Demographic and phenotypic features of 70 families segregating Barrett's oesophagus and oesophageal adenocarcinoma

Abstract

Background: Barrett's oesophagus (BO) also termed metaplastic columnar lined oesophageal epithelium, is believed to result from a continual reparative response to chronic reflux of gastric contents. Although traditionally considered to be an acquired disorder, with several epidemiological risk factors involved, it is now recognised that there is a genetic component, and that this is likely to be autosomal dominant. Clustering of BO and of oesophageal adenocarcinoma (OAC) or oesophagogastric junctional adenocarcinoma (OGJAC) has been shown in a number of studies. Methods: We investigated a large series of BO/OAC families to find evidence that a subset of BO/OAC is the result of a hereditary predisposition, and explored the potential of performing a linkage study with the families identified to date. Results: Of 957 individuals in 70 families, 173 had a reported diagnosis of BO or OAC/OGJAC: 101 had BO only, 52 had OAC/OGJAC, and 20 had both BO and OAC/OGJAC. There were 133 affected males and 40 affected females, a male:female ratio of 3.3:1. In addition, 124 participants (12.9%) had a reported diagnosis of cancer other than OAC. Of these, 15 did (affected) and 109 did not (unaffected) have a diagnosis of BO or OAC. A cancer other than OAC was found in 13.9% of unaffected and 8.7% of affected individuals. Conclusion: It is widely accepted that the majority of BO and OAC are sporadic, although familial clustering of BO and OAC has been recognised for at least three decades. Environment and lifestyle undoubtedly play a role in development of BO and OAC, and may affect the penetrance of the putative inherited factor. Although our 70 BO probands were not more likely to develop non-OAC/OGJAC cancers than normal, over a third had developed either OAC or OGJAC, and might have gone on to develop others. We intend to continue recruitment and initiate formal linkage studies to identify the causative gene(s).