Predicting bowel cancer in chronic Ulcerative Colitis

Abstract

Background: Ulcerative Colitis (UC) is an aggressive and incurable inflammatory bowel disease that affects young people typically in their teens and early twenties. The symptoms of UC include, bloody diarrhoea, incontinence and intractable fatigue that can be difficult to treat. There are almost 250, 000 patients with UC in the UK alone. Patients with UC for more than 8 years have a ten times increased risk of bowel cancer and undergo regular endoscopic surveillance of their large bowel. Unfortunately almost 50% of cancers are missed even in patients on surveillance. Furthermore cancer can develop in between surveillance episodes. There is a clear need to develop improved ways of predicting cancer in such patients.

Pilot data: DNA methylation is a key early event in many cancer types including bowel cancer. DNA methylation of genes involved in the Wnt pathway have been investigated previously by our group and shown to be silenced as a result of methylation. These events occur early in UC bowel cancers. Methylation of Wnt genes occurs not only in the cancer but also in surrounding bowel tissue suggesting that such changes may be ‘gatekeeper’ events for neoplastic transformation to occur.

Methods: This study aims to investigate the timeline of Wnt gene methylation and determine if these can be used within a clinical setting to PREDICT cancer in UC patients. To do this, 55 archived cancers from patients with UC will be analysed including colonic biopsies of the same patients taken up to three years before the development of cancer. DNA methylation changes will be analysed in all samples and will be compared to biopsies of UC patients that have similar disease parameters but no cancer. This study will help determine if such biomarkers can predict the onset of cancer in UC patients and if so determine the clinical lead-time that can be achieved through using this analysis as an adjunct to current surveillance strategies.

Outcomes: The outcome of such a study could lead to the development of a DNA based test that could enhance cancer risk stratification of UC patients. This could prevent hundreds of cancers each year in this young population.