A systematic review of the indications for genetic testing and prophylactic gastrectomy among patients with hereditary diffuse gastric cancer

Rajini Seevaratnam, Natalie Coburn, Roberta Cardoso, Matthew Dixon, Alina Bocicariu, Lucy Helyer

Research output: Contribution to journalReview article

32 Scopus citations


Background: Hereditary diffuse gastric cancer (HDGC) is a familial cancer syndrome specifically associated with germline mutations to the E-cadherin (CDH1) gene. HDGC is characterized by autosomal dominance and high penetrance and a high cumulative risk for advanced gastric cancer. Our purpose in this study was to identify and synthesize findings from all articles on: (1) current recommendations for CDH1 screening and prophylactic gastrectomy; (2) CDH1 testing results in HDGC patients; and (3) prophylactic gastrectomy results in HDGC patients. Methods: Systematic electronic literature searches were conducted using Medline, Embase, and the Cochrane Central Register of Controlled Trials from 1985 to 2009. Results: Seventy articles were included in this review. Among patients with a positive family history of gastric cancer, 1085 were screened from 454 families, and 38.4% tested positive. Mutation-positive families also had a considerable family history of breast and colon cancer. Of the 322 patients screened for CDH1 mutations by current HDGC screening criteria, 29.2% tested positive. Among the 76.8% of patients who underwent prophylactic gastrectomy following positive CDH1 test results, 87.0% had positive final histopathology results and 64.6% had signet ring cells identified. Some of the patients with negative final histopathology results had opted to undergo prophylactic gastrectomy prior to CDH1 testing, and were ultimately found to be negative for CDH1 mutations. Conclusion: CDH1 mutation testing in families with a history of gastric cancer and prophylactic gastrectomy in mutation-positive patients are recommended for the management of HDGC.

Original languageEnglish (US)
JournalGastric Cancer
Issue numberSUPPL.1
Publication statusPublished - Jan 1 2012


All Science Journal Classification (ASJC) codes

  • Oncology
  • Gastroenterology
  • Cancer Research

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