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Decision making, quality of life and prophylactic gastrectomy in carriers of pathogenic CDH1 mutations.

The management of inherited gastric cancer syndromes is a challenging field, with prophylactic total gastrectomy (PTG) the only effective preventive measure for at risk individuals. Germline mutations in CDH1 , encoding E-cadherin, account for around 30% of cases of hereditary diffuse gastric cancer (HDGC). Individuals carrying a pathogenic mutation in CDH1 have a high lifetime risk of developing diffuse gastric cancer, estimated to be 70% in men and 56% in women (1). Current international consensus guidelines recommend that PTG should be offered to carriers of pathogenic mutations (1). Individuals electing to defer surgery should undergo annual endoscopy with multiple biopsies following the Cambridge protocol (1). Our current limited understanding of what triggers the progression from non-invasive to invasive signet ring adenocarcinoma in this setting means that early surgery remains the chosen course of action for many.