A new genomic test can identify which people with inflammatory bowel disease (IBD) have the highest risk of bowel cancer, according to a new study by Cancer Research UK scientists working at the Institute of Cancer Research (ICR) in London.
The team is now working to develop this technology into a test which could improve diagnosis of bowel cancers linked to Crohn’s disease, ulcerative colitis and other types of IBD. The approach should also ensure fewer people with IBD need surgery or regular colonoscopies to lower or monitor their cancer risk.
Approximately 500,000 people in the UK have IBD. The most common types are Crohn’s disease and ulcerative colitis. Because they irritate the lining of the bowel, these conditions can sometimes cause abnormal, pre-cancerous cells to form there. Around 30% of people with these abnormal cells will develop bowel cancer within 10 years, but identifying those at risk has been very difficult.
The ICR team worked with doctors at St Mark’s Hospital, the UK’s specialist bowel hospital, to improve this process. By comparing the DNA changes in different samples, they found that pre-cancerous cells that gain or lose lots of copies of genes (short sections of DNA which carry out specific jobs) are far more likely to develop into bowel cancer. Using that information, the team then created an algorithm that calculates the risk of bowel cancer based on the exact pattern of DNA changes in pre-cancerous bowel cells.
The new study - published in the journal Gut - shows that the algorithm is more than 90% accurate at predicting which pre-cancerous cells will develop into bowel cancer within five years. The next step is to develop the technology into a test that can be used in hospitals.
Currently, all people with pre-cancerous growths (known as low grade dysplasia (LGD)) caused by IBD are classed as high-risk for bowel cancer. There are two options to lower that risk: bowel removal surgery, which has life-changing side effects, or regular monitoring with colonoscopies, which are invasive and time-consuming, and can cause worry and anxiety.
ICR Professor Trevor Graham, the senior author on the new paper, comments: “Our test and algorithm give people with IBD, and the doctors who care for them, the best possible information so that they can make the right decision about how to manage their cancer risk. We can accurately identify those people at high risk whilst putting the minds of many others at rest.”
To carry out the study, Graham’s team collected samples of LGD cells from 122 people with IBD and tested them for DNA changes. Around a third of the participants went on to develop bowel cancer over the next five years. Genomic sequencing showed that the cells in their samples had far more variations in the number of gene copies in their DNA.
The version of the test the team is now developing for hospitals will use the same genome sequencing approach to look for copy number changes in tissue samples taken during colonoscopy, the method currently used to identify and monitor LGD.
Information from the sequencing can then be fed into the team’s algorithm, which calculates risk based on specific DNA changes, alongside other information such as the size of the growth, how easy it was to remove during biopsy and how inflamed the gut is overall.
In future studies, the scientists are also hoping to develop a less invasive testing method involving a blood or a faecal sample.