR (ddPCR) and real time qPCR with flow cytometry in characterizing human T cells in peripheral blood.
Authors: Wiencke J.K. , Bracci P.M. , Hsuang G. , Zheng S. , Hansen H. , Wrensch M.R. , Rice T. , Eliot M. , Kelsey K.T. .
Source: Epigenetics, 2014 Oct; 9(10), p. 1360-5.
PMID: 25437051
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Variants near TERT and TERC influencing telomere length are associated with high-grade glioma risk.
Authors: Walsh K.M. , Codd V. , Smirnov I.V. , Rice T. , Decker P.A. , Hansen H.M. , Kollmeyer T. , Kosel M.L. , Molinaro A.M. , McCoy L.S. , et al. .
Source: Nature Genetics, 2014 Jul; 46(7), p. 731-5.
PMID: 24908248
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Exploring the association between melanoma and glioma risks.
Authors: Scarbrough P.M. , Akushevich I. , Wrensch M. , Il'yasova D. .
Source: Annals Of Epidemiology, 2014 Jun; 24(6), p. 469-74.
PMID: 24703682
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Genome-wide methylation analyses in glioblastoma multiforme.
Authors: Lai R.K. , Chen Y. , Guan X. , Nousome D. , Sharma C. , Canoll P. , Bruce J. , Sloan A.E. , Cortes E. , Vonsattel J.P. , et al. .
Source: Plos One, 2014; 9(2), p. e89376.
PMID: 24586730
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HMG CoA reductase inhibitors, NSAIDs and risk of glioma.
Authors: Ferris J.S. , McCoy L. , Neugut A.I. , Wrensch M. , Lai R. .
Source: International Journal Of Cancer, 2012-09-15 00:00:00.0; 131(6), p. E1031-7.
EPub date: 2012-09-15 00:00:00.0.
PMID: 22419506
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Allergy And Glioma Risk: Test Of Association By Genotype
Authors: Dobbins S.E. , Hosking F.J. , Shete S. , Armstrong G. , Swerdlow A. , Liu Y. , Yu R. , Lau C. , Schoemaker M.J. , Hepworth S.J. , et al. .
Source: International Journal Of Cancer, 2011-04-01 00:00:00.0; 128(7), p. 1736-40.
PMID: 20503266
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Genetic advances in glioma: susceptibility genes and networks.
Authors: Liu Y. , Shete S. , Hosking F. , Robertson L. , Houlston R. , Bondy M. .
Source: Current Opinion In Genetics & Development, 2010 Jun; 20(3), p. 239-44.
PMID: 20211558
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History of chickenpox in glioma risk: a report from the glioma international case-control study (GICC).
Authors: Amirian E.S. , Scheurer M.E. , Zhou R. , Wrensch M.R. , Armstrong G.N. , Lachance D. , Olson S.H. , Lau C.C. , Claus E.B. , Barnholtz-Sloan J.S. , et al. .
Source: Cancer Medicine, 2016 06; 5(6), p. 1352-8.
PMID: 26972449
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