title: Variation in age at cancer diagnosis in familial versus nonfamilial Barrett's esophagus.
abstract: BACKGROUND
  Genetic influences may be discerned in families that have multiple affected members and may manifest as an earlier age of cancer diagnosis. In this study, we determine whether cancers develop at an earlier age in multiplex Familial Barrett's Esophagus (FBE) kindreds, defined by 3 or more members affected by Barrett's esophagus (BE) or esophageal adenocarcinoma (EAC).
  
  
  METHODS
  Information on BE/EAC risk factors and family history was collected from probands at eight tertiary care academic hospitals. Age of cancer diagnosis and other risk factors were compared between nonfamilial (no affected relatives), duplex (two affected relatives), and multiplex (three or more affected relatives) FBE kindreds.
  
  
  RESULTS
  The study included 830 nonfamilial, 274 duplex, and 41 multiplex FBE kindreds with 274, 133, and 43 EAC and 566, 288, and 103 BE cases, respectively. Multivariable mixed models adjusting for familial correlations showed that multiplex kindreds were associated with a younger age of cancer diagnosis (P = 0.0186). Median age of cancer diagnosis was significantly younger in multiplex compared with duplex and nonfamilial kindreds (57 vs. 62 vs. 63 years, respectively, P = 0.0448). Mean body mass index was significantly lower in multiplex kindreds (P = 0.0033), as was smoking (P < 0.0001), and reported regurgitation (P = 0.0014).
  
  
  CONCLUSIONS
  Members of multiplex FBE kindreds develop EAC at an earlier age compared with nonfamilial EAC cases. Multiplex kindreds do not have a higher proportion of common risk factors for EAC, suggesting that this aggregation might be related to a genetic factor.
  
  
  CONCLUSIONS
  These findings indicate that efforts to identify susceptibility genes for BE and EAC will need to focus on multiplex kindreds.
authors.affiliation: Division of Gastroenterology, University Hospitals-Case Medical Center, 11100 Euclid Avenue, Cleveland, OH 44106, USA. Amitabh.chak@case.edu
authors.forename: Amitabh
authors.initials: A
authors.lastname: Chak
authors.forename: Yanwen
authors.initials: Y
authors.lastname: Chen
authors.forename: Jaime
authors.initials: J
authors.lastname: Vengoechea
authors.forename: Marcia I
authors.initials: MI
authors.lastname: Canto
authors.forename: Robert
authors.initials: R
authors.lastname: Elston
authors.forename: Gary W
authors.initials: GW
authors.lastname: Falk
authors.forename: William M
authors.initials: WM
authors.lastname: Grady
authors.forename: Kishore
authors.initials: K
authors.lastname: Guda
authors.forename: Margaret
authors.initials: M
authors.lastname: Kinnard
authors.forename: Sanford
authors.initials: S
authors.lastname: Markowitz
authors.forename: Sumeet
authors.initials: S
authors.lastname: Mittal
authors.forename: Ganapathy
authors.initials: G
authors.lastname: Prasad
authors.forename: Nicholas
authors.initials: N
authors.lastname: Shaheen
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Willis
authors.forename: Jill S
authors.initials: JS
authors.lastname: Barnholtz-Sloan
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics / Q000473:pathology; D000367:Age Factors; D001471:Barrett Esophagus / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics / Q000473:pathology; D004938:Esophageal Neoplasms / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D012307:Risk Factors; D014481:United States / Q000453:epidemiology