SummaryWorldwide, gastric cancer is one of the most common forms of cancer, with a high morbidity and mortality. Both environmental and genetic factors have a role in the aetiology of gastric cancer. Familial clustering of gastric cancer is seen in 10-15% of cases, and approximately 3% of gastric cancer cases arise in the setting of hereditary diffuse gastric cancer ( HDGC). In families with HDGC, gastric cancer presents at relatively young age. Germline mutations in the CDH1 gene are the major cause of HDGC and are identified in approximately 25-40% of families which fulfill strict criteria. Prophylactic gastrectomy is the only option to prevent gastric cancer in individuals with a CDH1 mutation. However, in the majority of families with multiple cases of gastric cancer no germline genetic abnormality can be identified and therefore preventative measures are not available, except for general lifestyle advice. Future research should focus on identifying new genetic predisposing factors for all types of familial gastric cancer.

Summary CDH1 is currently the only gene in which mutations are known to cause hereditary diffuse gastric cancer (HDGC). Hereditary diffuse gastric cancer is defined as a syndrome of inherited predisposition to cancer with autosomal dominant inheritance pattern. Specific criteria are used to identify patients with suspected HDGC and who should be investigated for CDH1 germline mutations. Accurate screening is mandatory for unaffected carriers ofCDH1 mutations and selected high-risk individuals could be considered for prophylactic gastrectomy.