Lynch Syndrome X-Talk of Enteral Mucosa With Immune System

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 Criteria (for participants with Lynch syndrome):

* 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

Inclusion Criteria (for participants without Lynch syndrome):

* 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 Criteria (for participants with or without Lynch syndrome):

* 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

Conditions23

Locations1 site

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