Liquid Biopsy Biomarkers for Endoscopic Surveillance in Lynch Syndrome

NCT07838246 | Completed

• 1 other identifier: INT 73/23
• Study Type: observational
• Target: 109
• Locations: 1 country
• Sites: 1

Brief Summary

Lynch syndrome (LS) is an autosomal dominant hereditary condition that markedly increases the risk of colorectal cancer (CRC) and other malignancies. Standard surveillance relies on colonoscopy every 1-2 years starting at age 20-25 years, an invasive and costly procedure that may become burdensome during lifelong follow-up and may miss interval cancers. This prospective, single-institution, observational study aims to identify minimally invasive plasma, stool, and urine biomarkers that could improve the detection of early colorectal lesions in individuals with LS and help refine surveillance protocols. Biomarker analyses include microsatellite instability (MSI) and MMR-related frameshift mutations in circulating tumor DNA, plasma and stool microRNA profiling, stool microbiome analysis, and exploratory urine cell-free DNA banking. Patients with genetically confirmed LS followed at Fondazione IRCCS Istituto Nazionale dei Tumori will be enrolled and followed for 24 months, undergoing surveillance colonoscopy at baseline, 12 months, and 24 months, with periodic venous blood sampling and stool, urine, and tissue collection according to protocol.

Conditions

Lynch Syndrome; Hereditary Nonpolyposis Colorectal Cancer; HNPCC; Colorectal Cancer (CRC); Colorectal Neoplasms

Keywords

Lynch Syndrome; Mismatch Repair Deficiency; MicroSatellite Instability; circulating tumor DNA; Liquid biopsy; Plasma biomarkers; microRNA; frameshift mutations; Colorectal cancer surveillance; Colonoscopy; Microbiome

Outcome Measures

Primary Outcomes (4)

• Plasma ctDNA Microsatellite Instability and colorectal lesions

  Association between microsatellite instability in plasma ctDNA and the presence of colorectal lesions in LS patients.

  Over the 24-month observation period (T0, T1 at 12 months, T2 at 24 months).

• miRNA Profiles and colorectal lesions

  Diagnostic and predictive value of miRNA profiles for the presence of colorectal lesions in LS subjects.

  Over the 24-month observation period (T0, T1 at 12 months, T2 at 24 months).

• Gut microbial signatures and colorectal lesions

  Diagnostic and predictive value of gut microbial signatures for the presence of colorectal lesions in LS subjects.

  Over the 24-month observation period (T0, T1 at 12 months, T2 at 24 months).

• Fecal ctDNA frameshift mutations and colorectal lesions

  Association between fecal ctDNA frameshift mutations and the presence of colorectal lesions in LS patients.

  Over the 24-month observation period (T0, T1 at 12 months, T2 at 24 months).

Secondary Outcomes (3)

• Urinary cell-free DNA collection and banking

  At each colonoscopy visit (T0, T1, T2) over the 24-month observation period.

• Dietary habits assessment

  At each colonoscopy visit (T0, T1, T2) over the 24-month observation period.

• Stool microbiome profiles and colorectal lesions

  At each colonoscopy visit (T0, T1, T2) over the 24-month observation period.

Study Arms (1)

Single Cohort

Patients with a confirmed pathogenic germline mismatch repair gene mutation (Lynch Syndrome) undergoing surveillance colonoscopy. There is no comparator or control arm; comparisons are made within the same cohort based on colonoscopy and histology findings.

Other: Study procedures

Interventions

Study procedures OTHER

1. Standard-of-care surveillance colonoscopy performed according to international guidelines at T0, T1 (12 months), and T2 (24 months), with additional colonoscopies if clinically indicated; 2. Collection of venous blood samples at each visit plus additional blood draws every 3 months, for a total of 12 blood collections per participant over the study. Plasma is isolated for extraction of circulating tumor DNA for MSI analysis by digital PCR and for miRNA analysis; 3. Collection of a urine sample at each visit for future exploratory biomarker analyses; 4. Collection of a stool sample at each visit for miRNA profiling, microbiome analysis, and fecal ctDNA frameshift mutation analysis; 5. Collection of paraffin-embedded biopsy material for possible future immunohistochemical analysis of mismatch repair proteins and/or molecular MSI testing; 6. Clinical evaluation at each scheduled colonoscopy visit and collection of dietary habits using the validated EPIC questionnaire.

Single Cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with a confirmed pathogenic germline mismatch repair gene mutation (Lynch Syndrome) undergoing surveillance colonoscopy.

You may qualify if:

• Patients with Lynch syndrome, defined as carriers of a pathogenic germline mutation in one of the mismatch repair genes (MLH1, MSH2, MSH6, PMS2, or EPCAM), able to sign informed consent.
• Age ≥18 years.
• Patients with Lynch syndrome without a cancer diagnosis in the 6 months preceding study entry (T0).

Sponsors & Collaborators

• Fondazione IRCCS Istituto Nazionale dei Tumori, Milano: lead

Study Sites (1)

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, Italy, 20133, Italy

Location

Biospecimen

Retention: SAMPLES WITH DNA

Blood, urine, and stool samples

MeSH Terms

Conditions

Colorectal Neoplasms, Hereditary Nonpolyposis; Colorectal Neoplasms; Turcot syndrome; Microsatellite Instability

Interventions

Methods

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Neoplastic Syndromes, Hereditary; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; DNA Repair-Deficiency Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Rectal Diseases; Genomic Instability; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Investigative Techniques

Study Officials

• Marco Vitellaro

  Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 11, 2026
• First Posted: September 24, 2026
• Study Start: June 20, 2023
• Primary Completion: June 25, 2026
• Study Completion: June 25, 2026
• Last Updated: September 24, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will share

Locations

IT (1)