Hereditary Diffuse Gastric Cancer: Approaches to Screening, Surveillance, and Treatment

Hereditary diffuse gastric cancer (HDGC) is a cancer syndrome associated with a significant lifetime risk of diffuse gastric cancer (DGC), a malignancy characterized by late clinical presentation and poor prognosis, as well as lobular breast cancer. HDGCis linked to germline pathogenic variants in the Ecadherin gene (CDH1) that are inherited in an autosomal dominant pattern; however, in many families with DGC clustering, no genetic cause has been identified. This review discusses key elements that allow risk assessment of potential inherited DGC susceptibility. We provide a practical overview of the recommendations for surveillance and treatment of individuals at risk and patients with early disease. The review also outlines future research avenues to improve our understanding of the genetic background and natural history of the disease, the endoscopic detection of early lesions, and the outcome of prophylactic surgery in young individuals.

Automated summary

Hereditary diffuse gastric cancer (HDGC) is a rare cancer syndrome associated with significant risks of gastric and lobular breast cancer, often presenting late in clinical settings. While most cases can be traced back to germline variants in the CDH1 gene, some families with clustering of DGC do not have a clear genetic cause. This review focuses on discussing key elements for assessing inherited DGC susceptibility, providing practical recommendations for surveillance and treatment of at-risk individuals and early-stage patients.