Lynch Syndrome X-Talk of Enteral Mucosa With Immune System
Impact of Immune-surveillance on the Development of Colorectal Cancer in Patients With Lynch Syndrome
San Raffaele University
300 participants
Jun 1, 2023
OBSERVATIONAL
Conditions
Summary
Lynch syndrome (OMIM #120435) is the most common dominantly inherited colorectal cancer syndrome with an estimated prevalence of 1:270 individuals. It increases the lifetime risk of colorectal and endometrial cancer primarily, but it is associated with a high risk of other cancers (pancreas, stomach, ovarian, central nervous system, skin, among others). It is caused by a germline mutation in one of four DNA mismatch repair genes or a terminal deletion of the MSH2-adjacent gene EpCAM. Despite adherence to cancer surveillance programs, many patients still develop colorectal cancer and endometrial cancer. The Prospective Lynch Syndrome Database (PLSD) suggests that more frequent surveillance intervals do not significantly improve cancer risk reduction. The PLSD also revealed that the incidence of colorectal cancer in MLH1 and MSH2 carriers was even higher than previously expected, reaching as high as 41-36% among MLH1 carriers, regardless of ethnic background. The development of colorectal cancer despite surveillance is an unresolved question. Therefore, there is an unmet need for effective cancer prevention strategies.
Eligibility
Inclusion Criteria11
- Age ≥18 years
- All sexes eligible
- Established diagnosis of Lynch syndrome performed as part of clinical practice, with a germline pathogenic/likely pathogenic variant in one of the following genes: MLH1, MSH2, MSH6, PMS2, and EpCAM
- Subjects with Lynch syndrome undergoing surveillance gastrointestinal endoscopy and/or surgery according to clinical practice
- Fertile patients (both males and females) are eligible
- Lactating women are eligible
- Age ≥18 years
- All sexes eligible
- Patients with sporadic colorectal lesions, including colorectal cancer and colorectal adenomas
- Healthy controls without colorectal cancer or adenomas undergoing lower gastrointestinal endoscopy for abdominal pain
- PREMM5 \< 2.5 \[PREMM5 is an online, free-to-use, clinical prediction algorithm that estimates the cumulative probability of an individual carrying a germline mutation in the mismatch repair genes responsible for Lynch syndrome\].
Exclusion Criteria4
- Age \< 18 years;
- Diseases that are known to predispose to colorectal cancer (personal past or recent history of inflammatory bowel disease);
- Patients unable/unwilling to provide consent;
- Pregnancy
Interventions
A combination of blood-based, mucosal-based, and hair-based analyses that evaluate the presence and the expression of: * a set of microRNAs (blood) * antibodies anti-frame shift peptides (blood) * mucosal-resident bacteria (healthy mucosa and cancer) * environmental exposure to potential carcinogens (hair matrix)
Locations(5)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT06708429