Pathophysiological mechanisms linking obesity and esophageal adenocarcinoma.
In recent decades there has been a dramatic rise in the incidence of esophageal adenocarcinoma (EAC) in the developed world. Over approximately the same period there has also been an increase in the prevalence of obesity. Obesity, especially visceral obesity, is an important independent risk factor for the development of gastro-esophageal reflux disease, Barrett's esophagus and EAC. Although the simplest explanation is that this mediated by the mechanical effects of abdominal obesity promoting gastro-esophageal reflux, the epidemiological data suggest that the EAC-promoting effects are independent of reflux. Several, not mutually exclusive, mechanisms have been implicated, which may have different effects at various points along the reflux-Barrett's-cancer pathway. These mechanisms include a reduction in the prevalence of Helicobacter pylori infection enhancing gastric acidity and possibly appetite by increasing gastric ghrelin secretion, induction of both low-grade systemic inflammation by factors secreted by adipose tissue and the metabolic syndrome with insulin-resistance. Obesity is associated with enhanced secretion of leptin and decreased secretion of adiponectin from adipose tissue and both increased leptin and decreased adiponectin have been shown to be independent risk factors for progression to EAC. Leptin and adiponectin have a set of mutually antagonistic actions on Barrett's cells which appear to influence the progression of malignant behaviour. At present no drugs are of proven benefit to prevent obesity associated EAC. Roux-en-Y reconstruction is the preferred bariatric surgical option for weight loss in patients with reflux. Statins and aspirin may have chemopreventative effects and are indicated for their circulatory benefits.
Leo Alexandre, Elizabeth Long, Ian LP Beales, Norwich Medical School, University of East Anglia, Norwich, Norfolk NR4 7TJ, United Kingdom.
Leo
L
Alexandre
Leo Alexandre, Elizabeth Long, Ian LP Beales, Norwich Medical School, University of East Anglia, Norwich, Norfolk NR4 7TJ, United Kingdom.
Elizabeth
E
Long
Leo Alexandre, Elizabeth Long, Ian LP Beales, Norwich Medical School, University of East Anglia, Norwich, Norfolk NR4 7TJ, United Kingdom.
Ian Lp
IL
Beales
Adipose; Barrett’s esophagus; Body mass index; Reflux