Hereditary diffuse gastric cancer: translation of CDH1 germline mutations into clinical practice

Gastric Cancer. 2010 Mar;13(1):1-10. doi: 10.1007/s10120-009-0531-x. Epub 2010 Apr 7.


Hereditary diffuse gastric cancer (HDGC) is the only known cancer syndrome that is dominated by gastric adenocarcinoma. HDGC is caused by germline mutation of the CDH1 gene that encodes the cell adhesion protein E-cadherin. Mutation carriers have a more than 70% lifetime risk of developing DGC and an elevated risk of lobular breast cancer. Intestinal-type gastric cancer is not part of the syndrome. Clinical management of HDGC involves predictive genetic testing beginning at or near 16 years of age. It is recommended that mutation carriers undergo prophylactic gastrectomy after about 20 years of age. Anatomical mapping has demonstrated that mutation carriers develop multifocal stage T1a signet ring cell carcinomas, with up to several hundred foci being observed in single stomachs. These foci develop following the somatic inactivation of the second CDH1 allele by mechanisms that include DNA promoter hypermethylation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antigens, CD
  • Cadherins / genetics*
  • Carcinoma, Signet Ring Cell / genetics*
  • Carcinoma, Signet Ring Cell / pathology
  • Carcinoma, Signet Ring Cell / prevention & control
  • Gastrectomy
  • Genetic Predisposition to Disease
  • Genetic Testing
  • Germ-Line Mutation*
  • Humans
  • Penetrance
  • Prognosis
  • Risk Factors
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology
  • Stomach Neoplasms / prevention & control


  • Antigens, CD
  • CDH1 protein, human
  • Cadherins