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

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).




SMAD4 immunohistochemistry reflects genetic status in juvenile polyposis syndrome.
Authors: Langeveld D. , van Hattem W.A. , de Leng W.W. , Morsink F.H. , Ten Kate F.J. , Giardiello F.M. , Offerhaus G.J. , Brosens L.A. .
Source: Clinical Cancer Research : An Official Journal Of The American Association For Cancer Research, 2010-08-15 00:00:00.0; 16(16), p. 4126-34.
EPub date: 2010-08-15 00:00:00.0.
PMID: 20682711
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Increased cyclooxygenase-2 expression in juvenile polyposis syndrome.
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Source: Clinical Gastroenterology And Hepatology : The Official Clinical Practice Journal Of The American Gastroenterological Association, 2009 Jan; 7(1), p. 93-7.
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Large genomic deletions of SMAD4, BMPR1A and PTEN in juvenile polyposis.
Authors: van Hattem W.A. , Brosens L.A. , de Leng W.W. , Morsink F.H. , Lens S. , Carvalho R. , Giardiello F.M. , Offerhaus G.J. .
Source: Gut, 2008 May; 57(5), p. 623-7.
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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. .
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Development and preliminary validation of the cancer family impact scale for colorectal cancer.
Authors: Sinicrope P.S. , Vernon S.W. , Diamond P.M. , Patten C.A. , Kelder S.H. , Rabe K.G. , Petersen G.M. .
Source: Genetic Testing, 2008 Mar; 12(1), p. 161-9.
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Risk of colorectal cancer in juvenile polyposis.
Authors: Brosens L.A. , van Hattem A. , Hylind L.M. , Iacobuzio-Donahue C. , Romans K.E. , Axilbund J. , Cruz-Correa M. , Tersmette A.C. , Offerhaus G.J. , Giardiello F.M. .
Source: Gut, 2007 Jul; 56(7), p. 965-7.
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Oral contraceptives and polyp regression in familial adenomatous polyposis.
Authors: Giardiello F.M. , Hylind L.M. , Trimbath J.D. , Hamilton S.R. , Romans K.E. , Cruz-Correa M. , Corretti M.C. , Offerhaus G.J. , Yang V.W. .
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Prostanoids, ornithine decarboxylase, and polyamines in primary chemoprevention of familial adenomatous polyposis.
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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.
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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.
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Primary chemoprevention of familial adenomatous polyposis with sulindac.
Authors: Giardiello F.M. , Yang V.W. , Hylind L.M. , Krush A.J. , Petersen G.M. , Trimbath J.D. , Piantadosi S. , Garrett E. , Geiman D.E. , Hubbard W. , et al. .
Source: The New England Journal Of Medicine, 2002-04-04 00:00:00.0; 346(14), p. 1054-9.
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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.
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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.
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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.
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Very high risk of cancer in familial Peutz-Jeghers syndrome.
Authors: Giardiello F.M. , Brensinger J.D. , Tersmette A.C. , Goodman S.N. , Petersen G.M. , Booker S.V. , Cruz-Correa M. , Offerhaus J.A. .
Source: Gastroenterology, 2000 Dec; 119(6), p. 1447-53.
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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.
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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.
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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.
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Missense mutations in disease genes: a Bayesian approach to evaluate causality.
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Source: American Journal Of Human Genetics, 1998 Jun; 62(6), p. 1516-24.
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Size-dependent increase in prostanoid levels in adenomas of patients with familial adenomatous polyposis.
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Source: Cancer Research, 1998-04-15 00:00:00.0; 58(8), p. 1750-3.
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Evidence against genetic anticipation in familial colorectal cancer.
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Genetic counseling and predictive testing for colorectal cancer risk.
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Genetic epidemiology of colorectal cancer.
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