title: Assessment of Esophageal Adenocarcinoma Risk Using Somatic Chromosome Alterations in Longitudinal Samples in Barrett's Esophagus.
abstract: Cancers detected at a late stage are often refractory to treatments and ultimately lethal. Early detection can significantly increase survival probability, but attempts to reduce mortality by early detection have frequently increased overdiagnosis of indolent conditions that do not progress over a lifetime. Study designs that incorporate biomarker trajectories in time and space are needed to distinguish patients who progress to an early cancer from those who follow an indolent course. Esophageal adenocarcinoma is characterized by evolution of punctuated and catastrophic somatic chromosomal alterations and high levels of overall mutations but few recurrently mutated genes aside from TP53. Endoscopic surveillance of Barrett's esophagus for early cancer detection provides an opportunity for assessment of alterations for cancer risk in patients who progress to esophageal adenocarcinoma compared with nonprogressors. We investigated 1,272 longitudinally collected esophageal biopsies in a 248 Barrett's patient case-cohort study with 20,425 person-months of follow-up, including 79 who progressed to early-stage esophageal adenocarcinoma. Cancer progression risk was assessed for total chromosomal alterations, diversity, and chromosomal region-specific alterations measured with single-nucleotide polymorphism arrays in biopsies obtained over esophageal space and time. A model using 29 chromosomal features was developed for cancer risk prediction (area under receiver operator curve, 0.94). The model prediction performance was robust in two independent esophageal adenocarcinoma sets and outperformed TP53 mutation, flow cytometric DNA content, and histopathologic diagnosis of dysplasia. This study offers a strategy to reduce overdiagnosis in Barrett's esophagus and improve early detection of esophageal adenocarcinoma and potentially other cancers characterized by punctuated and catastrophic chromosomal evolution.
authors.affiliation: Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Li
authors.affiliation: Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Paulson
authors.affiliation: Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Patricia C
authors.initials: PC
authors.lastname: Galipeau
authors.affiliation: Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Carissa A
authors.initials: CA
authors.lastname: Sanchez
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Karen
authors.initials: K
authors.lastname: Liu
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, Washington.
authors.forename: Mary K
authors.initials: MK
authors.lastname: Kuhner
authors.affiliation: Center for Evolution and Cancer, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California. School of Life Sciences, Arizona State University, Tempe, Arizona.
authors.forename: Carlo C
authors.initials: CC
authors.lastname: Maley
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington. Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Self
authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington. Epidemiology, University of Washington, Seattle, Washington.
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Vaughan
authors.affiliation: Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, Washington. Department of Genome Sciences, University of Washington, Seattle, Washington. Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington. Department of Medicine, University of Washington, Seattle, Washington. bjr@fredhutch.org.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Reid
authors.affiliation: Department of Medicine, University of Washington, Seattle, Washington.
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Blount
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001471:Barrett Esophagus / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D001706:Biopsy; D002869:Chromosome Aberrations; D015331:Cohort Studies; D018450:Disease Progression; D004724:Endoscopy / Q000379:methods; D004938:Esophageal Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D005260:Female; D015894:Genome, Human; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012372:ROC Curve; D018570:Risk Assessment / Q000379:methods*; D013269:Stochastic Processes