Early genetic counseling and detection of CDH1 mutation in asymptomatic carriers improves survival in hereditary diffuse gastric cancer

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Background:Hereditary diffuse gastric cancer is associated with E-cadherin (CDH1) germline mutations. The implications of CDH1 mutations detected with multigene panels in those without family history of HDGC are uncertain.Methods:A registry of patients who underwent genetic counseling for CDH1 mutation was queried for the period 2011–2017.Results:Twenty-one patients with CDH1 mutation were identified. The most common indication for CDH1 genetic screening was family history of hereditary diffuse gastric cancer (known risk) in 10 patients (48%); 11 patients (52%), however, were diagnosed by multigene cancer panels (unknown risk). Nine of the 21 patients underwent total gastrectomy, and 5 others had metastatic gastric cancer at presentation. In the gastrectomy group, 5 of the 9 patients (56%) were known to have gastric cancer based on preoperative screening endoscopy, but final pathologic examinations indicated diffuse gastric cancer in 8 of the 9 patients. The 11 patients with unknown risk for CDH1 mutation tended to be older (median 41 vs 24 years) and more likely to have metastatic disease and to die of the disease (43% vs 29%) compared with patients with family history of hereditary diffuse gastric cancer.Conclusion:CDH1 mutation–associated hereditary diffuse gastric cancer is a biologically aggressive variant of gastric cancer that appears to behave similarly in patients detected only by multigene panels. The detection of CDH1 mutation at a minimum warrants genetic counseling and preferably total gastrectomy.

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