Classifying Inflammatory Bowel Disease related Bowel Cancer

What is this research looking at? 

IBD patients with longstanding or extensive inflammation in the colon have an increased risk of developing bowel cancer (colorectal cancer). This risk is further increased in patients with an associated rare liver disease, called Primary Sclerosing Cholangitis (PSC). 

People without IBD or PSC can also develop bowel cancer – this can be referred to as ‘sporadic bowel cancer’. Research has shown that the pathway by which sporadic bowel cancer develops is different to that by which IBD related bowel cancer develops. The pathway to sporadic cancer has been thoroughly researched. Recent analysis of sporadic tumours has led to the development of a molecular classification system, and an understanding of the processes which lead to the cancer developing. This molecular classification has helped doctors to personalise treatment for patients with sporadic bowel cancer as it can help to determine the prognosis, and help doctors choose the best treatment option. However, there is still no classification for IBD associated bowel cancer, and little is known about the processes which lead to tumour formation in IBD. 

Bowel cancer in all patients (whether they have colitis or not) arises from benign (non-cancerous) precursor lesions. These are changes in the appearance or nature of a cell before it becomes cancerous - and can usually be removed in surveillance colonoscopies before they become cancerous. 

However, precursor lesions in IBD patients can be very flat and difficult to spot during a colonoscopy. They can also occur within large patches of the bowel lining – so even if the precursor lesion is removed, some of the mutated layer may be left behind. In this situation, the patient often faces the difficult decision whether or not to have a colectomy (total removal of the colon) before the cancer develops. To complicate matters further, patients with IBD can also develop sporadic polyps, which can be safely removed endoscopically. However, distinguishing between a sporadic and a true colitis-associated precursor can be very difficult using the current techniques available – the researchers want to look into ways of doing this by looking at the cells at a molecular level. 

The aim is to find a way of classifying the IBD related cancer at a molecular level, and also look at the changes in the cells in the bowel which lead to cancer. They hope that this will help doctors and patients to find the best way of managing the precursor lesions - and the best way of removing them. 

Conclusions: The researchers worked alongside specialist gastroenterologists to examine mutations (changes) in the DNA of colitis-associated cancers. They were able to find certain patterns of mutations that were more common in colitis-associated cancers and their precursor lesions. If we can discriminate between cancers in this way, we may also be able to use this type of investigation to discriminate between polyps and precursor lesions (which is currently difficult to do when looking under the microscope). This is an important distinction to make, as patients with true colitis-associated precursor lesions require much closer follow up than patients with simple sporadic polyps. 

What do the researchers hope that this could mean for people with IBD?

The researchers hope that this will lead to personalised treatments for patients with IBD related cancer. If they can find a way of distinguishing between IBD associated cancer and sporadic cancer, it will help doctors to decide on the best treatment plan for IBD patients. 

Who is leading the research: Simon Leedham, Wellcome Trust Centre for Human Genetics, University of Oxford 
Our Funding: £115,500 
Duration: 24 months
Official title of the application: Molecular characterisation of inflammatory bowel disease associated neoplasia 
Tags: Bowel cancer