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Supplement 2: Predictive Biomarkers for Esophageal Adenocarcinoma in Patients with Barrett's Esophagus

Project Summary

Project Leader:
Richard Sampliner, MD

Barrett's esophagus (BE) is a metaplastic change in the lining of the esophagus in which the normal squamous epithelium is replaced by intestinal metaplasia. The clinical significance of BE lies in its malignant potential. BE is the premalignant lesion for esophageal adenocarcinoma (EAC), the incidence of which is rising faster than that of any other cancer in the U.S.

A commonly cited concern regarding cancer prevention programs for those with BE is the lack of ability to adequately stratify risk among those with BE, and concentrate our efforts at prevention in those subjects at the highest risk of progression to cancer. This InterSPORE collaboration proposes a multi-center retrospective nested case-control study of biomarkers in patients with Barrett's esophagus (BE) progressing to high grade dysplasia (HGD) or adenocarcinoma of the esophagus (EAC) compared to patients without progression. Our hypothesis is that abnormalities of DNA methylation and FISH analysis in esophageal biopsies from BE patients will provide highly sensitive and specific biomarkers for distinguishing those patients who are likely to progress to HGD or EAC from those who are not.

Our specific aims include:

1. Utilizing methylation-specific PCR and FISH, to identify DNA methylation abnormalities and chromosomal aberrancies which represent biomarkers of risk for progression to EAC in the setting of BE.
2. To perform multivariate analysis of the risk of progression to HGD or esophageal adenocarcinoma in patients with methylation and FISH abnormalities after controlling for other known risk factors for EAC.

This project is a nested case-control study of biomarkers in the setting of BE. By bringing together research institutions with large populations of patients with BE, this supplement is performing a multi-center study of FISH and hypermethylation markers as possible prognostic factors in BE. The centers select from their cohorts who have progressed to HGD or to adenocarcinoma of the esophagus ("progressors"), and who also donated samples prior to the development of cancer, when their histology was felt to be benign. These subjects will be compared to individuals who have been under endoscopic surveillance, but who have not progressed to HGD or EAC ("non-progressors"). Using this approach, we hope to identify promising markers for risk stratification in BE. We expect to be able to make successful application for a prospective study of markers identified in this case-control study.

 

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