HEREDITARY CANCER SYNDROMES AND GASTRIC CANCER: CURRENT PERSPECTIVES

Abstract

Hereditary cancer syndromes play a significant role in the pathogenesis of various forms of gastric cancer beyond sporadic cases. Unlike sporadic gastric cancers, which often have a multifactorial etiology, these syndromes are driven by germline mutations in tumor suppressor genes or DNA mismatch repair genes. The identification of these mutations allows for early diagnosis, risk assessment in family members, and implementation of preventive strategies, including endoscopic surveillance and prophylactic surgeries. Among these, Lynch syndrome, associated with germline mutations in MLH1, MSH2, MSH6, PMS2, and EPCAM, increases the risk of gastric adenocarcinoma, particularly in the proximal stomach. Familial adenomatous polyposis (FAP), and its gastric variant, gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) are linked to mutations in the APC gene and contribute to diffuse-type and fundic gland polyposis-associated gastric cancers. Peutz-Jeghers syndrome, caused by mutations in STK11, and juvenile polyposis syndrome, related to mutations in SMAD4 and BMPR1A, also predispose individuals to gastrointestinal malignancies, including gastric carcinoma. Understanding these genetic syndromes is crucial for early detection, surveillance, and management of at-risk individuals.