Risk stratification and early diagnosis of bowel cancer in people with Lynch syndrome

Objective

Lynch syndrome (LS) is a hereditary condition that predisposes carriers to various cancers, particularly colorectal cancer (CRC). Approximately 40% of individuals with LS develop colorectal tumours before the age of 40, with adenomas often exhibiting higher dysplasia and an accelerated progression to carcinoma. Due to this elevated lifetime risk of CRC, clinical guidelines recommend biennial surveillance colonoscopies starting at age 25. However, colonoscopy is invasive, costly, and time-consuming, creating a significant burden for both patients and healthcare systems. Furthermore, it does not provide molecular-level data, which have significant potential to improve CRC risk stratification and inform the development of personalised prevention strategies. To address these unmet clinical needs, this proposal aims to develop a non-invasive and rapid surveillance tool based on circulating metabolite biomarkers. The objectives include evaluating the robustness of these biomarkers in stratifying CRC risk and early diagnosis of CRC among LS carriers, refining analytical methods for high-throughput sample processing, gathering end-user perspectives on the tool, and exploring intellectual property protection and commercialisation pathways. This tool will enable CRC risk stratification and longitudinal monitoring, potentially improving LS carriers’ compliance with routine screening. Additionally, the tool can provide metabolic profiles that may inform personalised nutritional interventions to reduce CRC risk in LS carriers.