Lynch Syndrome X-Talk of Enteral Mucosa With Immune System

Conditions

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

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• 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)

Study Details

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.

Key Dates

Start date

Jun 1, 2023

Status verified

Apr 2026

Primary completion

Jun 1, 2033

Completion

Jun 1, 2034

Study Design

Enrollment

300 participants (estimated)

Arms

• Arm: 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
• Arm: 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
• Arm: 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
• Arm: 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
• Arm: 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
• Arm: 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
• Arm: 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
• Arm: 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
• Arm: 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
• Arm: 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
• Arm: 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
• Arm: 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
• Arm: 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
• Arm: 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

Primary Outcome Measure

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

Central Contacts

• Giulia Martina Cavestro, MD, PhD
  0226436303
  [email protected]
• Alessandro Mannucci, MD
  0226436303
  [email protected]

Locations (1)

Find similar trials in Monrovia, CA

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