Professor Laurence Lovat

2016 - Core Development Grant

Professor Laurence Lovat - 2016 Core Development Grant
Professor Laurence Lovat – 2016 Core Development Grant

Title: Salivary EpigeNetics to Stratify Oesophageal Cancer Risk (SENSOR)

Project Start Date: 1 June 2017

Completion Date: 30 September 2018

Summary:

Every year, 8,000 people get oesophageal cancer in the UK. The vast majority of them will die from the disease. We need a simple, acceptable test to identify who is at risk of getting it before it develops. This project will explore whether a small sample of saliva can be used to create such a test. We will look at genetic markers  which have been passed from the blood stream into the saliva. Rather than looking at genes, we will explore ‘gene-switches’, which turn genes on and off. These switches change throughout life and in different disease states. If the project is successful, many people at risk could be screened easily without needing to undergo invasive tests such as endoscopy.

Professor Stephan Beck is the Professor of Medical Genomics at the UCL Cancer Institute. He has extensive experience in understanding epigenetic gene-switches and has done many similar studies using blood and tissue samples. Dr Amy Webster, post-doctoral research associate, works with Prof. Beck and will be organising the sample analysis.

Dr Hayley Whitaker is the Group Leader, Molecular Diagnostics & Therapeutics Group in the Division of Surgery and Interventional Science at UCL.  She will oversee sample collection and preparation.  Dr Rifat Hamoudi is a Senior Lecturer in Computational and Molecular Biology in the same department. He will oversee the complex computational analyses needed for the project.

We will collect 40 saliva samples from each of 4 groups of patients: normal; low-risk Barrett’s oesophagus; high-risk Barrett’s oesophagus with high-grade dysplasia; and patients with established oesophageal adenocarcinoma. We will therefore collect saliva from a total of 160 patients.  Using computational tools we will identify a group of markers to differentiate our 4 groups in the first 10 samples from each group and then confirm the markers we find from the other 30 samples in each group.

Although at the end of this project we will not have a fully-functioning screening test for oesophageal cancer risk, we will have proven the principle of whether this type of test might work. We will also have a series of potential gene-switch markers which we will go on to test in much larger field trials.  Success will lead to further funding from the National Institute for Health Research to demonstrate that our screening test can work in a large population. Ultimate success will be to replace current invasive endoscopy screening with a very simple test based on a spit of saliva in a sputum-pot!

How is the breath test (ECCO paper available here) different to the spit test?

A breath test measures chemicals that are found in the breath. These chemicals are found in very tiny quantities and may be coming directly from the abnormal areas of the stomach. The new spit test does something different. It is looking at changes in the way genes are expressed when cells start to turn from normal towards cancer. Cells release small amounts of their DNA and RNA into the blood which is then transferred into the saliva. DNA contains not only the genes which determine the blueprint of the body. It also has switches which can turn these genes on. This is called epigenetics. RNA is the molecule that is produced when particular genes are activated. It is then translated into proteins which do the work in the cells. The new spit test aims to assess how  DNA and RNA levels change from normal people to those in cancer and to use these changes to detect cancer risk.

We urgently need a cheap, accurate screening test to identify people at risk of oesophageal cancer. The funding from CORE will allow us to create this test using salivary epigenetics. This is a brand new field and we are so grateful for the opportunity CORE is giving us to do this exciting work.

Professor Laurence Lovat