Cancer Research UK scientists at the University of Oxford have identified a gene which plays a key role in the development of cancer of the oesophagus by triggering changes in the oesophagus lining. The discovery, reported today in the journal Proceedings of the National Academy of Sciences, sheds new light on the molecular mechanisms involved in the development of Barrett’s oesophagus, a condition which is a major predisposing factor causing cancer of the oesophagus.
Barrett’s oesophagus is a condition affecting up to two per cent of the population in Britain in which the cells lining the oesophagus begin to change to look more like the cells lining the intestine. The condition usually develops following injury to the lining of the oesophagus due to long-term gastric reflux, when stomach contents, including acid and bile, flow back into the oesophagus causing inflammation and heartburn. People with Barrett’s oesophagus are at least 50 times more likely to develop cancer of the oesophagus than those without. Cancer of the oesophagus is the ninth most common cancer in the UK with over 7,400 new cases each year, and is one of the most rapidly increasing cancers in the western world.
The Oxford team have now identified a gene, CDX1, which acts as a trigger for the changes to the cell lining that occur in Barrett’s oesophagus. CDX1 is known to play a key role in the development of the intestine and is normally switched on in the intestine and switched off in the oesophagus. The team discovered that exposure to bile salts and cytokines (chemicals released during inflammation) caused the gene to be inappropriately switched on, triggering a change in oesophageal lining cells to resemble intestinal cells.