Posted on: 24 October 2017
New research from scientists at Trinity College Dublin has unlocked a clue into how chronic heartburn (gastroesophageal reflux disease, GORD) damages the oesophagus, potentially paving the way for new treatments. This may help to prevent both the pre-cancerous condition, Barrett’s Oesophagus and oesophageal cancer.
There are over 390 new cases of oesophageal cancer in Ireland each year and the National Cancer Registry of Ireland project the number of cases of oesophageal cancer will increase by 34% in females and 84% in males by 2020.
Chronic heartburn occurs when the stomach contents repeatedly reflux into the oesophagus. This reflux damages the oesophagus and can lead to oesophageal inflammation (Oesophagitis). People with chronic GORD and oesophagitis are more prone to developing the pre-cancerous condition, Barrett’s Oesophagus. Approximately 10% of the population who have heartburn will have Barrett's Oesophagus. It is important to stress that while patients with Barrett’s Oesophagus are at increased risk of developing oesophageal cancer, fewer than 3% of people with Barrett’s Oesophagus will develop this cancer over their lifetime.
It was originally thought that, heartburn, oesophagitis and Barrett’s Oesophagus were caused by the acidic component of the reflux. As a consequence anti-acid medication is therefore routinely prescribed for people with these conditions. More recent research has shown that another component of the reflux (bile acids) also damage the cells lining the oesophagus.
In their research, the scientists from Trinity’s School of Medicine found a new mechanism for how bile acids contribute to the development of oesophagitis and Barrett’s Oesophagus; via its effects on a protein called Integrin-αν. This protein is on the surface of the oesophageal cells and is responsible for making oesophageal cells attach to each other and to the oesophageal wall. The oesophagus itself is made up of a number of layers of cells. The cells on the outside are robust and can stop the underlying cells from becoming damaged in response to hot/cold food etc.
The research team found that the robust outer layer of cells detach and are sloughed away when a bile acid causes the Integrin-αν to internalise so that it is not expressed on the cell surface anymore. As a result, the underlying cells become damaged and undergo changes to become more resistant to the reflux, a process called metaplasia. The presence of these metaplastic cells in the oesophagus is called Barrett’s Oesophagus.
The research suggests that targeting bile acid-induced injury in the oesophagus could be employed for better treatment of patients with heartburn, in order to prevent the development of Barrett’s Oesophagus and potentially, oesophageal cancer.
Lead author of the study Dr Anne-Marie Byrne, Senior Research Fellow in the Trinity Translational Medicine Institute, Trinity College Dublin and St James's Hospital said: “There is little public awareness that chronic heartburn is a risk factor for developing oesophageal cancer. Early detection is key to prevention and treatment of oesophageal cancer, therefore people who suffer from chronic heartburn should get it checked.”
Dr Byrne continued: “This research suggests that, in addition to the current anti-acid medication available, novel drugs targeting bile acids could be developed to further reduce the risk of developing oesophageal cancer. It is important to undertake both basic cell biology and clinical translational research, to understand how cancer develops in order to identify ways to prevent it.”
Co-lead author Dr David Prichard, Assistant Professor of Medicine at the Mayo Clinic College of Medicine and Science who conducted the research at Trinity said: “Anti-acid medications have significantly reduced, but not eliminated, the risks associated with heartburn. Heartburn is so common in western society that we cannot screen every patient for Barrett’s oesophagus or oesophageal cancer. The novel mechanism through which bile acids injure the oesophagus, identified through this research, suggests a new way in which complications of heartburn could be further reduced, therefore decreasing the necessity for screening. Preventing a disease like oesophageal cancer is much more effective than treating it and research like this allows us to move closer toward that goal.”
The article has been published in the Journal of Cellular and Molecular Medicine and is available here: http://onlinelibrary.wiley.com/doi/10.1111/jcmm.13271/full
This work was supported by the Molecular Medicine Ireland Clinician Scientist Fellowship Programme funded by the Higher Education Authority Programme for Research in Third Level Institutions Cycle 4, and co-funded by the European Regional Development Fund. This study also received funding from the Oesophageal Cancer Fund (http://www.lollipopday.ie/).
