08 June 2016

In a series of interviews, guest reporter Owen Haskins from Dendrite Clinical Systems, will be previewing this year’s ACPGBI annual meeting in Edinburgh, Scotland, July 4-6. He talked to Professor Sue Clark (Consultant Colorectal Surgeon, Dean at St Mark's Academic Institute and Adjunct Professor; Department of Surgery & Cancer, Imperial College) about the issues surrounding the ‘Genetics of Colorectal Disease’.

“We know that a low fibre diet, processed meat, red meat, alcohol, obesity and a lack of exercise are the major culprits in term of the environmental factors that can cause colorectal cancer,” said Professor Clark. “We also know that there are hereditary factors, which include inheriting a mutated gene. This can mean a patient has an extremely high-risk of developing colorectal cancer, independent of the influence of environmental factors. There is also a second group of patients who are at moderate risk of developing colorectal cancer - those who inherit some genetic mutations and coupled with environmental factors, face an increased risk. However, the genetic component in this group of patients is not as dramatic as it is in the high-risk category of patients, and the precise nature of these genetic mutations is unknown.”

With regard to the high-risk patients, she explained that about ten genes have been identified that dramatically increase the likelihood of developing bowel cancer. Most, but not all the genes have been identified. In addition, there are also families that appear to have a high-risk but, as of yet, their genetic predisposition has yet to be determined.

“To put this into context, if a patient has a high-risk gene they are at least ten times more likely to develop bowel cancer than the average patient. If a patient has inherited certain mutated genes, they will develop bowl cancer by the age of 40, but most gene mutations range between 40 and 100% lifetime risk. With regard to mutations in genes that coupled with environmental factors increase the risk of bowel cancer, we are just beginning to identify them. However, there will 100’s of these genes. We would have to look at a patient’s genetic ‘fingerprint’ in order to determine the level of risk in this patient group.”

She added that in theory a genetic test is just a simple blood test, but there are several issues about when one should perform a genetic test and what one should do with the results. For example, a patient with a genetic mutation who will develop bowl cancer by the age of 40 will probably have inherited the gene from a parent, so a blood sample is taken and the genetic mutation is identified. The patient’s family can also be screened to identify other family members at risk.

Ethics

In addition, there are also ethical issues around when genetic screening should take place. For example, at what age should you take a blood sample from a child - before they are born, at birth, in their teens or should you wait until they become an adult? Does the child have a right to say whether they want to be tested or not? And if a child is known to have an inherited disease will they be treated differently by their parent and their peers? Mutations can now be detected during pregnancy, but does this mean that this will result in a termination? Moreover, it is now possible to screen and implant an embryo, through IVF, that does not have one of the ten known genes. This has been sanctioned by the Reproduction and Embryology Authority.

“In theory, you could screen every child at birth, but is it ethical to say you have this condition and that condition? Do they have the right not to know?” she asked. “One can argue that by screening a baby you can ensure they have the appropriate treatment later in life, but alternatively, people should have the right to give their consent to screening in the first place. We already know the high-risk genes, but there are lots we do not know or understand about how the moderate-risk genes behave and interact, in order to be able to deal with the information in a meaningful way. Technically, genetic testing is straight forward, but there are lots of ethical and moral issues, as well as how one handles the information that is less straight forward.”

Resources

Although the cost of genetic screening has become considerably less expensive over the last two decades, one limitation is the lack of human resources to manage the volume of tests. Professor Clark explained that there are currently approximately 500 clinical geneticists in the UK dealing with all inherited diseases, not just cancer. In addition, there are not enough consultants, surgeons and gastroenterologists who understand these diseases and are able to interpret the data in a clinically meaningful way.

“How the advances in genetic screening are managed will have huge implications for healthcare systems. For example, you can currently pay for genetic screening and you may find that you have double the risk of colorectal cancer. Does this mean you can demand to have colonoscopies at regular intervals? In some ways one can argue that by identifying those low-risk patients, one could concentrate resources on those patients who are at a higher risk, but at the moment we cannot do that. The lack of knowledge and expertise is probably the bottleneck at the moment.”

She said that the aim of the ‘Genetics of Colorectal Disease’ session at this year’s meeting will be to try and help colorectal surgeons understand the impact of genetics and when and where it is relevant to think about genetic testing, and what to do about the results. He own presentation, ‘Genetic testing – all you need to know’, will focus on who should have a genetic test, patients selection, and how one should and should not do it.

“There is a well-documented knowledge gap in the colorectal and gastroenterologist community when it comes to genetics and colorectal cancer, especially compared to other specialties such as breast surgeons. In my experience, breast surgeons are better informed and have established pathways,” she explained. “These conditions are not uncommon with about 5% of bowel cancers due to a high risk inherited condition. Therefore, a unit dealing with 200 cases of bowel cancer a year will treat ten patients, which is one a month. The first cancer genes were identified in the early 1990’s, so this is a relatively new field and many practising surgeons were qualified and had careers before any of these discoveries were made. I think there is a perception that inherited colorectal disease is quite rare and subsequently there is a lack of awareness, willingness and knowledge. Hopefully, we can change that mind set at the meeting in Edinburgh.”

Professor Sue Clark's lecture is on Tuesday 5th July at 11:05am.

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