Prospective Multicenter Registry Study to Assess the Frequency of Lynch Syndrome Among Patients With Colorectal Cancer

Study Overview
=================
Brief Summary
-----------------
Prospective multicenter registry study to assess the frequency of Lynch syndrome among patients with colorectal cancer in Russia

Detailed Description
-----------------
Blood and tumor samples will be obtained from enrolled patients. 4 ml of venous blood samples will be taken into a tube with EDTA and stored at -20 0C. Tumor samples will be taken during endoscopy or surgical treatment, embedded in paraffin and stored at room temperature. Microsatellite instability in the tumor tissue will be determined by any method available in the participating center (immunohistochemical or molecular genetic study). In case of detection of microsatellite instability/deficiency in the repair system of unpaired bases blood samples will be analyzed for the fact that germinal mutations in the DNA mismatch repair genes. Patients will be followed up for 5 years after enrollment. During follow up correlation of spectrum of germinal mutations with clinical data, effectiveness of therapy with immune checkpoint inhibitors, the spectrum of malignant neoplasms in the families of patients with Lynch syndrome, the impact of the presence of microsatellite instability/deficiency in the DNA mismatch repair genes on treatment tactics in the Russian Federation will be assessed.

Official Title
-----------------
Prospective Multicenter Registry Study to Assess the Frequency of Lynch Syndrome Among Patients With Colorectal Cancer

Conditions
-----------------
Hereditary Colorectal Cancer, Colorectal Cancer, Lynch Syndrome, MSI

Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Provision of written informed consent; Patients with histologically verified colon adenocarcinoma or patients with histologically verified synchronous neoplasms who have not previously received treatment for a second tumor; Age ≥ 18 years; Absence of antitumor treatment for a real tumor (it is allowed to include patients who have a history of antitumor treatment for other malignant tumors, if the period after treatment is more than 12 months). The ability of the patient, according to the Researcher, to fulfill the requirements of the Protocol; Exclusion Criteria: - Patients receiving chemotherapy or radiotherapy for colon cancer at the time of screening

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients with colorectal cancer<br>Patients with colon adenocarcinoma who have not previously received antitumor treatment (chemo/radiation therapy) for a currently detected tumor | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of microsatellite instability and Lynch syndrome | To assess the frequency of microsatellite instability and Lynch syndrome in the population of patients with colorectal cancer in the Russian Federation. | up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of occurrence of microsatellite instability/deficiency | Assessment of the frequency of occurrence of microsatellite instability/deficiency in the repair system of unpaired bases in second tumors in patients with colorectal cancer of various stages. | up to 5 years | 
| Spectrum of germinal mutations in Lynch syndrome | The mlh1, msh2, msh6, pms2 and epcam genes will be examined for the presence of all types of pathogenic variants in patients with MSI in colon tumor. The possible correlation of gene-phenotype and pathogenic variants of each gene-phenotype will also be studied. To detect MSI in a tumor sample, need to do the fragment analysis (markers NR21, NR24, NR27, BAT25, BAT26). Рatients with MSI in the tumor will have DNA diagnostics of MMR EPCAM genes by sequencing and MLPA . The MMR and EPCAM genes will be examined in DNA isolated from blood lymphocytes. | up to 5 years | 
| Spectrum of malignant neoplasms | The family history of all oncological diseases will be studied to find out the main target organs of patients with Lynch syndrome in Russia | up to 5 years | 
| Effectiveness of therapy with immune checkpoint inhibitors | The frequency will be compared: the frequency of objective response rate (RECIST 1.1) while using immune checkpoint inhibitors in metastatic colon cancer and microsatellite instability associated/not associated with Lynch syndrome | up to 5 years | 
| Impact of the presence of microsatellite instability/deficiency | The frequency of adjuvant chemotherapy in stages II-III of colon cancer in the presence of microsatellite instability / deficiency in the repair system of unpaired bases in real clinical practice will be evaluated | up to 5 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Colorectal Cancer, Lynch Syndrome, Hereditary Colorectal Cancer, MSI, Frequency