Genetic Diversity Test Distinguishes Risk of Cancer in Barrett’s Esophagus Interview with:

Prof. Trevor A Graham, MSc, MRes, PhD Lead, Evolution and Cancer Laboratory Centre for Tumour Biology Barts Cancer Institute, Queen Mary University of London John Vane Science Centre London

Prof. Trevor Graham

Prof. Trevor A Graham, MSc, MRes, PhD
Lead, Evolution and Cancer Laboratory
Centre for Tumour Biology
Barts Cancer Institute, Queen Mary University of London
John Vane Science Centre
London What is the background for this study? What are the main findings?

Response: Barrett’s Oesophagus is a common condition that affects an estimated 1.5 million people in the UK alone, although many are undiagnosed . This condition involves normal cells in the oesophagus (food pipe) being replaced by a different, unusual cell type called Barrett’s Oesophagus, and the replacement of the cells is thought to be a consequence of chronic reflux (heartburn).

People with Barrett’s have an increased risk of developing oesophageal cancer – a cancer that sadly still has a five year survival of 15% . But although the overall lifetime risk of developing oesophageal cancer in people with Barrett’s is significant (some estimates suggest the risk is comparable to that associated with smoking and lung cancer), the risk for each patient per year is very low.

This presents a big problem – most Barrett’s patients will never develop cancer in their lifetime, but the unfortunate few develop an aggressive cancer. Doctors urgently need better tools to distinguish which people with Barrett’s are actually at risk of developing cancer, so that they can receive the best treatment, and everyone else at low risk of cancer can be reassured and not need to endure unnecessary treatment. But because good a way to distinguish high-risk people doesn’t exist, all people with Barrett’s have regular (every 3 years or thereabouts) endoscopy; a camera pushed into the oesophagus to look for early signs of cancer.

Together with Prof Sheila Krishnadath  and her colleagues at the Amsterdam Medical Centre, Holland, we confirmed that we can identify people at high risk of developing cancer from pre-cancerous condition Barrett’s oesophagus by measuring the genetic diversity of Barrett’s cells.

Importantly, we also showed level of genetic diversity amongst a person’s Barrett’s cells essentially being fixed over time – no significant changes in genetic diversity were found during the ~4 years that the patients were followed. This means that whenever someone’s Barrett’s is tested, it looks like their future risk of developing cancer can be predicted regardless of how long it’s been since the abnormal Barrett’s cells began to appear. What should readers take away from your report?

Response: Our report implies that a person with Barrett’s Oesophagus has a risk of developing oesophageal cancer that is fixed over time. In other words, we can predict from the outset which Barrett’s patients fall into a high risk group of developing cancer – and that risk is does not change thereafter.

What recommendations do you have for future research as a result of this study?

Response: Our findings of a fixed cancer risk needs to be verified in a second group of patients. Once this has been done, it would be appropriate to consider a clinical trial where the frequency of a person’s endoscopies is decided according to the genetic diversity of their Barrett’s cells.

We showed that a person’s risk of developing cancer from Barrett’s Oesophagus was fixed for an approximately 4-year window. An important next step will be to understand if the risk is actually fixed for an even longer time, because this would mean that low-risk people may be able to have even fewer endoscopies. Is there anything else you would like to add?

Response: The study was only possible because of the work of the study co-leader Prof Sheila Krishnadath and her team at the AMC in Amsterdam, Holland  who worked with their patients for many years to collect samples, and also performed all the genetic tests in their lab. They followed up more than 300 patients and assessed changes to chromosomal copy number (a type of genetic change found in pre-cancer and cancer) in approximately 50,000 individual cells using a technique called FISH. We are very grateful to all the patients who chose to participate in our study too. Thank you for your contribution to the community.


Dynamic clonal equilibrium and predetermined cancer risk in Barrett’s oesophagus’. Pierre Martinez, Margriet R. Timmer, Chiu T. Lau, Silvia Calpe, Maria del Carmen Sancho-Serra, Danielle Straub, Ann-Marie Baker, Sybren L. Meijer, Fiebo J.W. ten Kate, Rosalie C. Mallant-Hent, Anton H.J. Naber, Arnoud H.A.M. van Oijen, Lubbertus C. Baak, Pieter Scholten, Clarisse J.M. Böhmer, Paul Fockens, Jacques J.G.H.M. Bergman, Carlo C. Maley, Trevor A. Graham, Kausilia K. Krishnadath.
Nature Communications 2016. DOI: 10.1038/ncomms12158

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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Last Updated on August 19, 2016 by Marie Benz MD FAAD