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Grant Details

Grant Number: 5R01CA097075-10 Interpret this number
Primary Investigator: Petersen, Gloria
Organization: Mayo Clinic Rochester
Project Title: Pancreatic Cancer Genetic Epidemiology Consortium (PACGENE)
Fiscal Year: 2012
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Abstract

DESCRIPTION: This re-submitted proposal seeks continued funding for the Pancreatic Cancer Genetic Epidemiology (PACGENE) Consortium, a multicenter, multidisciplinary team which has the goal to identify susceptibility genes for familial pancreatic cancer (FPC). The PACGENE Consortium has shown that coordinated case finding, family recruitment, and linkage analysis are productive: we have identified three novel regions, and are positioned to use the pedigree material to further gene discovery. The PACGENE Consortium comprises 7 data collection/analysis centers in the U.S. and Canada, 2 Cores (Data Management/Analysis and Pathology/Tissue Genotyping), and is guided by Steering and External Advisory Committees. Our specific aims are: AIM 1. To validate linkage findings for gene discovery with an extended, final sample of FPC families. We will: a) Develop a set of 63 new FPC pedigrees and follow up our existing cohort of FPC pedigrees to increase their informativeness; b) Perform a genomewide (~6008 single nucleotide polymorphism (SNP)) validation linkage analysis (genotyping will be sought at the Center for Inherited Disease Research (CIDR) at no cost to this grant); AIM 2. To perform a familial case-control association study to validate SNP associations identified in other consortia studies. We will genotype 800 FPC probands and 800 unrelated family controls using a custom SNP marker panel identified by the PanScan genomewide association study of the Cohort Consortium, the Pancreatic Cancer Case-Control Consortium, and our own linkage analyses; AIM 3. To identify the genes in candidate regions identified by linkage and association. We will: a) Fine map regions identified through linkage analyses (including chromosomes 2p, 2q, and 10q); b) Perform genomewide loss of heterozygosity allelotyping of microdissected early stage tumors (PanINs and IPMNs) from FPC probands (comparing tumor to normal), with a focus on regions of interest; c) Resequence the best candidate genes in the regions identified. Public Health Relevance: Over 37,000 new cases of pancreatic cancer will occur in the U.S. in 2007, almost all rapidly fatal. Our research will help identify the genes for FPC, furthering knowledge about the etiology of pancreatic cancer that should accelerate translation to care. Risk assessment will be improved, and identified FPC genes will lead to development of more effective strategies for early detection, prevention, and therapy. PUBLIC HEALTH RELEVANCE: Over 37,000 new cases of pancreatic cancer will occur in the U.S. in 2007, almost all rapidly fatal. Our research will help identify the genes for familial pancreatic cancer (FPC), furthering knowledge about the cause(s) of pancreatic cancer that should accelerate translation to care. Risk assessment will be improved, and identified FPC genes will lead to development of more effective strategies for early detection, prevention, and therapy.

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Publications

Association between allergies and risk of pancreatic cancer.
Authors: Cotterchio M, Lowcock E, Hudson TJ, Greenwood C, Gallinger S
Source: Cancer Epidemiol Biomarkers Prev, 2014 Mar;23(3), p. 469-80.
EPub date: 2014 Feb 19.
PMID: 24554712
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An absolute risk model to identify individuals at elevated risk for pancreatic cancer in the general population.
Authors: Klein AP, Lindstr÷m S, Mendelsohn JB, Steplowski E, Arslan AA, Bueno-de-Mesquita HB, Fuchs CS, Gallinger S, Gross M, Helzlsouer K, Holly EA, Jacobs EJ, Lacroix A, Li D, Mandelson MT, Olson SH, Petersen GM, Risch HA, Stolzenberg-Solomon RZ, Zheng W, Amundadottir L, Albanes D, Allen NE, Bamlet WR, Boutron-Ruault MC, Buring JE, Bracci PM, Canzian F, Clipp S, Cotterchio M, Duell EJ, Elena J, Gaziano JM, Giovannucci EL, Goggins M, Hallmans G, Hassan M, Hutchinson A, Hunter DJ, Kooperberg C, Kurtz RC, Liu S, Overvad K, Palli D, Patel AV, Rabe KG, Shu XO, Slimani N, Tobias GS, Trichopoulos D, Van Den Eeden SK, Vineis P, Virtamo J, Wactawski-Wende J, Wolpin BM, Yu H, Yu K, Zeleniuch-Jacquotte A, Chanock SJ, Hoover RN, Hartge P, Kraft P
Source: PLoS One, 2013;8(9), p. e72311.
EPub date: 2013 Sep 13.
PMID: 24058443
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Ulcer, gastric surgery and pancreatic cancer risk: an analysis from the International Pancreatic Cancer Case-Control Consortium (PanC4).
Authors: Bosetti C, Lucenteforte E, Bracci PM, Negri E, Neale RE, Risch HA, Olson SH, Gallinger S, Miller AB, Bueno-de-Mesquita HB, Talamini R, Polesel J, Ghadirian P, Baghurst PA, Zatonski W, Fontham E, Holly EA, Gao YT, Yu H, Kurtz RC, Cotterchio M, Maisonneuve P, Zeegers MP, Duell EJ, Boffetta P, La Vecchia C
Source: Ann Oncol, 2013 Nov;24(11), p. 2903-10.
EPub date: 2013 Aug 22.
PMID: 23970016
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Interaction of polymorphisms in mitotic regulator genes with cigarette smoking and pancreatic cancer risk.
Authors: Jang JH, Cotterchio M, Borgida A, Liu G, Gallinger S, Cleary SP
Source: Mol Carcinog, 2013 Nov;52 Suppl 1, p. E103-9.
EPub date: 2013 Jun 12.
PMID: 23908141
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Genetic variants in vitamin d pathway genes and risk of pancreas cancer; results from a population-based case-control study in ontario, Canada.
Authors: Anderson LN, Cotterchio M, Knight JA, Borgida A, Gallinger S, Cleary SP
Source: PLoS One, 2013;8(6), p. e66768.
EPub date: 2013 Jun 24.
PMID: 23826131
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Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes.
Authors: Biankin AV, Waddell N, Kassahn KS, Gingras MC, Muthuswamy LB, Johns AL, Miller DK, Wilson PJ, Patch AM, Wu J, Chang DK, Cowley MJ, Gardiner BB, Song S, Harliwong I, Idrisoglu S, Nourse C, Nourbakhsh E, Manning S, Wani S, Gongora M, Pajic M, Scarlett CJ, Gill AJ, Pinho AV, Rooman I, Anderson M, Holmes O, Leonard C, Taylor D, Wood S, Xu Q, Nones K, Fink JL, Christ A, Bruxner T, Cloonan N, Kolle G, Newell F, Pinese M, Mead RS, Humphris JL, Kaplan W, Jones MD, Colvin EK, Nagrial AM, Humphrey ES, Chou A, Chin VT, Chantrill LA, Mawson A, Samra JS, Kench JG, Lovell JA, Daly RJ, Merrett ND, Toon C, Epari K, Nguyen NQ, Barbour A, Zeps N, Australian Pancreatic Cancer Genome Initiative, Kakkar N, Zhao F, Wu YQ, Wang M, Muzny DM, Fisher WE, Brunicardi FC, Hodges SE, Reid JG, Drummond J, Chang K, Han Y, Lewis LR, Dinh H, Buhay CJ, Beck T, Timms L, Sam M, Begley K, Brown A, Pai D, Panchal A, Buchner N, De Borja R, Denroche RE, Yung CK, Serra S, Onetto N, Mukhopadhyay D, Tsao MS, Shaw PA, Petersen GM, Gallinger S, Hruban RH, Maitra A, Iacobuzio-Donahue CA, Schulick RD, Wolfgang CL, Morgan RA, Lawlor RT, Capelli P, Corbo V, Scardoni M, Tortora G, Tempero MA, Mann KM, Jenkins NA, Perez-Mancera PA, Adams DJ, Largaespada DA, Wessels LF, Rust AG, Stein LD, Tuveson DA, Copeland NG, Musgrove EA, Scarpa A, Eshleman JR, Hudson TJ, Sutherland RL, Wheeler DA, Pearson JV, McPherson JD, Gibbs RA, Grimmond SM
Source: Nature, 2012 Nov 15;491(7424), p. 399-405.
EPub date: 2012 Oct 24.
PMID: 23103869
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Genome-wide somatic copy number alterations in low-grade PanINs and IPMNs from individuals with a family history of pancreatic cancer.
Authors: Hong SM, Vincent A, Kanda M, Leclerc J, Omura N, Borges M, Klein AP, Canto MI, Hruban RH, Goggins M
Source: Clin Cancer Res, 2012 Aug 15;18(16), p. 4303-12.
EPub date: 2012 Jun 21.
PMID: 22723370
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Pathway analysis of genome-wide association study data highlights pancreatic development genes as susceptibility factors for pancreatic cancer.
Authors: Li D, Duell EJ, Yu K, Risch HA, Olson SH, Kooperberg C, Wolpin BM, Jiao L, Dong X, Wheeler B, Arslan AA, Bueno-de-Mesquita HB, Fuchs CS, Gallinger S, Gross M, Hartge P, Hoover RN, Holly EA, Jacobs EJ, Klein AP, LaCroix A, Mandelson MT, Petersen G, Zheng W, Agalliu I, Albanes D, Boutron-Ruault MC, Bracci PM, Buring JE, Canzian F, Chang K, Chanock SJ, Cotterchio M, Gaziano JM, Giovannucci EL, Goggins M, Hallmans G, Hankinson SE, Hoffman Bolton JA, Hunter DJ, Hutchinson A, Jacobs KB, Jenab M, Khaw KT, Kraft P, Krogh V, Kurtz RC, McWilliams RR, Mendelsohn JB, Patel AV, Rabe KG, Riboli E, Shu XO, Tj°nneland A, Tobias GS, Trichopoulos D, Virtamo J, Visvanathan K, Watters J, Yu H, Zeleniuch-Jacquotte A, Amundadottir L, Stolzenberg-Solomon RZ
Source: Carcinogenesis, 2012 Jul;33(7), p. 1384-90.
EPub date: 2012 Apr 20.
PMID: 22523087
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Genome-wide CpG island profiling of intraductal papillary mucinous neoplasms of the pancreas.
Authors: Hong SM, Omura N, Vincent A, Li A, Knight S, Yu J, Hruban RH, Goggins M
Source: Clin Cancer Res, 2012 Feb 1;18(3), p. 700-12.
EPub date: 2011 Dec 15.
PMID: 22173550
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Cigarette smoking and pancreatic cancer: an analysis from the International Pancreatic Cancer Case-Control Consortium (Panc4).
Authors: Bosetti C, Lucenteforte E, Silverman DT, Petersen G, Bracci PM, Ji BT, Negri E, Li D, Risch HA, Olson SH, Gallinger S, Miller AB, Bueno-de-Mesquita HB, Talamini R, Polesel J, Ghadirian P, Baghurst PA, Zatonski W, Fontham E, Bamlet WR, Holly EA, Bertuccio P, Gao YT, Hassan M, Yu H, Kurtz RC, Cotterchio M, Su J, Maisonneuve P, Duell EJ, Boffetta P, La Vecchia C
Source: Ann Oncol, 2012 Jul;23(7), p. 1880-8.
EPub date: 2011 Nov 21.
PMID: 22104574
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Molecular signatures of pancreatic cancer.
Authors: Hong SM, Park JY, Hruban RH, Goggins M
Source: Arch Pathol Lab Med, 2011 Jun;135(6), p. 716-27.
PMID: 21631264
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Telomeres are shortened in acinar-to-ductal metaplasia lesions associated with pancreatic intraepithelial neoplasia but not in isolated acinar-to-ductal metaplasias.
Authors: Hong SM, Heaphy CM, Shi C, Eo SH, Cho H, Meeker AK, Eshleman JR, Hruban RH, Goggins M
Source: Mod Pathol, 2011 Feb;24(2), p. 256-66.
EPub date: 2010 Sep 24.
PMID: 20871595
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Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations and risk for pancreatic adenocarcinoma.
Authors: McWilliams RR, Petersen GM, Rabe KG, Holtegaard LM, Lynch PJ, Bishop MD, Highsmith WE Jr
Source: Cancer, 2010 Jan 1;116(1), p. 203-9.
PMID: 19885835
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Fluorescence in situ hybridization to visualize genetic abnormalities in interphase cells of acinar cell carcinoma, ductal adenocarcinoma, and islet cell carcinoma of the pancreas.
Authors: Dewald GW, Smyrk TC, Thorland EC, McWilliams RR, Van Dyke DL, Keefe JG, Belongie KJ, Smoley SA, Knutson DL, Fink SR, Wiktor AE, Petersen GM
Source: Mayo Clin Proc, 2009 Sep;84(9), p. 801-10.
PMID: 19720778
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Analysis of the gene coding for the BRCA2-interacting protein PALB2 in familial and sporadic pancreatic cancer.
Authors: Tischkowitz MD, Sabbaghian N, Hamel N, Borgida A, Rosner C, Taherian N, Srivastava A, Holter S, Rothenmund H, Ghadirian P, Foulkes WD, Gallinger S
Source: Gastroenterology, 2009 Sep;137(3), p. 1183-6.
EPub date: 2009 Jul 25.
PMID: 19635604
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Lifestyle, dietary, and medical history factors associated with pancreatic cancer risk in Ontario, Canada.
Authors: Anderson LN, Cotterchio M, Gallinger S
Source: Cancer Causes Control, 2009 Aug;20(6), p. 825-34.
EPub date: 2009 Feb 5.
PMID: 19194662
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Polymorphisms in DNA repair genes, smoking, and pancreatic adenocarcinoma risk.
Authors: McWilliams RR, Bamlet WR, Cunningham JM, Goode EL, de Andrade M, Boardman LA, Petersen GM
Source: Cancer Res, 2008 Jun 15;68(12), p. 4928-35.
EPub date: 2008 Jun 10.
PMID: 18544627
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Genome-wide allelotypes of familial pancreatic adenocarcinomas and familial and sporadic intraductal papillary mucinous neoplasms.
Authors: Abe T, Fukushima N, Brune K, Boehm C, Sato N, Matsubayashi H, Canto M, Petersen GM, Hruban RH, Goggins M
Source: Clin Cancer Res, 2007 Oct 15;13(20), p. 6019-25.
PMID: 17947463
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Allergies are associated with reduced pancreas cancer risk: A population-based case-control study in Ontario, Canada.
Authors: Eppel A, Cotterchio M, Gallinger S
Source: Int J Cancer, 2007 Nov 15;121(10), p. 2241-5.
PMID: 17582608
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The P239S palladin variant does not account for a significant fraction of hereditary or early onset pancreas cancer.
Authors: Zogopoulos G, Rothenmund H, Eppel A, Ash C, Akbari MR, Hedley D, Narod SA, Gallinger S
Source: Hum Genet, 2007 Jun;121(5), p. 635-7.
EPub date: 2007 Apr 6.
PMID: 17415588
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The prevalence of BRCA2 mutations in familial pancreatic cancer.
Authors: Couch FJ, Johnson MR, Rabe KG, Brune K, de Andrade M, Goggins M, Rothenmund H, Gallinger S, Klein A, Petersen GM, Hruban RH
Source: Cancer Epidemiol Biomarkers Prev, 2007 Feb;16(2), p. 342-6.
PMID: 17301269
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Multifocal neoplastic precursor lesions associated with lobular atrophy of the pancreas in patients having a strong family history of pancreatic cancer.
Authors: Brune K, Abe T, Canto M, O'Malley L, Klein AP, Maitra A, Volkan Adsay N, Fishman EK, Cameron JL, Yeo CJ, Kern SE, Goggins M, Hruban RH
Source: Am J Surg Pathol, 2006 Sep;30(9), p. 1067-76.
PMID: 16931950
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Pancreatic cancer genetic epidemiology consortium.
Authors: Petersen GM, de Andrade M, Goggins M, Hruban RH, Bondy M, Korczak JF, Gallinger S, Lynch HT, Syngal S, Rabe KG, Seminara D, Klein AP
Source: Cancer Epidemiol Biomarkers Prev, 2006 Apr;15(4), p. 704-10.
PMID: 16614112
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Risk of malignancy in first-degree relatives of patients with pancreatic carcinoma.
Authors: McWilliams RR, Rabe KG, Olswold C, De Andrade M, Petersen GM
Source: Cancer, 2005 Jul 15;104(2), p. 388-94.
PMID: 15912495
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Prospective risk of pancreatic cancer in familial pancreatic cancer kindreds.
Authors: Klein AP, Brune KA, Petersen GM, Goggins M, Tersmette AC, Offerhaus GJ, Griffin C, Cameron JL, Yeo CJ, Kern S, Hruban RH
Source: Cancer Res, 2004 Apr 1;64(7), p. 2634-8.
PMID: 15059921
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