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Grant Details

Grant Number: 5R21CA197502-02 Interpret this number
Primary Investigator: Dai, James
Organization: Fred Hutchinson Cancer Research Center
Project Title: Genomic Studies for Understanding Etiology of Esophageal Adenocarcinoma
Fiscal Year: 2016


Abstract

 DESCRIPTION (provided by applicant): Esophageal carcinoma is the eighth most common cancer and the sixth leading cause of cancer-related mortality worldwide. The incidence of esophageal cancer varies widely by histology and geographic region. Over the past four decades, the predominant histological type in the United States (US) has shifted drastically from esophageal squamous-cell carcinoma (ESCC) to esophageal adenocarcinoma (EA). In China and its surrounding areas, however, ESCC is the predominant type; EA remains rare without association of Barrett's esophagus (BE). While prevention and therapeutic strategies are urgently needed, the genetic and environmental architecture of EA etiology that underwrites this profound temporal, spatial and histological variation remains unclear. Recent high-throughput genomic studies have made progress in understanding germline and somatic mutations of EA. Significant gaps remain for understanding genetic basis of EA. First, how do genetic susceptibility loci contribute to risk prediction for EA, in concert with the risk factors that hav been studied for over 20 years? Second, what are mutated genes that drive carcinogenesis of EA, given the majority of somatic mutations already occur in BE and most BE cases do not progress to EA? In this project, we propose genomic studies for understanding the etiology of esophageal adenocarcinoma, leveraging existing genome-wide association data and cancer genome data. A number of innovative approaches will be undertaken include integrative analyses of germline and somatic mutations, genome-wide searching for gene-environment interaction, and comparative genomics between US and China. The ultimate goal is to dis- cover genetic markers, both germline and somatic mutations, for early detection and treatment of esophageal adenocarcinoma.



Publications

Case-only approach to identifying markers predicting treatment effects on the relative risk scale.
Authors: Dai J.Y. , Liang C.J. , LeBlanc M. , Prentice R.L. , Janes H. .
Source: Biometrics, 2018 06; 74(2), p. 753-763.
EPub date: 2017-09-28.
PMID: 28960244
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Whole-genome sequencing of esophageal adenocarcinoma in Chinese patients reveals distinct mutational signatures and genomic alterations.
Authors: Dai J.Y. , Wang X. , Buas M.F. , Zhang C. , Ma J. , Wei B. , Li Y. , Zhao B. , Hyun T.S. , Chen X. , et al. .
Source: Communications biology, 2018; 1, p. 174.
EPub date: 2018-10-24.
PMID: 30374464
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The Evolving Genomic Landscape of Barrett's Esophagus and Esophageal Adenocarcinoma.
Authors: Contino G. , Vaughan T.L. , Whiteman D. , Fitzgerald R.C. .
Source: Gastroenterology, 2017 09; 153(3), p. 657-673.e1.
EPub date: 2017-07-14.
PMID: 28716721
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Constrained Score Statistics Identify Genetic Variants Interacting with Multiple Risk Factors in Barrett's Esophagus.
Authors: Dai J.Y. , Tapsoba J.D. , Buas M.F. , BEACON Consortium , Risch H.A. , Vaughan T.L. .
Source: American journal of human genetics, 2016-08-04; 99(2), p. 352-65.
PMID: 27486777
Related Citations

A newly identified susceptibility locus near FOXP1 modifies the association of gastroesophageal reflux with Barrett's esophagus.
Authors: Dai J.Y. , de Dieu Tapsoba J. , Buas M.F. , Onstad L.E. , Levine D.M. , Risch H.A. , Chow W.H. , Bernstein L. , Ye W. , Lagergren J. , et al. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2015 Nov; 24(11), p. 1739-47.
EPub date: 2015-09-16.
PMID: 26377193
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Copy number alterations detected by whole-exome and whole-genome sequencing of esophageal adenocarcinoma.
Authors: Wang X. , Li X. , Cheng Y. , Sun X. , Sun X. , Self S. , Kooperberg C. , Dai J.Y. .
Source: Human genomics, 2015-09-15; 9, p. 22.
EPub date: 2015-09-15.
PMID: 26374103
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