Recruiting

Observational Study

Sponsor:

San Raffaele University

Code:

NCT06708429

Conditions

Lynch Syndrome

Lynch Syndrome I

Lynch Syndrome II

Lynch Syndrome I (Site-specific Colonic Cancer)

HNPCC

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

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

Study Details

Brief 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.

Conditions

Lynch Syndrome

Lynch Syndrome I

Lynch Syndrome II

Lynch Syndrome I (Site-specific Colonic Cancer)

HNPCC

Study ID

NCT06708429

Start date

Jun 1, 2023

Status verified date

Apr, 2026

Completion date

Jun 1, 2034

Anticipated

Primary completion date

Jun 1, 2033

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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

Study Design

Enrollment

300 participants

Anticipated

Interventions and Outcome Measures

Arms

Lynch syndrome (MLH1), without colorectal cancer and without advanced adenomas

A cohort of individuals with a germline pathogenic variant in the MLH1 gene, that confers a diagnosis of Lynch syndrome, who are found to be cancer-free and adenoma-free at the time of colonoscopy evaluation

Lynch syndrome (MLH1), with colorectal cancer or advanced adenomas

A cohort of individuals with a germline pathogenic variant in the MLH1 gene, that confers a diagnosis of Lynch syndrome, who are found to have colorectal cancer or an adenoma at the time of colonoscopy evaluation

Lynch syndrome (MSH2), without colorectal cancer and without advanced adenomas

A cohort of individuals with a germline pathogenic variant in the MSH2 gene, that confers a diagnosis of Lynch syndrome, who are found to be cancer-free and adenoma-free at the time of colonoscopy evaluation

Lynch syndrome (MSH2), with colorectal cancer or advanced adenomas

A cohort of individuals with a germline pathogenic variant in the MSH2 gene, that confers a diagnosis of Lynch syndrome, who are found to have colorectal cancer or an adenoma at the time of colonoscopy evaluation

Lynch syndrome (MSH6, without colorectal cancer and without advanced adenomas

A cohort of individuals with a germline pathogenic variant in the MSH6 gene, that confers a diagnosis of Lynch syndrome, who are found to be cancer-free and adenoma-free at the time of colonoscopy evaluation

Lynch syndrome (MSH6), with colorectal cancer or advanced adenomas

A cohort of individuals with a germline pathogenic variant in the MSH6 gene, that confers a diagnosis of Lynch syndrome, who are found to have colorectal cancer or an adenoma at the time of colonoscopy evaluation

Lynch syndrome (PMS2), without colorectal cancer and without advanced adenomas

A cohort of individuals with a germline pathogenic variant in the PMS2 gene, that confers a diagnosis of Lynch syndrome, who are found to be cancer-free and adenoma-free at the time of colonoscopy evaluation

Lynch syndrome (PMS2), with colorectal cancer or advanced adenomas

A cohort of individuals with a germline pathogenic variant in the PMS2 gene, that confers a diagnosis of Lynch syndrome, who are found to have colorectal cancer or an adenoma at the time of colonoscopy evaluation

Lynch syndrome (MSH2, exon 8 deletion), without colorectal cancer and without advanced adenomas

A cohort of individuals with a germline pathogenic exon 8 deletion in the MSH2 gene, that confers a diagnosis of Lynch syndrome, who are found to be cancer-free and adenoma-free at the time of colonoscopy evaluation

Lynch syndrome (MSH2, exon 8 deletion), with colorectal cancer or advanced adenomas

A cohort of individuals with a germline pathogenic exon 8 deletion in the MSH2 gene, that confers a diagnosis of Lynch syndrome, who are found to have colorectal cancer or an adenoma at the time of colonoscopy evaluation

Non-Lynch syndrome, with colorectal cancer

A cohort of individuals without a germline pathogenic variant in any of the mismatch repair genes (MLH1, MSH2, MSH6, PMS2), who are found to have colorectal cancer at the time of colonoscopy evaluation

Non-Lynch syndrome, with high-risk adenomas

A cohort of individuals without a germline pathogenic variant in any of the mismatch repair genes (MLH1, MSH2, MSH6, PMS2), who are found to have high-risk adenomas at the time of colonoscopy evaluation

Non-Lynch syndrome, with low-risk adenomas

A cohort of individuals without a germline pathogenic variant in any of the mismatch repair genes (MLH1, MSH2, MSH6, PMS2), who are found to have low-risk adenomas at the time of colonoscopy evaluation

Non-Lynch syndrome, without colorectal cancer and without colorectal adenomas

A cohort of individuals without a germline pathogenic variant in any of the mismatch repair genes (MLH1, MSH2, MSH6, PMS2), who are found to be cancer-free and adenoma-free at the time of colonoscopy evaluation

Interventions

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

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)

Primary outcome measure

  • Sensitivity [ Time Frame: Through study completion, an average of 1 year ]

Central Contacts and Locations

Central contacts

Giulia Martina Cavestro, MD, PhD

0226436303cavestro.giuliamartina@hsr.it

Alessandro Mannucci, MD

0226436303mannucci.alessandro@hsr.it

Locations

Beckman Research Institute at City of Hope

Recruiting

Monrovia, California, United States, 91016

Contacts

Ajay Goel, PhD

AJGOEL@COH.ORG

More Information

Sponsor

San Raffaele University

Last update posted

Apr 24, 2026

Last verified

Apr, 2026

Keywords

  • Colorectal cancer
  • Endometrial cancer
  • Lynch syndrome-associated cancer
  • Surveillance
  • Cancer surveillance
  • Immune profile
  • Immune escape
  • Mismatch repair deficiency
  • Microbiota
  • Liquid biopsy
  • MicroRNA
  • Transcriptomic
  • Frame shift peptides
  • MLH1
  • MSH2
  • EpCAM
  • MSH6
  • PMS2
  • Hair matrix

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by San Raffaele University on 2026-04-24.