Impact of Immune-surveillance on the Development of Colorectal Cancer in Patients With Lynch Syndrome

Status: Recruiting

Location: See all (5) locations...

Intervention Type: Diagnostic test

Study Type: Observational

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

Participation Requirements

Sex: All

Minimum Age: 18

View:

• 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

• 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 \[PREMM5 is an online, free-to-use, clinical prediction algorithm that estimates the cumulative probability of an individual carrying a germline mutation in the mismatch repair genes responsible for Lynch syndrome\].

Locations

United States

California

Beckman Research Institute at City of Hope

RECRUITING

Monrovia

Other Locations

Italy

Chirurgia Generale, Azienda Ospedaliero Universitaria di Cagliari

RECRUITING

Cagliari

Dipartimento di Chirurgia Oncologica e Dipartimento di Oncologia Sperimentale Istituto Nazionale Tumori

RECRUITING

Milan

Gastronterology and Gastrointestinal Endoscopy Unit, IRCCS San Raffaele Hospital

RECRUITING

Milan

Dipartimento di controllo qualità e rischio chimico biologico, AOOR Villa Sofia Cervello

RECRUITING

Palermo

Contact Information

Primary

Giulia Martina Cavestro, MD, PhD

cavestro.giuliamartina@hsr.it

0226436303

Backup

Alessandro Mannucci, MD

mannucci.alessandro@hsr.it

0226436303

Time Frame

Start Date: 2023-06-01

Estimated Completion Date: 2034-06-01

Participants

Target number of participants: 300

Treatments

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

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