# Project 1 - Genetic Predisposition To Barrett's Esophagus and Esophageal Adenocarcinoma

> **NIH NIH U54** · CASE WESTERN RESERVE UNIVERSITY · 2021 · $260,494

## Abstract

PROJECT SUMMARY 
Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) are complex diseases with undiscovered 
genetic factors. We successfully discovered a deleterious variant in VSIG10L segregating in a large family. This 
is the first such reported gene for susceptibility to BE and EAC. VSIG10L appears to function in adhesion and 
differentiation/maturation of stratified squamous epithelium. Further clues for a genetic basis comes from our 
admixture mapping study, which has identified two specific chromosomal regions associated with excess 
European ancestry in African Americans. The BETRNet focus of Project 1 is thus to identify the genetic basis of 
racial disparity in the prevalence of BE and EAC. A second BETRNet focus of Project 1 is to create a genetically 
engineered mouse model based on VSIG10L to understand the transformation from squamous epithelium to 
metaplastic Barrett's epithelium. This project will now build on these discoveries by: 
 1) Using dense SNP genotyping, NextGen sequencing, and ATAC-seq to identify racially disparate genetic 
 variants that explain racial differences in prevalence of BE and EAC; 
 2) Using genetically engineered VSIG10L knockout and VSIG10L S631G variant carrying mice to 
 understand how VSIG10L contributes to the normal squamous epithelium  esophagitis  BE 
 metaplasia  dysplasia  cancer progression; 
The significance of Project 1 is first to translate the clinical observation of racial disparity in BE and EAC into the 
laboratory to identify a causative genetic basis. Furthermore, the project will build on our successful discovery of 
the first familial susceptibility genetic variant by understanding how this gene functions in metaplastic 
transformation of Barrett's epithelium.

## Key facts

- **NIH application ID:** 10153702
- **Project number:** 5U54CA163060-10
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** AMITABH CHAK
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $260,494
- **Award type:** 5
- **Project period:** 2011-09-26 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10153702

## Citation

> US National Institutes of Health, RePORTER application 10153702, Project 1 - Genetic Predisposition To Barrett's Esophagus and Esophageal Adenocarcinoma (5U54CA163060-10). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10153702. Licensed CC0.

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