Scientists, including those of Indian origin, have discovered that a rare genetic mutation is associated with susceptibility to oesophageal cancer and familial Barrett oesophagus. Researchers at University Hospitals Case Medical Centre in the US, including Amitabh Chak, set out to identify novel disease susceptibility variants in familial Barrett oesophagus (FBO) in affected individuals from a large multigenerational family. Barrett’s oesophagus is a serious complication of gastroesophageal reflux disease. In Barrett’s oesophagus (BO), normal tissue lining the oesophagus – the tube that carries food from the mouth to the stomach – changes to tissue that resembles the lining of the intestine. The team, led by Chak along with Kishore Guda, of the Case Comprehensive Cancer Centre, used targeted next generation gene sequencing to find a rare mutation (S631G) in FBO in the uncharacterised gene VSIG10L that segregated with disease in affected family members. Studies showed that this mutation disrupts maturation of the normal oesophageal lining. “Instances of oesophageal cancer are on the rise, and the disease has a poor five-year survival rate of less than 15 per cent,” said Chak. “However early detection through screening can prevent the development of oesophageal cancer. Further research assessing this gene variant may reveal pathways important for the pathogenesis of BO and oesophageal adenocarcinoma, leading to earlier detection and better treatment options,” he said. Affecting up to 6.8 per cent of the population, BO is a leading predictor of oesophageal cancer. Compared with the general population, patients with BO have an 11-fold higher risk of developing adenocarcinoma of the oesophagus. However, despite a dramatic increase in the disease over the past four decades, there have been few advances in understanding and improving treatment options. Discovery of this variant, which is the first susceptibility variant discovered in FBO, shows novel biology in disease pathogenesis, and indicates early screening and close clinical monitoring for individuals harbouring this germline variant. “This is a step forward in combating this deadly disease as we discovered a new way to categorise those at risk for oesophageal adenocarcinoma,” said Chak. The study was published in the journal JAMA Oncology.