Familial clustering of Barrett's esophagus and esophageal adenocarcinoma in a European cohort.
OBJECTIVE
Up to 7% of cases of Barrett's esophagus (BE) or esophageal adenocarcinoma (EAC) in the United States occur in family clusters. We identified first-degree and second-degree relatives of patients with BE and EAC to determine the extent of familial clustering in a European cohort and studied differences between familial and nonfamilial cases.


METHODS
A questionnaire was sent to all patients diagnosed with BE or EAC from 2000-2011 at 3 hospitals in the Netherlands (n = 838). Diagnoses of affected relatives were confirmed by using the Dutch Pathology Registry. Familial statuses of BE were defined as definitive (≥1 first-degree or second-degree relative with BE or EAC), possible (≥1 reported relative with BE or esophageal cancer without histologic confirmation), unlikely (no family history), or unknown.


RESULTS
A total of 603 patients with BE or EAC (71%) responded and were included in the analysis. Familial BE was definitive for 7% of cases (n = 39, 10% of first-degree relatives affected), possible for 6% (n = 36), unlikely for 49% (n = 297), and unknown for 38% (n = 231). Definitive cases of familial BE were younger at onset of heartburn and EAC diagnosis; their first-degree relatives more frequently had reflux symptoms and a prior upper endoscopy, compared with unlikely cases of familial BE.


CONCLUSIONS
In a database analysis of patients diagnosed with BE or EAC in the Netherlands, 7% of cases of BE and EAC were familial. These cases have a younger average age of onset of reflux symptoms and diagnosis of EAC than unlikely familial cases. These findings may indicate that genetic factors contribute to BE susceptibility, with a possible central role of gastroesophageal reflux.
Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, The Netherlands. Electronic address: r.e.verbeek@umcutrecht.nl.
Romy E
RE
Verbeek
Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, The Netherlands.
Lisanne F
LF
Spittuler
Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, The Netherlands.
Anique
A
Peute
Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, The Netherlands.
Martijn G H
MG
van Oijen
Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
Fiebo J
FJ
Ten Kate
Department of Gastroenterology, Meander Medical Center, Amersfoort, The Netherlands.
Jacob R
JR
Vermeijden
Department of Gastroenterology, Diakonessenhuis, Utrecht, The Netherlands.
Ardi
A
Oberndorff
Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, The Netherlands.
Jantine W P M
JW
van Baal
Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, The Netherlands.
Peter D
PD
Siersema
D000230:Adenocarcinoma / Q000453:epidemiology*; D000328:Adult; D000368:Aged; D001471:Barrett Esophagus / Q000453:epidemiology*; D016000:Cluster Analysis; D004938:Esophageal Neoplasms / Q000453:epidemiology*; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D011795:Surveys and Questionnaires
Cancer; Genetic; PALGA; Pathogenesis