Hereditary diffuse gastric cancer

Abstract

Hereditary diffuse gastric cancer (HDGC) is an inherited form of the diffuse type of gastric cancer and a highly invasive type of tumour. Approximately 10% of patients with gastric cancer showfamiliar clustering and 3% autosomal dominance with a high HDGC penetration. It is an autosomal dominant inherited cancer syndrome in which affected individuals develop a diffuse type of gastric cancer at a young age. Inactivating mutations in the E-cadherin gene CDH1 have been identified in 30-50% of patients. CDH1 mutations carriers have an approximately 70% lifetime risk for developing diffuse gastric cancer (DGC) and affected women carry an additional 20-40% risk for developing lobular breast cancer. Common white light endoscopic surveillance is ineffective in identifying early HDGC. Gene-directed prophylactic total gastrectomy is currently being offered for CDH1 mutations carriers. Total gastrectomy is offered to patients who are five years younger than the youngest family member who developed gastric cancer, usually to patients older than 20. When refusing surgery, intensive endoscopic surveillance twice a year with multiple "protocol-based" and targeted biopsies combined with chromoendoscopy or NBI respectively are offered as an alternative option. Preventive total gastrectomy currently remains the only curative option for patients with HDGC.