Early immune and genetic events in Lynch syndrome
Research type
Research Study
Full title
Study of genetic and immunological events in Lynch syndrome and progression to colorectal cancer
IRAS ID
276293
Contact name
Kevin Monahan
Contact email
Sponsor organisation
London North West University Hospitals NHS Trust
Duration of Study in the UK
10 years, 0 months, 1 days
Research summary
Colorectal cancer (CRC) is the 3rd most common cancer worldwide, with around 3-4% of cases occurring due to a hereditary disease called Lynch syndrome (LS). LS occurrence is estimated as 1 in 125 people. The diagnosis of LS is defined by a fault in the DNA mismatch repair (MMR) genes. CRC can be developed through the loss of function in the remaining healthy copy of this gene. The lifetime risk of CRC is up to 70% in LS patients. However, there is a lack of understanding in the precise occurrence of early events leading to cancer in LS and understanding this may be helpful in prevention.
Recent studies have demonstrated the presence of MMR deficient (MMR-d) cells in otherwise normal appearing tissue adjacent to cancer or polyps in LS, which is not present in people that do not have LS. There is evidence of an increased presence of immune cells in LS CRC compared to sporadic CRC. The interaction between MMR-d in LS and the immune response has not yet been elucidated. There has been much interest in improving predictive techniques, early detection and chemoprevention in LS. To further address these issues, the early events leading to MMR-d as well as continuing evolution to cancer must be fully understood.
This study aims to explore the interaction between genetic changes and immune response taking place within Lynch patients’ bowel and the specific sequence leading to CRC development. We aim to determine the genetic consequence, principally driver mutation, of MMR-d in otherwise normal LS as well as the immune remodelling response to MMR-d. A multidisciplinary team of scientists and clinicians would undertake an analysis of Lynch patient tissue alterations from normal tissue through to cancerous lesions and associated metastases.
REC name
North West - Haydock Research Ethics Committee
REC reference
20/NW/0190
Date of REC Opinion
15 May 2020
REC opinion
Further Information Favourable Opinion