Hereditary Diffuse Gastric Cancer

Hereditary diffuse gastric cancer (HDGC) is a dominantly inherited cancer syndrome characterized by a high inci-dence of diffuse gastric cancer (DGC) and lobular breast cancer (LBC). HDGC is caused by germline mutations in 2 genes involved in the epithelial adherens junction complex, CDH1 and CTNNA1. We discuss the genetics of HDGC and the variability of its clinical phenotype, in particular the variable penetrance of advanced DGC and LBC, both within and between families. We review the pathology of the disease, the mechanism of tumor initiation, and its natural history.Finally, we describe current best practice for the clinical management of HDGC, including emerging genetic testing criteria for the identification of new families, methods for endoscopic surveillance, the complications associated with prophylactic surgery, postoperative quality of life, and the emerging field of HDGC chemoprevention.

Automated summary

Hereditary diffuse gastric cancer (HDGC) is a dominantly inherited cancer syndrome characterized by a high incidence of diffuse gastric cancer (DGC) and lobular breast cancer (LBC). It is caused by germline mutations in the CDH1 and CTNNA1 genes. This article discusses the genetics, clinical phenotype, pathology, tumor initiation mechanism, natural history, and clinical management of HDGC.