Researchers have identified genetic variations that can be linked to the onset of Barrett's esophagus (BE). This discovery can make it possible to develop screening tests for people who are at a higher risk of developing BE.
Barrett's esophagus is a condition in which the lining of the esophagus is damaged. This damage occurs when parts of the esophageal lining are repeatedly exposed to stomach acid, and are replaced by tissue that is similar to what is found intestine.
It has been thought for some time that there may be a genetic cause for BE, along with other causes such as an increased risk with gastroesophageal reflux disease. However, researchers hadn't found any genetic variations that could cause BE. Until now.
Professor Janusz Jankowski of the Blizard Institute of Cell and Molecular Science at Queen Mary, University of London led a multi-national team of researchers found variations on chromosomes 6p21 and 16p24. Their research has been published in Nature Genetics.
Professor Jankowski and colleagues, from over 100 centres in the UK and 20 more around the world, conducted a genome-wide analysis in which they analysed 660,000 genetic variations in 1,800 patients with BE and tested the top 200,000 genetic variations in another set of 1,105 patients, comparing them with large groups of people (over 5,000 in total), acting as controls, who did not have BE. During this process they identified variations in the sequence of single nucleotides - the molecules, A, T, C or G that make up DNA - in two chromosomes. They then tested these two single nucleotide polymorphisms (SNPs) in a further 4,500 patients.
Professor Jankowski stated about the results of this research: "After these stages, the two SNPs on chromosomes 6p21 and 16q24 showed compelling evidence that they were associated with the development of Barrett's oesophagus." He added, "Our findings provide a basis for genetically screening 30 per cent of the Western population who get acid reflux to see which 10 to 20 per cent of them - three per cent of the population overall - will go on to develop BE. These genetic variations will also form the basis for developing new targets for therapy. Given that BE is known to be a precursor to oesophageal cancer, it is quite possible that these genetic variations could also be risk factors for developing the cancer and they may give us clues as to the biological mechanisms involved."
The researchers plan to test another 10,000 patients in order to replicate these results and to see if they can find any other genes that can predict who will go on to develop BE.
"We now know that BE can be inherited like Crohn's or coeliac disease. We have shown that it is likely that the body's control of inflammation and subtle changes to repair mechanisms dictate predisposition to the disease. Our findings make it possible to screen people to predict who will progress to develop BE, and enable us to design new drugs to treat the condition. Given that reflux oesophagitis is the commonest medical condition in the Western adult population, affecting one in three people, these finding have a huge potential impact," concluded Professor Jankowski.
"Common variants at the MHC locus and at chromosome 16q24.1 predispose to Barrett's esophagus", by Janusz A.Z. Jankowski et al. Nature Genetics. doi:10.1038/10.1038/ng.2408
Barrett's oesophagus is named after Norman Barrett, a British surgeon who first described the condition in 1950.
Jankowski JA, Provenzale D, Moayyedi P. "Esophageal adenocarcinoma arising from Barrett's metaplasia has regional variations in the West (systematic review)".