Study by the Wellcome Trust Sanger Institute and Cambridge University Hospitals finds that long-term inflammation disrupts the tissue integrity of the colon, allowing cells to expand over an abnormally wide area.
Inflammatory bowel disease (IBD) primarily refers to ulcerative colitis and Crohn’s disease, chronic illnesses characterised by inflammation of the digestive system that can be highly disruptive to a patient’s quality of life. Between 1990 and 2017, the number of IBD cases worldwide rose from 3.7 million to 6.8 million*. The causes of the disease remain unknown, though it is thought that inflammation occurs as a result of an inappropriate immune response to gut microbes.
People suffering from IBD are at an increased risk of developing gastrointestinal cancers compared to the general population. Patients will undergo regular surveillance for this and may, in some cases, opt to undergo surgery to remove their entire colon in order to mitigate this risk.
In a news study, researchers have compared diseased colon with healthy tissue to better understand how inflammatory bowel disease (IBD) is linked to an increased risk of colorectal cancers, at a molecular level. Researchers from the Wellcome Sanger Institute and Cambridge University Hospitals found that the rate of DNA change within colon cells affected by IBD was more than double that in healthy colon, increasing the likelihood of these cells gaining DNA changes that could lead to cancer.
The study was published in July 2020 in Cell, it also found that chronic inflammation associated with IBD disrupts the tissue structure of the colon. The results demonstrated valuable insights to the development of IBD and colorectal cancers.
Tissue samples for the study were donated by 46 IBD patients, along with anonymised information about their medical history and treatment provided by the clinicians at Addenbrooke’s Hospital, Cambridge. Researchers at the Wellcome Sanger Institute then used laser-capture microdissection to cut out 446 individual crypts, the tiny cavities that make up colon tissue, so they could be whole-genome sequenced.
Based on the analysis, the team discovered that there were more than two times as many DNA changes in the diseases tissue compared to normal tissue. Duration of the disease also showed increased of excess DNA changes.
The study also uncovered evidence of an evolutionary process whereby mutations in particular genes are under positive selection. Some of these positively-selected mutations were enriched in genes associated with colorectal cancers, shedding light on the link between IBD and certain cancers. The researchers also detected evidence of positive selection of mutations in genes associated with immune system regulation in the gut and the ability of the cells to fend off the bacteria resident in the colon.
Dr Carl Anderson, lead author of the study from the Wellcome Sanger Institute, said: “We know that DNA changes contribute to the development of cancer, but their role in common non-cancerous diseases like inflammatory bowel disease (IBD) has not been extensively studied. Our study revealed that somatic changes in the DNA sequence of the cells that line our gut may contribute to the development of IBD.”
Dr Anderson also shared that he strongly believes that studying somatic mutations in all common diseases, not just IBD and cancers, has the potential to provide novel insights into disease biology and highlight potential drug targets. [APBN]