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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

Germline rearrangements in families with strong family history of glioma and malignant melanoma, colon, and breast cancer.
Authors: Andersson U, Wibom C, Cederquist K, Aradottir S, Borg A, Armstrong GN, Shete S, Lau CC, Bainbridge MN, Claus EB, Barnholtz-Sloan J, Lai R, Il'yasova D, Houlston RS, Schildkraut J, Bernstein JL, Olson SH, Jenkins RB, Lachance DH, Wrensch M, Davis FG, Merrell R, Johansen C, Sadetzki S, Gliogene Consortium, Bondy ML, Melin BS
Source: Neuro Oncol, 2014 Oct;16(10), p. 1333-40.
EPub date: 2014 Apr 9.
PMID: 24723567
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Integration of epidemiology, immunobiology, and translational research for brain tumors.
Authors: Okada H, Scheurer ME, Sarkar SN, Bondy ML
Source: Ann N Y Acad Sci, 2013 May;1284, p. 17-23.
PMID: 23651189
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Low penetrance susceptibility to glioma is caused by the TP53 variant rs78378222.
Authors: Enciso-Mora V, Hosking FJ, Di Stefano AL, Zelenika D, Shete S, Broderick P, Idbaih A, Delattre JY, Hoang-Xuan K, Marie Y, Labussière M, Alentorn A, Ciccarino P, Rossetto M, Armstrong G, Liu Y, Gousias K, Schramm J, Lau C, Hepworth SJ, Schoemaker M, Strauch K, Müller-Nurasyid M, Schreiber S, Franke A, Moebus S, Eisele L, Swerdlow A, Simon M, Bondy M, Lathrop M, Sanson M, Houlston RS
Source: Br J Cancer, 2013 May 28;108(10), p. 2178-85.
EPub date: 2013 Apr 9.
PMID: 23571737
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Deciphering the 8q24.21 association for glioma.
Authors: Enciso-Mora V, Hosking FJ, Kinnersley B, Wang Y, Shete S, Zelenika D, Broderick P, Idbaih A, Delattre JY, Hoang-Xuan K, Marie Y, Di Stefano AL, Labussière M, Dobbins S, Boisselier B, Ciccarino P, Rossetto M, Armstrong G, Liu Y, Gousias K, Schramm J, Lau C, Hepworth SJ, Strauch K, Müller-Nurasyid M, Schreiber S, Franke A, Moebus S, Eisele L, Forsti A, Hemminki K, Tomlinson IP, Swerdlow A, Lathrop M, Simon M, Bondy M, Sanson M, Houlston RS
Source: Hum Mol Genet, 2013 Jun 1;22(11), p. 2293-302.
EPub date: 2013 Feb 11.
PMID: 23399484
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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 Apr;49(6), p. 1335-45.
EPub date: 2013 Jan 4.
PMID: 23290425
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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, 2013 May 15;132(10), p. 2464-8.
EPub date: 2012 Nov 21.
PMID: 23115063
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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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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
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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
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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
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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
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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
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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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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
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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
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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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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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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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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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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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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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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
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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
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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
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