Hereditary Diffuse Gastric Cancer
Conditions
Keywords
gastrectomy, somatic mutations, endoscopy, biopsies, methylation profil
Brief summary
Activating somatic mutations and methylation profiles identified by liquid biopsies could identify CDH1 and CTNNA1 pathogenic variants carriers with invasive diffuse gastric cancer undetectable by upper G-I endoscopy.
Detailed description
Carriers of germline pathogenic variants in the CDH1 and CTNNA1 genes have the Hereditary Diffuse Gastric Cancer Syndrome. Asymptomatic carriers have at high lifetime risk of diffuse gastric cancer (30-70%). Screening upper gastrointestinal endoscopy, even with multiple random biopsies, misses signet ring cell cancer foci. Invasive cancers can thus go undetected. There is therefore a recommendation of total risk-reducing gastrectomy, at least in carriers with a family history of gastric cancer. Novel screening strategies are needed. In this pilot project, the investigators will perform liquid biopsies of both blood and gastric fluid in asymptomatic carriers who refuse gastrectomy and in controls. The investigators aim to show that somatic mutations in a panel of genes involved in gastric cancer and methylation profiles are detected in a subset of carriers, and not in controls. These could be indicative of invasive cancer undetected by endoscopy, and would thus be a strong argument for risk-reducing gastrectomy. On the contrary, in the absence of somatic mutations in liquid biopsies, endoscopic surveillance could continue.
Interventions
GENETICLiquid biopsies (blood, gastric fluid).
Next generation sequencing of a panel of diffuse gastric cancer genes, methylation analysis. Samples collected during routine screening endoscopy.
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Intervention model description
Multicentric, prospective non-randomized study prognostic aim. Control group planned to have standard values.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Case: * Patient ≥ 18 years old * CDH1 or CTNNA1 germline pathogenic variant. * No history of diffuse gastric cancer. * French social security. * Ability to understand and willingness to sign a written informed consent document. Volunteers: * Patients ≥ 18 years old * Patients with no oncological history * Patients with macroscopically normal oeso-gastroduodenal fibroscopy * French social security. * Ability to understand and willingness to sign a written informed consent
Exclusion criteria
for both arms * Patients with cancer being treated * Patients with metastatic cancer * Medical contraindication to general anesthesia or FOGD (bleeding disorder, pregnant women ) * Patients under guardianship or curator
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of subjects in whom somatic mutations or methylation profiles are detected. | Over two years of surveillance |
Secondary
| Measure | Time frame |
|---|---|
| Replicability of observations over successive endoscopies. Correlation between blood and gastric fluid. | Over two years of surveillance |
Countries
France
Outcome results
None listed