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Grant Details

Grant Number: 7R01CA119215-06 Interpret this number
Primary Investigator: Bondy, Melissa
Organization: Baylor College Of Medicine
Project Title: Genetic Epidemiology of Glioma International Consortium
Fiscal Year: 2010
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Abstract

DESCRIPTION (provided by applicant): Although no major causative genes have yet been identified there is strong evidence that the risk of glioma has a genetic predisposition. In 2007, we established the international Gliogene Consortium involving 14 centers in the US, Sweden, Denmark, Israel, and the UK to identify genetic determinants of familial glioma. We have shown evidence for genetic linkage of familial glioma to chromosomal region 17q12-q21.32. For this competing renewal we propose to collect 500 additional families to allow us to conduct our gene discovery effort stratifying by molecular subgroups, and to apply emerging genetic methodologies, including exomic sequencing, to identify the specific genes involved in risk of familial glioma syndrome(s). To accomplish our overarching goal of identifying glioma risk genes, we propose for Aim 1 to characterize a cohort of 1000 glioma families with 2 or more cases of histologically verified glioma. We will stratify by molecular subtype, clinical presentation including age of onset, number of affected family members (i.e. to estimate penetrance), and familial patterns of cancers at other organ sites to define new cancer syndromes. For Aim 2 we will perform array-based genotyping for linkage analysis on all informative glioma families to identify families linked to genetic loci, and to have sufficient power to stratify our linkage analysis by: a) age of onset; b) presumptive mode of inheritance, c) co-occurrence of cancers (glioma and melanoma, and pancreas), d) histology, and e) molecular subtype. Aim 3 is to perform high-throughput whole exome sequencing in familial glioma cases, prioritized by number of glioma cases in the family (3 or more), and available DNA from at least two family members to identify causative germ line mutations. We expect from these analyses we will have a >80% probability of detecting a disease-causing allele with frequencies of >0.005. In summary, this study capitalizes on the outstanding infrastructure, and builds upon a unique annotated data and specimen repository which is a resource for future studies. We will be able to conduct a detailed assessment of the relationships between genotypes, molecular subtype, and clinical pathological phenotypes, and quantification of mutation penetrance. In addition, the ultimate goal of this research is to develop information directly relevant for genetic counseling of individuals at risk of inherited glioma. PUBLIC HEALTH RELEVANCE: Glioma is a tumor with poor prognosis where it is critical to develop additional treatment and surveillance strategies. The goal of this international Consortium study is to identify susceptibility loci explaining familial glioma. With a large number of glioma families we will conduct our gene discovery effort stratifying by glioma molecular subgroups, and apply emerging genetic methodologies, including exomic sequencing, to identify the specific genes involved in risk of familial glioma syndrome(s).

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Publications

Description of selected characteristics of familial glioma patients - Results from the Gliogene Consortium.
Authors: Sadetzki S, Bruchim R, Oberman B, Armstrong GN, Lau CC, Claus EB, Barnholtz-Sloan JS, Il'yasova D, Schildkraut J, Johansen C, Houlston RS, Shete S, Amos CI, Bernstein JL, Olson SH, Jenkins RB, Lachance D, Vick NA, Merrell R, Wrensch M, Davis FG, McCarthy BJ, Lai R, Melin BS, Bondy ML, Gliogene Consortium
Source: Eur J Cancer, 2013 Jan 4;null, p. null.
EPub date: 2013 Jan 4.
PMID: 23290425
Related Citations

Grant Numbers:
NCI NIH HHS - R01 CA119215 NCI NIH HHS - R01 CA052689

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Known glioma risk loci are associated with glioma with a family history of brain tumours-A case-control gene association study.
Authors: Melin B, Dahlin AM, Andersson U, Wang Z, Henriksson R, Hallmans G, Bondy ML, Johansen C, Feychting M, Ahlbom A, Kitahara CM, Wang SS, Ruder AM, Carreón T, Butler MA, Inskip PD, Purdue M, Hsing AW, Mechanic L, Gillanders E, Yeager M, Linet M, Chanock SJ, Hartge P, Rajaraman P
Source: Int J Cancer, 2012 Nov 1;null, p. null.
EPub date: 2012 Nov 1.
PMID: 23115063
Related Citations

Grant Numbers:
NCI NIH HHS - R01 CA119215

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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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Grant Numbers:
NCI NIH HHS - 5R01 CA070917 NCI NIH HHS - R01 CA52689 NCI NIH HHS - P30 CA016672
NCI NIH HHS - 5P30 CA16672 NCRR NIH HHS - UL1 RR024989 NCI NIH HHS - R01 CA119215
NCI NIH HHS - P50 CA097257 NCI NIH HHS - P30 CA043703 NCI NIH HHS - R01 CA052689
NCI NIH HHS - R01 CA126831 NCI NIH HHS - R01 CA070917 NCI NIH HHS - 5R01 CA119215

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Insight in glioma susceptibility through an analysis of 6p22.3, 12p13.33-12.1, 17q22-23.2 and 18q23 SNP genotypes in familial and non-familial glioma.
Authors: Liu Y, Melin BS, Rajaraman P, Wang Z, Linet M, Shete S, Amos CI, Lau CC, Scheurer ME, Tsavachidis S, Armstrong GN, Houlston RS, Hosking FJ, Claus EB, Barnholtz-Sloan J, Lai R, Il'yasova D, Schildkraut J, Sadetzki S, Johansen C, Bernstein JL, Olson SH, Jenkins RB, LaChance D, Vick NA, Wrensch M, Davis F, McCarthy BJ, Andersson U, Thompson PA, Chanock S, Gliogene Consortium, Bondy ML
Source: Hum Genet, 2012 Sep;131(9), p. 1507-17.
EPub date: 2012 Jun 12.
PMID: 22688887
Related Citations

Grant Numbers:
NCI NIH HHS - 5R01 CA070917 NCI NIH HHS - R01CA52689 NCI NIH HHS - R01 CA052689
Wellcome Trust - null NCI NIH HHS - 5R01 CA119215

MeSH Terms:
Brain Neoplasms Polymorphism, Single Nucleotide Haplotypes
Humans Adult Middle Aged
Glioma Genetic Predisposition to Disease Adolescent
Chromosome Mapping Male Female

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Genome-wide high-density SNP linkage search for glioma susceptibility loci: results from the Gliogene Consortium.
Authors: Shete S, Lau CC, Houlston RS, Claus EB, Barnholtz-Sloan J, Lai R, Il'yasova D, Schildkraut J, Sadetzki S, Johansen C, Bernstein JL, Olson SH, Jenkins RB, Yang P, Vick NA, Wrensch M, Davis FG, McCarthy BJ, Leung EH, Davis C, Cheng R, Hosking FJ, Armstrong GN, Liu Y, Yu RK, Henriksson R, Gliogene Consortium, Melin BS, Bondy ML
Source: Cancer Res, 2011 Dec 15;71(24), p. 7568-75.
EPub date: 2011 Oct 28.
PMID: 22037877
Related Citations

Grant Numbers:
NCI NIH HHS - 5R01 CA070917 NCI NIH HHS - R01CA52689 NCI NIH HHS - R01 CA126831-05
NCI NIH HHS - R01 CA119215-05 PHS HHS - P50097257 NCI NIH HHS - R01 CA052689-22
NCI NIH HHS - R01 CA052689-17 NCI NIH HHS - R01CA126831 NCI NIH HHS - R01 CA070917-09
NCI NIH HHS - 5P30CA16672 NCI NIH HHS - 5R01 CA119215

MeSH Terms:
United States Pedigree Young Adult
Polymorphism, Single Nucleotide Genome, Human Humans
Aged Child Linkage Disequilibrium
Chromosome Mapping Genetic Heterogeneity Genome-Wide Association Study
Genotype Brain Neoplasms Lod Score
Adult Middle Aged Glioma
Genetic Predisposition to Disease Adolescent Family Health
Male Female

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A novel approach to exploring potential interactions among single-nucleotide polymorphisms of inflammation genes in gliomagenesis: an exploratory case-only study.
Authors: Amirian ES, Scheurer ME, Liu Y, D'Amelio AM Jr, Houlston RS, Etzel CJ, Shete S, Swerdlow AJ, Schoemaker MJ, McKinney PA, Fleming SJ, Muir KR, Lophatananon A, Bondy ML
Source: Cancer Epidemiol Biomarkers Prev, 2011 Aug;20(8), p. 1683-9.
EPub date: 2011 Jul 1.
PMID: 21724854
Related Citations

Grant Numbers:
NCI NIH HHS - CA056452 NCI NIH HHS - R01CA070917 NCI NIH HHS - K07CA131505
NCI NIH HHS - R01CA119215

MeSH Terms:
Genotype Brain Neoplasms Polymorphism, Single Nucleotide
Risk Factors Humans Middle Aged
Glioma Male Female
Cell Transformation, Neoplastic Inflammation

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Chromosome 7p11.2 (EGFR) variation influences glioma risk.
Authors: Sanson M, Hosking FJ, Shete S, Zelenika D, Dobbins SE, Ma Y, Enciso-Mora V, Idbaih A, Delattre JY, Hoang-Xuan K, Marie Y, Boisselier B, Carpentier C, Wang XW, Di Stefano AL, Labussière M, Gousias K, Schramm J, Boland A, Lechner D, Gut I, Armstrong G, Liu Y, Yu R, Lau C, Di Bernardo MC, Robertson LB, Muir K, Hepworth S, Swerdlow A, Schoemaker MJ, Wichmann HE, Müller M, Schreiber S, Franke A, Moebus S, Eisele L, Försti A, Hemminki K, Lathrop M, Bondy M, Houlston RS, Simon M
Source: Hum Mol Genet, 2011 Jul 15;20(14), p. 2897-904.
EPub date: 2011 Apr 29.
PMID: 21531791
Related Citations

Grant Numbers:
NCI NIH HHS - 5R01 CA070917 Wellcome Trust - 085475 Cancer Research UK - C1298/A8362
Wellcome Trust - 076113 NCI NIH HHS - 5R01 CA119215

MeSH Terms:
Polymorphism, Single Nucleotide Receptor, Epidermal Growth Factor Humans
Chromosomes, Human, Pair 7 Gene Amplification Gene Deletion
Genome-Wide Association Study Cyclin-Dependent Kinase Inhibitor p16 Risk Factors
Adult Case-Control Studies Isocitrate Dehydrogenase
Glioma Female Male

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Modulation of glioma risk and progression by dietary nutrients and antiinflammatory agents.
Authors: Kyritsis AP, Bondy ML, Levin VA
Source: Nutr Cancer, 2011;63(2), p. 174-84.
PMID: 21302177
Related Citations

Grant Numbers:
NCI NIH HHS - R01 CA119215-05 NCI NIH HHS - CA 070917 NCI NIH HHS - R01 CA070917-09
NCI NIH HHS - CA 119215

MeSH Terms:
Anti-Inflammatory Agents Models, Animal Animals
Food Humans Clinical Trials as Topic
Disease Progression Life Style Fatty Acids, Unsaturated
Vitamins Risk Factors Oxidative Stress
Chemoprevention Diet Glioma

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Inherited variation in immune genes and pathways and glioblastoma risk.
Authors: Schwartzbaum JA, Xiao Y, Liu Y, Tsavachidis S, Berger MS, Bondy ML, Chang JS, Chang SM, Decker PA, Ding B, Hepworth SJ, Houlston RS, Hosking FJ, Jenkins RB, Kosel ML, McCoy LS, McKinney PA, Muir K, Patoka JS, Prados M, Rice T, Robertson LB, Schoemaker MJ, Shete S, Swerdlow AJ, Wiemels JL, Wiencke JK, Yang P, Wrensch MR
Source: Carcinogenesis, 2010 Oct;31(10), p. 1770-7.
EPub date: 2010 Jul 28.
PMID: 20668009
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Grant Numbers:
NCI NIH HHS - 5R01 CA070917 NCI NIH HHS - P50 CA108961 NCI NIH HHS - R01CA122163
Cancer Research UK - C1298/A8362 NCI NIH HHS - R01CA52689 NCI NIH HHS - P50CA097257
NCI NIH HHS - R25 CA 112355 NCI NIH HHS - P30 CA15083 NCI NIH HHS - R01 CA052689-22
Wellcome Trust - null NCI NIH HHS - 5R01 CA119215

MeSH Terms:
Glioblastoma Brain Neoplasms Polymorphism, Single Nucleotide
Humans Adult Cytokines
Signal Transduction Male Female
Genome-Wide Association Study

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Gamma-radiation sensitivity and polymorphisms in RAD51L1 modulate glioma risk.
Authors: Liu Y, Shete S, Wang LE, El-Zein R, Etzel CJ, Liang FW, Armstrong G, Tsavachidis S, Gilbert MR, Aldape KD, Xing J, Wu X, Wei Q, Bondy ML
Source: Carcinogenesis, 2010 Oct;31(10), p. 1762-9.
EPub date: 2010 Jul 7.
PMID: 20610542
Related Citations

Grant Numbers:
NCI NIH HHS - CA98897 NCI NIH HHS - 5R01CA070917 NCI NIH HHS - CA74880
Wellcome Trust - null NCI NIH HHS - 5R01CA119215

MeSH Terms:
Polymorphism, Single Nucleotide Gamma Rays DNA-Binding Proteins
Humans Aged DNA Breaks, Double-Stranded
Linkage Disequilibrium Risk Brain Neoplasms
Haplotypes Adult Middle Aged
Glioma Female Male

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Allergy and glioma risk: test of association by genotype.
Authors: Dobbins SE, Hosking FJ, Shete S, Armstrong G, Swerdlow A, Liu Y, Yu R, Lau C, Schoemaker MJ, Hepworth SJ, Muir K, Bondy M, Houlston RS
Source: Int J Cancer, 2011 Apr 1;128(7), p. 1736-40.
EPub date: 2010 May 25.
PMID: 20503266
Related Citations

Grant Numbers:
NCI NIH HHS - 5R01 CA070917 Cancer Research UK - C1298/A8362 Wellcome Trust - null
NCI NIH HHS - 5R01 CA119215

MeSH Terms:
Genotype Risk Brain Neoplasms
Hypersensitivity Alleles Oligonucleotide Array Sequence Analysis
Polymorphism, Genetic Humans Genetic Markers
Glioma Eczema

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Role of type 1 IFNs in antiglioma immunosurveillance--using mouse studies to guide examination of novel prognostic markers in humans.
Authors: Fujita M, Scheurer ME, Decker SA, McDonald HA, Kohanbash G, Kastenhuber ER, Kato H, Bondy ML, Ohlfest JR, Okada H
Source: Clin Cancer Res, 2010 Jul 1;16(13), p. 3409-19.
EPub date: 2010 May 14.
PMID: 20472682
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Grant Numbers:
NINDS NIH HHS - R01 NS055140-03 NCI NIH HHS - 1R01CA119215 NCI NIH HHS - R01 CA119215-05
NINDS NIH HHS - 2P01NS40923 NINDS NIH HHS - 1R21NS055738 NCI NIH HHS - P01 CA132714-028081
NCI NIH HHS - K07CA131505 NCI NIH HHS - R01 CA160782-02 NCI NIH HHS - K07 CA131505-02
NINDS NIH HHS - P01 NS040923-080005 NCI NIH HHS - 1P01CA132714 NINDS NIH HHS - R21 NS055738-02
NCI NIH HHS - K07 CA131505-04 NCI NIH HHS - K07 CA131505-03 NINDS NIH HHS - 1F31NS067937-01
NCI NIH HHS - K07 CA131505 NINDS NIH HHS - F31 NS067937-02 Wellcome Trust - null
NCI NIH HHS - R01 CA070917-09 NINDS NIH HHS - 1R01NS055140 NCI NIH HHS - 1R01CA070917
NINDS NIH HHS - P01 NS040923

MeSH Terms:
Animals Dendritic Cells T-Lymphocytes, Regulatory
Adaptive Immunity Polymorphism, Single Nucleotide Prognosis
Interferon Type I Mice Mice, Transgenic
Lymphocytes, Tumor-Infiltrating Receptor, Interferon alpha-beta Brain Neoplasms
Monitoring, Immunologic T-Lymphocytes, Cytotoxic Mice, Inbred C57BL
Glioma Chemokine CXCL10 Signal Transduction

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Survey of familial glioma and role of germline p16INK4A/p14ARF and p53 mutation.
Authors: Robertson LB, Armstrong GN, Olver BD, Lloyd AL, Shete S, Lau C, Claus EB, Barnholtz-Sloan J, Lai R, Il'yasova D, Schildkraut J, Bernstein JL, Olson SH, Jenkins RB, Yang P, Rynearson AL, Wrensch M, McCoy L, Wienkce JK, McCarthy B, Davis F, Vick NA, Johansen C, Bødtcher H, Sadetzki S, Bruchim RB, Yechezkel GH, Andersson U, Melin BS, Bondy ML, Houlston RS
Source: Fam Cancer, 2010 Sep;9(3), p. 413-21.
PMID: 20455025
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Grant Numbers:
NINDS NIH HHS - RC1 NS068222-01 Cancer Research UK - C1298/A8362 NINDS NIH HHS - RC1 NS068222-02
NCI NIH HHS - R01 CA119215-05 NCI NIH HHS - R01 CA052689-22 NCI NIH HHS - R01 CA119215 01

MeSH Terms:
Pedigree Young Adult Humans
DNA Mutational Analysis Aged Child
Genes, p16 Child, Preschool Polymerase Chain Reaction
Brain Neoplasms Genes, p53 Adult
Middle Aged Genetic Predisposition to Disease Germ-Line Mutation
Glioma Adolescent Male
Female

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Polymorphisms of LIG4, BTBD2, HMGA2, and RTEL1 genes involved in the double-strand break repair pathway predict glioblastoma survival.
Authors: Liu Y, Shete S, Etzel CJ, Scheurer M, Alexiou G, Armstrong G, Tsavachidis S, Liang FW, Gilbert M, Aldape K, Armstrong T, Houlston R, Hosking F, Robertson L, Xiao Y, Wiencke J, Wrensch M, Andersson U, Melin BS, Bondy M
Source: J Clin Oncol, 2010 May 10;28(14), p. 2467-74.
EPub date: 2010 Apr 5.
PMID: 20368557
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Grant Numbers:
NCI NIH HHS - R01CA52689 NCI NIH HHS - P50CA097257 NCI NIH HHS - K07CA093592
NCI NIH HHS - R01 CA052689-22 NCI NIH HHS - 5R01CA070917 NCI NIH HHS - 5R01CA119215

MeSH Terms:
Glioblastoma Age Factors Odds Ratio
Polymorphism, Single Nucleotide Chi-Square Distribution Humans
DNA Ligases HMGA2 Protein Risk Assessment
Gene Expression Regulation, Neoplastic Treatment Outcome Genetic Predisposition to Disease
Survivors Time Factors Male
DNA Repair Carrier Proteins DNA Breaks, Double-Stranded
Kaplan-Meier Estimate Brain Neoplasms DNA Helicases
Risk Factors Decision Trees Middle Aged
Female Proportional Hazards Models

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New insights into susceptibility to glioma.
Authors: Liu Y, Shete S, Hosking FJ, Robertson LB, Bondy ML, Houlston RS
Source: Arch Neurol, 2010 Mar;67(3), p. 275-8.
PMID: 20212223
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Grant Numbers:
NCI NIH HHS - 5R01CA070917 Wellcome Trust - null NCI NIH HHS - 5R01CA119215

MeSH Terms:
Genetic Variation Alleles Humans
Glioma Genetic Predisposition to Disease Central Nervous System Neoplasms

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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: Curr Opin Genet Dev, 2010 Jun;20(3), p. 239-44.
EPub date: 2010 Mar 6.
PMID: 20211558
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Grant Numbers:
NCI NIH HHS - R01 CA070917-05A1 NCI NIH HHS - 1R01CA139020-01A1 NCI NIH HHS - P01 CA055261-050005
NCI NIH HHS - 5R01CA070917 NCI NIH HHS - R01 CA119215-01A1 NCI NIH HHS - 5R01CA119215

MeSH Terms:
Polymorphism, Single Nucleotide Humans Gene Regulatory Networks
Glioma Genetic Predisposition to Disease Genome-Wide Association Study

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Inherited predisposition to glioma.
Authors: Kyritsis AP, Bondy ML, Rao JS, Sioka C
Source: Neuro Oncol, 2010 Jan;12(1), p. 104-13.
EPub date: 2009 Nov 23.
PMID: 20150373
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Grant Numbers:
NCI NIH HHS - CA 75557 NCI NIH HHS - CA 95058 NCI NIH HHS - CA119215
NCI NIH HHS - CA 070917 NCI NIH HHS - CA 116708 NCI NIH HHS - CA 92393

MeSH Terms:
Brain Neoplasms Polymorphism, Genetic Humans
Glioma Germ-Line Mutation Genetic Predisposition to Disease

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Genome-wide association study identifies five susceptibility loci for glioma.
Authors: Shete S, Hosking FJ, Robertson LB, Dobbins SE, Sanson M, Malmer B, Simon M, Marie Y, Boisselier B, Delattre JY, Hoang-Xuan K, El Hallani S, Idbaih A, Zelenika D, Andersson U, Henriksson R, Bergenheim AT, Feychting M, Lönn S, Ahlbom A, Schramm J, Linnebank M, Hemminki K, Kumar R, Hepworth SJ, Price A, Armstrong G, Liu Y, Gu X, Yu R, Lau C, Schoemaker M, Muir K, Swerdlow A, Lathrop M, Bondy M, Houlston RS
Source: Nat Genet, 2009 Aug;41(8), p. 899-904.
EPub date: 2009 Jul 5.
PMID: 19578367
Related Citations

Grant Numbers:
NCI NIH HHS - 5R01 CA070917 Cancer Research UK - C1298/A8362 NCI NIH HHS - R01 CA119215
Wellcome Trust - null NCI NIH HHS - 5R01 CA119215

MeSH Terms:
Polymorphism, Single Nucleotide Alleles Reproducibility of Results
Humans Glioma Genetic Predisposition to Disease
Linkage Disequilibrium Genome-Wide Association Study

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Molecular epidemiology of primary brain tumors.
Authors: Gu J, Liu Y, Kyritsis AP, Bondy ML
Source: Neurotherapeutics, 2009 Jul;6(3), p. 427-35.
PMID: 19560733
Related Citations

Grant Numbers:
NCI NIH HHS - 5R01 CA070917 NCI NIH HHS - 5R01 CA119215

MeSH Terms:
Polymorphism, Single Nucleotide DNA Repair Humans
Models, Biological Genome-Wide Association Study Brain Neoplasms
Meningioma Genetic Predisposition to Disease Glioma
Neuroimmunomodulation Cell Cycle Biological Markers
Metabolism

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GLIOGENE an International Consortium to Understand Familial Glioma.
Authors: Malmer B, Adatto P, Armstrong G, Barnholtz-Sloan J, Bernstein JL, Claus E, Davis F, Houlston R, Il'yasova D, Jenkins R, Johansen C, Lai R, Lau C, McCarthy B, Nielsen H, Olson SH, Sadetzki S, Shete S, Wiklund F, Wrensch M, Yang P, Bondy M
Source: Cancer Epidemiol Biomarkers Prev, 2007 Sep;16(9), p. 1730-4.
PMID: 17855690
Related Citations

Grant Numbers:
NCI NIH HHS - R01 CA11921501

MeSH Terms:
Genetic Linkage Pedigree North America
Polymorphism, Single Nucleotide Genome, Human Humans
Genetic Markers Europe International Agencies
Israel Brain Neoplasms Cohort Studies
Genetic Predisposition to Disease Glioma

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