title: A segregation analysis of Barrett's esophagus and associated adenocarcinomas.
abstract: Familial aggregation of esophageal adenocarcinomas, esophagogastric junction adenocarcinomas, and their precursor Barrett's esophagus (BE) has been termed familial BE (FBE). Numerous studies documenting increased familial risk for these diseases raise the hypothesis that there may be an inherited susceptibility to the development of BE and its associated cancers. In this study, using segregation analysis for a binary trait as implemented in S.A.G.E. 6.0.1, we analyzed data on 881 singly ascertained pedigrees to determine whether FBE is caused by a common environmental or genetic agent and, if genetic, to identify the mode of inheritance of FBE. The inheritance models were compared by likelihood ratio tests and Akaike's A Information Criterion. Results indicated that random environmental and/or multifactorial components were insufficient to fully explain the familial nature of FBE, but rather, there is segregation of a major type transmitted from one generation to the next (P < 10(-10)). An incompletely dominant inheritance model together with a polygenic component fits the data best. For this dominant model, the estimated penetrance of the dominant allele is 0.1005 [95% confidence interval (95% CI), 0.0587-0.1667] and the sporadic rate is 0.0012 (95% CI, 0.0004-0.0042), corresponding to a relative risk of 82.53 (95% CI, 28.70-237.35) or odds ratio of 91.63 (95% CI, 32.01-262.29). This segregation analysis provides epidemiologic evidence in support of one or more rare autosomally inherited dominant susceptibility allele(s) in FBE families and, hence, motivates linkage analyses.
authors.affiliation: Department of Epidemiology and Biostatistics, Case Western Reserve University, 2103 Cornell Road, Cleveland, OH 44106, USA. xsun@darwin.cwru.edu
authors.forename: Xiangqing
authors.initials: X
authors.lastname: Sun
authors.forename: Robert
authors.initials: R
authors.lastname: Elston
authors.forename: Jill
authors.initials: J
authors.lastname: Barnholtz-Sloan
authors.forename: Gary
authors.initials: G
authors.lastname: Falk
authors.forename: William M
authors.initials: WM
authors.lastname: Grady
authors.forename: Margaret
authors.initials: M
authors.lastname: Kinnard
authors.forename: Sumeet K
authors.initials: SK
authors.lastname: Mittal
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Willis
authors.forename: Sanford
authors.initials: S
authors.lastname: Markowitz
authors.forename: Wendy
authors.initials: W
authors.lastname: Brock
authors.forename: Amitabh
authors.initials: A
authors.lastname: Chak
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D001471:Barrett Esophagus / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000235:genetics*; D005260:Female; D018703:Founder Effect; D020022:Genetic Predisposition to Disease; D005828:Genetics, Population; D006801:Humans; D008297:Male; D008957:Models, Genetic; D010375:Pedigree