: Barrett's esophagus is the precursor of esophageal adenocarcinoma. Both Barrett's esophagus and esophageal adenocarcinoma are closely associated with gastroesophageal reflux. Screening endoscopy is therefore recommended for the evaluation of chronic gastroesophageal reflux symptoms. Endoscopic surveillance, performed in those identified with Barrett's esophagus, detects cancer at an early stage. However, the large majority of these cancers occur in previously undiagnosed Barrett's esophagus and nearly half of these persons have no history of gastroesophageal reflux symptoms. Identification of genetic risk factors would lead to more effective screening programs and improved understanding of the molecular pathogenesis of these diseases. Our prior case control study demonstrated familial aggregation of Barrett's esophagus and its associated cancers, which we termed Familial Barrett's Esophagus. We have since developed family recruitment and endoscopic screening methods to identify Familial Barrett's Esophagus. Recent molecular genetic studies have identified one putative locus and suggest the existence of at least one other locus linked to these diseases. These family recruitment, endoscopic screening, and genetic analysis methods will now be used to test the following central hypothesis: Familial Barrett Esophagus has a genetic basis.
The specific aims of this proposal are: (1) To recruit and screen family members of esophageal adenocarcinoma patients, comparing age of cancer onset between probands classified as familial with those classified as apparently sporadic; (2) To perform endoscopic screening and measure the recurrence risk of Barrett's esophagus in siblings of probands with Barrett's esophagus and esophageal adenocarcinoma; and (3) To identify loci and map susceptibility genes associated with Familial Barrett's Esophagus. Using the multidisciplinary approach of our collaborative team of investigators, these aims will result in new information regarding a genetic predisposition to the development of Barrett's esophagus and esophageal adenocarcinoma.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
1R01DK070863-01
Application #
6905968
Study Section
Clinical and Integrative Gastrointestinal Pathobiology Study Section (CIGP)
Program Officer
Karp, Robert W
Project Start
2005-09-30
Project End
2010-08-31
Budget Start
2005-09-30
Budget End
2006-08-31
Support Year
1
Fiscal Year
2005
Total Cost
$756,367
Indirect Cost
Name
Case Western Reserve University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
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