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National Institutes of Health: National Cancer Institute: Division of Cancer Control and Population Sciences
Grant Details

Grant Number: 5R01CA063721-05 Interpret this number
Primary Investigator: Petersen, Gloria
Organization: Johns Hopkins University
Project Title: Genetic Epidemiology of Hereditary Colonic Cancers
Fiscal Year: 1998
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Abstract

This study proposes to use the large registries of colorectal cancer (CRC) families accumulated by the John Hopkins University (JHU) and University of Utah research groups to systematically evaluate the phenotypic and genetic heterogeneity of hereditary non-polyposis colon cancer (HNPCC), familial adenomatous polyposis (FAP), and multiplex colorectal cancer kindreds. These studies are crucial to our understanding of gene-environment interactions in colon cancer etiology. Our aims are outlined below. Using our combined CRC (hereditary and sporadic) registry resources we propose to: 1. Evaluate the rate of occurrence of the newly-described replication error (RER) molecular phenotype in CRCs of 200 incident sporadic CRC patients seen at JHU, 50 patients (JHU and Utah) from unrelated families which fulfill diagnostic criteria of HNPCC, and 50 patients (JHU and Utah) from unrelated multiplex CRC kindreds which do not meet the criteria for HNPCC. 2. Test for differences between RER phenotype and clinical/epidemiologic data on the patients tested in Specific Aim 1. These data include age at diagnosis, cancer site, multiplicity of cancers in the patient, family history of CRC, and p53, DCC, and RAS gene changes in the CRCs. 3. Determine concordance of RER phenotype in CRCs of relatives from multiplex families and 20 CRC kindreds). This analysis will stratify the families based on evidence of linkage or non-linkage to chromosome 2. Using the John Hopkins FAP registry resource, we propose to: 4. Characterize mutations in the FAP-causing gene (APC) in 250 unrelated FAP patients, and test for differences between mutations in different APC domains and clinical/epidemiologic data (age at onset, presence of extracolonic tumors, number of polyps, etc.). 5. Compare clinical/epidemiologic characteristics of affected individuals in FAP families that are and are not linked to the APC gene. 6. Test for the effect of dietary factors on the age of onset of colonic polyps in a cohort of 100 at-risk individuals known by genetic testing to have inherited mutant APC genes. To achieve these aims, concurrently submitted proposals will perform linkage studies (M. Skolnick, PI) and P53 and RAS gene studies (S. Hamilton, PI).

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Publications

Genetic Epidemiology Of Colorectal Cancer
Authors: Petersen G.M. .
Source: European Journal Of Cancer (oxford, England : 1990), 1995 Jul-Aug; 31A(7-8), p. 1047-50.
PMID: 7576989
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Genetic Counseling And Predictive Testing For Colorectal Cancer Risk
Authors: Petersen G.M. .
Source: International Journal Of Cancer, 1996-02-20 00:00:00.0; 69(1), p. 53-4.
PMID: 8600062
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Genetic Testing For Cancer In Children. Short-term Psychological Effect
Authors: Codori A.M. , Petersen G.M. , Boyd P.A. , Brandt J. , Giardiello F.M. .
Source: Archives Of Pediatrics & Adolescent Medicine, 1996 Nov; 150(11), p. 1131-8.
PMID: 8904852
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The Use And Interpretation Of Commercial Apc Gene Testing For Familial Adenomatous Polyposis
Authors: Giardiello F.M. , Brensinger J.D. , Petersen G.M. , Luce M.C. , Hylind L.M. , Bacon J.A. , Booker S.V. , Parker R.D. , Hamilton S.R. .
Source: The New England Journal Of Medicine, 1997-03-20 00:00:00.0; 336(12), p. 823-7.
PMID: 9062090
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Evidence Against Genetic Anticipation In Familial Colorectal Cancer
Authors: Tsai Y.Y. , Petersen G.M. , Booker S.V. , Bacon J.A. , Hamilton S.R. , Giardiello F.M. .
Source: Genetic Epidemiology, 1997; 14(4), p. 435-46.
PMID: 9271715
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Prostaglandin Levels In Human Colorectal Mucosa: Effects Of Sulindac In Patients With Familial Adenomatous Polyposis
Authors: Giardiello F.M. , Spannhake E.W. , DuBois R.N. , Hylind L.M. , Robinson C.R. , Hubbard W.C. , Hamilton S.R. , Yang V.W. .
Source: Digestive Diseases And Sciences, 1998 Feb; 43(2), p. 311-6.
PMID: 9512123
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Size-dependent Increase In Prostanoid Levels In Adenomas Of Patients With Familial Adenomatous Polyposis
Authors: Yang V.W. , Shields J.M. , Hamilton S.R. , Spannhake E.W. , Hubbard W.C. , Hylind L.M. , Robinson C.R. , Giardiello F.M. .
Source: Cancer Research, 1998-04-15 00:00:00.0; 58(8), p. 1750-3.
PMID: 9563494
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Pathogenesis Of Adenocarcinoma In Peutz-jeghers Syndrome
Authors: Gruber S.B. , Entius M.M. , Petersen G.M. , Laken S.J. , Longo P.A. , Boyer R. , Levin A.M. , Mujumdar U.J. , Trent J.M. , Kinzler K.W. , et al. .
Source: Cancer Research, 1998-12-01 00:00:00.0; 58(23), p. 5267-70.
PMID: 9850045
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Genetic Testing And Counseling For Hereditary Forms Of Colorectal Cancer
Authors: Petersen G.M. , Brensinger J.D. , Johnson K.A. , Giardiello F.M. .
Source: Cancer, 1999-12-01 00:00:00.0; 86(11 Suppl), p. 2540-50.
PMID: 10630180
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Tissue Prostanoids As Biomarkers For Chemoprevention Of Colorectal Neoplasia: Correlation Between Prostanoid Synthesis And Clinical Response In Familial Adenomatous Polyposis
Authors: Yang V.W. , Geiman D.E. , Hubbard W.C. , Spannhake E.W. , Hylind L.M. , Hamilton S.R. , Giardiello F.M. .
Source: Prostaglandins & Other Lipid Mediators, 2000 Jan; 60(1-3), p. 83-96.
PMID: 10680778
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Population Carrier Frequency Of Hmsh2 And Hmlh1 Mutations
Authors: Dunlop M.G. , Farrington S.M. , Nicholl I. , Aaltonen L. , Petersen G. , Porteous M. , Carothers A. .
Source: British Journal Of Cancer, 2000 Dec; 83(12), p. 1643-5.
PMID: 11104559
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Health Beliefs And Endoscopic Screening For Colorectal Cancer: Potential For Cancer Prevention
Authors: Codori A.M. , Petersen G.M. , Miglioretti D.L. , Boyd P. .
Source: Preventive Medicine, 2001 Aug; 33(2 Pt 1), p. 128-36.
PMID: 11493046
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Review Article: Genetic Testing And Counselling For Hereditary Colorectal Cancer
Authors: Trimbath J.D. , Giardiello F.M. .
Source: Alimentary Pharmacology & Therapeutics, 2002 Nov; 16(11), p. 1843-57.
PMID: 12390093
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Genetic Testing For Hereditary Colorectal Cancer In Children: Long-term Psychological Effects
Authors: Codori A.M. , Zawacki K.L. , Petersen G.M. , Miglioretti D.L. , Bacon J.A. , Trimbath J.D. , Booker S.V. , Picarello K. , Giardiello F.M. .
Source: American Journal Of Medical Genetics. Part A, 2003-01-15 00:00:00.0; 116A(2), p. 117-28.
PMID: 12494429
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Café-au-lait Spots And Early Onset Colorectal Neoplasia: A Variant Of Hnpcc?
Authors: Trimbath J.D. , Petersen G.M. , Erdman S.H. , Ferre M. , Luce M.C. , Giardiello F.M. .
Source: Familial Cancer, 2001; 1(2), p. 101-5.
PMID: 14574005
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Increased Expression Of Cytoplasmic Hur In Familial Adenomatous Polyposis
Authors: Brosens L.A. , Keller J.J. , Pohjola L. , Haglund C. , Morsink F.H. , Iacobuzio-Donahue C. , Goggins M. , Giardiello F.M. , Ristimäki A. , Offerhaus G.J. .
Source: Cancer Biology & Therapy, 2008 Mar; 7(3), p. 424-7.
PMID: 18094611
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