Trial Information

Barrett's Esophagus Early Detection Study

Background:

The incidence rate for esophageal adenocarcinoma (EAC) has risen 10% per year over the past
two decades and is the most rapidly increasing cancer in the U.S.

Barrett's esophagus (BE), a metaplastic change from the normal squamous esophageal
epithelium to a specialized intestinal-type columnar mucosa, increases the risk of EAC by
30-125 fold (1), and is considered a precursor lesion for EAC.

Individuals diagnosed with BE are currently entered into endoscopic surveillance programs to
look for dysplasia or EAC. However, only 5% of subjects diagnosed with EAC have a previous
diagnosis of BE or have been part of a surveillance program, so alternative screening
methods are needed.

Objectives:

The primary goal of this project is to identify a practical blood-based biomarker(s) that
can be used as a screening test to determine who has BE and who does not.

Secondary goals of the project are to characterize germ line and tissue biomarkers
associated with BE, and to compare biomarkers in non-BE patients with and without GERD.

Tertiary goals are to explore associations between biomarkers in blood or tissue and
progression from BE to dysplasia or EAC, and to assess the stability of proteomic patterns
over time.

Eligibility:

This study will be conducted among patients in the Barretts' Esophagus Registry (currently
with 206 registrants) established at the National Naval Medical Center (NNMC) in Bethesda
beginning in 1992 as well as comparison group of approximately 600 matched non-BE patients
endoscoped in the GI clinic at NNMC for other conditions.

Design:

Blood and tissue samples will be collected as well as questionnaire data on risk factors and
medications as well as GERD.

Data analysis will be based primarily on laboratory testing of newly collected esophageal
biopsies, brush samples, and blood samples, but secondarily will also include use of
archival tissue biopsy samples.

Follow-up of BE Registry patients will include standard periodic surveillance endoscopies,
additional blood samples, and ascertainment of disease status (i.e, progression).

To distinguish BE versus non-BE patients, we will: (1) assess predictability of BE status
from serum proteomic patters; (2) characterize esophageal biopsies and brush samples for
selected DNA alterations, RNA expression, and proteomic profiles; (3) genotype patients for
selected polymorphisms potentially associated with BE; (4) compare blood and tissue
biomarkers in non-BE patients with and without GERD; (5) explore the association of
biomarkers with progression from BE to dysplasia or EAC; and (6) assess proteomic pattern
stability over time in BE patients.