title: Linkage and related analyses of Barrett's esophagus and its associated adenocarcinomas.
abstract: BACKGROUND
  Familial aggregation and segregation analysis studies have provided evidence of a genetic basis for esophageal adenocarcinoma (EAC) and its premalignant precursor, Barrett's esophagus (BE). We aim to demonstrate the utility of linkage analysis to identify the genomic regions that might contain the genetic variants that predispose individuals to this complex trait (BE and EAC).
  
  
  METHODS
  We genotyped 144 individuals in 42 multiplex pedigrees chosen from 1000 singly ascertained BE/EAC pedigrees, and performed both model-based and model-free linkage analyses, using S.A.G.E. and other software. Segregation models were fitted, from the data on both the 42 pedigrees and the 1000 pedigrees, to determine parameters for performing model-based linkage analysis. Model-based and model-free linkage analyses were conducted in two sets of pedigrees: the 42 pedigrees and a subset of 18 pedigrees with female affected members that are expected to be more genetically homogeneous. Genome-wide associations were also tested in these families.
  
  
  RESULTS
  Linkage analyses on the 42 pedigrees identified several regions consistently suggestive of linkage by different linkage analysis methods on chromosomes 2q31, 12q23, and 4p14. A linkage on 15q26 is the only consistent linkage region identified in the 18 female-affected pedigrees, in which the linkage signal is higher than in the 42 pedigrees. Other tentative linkage signals are also reported.
  
  
  CONCLUSIONS
  Our linkage study of BE/EAC pedigrees identified linkage regions on chromosomes 2, 4, 12, and 15, with some reported associations located within our linkage peaks. Our linkage results can help prioritize association tests to delineate the genetic determinants underlying susceptibility to BE and EAC.
authors.affiliation: Department of Epidemiology and Biostatistics Case Western Reserve University Cleveland Ohio.
authors.forename: Xiangqing
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Epidemiology and BiostatisticsCase Western Reserve UniversityClevelandOhio; Case Comprehensive Cancer CenterCase Western Reserve University School of MedicineClevelandOhio.
authors.forename: Robert
authors.initials: R
authors.lastname: Elston
authors.affiliation: University of Pennsylvania Perelman School of Medicine Philadelphia Pennsylvania.
authors.forename: Gary W
authors.initials: GW
authors.lastname: Falk
authors.affiliation: Clinical Research DivisionFred Hutchinson Cancer Research CenterSeattleWashington; Gastroenterology DivisionUniversity of Washington School of MedicineSeattleWashington.
authors.forename: William M
authors.initials: WM
authors.lastname: Grady
authors.affiliation: Division of Gastroenterology and HepatologyUniversity Hospitals Case Medical CenterCase Western Reserve University School of MedicineClevelandOhio; Division of Gastroenterology and HepatologyLouis Stokes Veterans Administration Medical CenterCase Western Reserve University School of MedicineClevelandOhio.
authors.forename: Ashley
authors.initials: A
authors.lastname: Faulx
authors.affiliation: Department of Surgery Creighton University School of Medicine Omaha Nebraska.
authors.forename: Sumeet K
authors.initials: SK
authors.lastname: Mittal
authors.affiliation: Division of Gastroenterology Johns Hopkins Medical Institutions Baltimore Maryland.
authors.forename: Marcia I
authors.initials: MI
authors.lastname: Canto
authors.affiliation: Center for Esophageal Diseases & Swallowing University of North Carolina at Chapel Hill School of Medicine Chapel Hill North Carolina.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Shaheen
authors.affiliation: Division of Gastroenterology Washington University School of Medicine St. Louis Missouri.
authors.forename: Jean S
authors.initials: JS
authors.lastname: Wang
authors.affiliation: Division of Gastroenterology and Hepatology Mayo Clinic Rochester Minnesota.
authors.forename: Prasad G
authors.initials: PG
authors.lastname: Iyer
authors.affiliation: Department of Medicine Columbia University Medical Center New York New York.
authors.forename: Julian A
authors.initials: JA
authors.lastname: Abrams
authors.affiliation: Department of Pathology University Hospitals Case Medical Center Case Western Reserve University School of Medicine Cleveland Ohio.
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Willis
authors.affiliation: Division of General Medical Sciences (Oncology) Case Comprehensive Cancer Center Cleveland Ohio.
authors.forename: Kishore
authors.initials: K
authors.lastname: Guda
authors.affiliation: Department of Medicine and Case Comprehensive Cancer Center Case Medical Center Case Western Reserve University Cleveland Ohio.
authors.forename: Sanford
authors.initials: S
authors.lastname: Markowitz
authors.affiliation: Department of Epidemiology and BiostatisticsCase Western Reserve UniversityClevelandOhio; Case Comprehensive Cancer CenterCase Western Reserve University School of MedicineClevelandOhio.
authors.forename: Jill S
authors.initials: JS
authors.lastname: Barnholtz-Sloan
authors.affiliation: Division of Gastroenterology and Hepatology University Hospitals Case Medical Center Case Western Reserve University School of Medicine Cleveland Ohio.
authors.forename: Apoorva
authors.initials: A
authors.lastname: Chandar
authors.affiliation: Division of Gastroenterology and Hepatology University Hospitals Case Medical Center Case Western Reserve University School of Medicine Cleveland Ohio.
authors.forename: Wendy
authors.initials: W
authors.lastname: Brock
authors.affiliation: Case Comprehensive Cancer CenterCase Western Reserve University School of MedicineClevelandOhio; Division of Gastroenterology and HepatologyUniversity Hospitals Case Medical CenterCase Western Reserve University School of MedicineClevelandOhio.
authors.forename: Amitabh
authors.initials: A
authors.lastname: Chak
keywords: Barrett's esophagus; esophageal adenocarcinoma; familial; genetics; linkage