| [ Summary ] |
Hereditary diffuse gastric cancer (HDGC) is an inherited disease characterized by the onset of diffuse type gastric cancer consisting of poorly differentiated adenocarcinoma and/or signet‒ring cell carcinoma. HDGC is predominantly caused by CDH1 (which encodes E‒cadherin) germline mutations, and in a minority of cases, it is caused by mutations in other genes, including CTNNA1 and MAP3K6. The cumulative risk of gastric cancer for CDH1 mutation carriers by age 80 years is reported to be 70 % for men and 56 % for women. The risk of lobular breast cancer is also high in female CDH1 mutation carriers. A truncating mutation is the most common type of CDH1 germline mutation, and a large genomic deletion at the CDH1 locus occurs in a small subset of HDGC families. Several Japanese patients with germline CDH1 mutations that are associated with HDGC and early‒onset gastric cancer have been reported, and interestingly, a large genomic deletion is present in more than half of the CDH1 mutations in the known Japanese cases. Recently, in addition to HDGC, gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS), a new heritable syndrome characterized by gastric polyposis and an elevated risk of gastric cancer, has been identified, and point mutations in the APC promoter 1B may be associated with this syndrome. |