Gastric Cancer

, Volume 13, Issue 1, pp 1–10

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

  • Parry Guilford
  • Bostjan Humar
  • Vanessa Blair
Review Article

DOI: 10.1007/s10120-009-0531-x

Cite this article as:
Guilford, P., Humar, B. & Blair, V. Gastric Cancer (2010) 13: 1. doi:10.1007/s10120-009-0531-x

Abstract

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. Intestinaltype 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.

Key words

E-cadherinHereditary diffuse gastric cancer
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Copyright information

© The International Gastric Cancer Association and The Japanese Gastric Cancer Association 2010

Authors and Affiliations

  • Parry Guilford
    • 1
  • Bostjan Humar
    • 1
  • Vanessa Blair
    • 2
  1. 1.Cancer Genetics Laboratory, Department of BiochemistryUniversity of OtagoDunedinNew Zealand
  2. 2.Department of Surgery, Faculty of Medicine and Health SciencesUniversity of AucklandAucklandNew Zealand