E-cadherin mutations and hereditary gastric cancer: prevention by resection?

Dig Dis. 2002;20(1):23-31. doi: 10.1159/000063162.


Background: A small percentage of gastric cancers (1-3%) arise as a result of clearly identified inherited gastric cancer predisposition syndromes. Recently, linkage analysis has implicated E-cadherin (CDH1) mutations in a subset of dominantly inherited gastric cancers termed hereditary diffuse gastric cancer (HDGC). Heterozygotes with the CDH1 mutation have a 70-80% chance of developing gastric cancer and once patients have invasive, symptomatic disease there is a high associated morbidity and mortality. As a result prophylactic gastrectomy has been advocated for affected family members identified by genetic screening. There are many issues to be considered in order to determine whether prophylactic gastrectomy is the optimal management strategy for these patients.

Methods: A MEDLINE literature search was performed and combined with our own experience in order to identify relevant background information on hereditary gastric cancer. In particular we extracted information about prophylactic gastrectomy in HDGC patients.

Results: Once the decision has been undertaken to perform genetic testing, the therapeutic options are either endoscopic screening with the aim of identifying an early, curable lesion or prophylactic surgery. Two groups have published their data on prophylactically resected stomachs in asymptomatic patients from affected families. In these series all of the post-gastrectomy specimens had microscopic evidence of diffuse gastric cancer confined within the mucosal layer. These early cancers had not been identified by endoscopic surveillance. Technical issues surrounding the age at which to operate, the best operation to reduce the risk of post-operative complications and the risk of other cancers developing in other organs in these patients are still controversial. Long-term follow-up studies in specialist centres are required to resolve these issues.

Conclusions: From the limited experience so far the estimated risk reduction of gastric cancer by gastrectomy is significant.

Publication types

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

MeSH terms

  • Cadherins / genetics*
  • Follow-Up Studies
  • Gastrectomy*
  • Genetic Linkage
  • Humans
  • Mutation*
  • Neoplastic Syndromes, Hereditary / prevention & control*
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / prevention & control
  • Stomach Neoplasms / surgery
  • Time Factors


  • Cadherins