DNA Testing Predicts Bowel Cancer Risk in IBD Patients

In the UK, approximately 500,000 people live with inflammatory bowel disease (IBD), with Crohn's disease and ulcerative colitis being the most prevalent types. These conditions cause inflammation in the bowel lining, which can sometimes lead to the formation of abnormal, pre-cancerous cells. Around 30% of people with these abnormal cells may develop bowel cancer within 10 years. However, there has been no reliable way to predict who is at risk. Currently, everyone with pre-cancerous growths, referred to as low-grade dysplasia (LGD), due to IBD is classified as high-risk for bowel cancer. To reduce this risk, patients are faced with two options: bowel removal surgery, which can lead to significant life-changing side effects, or regular monitoring through colonoscopies, which are invasive, time-consuming, and often cause anxiety. Now, a new DNA testing technique has been developed that can identify which individuals with IBD are at the highest risk of developing bowel cancer. This technology could eventually be used in a test to help doctors better intercept and prevent cancers linked to Crohn’s disease, ulcerative colitis, and other forms of IBD, while minimizing the need for surgery or frequent colonoscopies.

Scientists at the Institute of Cancer Research (ICR, London, UK) sought to find clues to more accurately predict which IBD patients might develop bowel cancer. The team collected LGD cell samples from 122 IBD patients and tested them for DNA alterations. By comparing DNA changes in the samples, they discovered that pre-cancerous cells that gained or lost many copies of genes (short DNA segments with specific functions) were more likely to progress into bowel cancer. Based on these findings, the researchers developed an algorithm to assess the risk of bowel cancer by analyzing the exact pattern of DNA changes in the pre-cancerous cells. The study, published in the journal Gut, demonstrated that the algorithm is over 90% accurate in predicting which pre-cancerous cells will evolve into bowel cancer within five years. Around a third of the study participants developed bowel cancer within that timeframe. Genomic sequencing revealed that these individuals' samples had significantly more variations in the number of gene copies in their DNA.

The next step is to refine the technology into a test suitable for hospital use. The version being developed for clinical settings will utilize the same genomic sequencing method to identify copy number changes in tissue samples collected during colonoscopy, the current method for detecting and monitoring LGD. This sequencing data will then be processed by the algorithm to assess risk, factoring in DNA alterations along with other information, such as the size of the growth, how easily it was removed during biopsy, and the degree of inflammation in the gut. In future studies, the researchers aim to create a less invasive test using blood or stool samples for easier screening.

“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,” said ICR Professor Trevor Graham, the senior author on the new paper. “We can accurately identify those people at high risk whilst putting the minds of many others at rest.”

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