Professor Sir John Burn is a world renowned geneticist known for his research into chemo-prevention for colorectal cancer. He is currently Professor of Clinical Genetics at Newcastle University and is also a Director of the European Hereditary Tumour Group (EHTG).
At this year’s ESCP Annual Meeting in Nice, Prof Burn will present on The Role of Epigenetic Factors as part of the ESCP/EHTG Joint Symposium on Hereditary Colorectal Cancer on Wednesday 26th September.
Prof. Burn is most widely known for the CAPP international trials programme, which began in 1993 studying the connections between hereditary cancer, mismatch repair genes, and how epigenetics and chemoprevention could decrease the risk of people developing cancer.
CAPP1 randomised patients with Familial Adenomatous Polyposis (FAP) to aspirin and resistant starch. During this time the first gene was discovered for Hereditary Non-Polyposis Colon Cancer (HNPCC), now more commonly referred to as Lynch syndrome. In 2011 the results of CAPP2 established that daily doses of aspirin significantly reduces the risk of cancer developing in people with Lynch syndrome.
The CaPP3 trial is now underway and is focussing on finding the best dose of aspirin to decrease the risk of people with a mismatch repair gene defect (Lynch syndrome) developing cancer. This blinded dose non-inferiority trial will have participation from 2,000 patients in the UK, Australia, Finland, Israel and Spain. Some patients will be on 100mg of aspirin per day while others will take 300mg or 600mg. The trial will then measure the impact of the different doses on the rates at which patients develop cancer to find the optimum dose.
The Role of Epigenetics
In his presentation Prof Burn will discuss various epigenetic factors which can have a bearing on the rate at which people develop cancer – including the impact of diet, obesity and age. He says:
“We tend to think in very simplistic terms that either you inherit a cancer or you eat something poisonous that causes you to develop the cancer but it’s actually much more complicated than that. The key thing we need to understand is that it’s the microenvironment around the cells in the body that may become colon cancer which are profoundly influential on the likelihood of a cancer progressing.”
In CAPP2 Prof Burn and his researchers found that when patients were on a high resistance carbohydrate diet they were far less likely to develop bowel cancer. However, while they were able to identify the indirect benefits, the research was unable to prove that this could prevent cancers developing. He continues:
“We know that the trillions of bacteria in the gut help people break down high resistance carbohydrates and we know this produces short chain fatty acids which are good for the bowel, but we weren’t quite able to prove that this could prevent cancer with CAPP2. So, this is something we hope to explore further in CaPP3. Is aspirin effective because it’s affecting the microbiome in the same way that diet does?”
Another key finding of CAPP2 was that obese participants were twice as likely to develop cancer as participants who were a healthy weight but that if they took aspirin this increased risk was taken away.
Prof Burn believes a driver for the development of cancer in these patients could be the inflammatory effect of obesity which may be reduced through the use of anti-inflammatories, such as aspirin. Both the inflammation and its reduction through anti-inflammatories could be seen as epigenetics at work on the risk of bowel cancer.
A further epigenetic factor to be explored in Prof Burn’s presentation is the impact of aging and how this alters the body’s ability to fight cancer. It has been known for many years that bowel cancer risk rises significantly in patients after the age of 65. One of the reasons for this is the breakdown of mitochondrial function in the bowel. One of first lines of defence the human body has against cancer is through apoptosis or programmed cell death but this process is driven by mitochondria. The presence of mitochondria in the gut wall dramatically reduces after people reach the age of 65 and with that goes the ability to undergo apoptosis.
The CAPP studies found that giving aspirin to older people doesn’t have the same impact on reducing the risk of bowel cancer. Prof Burn believes this is likely related to older people’s lower levels of mitochondria. He says:
“I would hypothesise that the reason that giving aspirin to older patients doesn’t affect their risk of developing cancer is because the way that aspirin works in younger patients, as it does in plants, is by promoting apoptosis.”
“Our conclusions may be that we should not use aspirin in the frail and elderly because of the increasing incidence of H pylori and loss of mitochondria increases the risk of unwelcome side effects for those patients and reduces the effectiveness of aspirin. Instead aspirin should be used earlier as a preventative measure. I believe this would dramatically reduce mortality by preventing cancers from developing in the wider population.”
In the earlier CAPP studies, it was found that aspirin doesn’t have any impact on patient’s risk of developing cancer until they have been taking it systematically for a period of over two years. Therefore, Prof Burn believes this is because during this time apoptosis of the cancer precursor cells is happening, leading to the prevention of future cancers rather than working on cancers which have already started to develop.
Prof Burn summarises the session’s focus, stating:
“Understanding epigenetics is pivotal to understanding how we cure cancer or how we will treat it more effectively.”
Why delegates should attend this session
The presentation will focus on what surgeons need to know about genomics and explore the interface between our genes and our environment and how they go together to cause cancer. Prof Burn says:
“Bowel cancer is genetic in all cases - sometimes patients inherit the predisposition, sometimes patients acquire it through exposure to external factors which change their genetics. Regardless, it is becoming increasingly important for all clinicians to understand the genomics underlying bowel cancer. In the future they won’t be able to do their jobs properly without an understanding of the molecular mechanism underlying the disease.”
Book your place at the 13th Scientific and Annual meeting of ESCP in Nice here
EHTG/ESCP Symposium: Hereditary Colorectal Cancer - Wednesday 26 September at 10:00
