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CDH1/E-cadherin germline mutations in early-onset gastric cancer
  1. J T Bacani1,4,5,
  2. M Soares1,
  3. R Zwingerman1,
  4. N di Nicola1,
  5. J Senz6,
  6. R Riddell2,
  7. D G Huntsman4,6,
  8. S Gallinger1,3
  1. 1Centre for Cancer Genetics–Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
  2. 2Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada
  3. 3Department of Surgery, and Familial Gastrointestinal Cancer Registry, Mount Sinai Hospital, Toronto, Ontario, Canada
  4. 4Department of Pathology and Laboratory Medicine, Vancouver General Hospital, University of British Columbia, Vancouver, British Columbia, Canada
  5. 5Clinician Investigator Program, Saint Paul’s Hospital, University of British Columbia, Vancouver, British Columbia, Canada
  6. 6Genetic Pathology Evaluation Centre, Vancouver, British Columbia, Canada
  1. Correspondence to:
 Dr S Gallinger
 Room 1225, 600 University Avenue, Toronto, Ontario, Canada M5G 1X5; sgallinger{at}


Background: Gastric cancer remains a leading cause of cancer deaths worldwide. Genetic factors, including germline mutations in E-cadherin (CDH1, MIM#192090) in hereditary diffuse gastric cancer (HDGC, MIM#137215), are implicated in this disease. Family studies have reported CDH1 germline mutations in HDGC but the role of CDH1 germline mutations in the general population remains unclear.

Aims: To examine the frequency of CDH1 germline mutations in a population-based series of early-onset gastric cancer (EOGC <50 years old).

Methods: 211 cases of EOGC were identified in Central-East Ontario region from 1989 to 1993, with archival material and histological confirmation of non-intestinal type gastric cancer available for 81 subjects. Eligible cases were analysed for CDH1 germline mutations by single-strand conformation polymorphism, variants were sequenced, and tumours from cases with functional mutations were stained for E-cadherin (HECD-1) using immunohistochemistry.

Results: 1155 (89%) of 1296 polymerase chain reactions amplified successfully. One new germline deletion (nt41delT) was identified in a 30-year-old patient with isolated cell gastric cancer. The overall frequency of germline CDH1 mutations was 1.3% (1/81) for EOGC and 2.8% (1/36) for early-onset isolated cell gastric cancer.

Conclusion: This is the first population-based study, in a low-incidence region, of genetic predisposition to gastric cancer. Combined with our previous report of germline hMLH1 mutations in two other subjects from this series, it is suggested that 2–3% of EOCG cases in North Americans may be owing to high-risk genetic mutations. These data should inform cancer geneticists on the utility of searching for specific genetic mutations in EOGC.

  • DGC, diffuse-type gastric cancer
  • EOGC, early-onset gastric cancer
  • HDGC, hereditary diffuse gastric cancer
  • IGCLC, International Gastric Cancer Linkage Consortium
  • PCR, polymerase chain reaction
  • SSCP, single-strand conformation polymorphism

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  • Published Online First 26 June 2006

  • Funding: JTB was supported by the Clinician Investigator Program of the University of British Columbia, the National Cancer Institute of Canada-Terry Fox Foundation Post MD Biomedical Research Fellowship and by the Pathology and Laboratory Medicine of the University of Toronto. DGH is a Michael Smith Foundation Scholar for Health Research.

  • Competing interests: None.