LAUSR

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). HDGC is caused by germline mutations in two genes involved in the epithelial adherens junction complex, CDH1 and CTNNA1. Here, 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, post-operative quality of life and the emerging field of HDGC chemoprevention.