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Predicting Risk of Cancer in Barrett's Esophagus (BE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00431756
Recruitment Status : Enrolling by invitation
First Posted : February 6, 2007
Last Update Posted : February 18, 2019
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Johns Hopkins University

Brief Summary:
The purpose of this study is to determine if there are any early changes in DNA markers of blood and esophageal tissue in people with gastric reflux, Barrett's esophagus or esophageal cancer that can warn of a progression to esophageal cancer.

Condition or disease
Barrett Esophagus Esophageal Neoplasm Gastroesophageal Reflux

Detailed Description:

Patients with Barrett's esophagus (BE) have an increased risk of esophageal adenocarcinoma which is 40-125 fold higher than in the general population. However, the current techniques of detecting dysplasia and observing abnormal p53 immunohistochemical staining are not accurate or reliable methods for determining which BE patients will progress to cancer. DNA hypermethylation is an epigenetic process that occurs in the promoter region of certain genes, resulting in suppression of gene expression. Inactivation of specific genes via hypermethylation has been highly associated with cancer.

The primary objective of this research is to determine whether DNA hypermethylation is a biomarker that will predict which patients with BE are likely to progress to adenocarcinoma. Patients with BE and/or esophageal adenocarcinoma who undergo endoscopy at the Johns Hopkins Hospital will comprise the cohort of subjects. Gene hypermethylation will be assessed by performing methylation-specific Polymerase Chain Reaction (PCR) on a panel of 8 cancer-related genes.

Specific Aim 1: To compare the prevalence of gene hypermethylation in BE patients with different grades of dysplasia and/or adenocarcinoma, using archived specimens.

Specific Aim 2: To determine whether the presence of gene hypermethylation in initial biopsies of BE patients is associated with progression to adenocarcinoma, using archived specimens. To compare gene hypermethylation with currently available markers for neoplastic progression.

Specific Aim 3: To determine whether methylated DNA from BE and/or adenocarcinoma can be detected in the peripheral blood of patients, by comparing methylation profiles of esophageal biopsy specimens with peripheral blood samples taken at the same time in prospectively enrolled patients.

If hypermethylation of one or more genes is detected at an early stage in BE patients who later progress to adenocarcinoma, hypermethylation could be used as an early predictor for adenocarcinoma even before pathologic changes are evident. Furthermore, this research will help determine the specific genetic events that occur in the neoplastic transformation from BE to adenocarcinoma.

The long-term goal of this project is to determine whether hypermethylation can identify BE patients who are at high risk for neoplastic progression, thus allowing for early intervention in the form of more frequent endoscopic surveillance, chemoprevention, ablative therapy, or surgery.

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Study Type : Observational
Estimated Enrollment : 540 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Methylation in Cancer Progression of Barrett's Esophagus
Study Start Date : January 2002
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : June 2020

Resource links provided by the National Library of Medicine

Primary Outcome Measures :
  1. early predictors of esophageal cancer [ Time Frame: 3 ]
    To see if changes in certain areas of DNA can predict risk for esophageal cancer

Biospecimen Retention:   Samples With DNA
approx. 24 ml blood, 1-8 esophageal mucosal pinch specimens and or esophageal brushings

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 95 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
People scheduled for endoscopy at Johns Hopkins who have esophageal cancer, Barrett's esophagus or gastro-esophageal reflux disease

Inclusion Criteria:

  • People who are undergoing upper endoscopy as part of their medical care with a history of esophageal cancer, Barrett's esophagus, or upper gastrointestinal symptoms.

Exclusion Criteria:

  • People who are are currently having chemotherapy, or who have completed chemotherapy within the last 4 weeks.
  • People who have ever had radiation treatments to their chest.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00431756

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United States, Maryland
Johns Hopkins Hospital
Baltimore, Maryland, United States, 21287
Johns Hopkins at Howard County General Hospital
Columbia, Maryland, United States, 21044
Sponsors and Collaborators
Johns Hopkins University
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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Principal Investigator: Marcia Canto, M.D. Johns Hopkins University

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Responsible Party: Johns Hopkins University Identifier: NCT00431756     History of Changes
Other Study ID Numbers: IRB00026956
1K23DK068149 ( U.S. NIH Grant/Contract )
First Posted: February 6, 2007    Key Record Dates
Last Update Posted: February 18, 2019
Last Verified: February 2019

Keywords provided by Johns Hopkins University:
Barrett's esophagus
gastroesophageal reflux disease (GERD)
esophageal cancer
DNA methylation

Additional relevant MeSH terms:
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Barrett Esophagus
Gastroesophageal Reflux
Esophagitis, Peptic
Esophageal Neoplasms
Esophageal Motility Disorders
Deglutition Disorders
Esophageal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Peptic Ulcer
Duodenal Diseases
Intestinal Diseases
Stomach Diseases
Precancerous Conditions
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Head and Neck Neoplasms