E. Strong (ed.). Gastric cancer. Principles and practice. Springer (2015)
Familial gastric cancer (GC) with an autosomal dominant pattern has been documented for many years, the earliest possibly being Napoleon Bonaparte’s family, with a number of his family members potentially succumbing to GC [1–3]. Approximately 1–3% of all GCs are now thought to occur as part of a known hereditary syndrome [4–8]. The most common hereditary syndrome associated with GC is hereditary diffuse gastric cancer (HDGC) (MIM#137215), an autosomal dominant condition that results in the development of diffuse gastric cancer (DGC), as classified by the Lauren classification , (see Chap. 4: Pathologic classifications) and typically diagnosed at a younger age than sporadic GC [10, 11]. The gene responsible for HDGC was identified as the cadherin 1 (CDH1) gene or E-cadherin (see section below). The penetrance of disease in carriers is high, but not complete. Carriers of a CDH1 mutation have a lifetime risk of developing GC of approximately 80% . Surveillance for DGC of known mutation carriers is problematic because of the difficulty in identifying DGC at an early stage. Carriers are often asymptomatic, and may have no evidence of disease on surveillance investigations, but at gastrectomy are often found to harbour multifocal intramucosal signet ring cells (SRCs), consistent with early carcinoma, throughout the stomach. These SRC lesions are frequently multifocal and are characteristically indolent. Once a family is identified as at-risk of HDGC by clinical criteria, they are referred to appropriate genetic services for genetic diagnosis and multidisciplinary management that usually requires carriers to have prophylactic gastrectomy.
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