Lynch Syndrome X-Talk of Enteral Mucosa With Immune System

ConditionsLynch Syndrome Lynch Syndrome I Lynch Syndrome II Lynch Syndrome I (Site-specific Colonic Cancer)HNPCC HNPCC Gene Mutation Hereditary Cancer Syndrome Hereditary Cancer MLH1 Gene Mutation MLH1 Gene Deletion+Duplication MLH1 Loss of Expression MLH1 Gene Inactivation MSH2 Gene Mutation MSH2 Gene Deletion+Duplication MSH2 Loss of Expression MSH2 Gene Inactivation MSH6 Gene Mutation MSH6 Loss of Expression MSH6 Gene Inactivation PMS2 Gene Mutation PMS2 Gene Inactivation PMS2 Loss of Expression

Trial statusRecruiting

Trial phaseNot listed

Trial typeObservational

Biological sexAll

Age18+

SponsorSan Raffaele University

About this trial

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 criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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

Trial population

This study will enroll patients with and without Lynch syndrome, with and without colorectal cancer or colorectal adenomas.

Trial design

Design model

Cohort

Time perspective

Prospective

Treatments tested in this trial

LYNX EYE (Lynch syndrome X-Talk of Enteral mucosa with Immune System)
Diagnostic test
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)

Treatment groups

300 Participants

are divided into 14 treatment groups

Treatment groups

See each treatment group below.

Group A: Lynch syndrome (MLH1), without colorectal cancer and without advanced adenomas1 intervention

Group B: Lynch syndrome (MLH1), with colorectal cancer or advanced adenomas1 intervention

Group C: Lynch syndrome (MSH2), without colorectal cancer and without advanced adenomas1 intervention

Group D: Lynch syndrome (MSH2), with colorectal cancer or advanced adenomas1 intervention

Group E: Lynch syndrome (MSH6, without colorectal cancer and without advanced adenomas1 intervention

Group F: Lynch syndrome (MSH6), with colorectal cancer or advanced adenomas1 intervention

Group G: Lynch syndrome (PMS2), without colorectal cancer and without advanced adenomas1 intervention

Group H: Lynch syndrome (PMS2), with colorectal cancer or advanced adenomas1 intervention

Group I: Lynch syndrome (MSH2, exon 8 deletion), without colorectal cancer and without advanced adenomas1 intervention

Group J: Lynch syndrome (MSH2, exon 8 deletion), with colorectal cancer or advanced adenomas1 intervention

Group K: Non-Lynch syndrome, with colorectal cancer1 intervention

Group L: Non-Lynch syndrome, with high-risk adenomas1 intervention

Group M: Non-Lynch syndrome, with low-risk adenomas1 intervention

Group N: Non-Lynch syndrome, without colorectal cancer and without colorectal adenomas1 intervention

Trial outcomes

Primary outcomes

Sensitivity

True positive rate: the probability of a positive test result, conditioned on the individual truly being positive

Time frame