Barretts Esophagus Methylation Profiles

Abbreviated Name
BARRETTS ESOPHAGUS
Lead Investigator
Meltzer, Stephen — Johns Hopkins University
Coordinating Investigator
Zheng, Yingye — Fred Hutchinson Cancer Center
Involved Investigators

Abstract

We propose a nested case-control study of biomarkers in the setting of BE. By bringing together research institutions with large populations of patients with BE, we will perform a multi-center study of FISH and hypermethylation markers as possible prognostic factors in BE. The centers will 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.

Aims

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 denocarcinoma in patients with methylation and FISH abnormalities after controlling for other known risk factors for EAC

Analytic Method

The first step in evaluating a candidate marker is to show that there is a significant difference in the marker between cases and controls. If a marker is positive in only 5% of controls (i.e., 95% specificity), then this Project PI: Richard Sampliner, MD Principal Investigator/Program Director (Last, First, Middle): Gerner, Eugene W sample size (100 cases and 200 controls) will provide over 90% power to detect a positivity rate in cases of 18% or greater, based on a two-group Fisher's exact test at a two-sided 0.05 significance level. If a marker is positive in 10% of controls, then this sample size will provide over 90% power to detect a positivity rate in cases of 26% or greater. If a marker is positive in 25% of controls, then this sample size will provide over 90% power to detect a positivity rate in cases of 45% or greater. Looked at another way, if a marker is positive in 90% of cases (i.e., 90% sensitivity), then this sample size will provide over 90% power to detect a positivity rate in controls of 74% or lower. Given the exploratory nature of this study, a formal adjustment for multiple statistical comparisons is not planned; however, significance levels will be interpreted cautiously.

Outcome

We propose a nested case-control study of biomarkers in the setting of BE. By bringing together research institutions with large populations of patients with BE, we will perform a multi-center study of FISH and hypermethylation markers as possible prognostic factors in BE. The centers will 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.

Publications

  • No publications available at this time for this protocol.

Biomarkers

Data Collections

Start Date
Jul 15 2007
Estimated Finish Date
Aug 15 2008
Finish Date
Mar 2 2009
Protocol ID
137
Protocol Type
Validation
Fields of Research
  • Other
Collaborative Group
G.I. and Other Associated Cancers Research Group
Cancer Types
  • Malignant neoplasm of esophagus

Associated Forms