A Comprehensive Literature Review of the CDH1 Mutation and Its Role in Gastric Cancer

Hereditary diffuse gastric cancer (HDGC) is a significant genetic predisposition syndrome, primarily caused by germline mutations in the CDH1 gene, which encodes the E-cadherin protein - a critical component for cell adhesion and tissue integrity. Individuals with HDGC have an increased risk of developing diffuse-type gastric cancer, which is characterized by the infiltration of the stomach wall by poorly cohesive, single-cell carcinoma. This aggressive form of gastric cancer is challenging to detect at an early stage and is associated with a poor prognosis. The identification and understanding of the genetic basis of HDGC are crucial for improving early detection, risk assessment, and the development of targeted treatment strategies for this hereditary cancer syndrome. This review aims to provide a comprehensive overview of the genetic and molecular mechanisms underlying HDGC, with a focus on the role of CDH1 mutations. It discusses current diagnostic criteria, genetic testing strategies, and the implications of a positive CDH1 mutation for clinical management - including surveillance, prophylactic gastrectomy, and family counseling. Additionally, this review highlights recent advancements in understanding the impact of CDH1 loss on cellular pathways and the potential for novel therapeutic approaches targeting these molecular changes. By consolidating the existing knowledge and addressing current gaps, this review aims to support clinicians and researchers in enhancing the care and outcomes of individuals and families affected by HDGC.