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Barrett's Esophagus Methylation Profiles

Feng, ZidingFred Hutchinson Cancer Research Center
p16, RUNX3, HPP1, qMSP, NELL1, TAC1, AKAP12, CDH13, SST
Other, Specify
G.I. and Other Associated Cancers Research Group

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.

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
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.

Announcement 7/2/2018

The 33rd EDRN Steering Committee Meeting is from September 5-6, 2018 in Boston, MA. Please click here for meeting registration and hotel information.

Announcement 6/1/2018

Dr. Sudhir Srivastava was honored with the 2017 Human Proteome Organization (HUPO) Award for a Distinguished Scientist in Clinical and Translational Proteomics. Please join us in congratulating him on his accomplishments and contributions. The awards were presented at HUPO 2017 in Dublin, Ireland and the winners were present to provide a small talk during the Awards Ceremony and HUPO Lectures.