Gene Expression and DNA Methylation in Barrett's Oesophagus and Oesophageal Adenocarcinoma

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The oesophagus (gullet) is the tube through which food and drinks pass from the mouth to the stomach. In Barrett's oesophagus, the normal lining of the lower oesophagus is replaced by an abnormal type of lining called intestinal metaplasia as a result of severe gastroesophageal reflux. Gastroesophageal reflux is one of the most common of all diseases, affecting up to a quarter of all adults, and Barrett's oesophagus itself occurs in 0.5 - 1% of the adult population. In a minority of patients with Barrett's oesophagus, further abnormalities in the cells lining the lower oesophagus occur, leading to dysplasia and adenocarcinoma (glandular cell type cancer). This project will provide the first comprehensive map of two of the most important genetic mechanisms (gene expression and DNA methylation) by which Barrett's oesophagus evolves into Barrett's dysplasia and adenocarcinoma. The specimens studied in this project differ from previous studies in that they are taken from the same patients at different times, as these patients' Barrett's oesophagus either remains stable or progresses to worse disease. Essentially all the known human genes will be studied and the relevance of genes identified as important will be confirmed using highly accurate methods. With this information, it may be possible to develop genetic tests that can predict which patients are at risk of developing worse disease including cancer. In other parts of this project, genes which influence the likelihood of survival for patients with oesophageal adenocarcinoma will be identified, a simple test to more accurately identify patients with cancer spread to lymph nodes may be developed, and a blood test to detect oesophageal adenocarcinoma will be tested.