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- APC, adenomatous polyposis coli
- BMDC, bone marrow-derived stem cell
- COX2, cyclooxygenase 2
- GORD, gastro-oesophageal reflux disease
- LOH, loss of heterozygosity
- MAPK, mitogen-activated protein kinase
- PPI, proton pump inhibitor
- TGFβ, tumour growth factor β
Barrett’s oesophagus is the eponym used to describe the change from the normal stratified, squamous epithelium of the lower oesophagus to a polarised, columnar-lined epithelium with intestinal-type differentiation.1 This condition develops in the context of chronic gastro-oesophageal reflux disease (GORD)2 and is associated with a 0.5–1% annual conversion rate to oesophageal adenocarcinoma.3,4 The overall 5-year survival rate in patients presenting with symptomatic adenocarcinoma is a dismal 13%.5 An understanding of the molecular basis for the development and progression of Barrett’s metaplasia is required to develop effective clinical management strategies. Before discussing the molecular changes at the level of the tissue, it is important to briefly consider the environmental and inherited genetic factors that contribute to an individual’s susceptibility to these conditions.
EFFECT OF ENVIRONMENTAL AND INHERITED FACTORS ON INDIVIDUAL SUSCEPTIBILITY
The role of environmental factors is evident from the short time period over which the incidence of Barrett’s oesophagus6 and oesophageal adenocarcinoma7 has increased. Furthermore, the demonstration of a “birth cohort effect”, with higher incidence rates in younger cohorts,8 would support the idea that exposure to environmental factors in early life is an important determinant of risk. Identification of specific environmental exposures is difficult, but factors that increase gastro-oesophageal reflux, such as dietary components, increasing body mass index and eradication of Helicobacterpylori, may be relevant.9 Whether or not smoking and alcohol consumption are risk factors for Barrett’s oesophagus is controversial; however, an association was found in a recent population study.10 In order for an individual to develop Barrett’s oesophagus, and in some cases oesophageal adenocarcinoma, these environmental exposures probably need to interact with genetically determined characteristics that define personal susceptibility11 (fig 1). As most cases are sporadic, occurring in the absence of a family history, these inherited genetic factors are likely to be normal variations or polymorphisms …