title: The role of obesity in oesophageal cancer development.
abstract: The incidence of oesophageal adenocarcinoma has increased dramatically in the developed world in the last half century. Over approximately the same period there has been an increase in the prevalence of obesity. Multiple epidemiological studies and meta-analyses have confirmed that obesity, especially abdominal, visceral obesity, is a risk factor for gastro-oesophageal reflux, Barrett's oesophagus and oesophageal adenocarcinoma. Although visceral obesity enhances gastro-oesophageal reflux, the available data also show that visceral obesity increases the risk of Barrett's oesophagus and adenocarcinoma via reflux-independent mechanisms. Several possible mechanisms could link obesity with the risk of oesophageal adenocarcinoma in addition to mechanical effects increasing reflux. These include reduced gastric Helicobacter pylori infection, altered intestinal microbiome, factors related to lifestyle, the metabolic syndrome and associated low-grade inflammation induced by obesity and the secretion of mediators by adipocytes which may directly influence the oesophageal epithelium. Of these adipocyte-derived mediators, increased leptin levels have been independently associated with progression to oesophageal adenocarcinoma and in laboratory studies leptin enhances malignant behaviours in cell lines. Adiponectin is also secreted by adipocytes and levels decline with obesity: decreased serum adiponectin levels are associated with malignant progression in Barrett's oesophagus and experimentally adiponectin exerts anticancer effects in Barrett's cell lines and inhibits growth factor signalling. At present there are no proven chemopreventative interventions that may reduce the incidence of obesity-associated oesophageal cancer: observational studies suggest that the combined use of a statin and aspirin or another cyclo-oxygenase inhibitor is associated with a significantly reduced cancer incidence in patients with Barrett's oesophagus.
authors.affiliation: Norwich Medical School, University of East Anglia, Norwich NR4 7TJ, UK.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Long
authors.affiliation: Norwich Medical School, University of East Anglia, Norwich NR4 7TJ, UK.
authors.forename: Ian L P
authors.initials: IL
authors.lastname: Beales
keywords: Barrett oesophagus; adiponectin; gastro-oesophageal reflux; leptin; obesity; oesophageal neoplasms