Principaux syndromes de prédisposition héréditaires à l'adénocarcinome de l'estomac : orientations diagnostiques et dépistage.

Worldwide, gastric adenocarcinoma is a major public health problem, accounting for 6% of all cancers. In France, the incidence of gastric adenocarcinoma has been stabilized at around 4,700 new cases/year, thanks to better control of risk factors, in particular the eradication of Helicobacter pylori. Around 3% of all cases are hereditary forms of the disease, which are part of cancer predisposition syndromes resulting from the presence of constitutional pathogenic variants in some tumor suppressor genes. The best-known predisposition syndromes that increase the risk of developing gastric adenocarcinoma are hereditary diffuse gastric cancer syndrome (CDH1 and CTNNA1 genes; estimated lifetime risk of around 40%), Lynch syndrome (germline alteration of one of the genes in the Mismatch Repair (MMR) system for repairing DNA mismatches (MLH1, PMS2, MSH2, MSH6); estimated lifetime risk of around 10 %) or certain digestive polyposis (Peutz-Jeghers syndrome linked to STK11, juvenile polyposis linked to SMAD4, GAPPS syndrome linked to APC). Identifying these patients is essential in order to implement preventive strategies and screening for gastric adenocarcinoma in unaffected relatives, as well as to be able to guide treatment strategies in patients with gastric adenocarcinoma (prognostic impact, treatment and risk of second cancer). Screening strategies for gastric adenocarcinoma in these patients include upper gastrointestinal endoscopy, and sometimes lead to discussion of prophylactic surgery, warranting management in an expert centre with a multidisciplinary referral committee. Although these syndromes are rare, the role of oncogenetics in the management of patients at high risk of developing gastric adenocarcinoma (or suffering from this cancer) is crucial, and new predisposition genes are regularly described which may also have therapeutic implications. [ABSTRACT FROM AUTHOR]