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Juvenile polyposis, hereditary hemorrhagic telangiectasia, and early onset colorectal cancer in patients with SMAD4 mutation.

https://arctichealth.org/en/permalink/ahliterature127029
Source
J Gastroenterol. 2012 Jul;47(7):795-804
Publication Type
Article
Date
Jul-2012
Author
Frank Schwenter
Marie E Faughnan
Abigail B Gradinger
Terri Berk
Robert Gryfe
Aaron Pollett
Zane Cohen
Steven Gallinger
Carol Durno
Author Affiliation
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, ON M5T 3L9, Canada. frank.schwenter@gmail.com
Source
J Gastroenterol. 2012 Jul;47(7):795-804
Date
Jul-2012
Language
English
Publication Type
Article
Keywords
Adolescent
Adult
Age of Onset
Child
Colorectal Neoplasms - genetics
Databases, Factual
Genetic Testing
Humans
Intestinal Polyposis - congenital - genetics
Mutation
Neoplastic Syndromes, Hereditary - genetics
Ontario
Prospective Studies
Smad4 Protein - genetics
Telangiectasia, Hereditary Hemorrhagic - genetics
Young Adult
Abstract
Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder most often caused by mutation in the endoglin or ALK1 genes. A distinct syndrome combines the clinical features of HHT and juvenile polyposis (JP) and has been associated with SMAD4 mutation. The aim of this study was to describe the phenotype of patients with JP-HHT and SMAD4 mutations and to compare this phenotype with HHT or JP patients with mutations other than SMAD4.
Patients prospectively enrolled in the Toronto HHT and JP databases who underwent genotyping were included. The phenotypic characteristics of JP-HHT patients with SMAD4 mutations and patients with mutations other than SMAD4 were analyzed and compared.
Three hundred and fifty-eight patients underwent genetic testing (HHT, n = 332; JP, n = 26). Among fourteen patients identified with SMAD4 mutations, ten met the clinical diagnostic criteria for both JP and HHT (71%). Patients with SMAD4 mutations had 100% penetrance of the polyposis phenotype. All patients with JP and SMAD4 mutation had features of HHT. Three JP-HHT patients developed early onset colorectal cancer (CRC) (mean age 28 years). JP-HHT patients with SMAD4 mutation had a significantly higher rate of anemia than HHT patients with mutations other than SMAD4.
Patients with HHT and SMAD4 mutations are at significant risk of JP and CRC. The gastrointestinal phenotype is similar to JP patients without SMAD4 mutation. It is essential for HHT patients to undergo genetic testing to determine if they have SMAD4 mutations so that appropriate gastrointestinal screening and surveillance for JP and CRC can be completed.
PubMed ID
22331366 View in PubMed
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A large novel deletion in the APC promoter region causes gene silencing and leads to classical familial adenomatous polyposis in a Manitoba Mennonite kindred.

https://arctichealth.org/en/permalink/ahliterature154409
Source
Hum Genet. 2008 Dec;124(5):535-41
Publication Type
Article
Date
Dec-2008
Author
George S Charames
Lily Ramyar
Angela Mitri
Terri Berk
Hong Cheng
Jack Jung
Patricia Bocangel
Bernie Chodirker
Cheryl Greenberg
Elizabeth Spriggs
Bharati Bapat
Author Affiliation
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 60 Murray St., Toronto, Box 30, ON, M5T 3L9, Canada. charames@lunenfeld.ca
Source
Hum Genet. 2008 Dec;124(5):535-41
Date
Dec-2008
Language
English
Publication Type
Article
Keywords
Adenomatous Polyposis Coli - genetics
Adult
Base Sequence
DNA Primers - genetics
Ethnic Groups - genetics
Female
Founder Effect
Gene Silencing
Genes, APC
Genetic Linkage
Germ-Line Mutation
Humans
Male
Manitoba
Pedigree
Promoter Regions, Genetic
Sequence Deletion
Abstract
Familial adenomatous polyposis (FAP) is an autosomal dominant syndrome caused by the inheritance of germline mutations in the APC tumour suppressor gene. The vast majority of these are nonsense and frameshift mutations resulting in a truncated protein product and abnormal function. While APC promoter hypermethylation has been previously documented, promoter-specific deletion mutations have not been reported. In a large Canadian Mennonite polyposis kindred, we identified a large novel germline deletion in the APC promoter region by linkage analysis and MLPA. By RT-PCR and sequence analysis, this mutation was found to result in transcriptional silencing of the APC allele. A few genetic disorders have been characterized as over-represented in the Manitoba Mennonite population, however, the incidence of cancer has not been recognized as increased in this population as compared to other Manitoba ethnic groups. This study strengthens the likelihood that this novel APC promoter mutation is linked to this unique population as a founder mutation.
PubMed ID
18982352 View in PubMed
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Quality of life in adults diagnosed with familial adenomatous polyposis and desmoid tumor.

https://arctichealth.org/en/permalink/ahliterature180991
Source
Dis Colon Rectum. 2004 May;47(5):687-95; discussion 695-6
Publication Type
Article
Date
May-2004
Author
Mary Jane Esplen
Terri Berk
Kate Butler
Steven Gallinger
Zane Cohen
Mateya Trinkhaus
Author Affiliation
Division of Behavioral Sciences and Health, Toronto General Research Institute, University Health Network and Faculty of Medicine and Nursing, University of Toronto, Toronto, Canada. mesplen@uhnres.utoronto.ca
Source
Dis Colon Rectum. 2004 May;47(5):687-95; discussion 695-6
Date
May-2004
Language
English
Publication Type
Article
Keywords
Adenomatous Polyposis Coli - psychology
Adult
Aged
Body Image
Canada
Cross-Sectional Studies
Family Relations
Female
Fibromatosis, Aggressive - psychology
Health status
Humans
Male
Middle Aged
Neoplasms, Second Primary - psychology
Personal Satisfaction
Quality of Life - psychology
Abstract
The purpose of this study was to examine the health-related quality of life in a sample of Canadian adults diagnosed with familial adenomatous polyposis and desmoid tumor.
The study was conducted in two parts. Seven individuals participated in a focus group prior to a mail-out survey. A cross-sectional mail-out survey was administered to eligible individuals who were actively followed at the Familial Gastrointestinal Cancer Registry at Mount Sinai Hospital.
Forty-one individuals (25 female and 16 male) were available to be contacted by the registry coordinator and 23 questionnaire packages were completed, resulting in a 56.1 percent participation rate. The results of this study demonstrated a reduced health-related quality of life for individuals living with familial adenomatous polyposis and desmoid tumor for over 10 years. The main predictors of health-related quality of life in this analysis included marital status (married vs. not married), prior knowledge of desmoid tumor in the family, and current level of hopelessness (R(2) = 0.856, df = 13, F = 26.8, P
PubMed ID
15037938 View in PubMed
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Slow progression of periampullary neoplasia in familial adenomatous polyposis.

https://arctichealth.org/en/permalink/ahliterature187219
Source
J Gastrointest Surg. 2002 Nov-Dec;6(6):831-7; discussion 837
Publication Type
Article
Author
Kouros L Moozar
Lisa Madlensky
Terri Berk
Steven Gallinger
Author Affiliation
Department of Surgery, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario M5G 1X5, Canada.
Source
J Gastrointest Surg. 2002 Nov-Dec;6(6):831-7; discussion 837
Language
English
Publication Type
Article
Keywords
Adenomatous Polyposis Coli - diagnosis - epidemiology - genetics
Adolescent
Adult
Age Distribution
Aged
Analysis of Variance
Biopsy, Needle
Colonoscopy - methods
Disease Progression
Duodenal Neoplasms - diagnosis - epidemiology - genetics
Female
Follow-Up Studies
Genetic Predisposition to Disease
Humans
Incidence
Male
Mass Screening - methods
Middle Aged
Monitoring, Physiologic - methods
Neoplasm Staging
Ontario - epidemiology
Prognosis
Prospective Studies
Risk assessment
Sex Distribution
Abstract
Variable endoscopic surveillance protocols and treatment strategies have been proposed for periampullary neoplasia in familial adenomatous polyposis (FAP), primarily because of the lack of long-term, prospective natural history data. A total of 115 patients with FAP were followed prospectively for 10 years with periodic side-viewing upper gastrointestinal endoscopy by a single surgeon. The appearance of the duodenum was classified as stages 1 to 5. Statistical analysis included one-way analysis of variance for age comparisons between stage groupings and Kaplan-Meier analysis for the lifetime risks of having a particular stage of duodenal polyposis. Eighty-seven patients had multiple endoscopies over an average of 6.6 years. Thirty-three subjects had a change in stage, within an average time of 3.9 years at an average age of 41 years. The risk of having stage 3 or 4 duodenal neoplasia increased exponentially after the age of 40. The degree of dysplasia did not correlate with stage at initial classification. Progression of neoplasia in the duodenum of patients with FAP is slow. The severity of duodenal polyposis increases with age and is not influenced by the initial stage. The average time for progression of adenoma to carcinoma is likely long.
PubMed ID
12504221 View in PubMed
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