[From gene to disease; E-cadherin and hereditary diffuse gastric cancer]

Abstract

Hereditary diffuse gastric cancer (HDGC) is a rare autosomal dominant syndrome associated with an early-onset, histologically diffuse, signet ring cell type gastric cancer and the occurrence of cancer at other anatomical sites, i.e. breast, colon, prostate and ovary. Inactivating germline mutations in the CDH1 gene, encoding the cell to cell adhesion protein E-cadherin, predispose to HDGC. About 30% of HDGC families have a proven pathogenic CDH1 mutation. Lifetime penetrance of HDGC is about 70%. In HDGC families the recommendation for prophylactic total gastrectomy is restricted to carriers of an inactivating CDH1 mutation.