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 |
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).
Publications
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
Related Citations
Increased cyclooxygenase-2 expression in juvenile polyposis syndrome.
Authors: van Hattem W.A.
, Brosens L.A.
, Marks S.Y.
, Milne A.N.
, van Eeden S.
, Iacobuzio-Donahue C.A.
, Ristimäki A.
, Giardiello F.M.
, Offerhaus G.J.
.
Source: Clinical Gastroenterology And Hepatology : The Official Clinical Practice Journal Of The American Gastroenterological Association, 2009 Jan; 7(1), p. 93-7.
PMID: 19124115
Related Citations
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.
PMID: 18178612
Related Citations
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
Related Citations
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.
PMID: 18373413
Related Citations
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.
PMID: 17303595
Related Citations
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.
.
Source: Gastroenterology, 2005 Apr; 128(4), p. 1077-80.
PMID: 15825088
Related Citations
Prostanoids, ornithine decarboxylase, and polyamines in primary chemoprevention of familial adenomatous polyposis.
Authors: Giardiello F.M.
, Casero R.A.
, Hamilton S.R.
, Hylind L.M.
, Trimbath J.D.
, Geiman D.E.
, Judge K.R.
, Hubbard W.
, Offerhaus G.J.
, Yang V.W.
.
Source: Gastroenterology, 2004 Feb; 126(2), p. 425-31.
PMID: 14762779
Related Citations
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
Related Citations
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
Related Citations
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.
PMID: 11932472
Related Citations
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
Related Citations
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
Related Citations
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
Related Citations
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.
PMID: 11113065
Related Citations
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
Related Citations
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
Related Citations
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
Related Citations
Missense mutations in disease genes: a Bayesian approach to evaluate causality.
Authors: Petersen G.M.
, Parmigiani G.
, Thomas D.
.
Source: American Journal Of Human Genetics, 1998 Jun; 62(6), p. 1516-24.
PMID: 9585599
Related Citations
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
Related Citations
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
Related Citations
Phenotypic expression of disease in families that have mutations in the 5' region of the adenomatous polyposis coli gene.
Authors: Giardiello F.M.
, Brensinger J.D.
, Luce M.C.
, Petersen G.M.
, Cayouette M.C.
, Krush A.J.
, Bacon J.A.
, Booker S.V.
, Bufill J.A.
, Hamilton S.R.
.
Source: Annals Of Internal Medicine, 1997-04-01 00:00:00.0; 126(7), p. 514-9.
PMID: 9092316
Related Citations
APC gene mutations and extraintestinal phenotype of familial adenomatous polyposis.
Authors: Giardiello F.M.
, Petersen G.M.
, Piantadosi S.
, Gruber S.B.
, Traboulsi E.I.
, Offerhaus G.J.
, Muro K.
, Krush A.J.
, Booker S.V.
, Luce M.C.
, et al.
.
Source: Gut, 1997 Apr; 40(4), p. 521-5.
PMID: 9176082
Related Citations
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
Related Citations
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
Related Citations
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
Related Citations
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
Related Citations
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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