title: Genetic Insights in Barrett's Esophagus and Esophageal Adenocarcinoma.
abstract: Beginning in the 1980s, an alarming rise in the incidence of esophageal adenocarcinoma (EA) led to screening of patients with reflux to detect Barrett's esophagus (BE) and surveillance of BE to detect early EA. This strategy, based on linear progression disease models, resulted in selective detection of BE that does not progress to EA over a lifetime (overdiagnosis) and missed BE that rapidly progresses to EA (underdiagnosis). Here we review the historical thought processes that resulted in this undesired outcome and the transformation in our understanding of genetic and evolutionary principles governing neoplastic progression that has come from application of modern genomic technologies to cancers and their precursors. This new synthesis provides improved strategies for prevention and early detection of EA by addressing the environmental and mutational processes that can determine "windows of opportunity" in time to detect rapidly progressing BE and distinguish it from slowly or nonprogressing BE.
authors.affiliation: Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington; Department of Genome Sciences, University of Washington, Seattle, Washington; Department of Medicine, University of Washington, Seattle, Washington. Electronic address: bjr@fredhutch.org.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Reid
authors.affiliation: Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Paulson
authors.affiliation: Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Li
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000235:genetics* / Q000517:prevention & control*; D001471:Barrett Esophagus / Q000209:etiology / Q000473:pathology*; D018450:Disease Progression; D055088:Early Detection of Cancer / Q000379:methods* / Q000639:trends; D004777:Environment; D004938:Esophageal Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000517:prevention & control*; D005764:Gastroesophageal Reflux / Q000150:complications; D020022:Genetic Predisposition to Disease; D023281:Genomics / Q000379:methods / Q000639:trends*; D006801:Humans; D009154:Mutation
keywords: Chromosome Instability; Evolution; Genomics; Overdiagnosis