{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T00:47:44Z","timestamp":1775868464859,"version":"3.50.1"},"reference-count":112,"publisher":"BMJ","issue":"6","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2015,3,18]]},"published-print":{"date-parts":[[2015,6]]},"abstract":"<jats:p>Germline <jats:italic>CDH1<\/jats:italic> mutations confer a high lifetime risk of developing diffuse gastric (DGC) and lobular breast cancer (LBC). A multidisciplinary workshop was organised to discuss genetic testing, surgery, surveillance strategies, pathology reporting and the patient's perspective on multiple aspects, including diet post gastrectomy. The updated guidelines include revised <jats:italic>CDH1<\/jats:italic> testing criteria (taking into account first-degree and second-degree relatives): (1) families with two or more patients with gastric cancer at any age, one confirmed DGC; (2) individuals with DGC before the age of 40 and (3) families with diagnoses of both DGC and LBC (one diagnosis before the age of 50). Additionally, <jats:italic>CDH1<\/jats:italic> testing could be considered in patients with bilateral or familial LBC before the age of 50, patients with DGC and cleft lip\/palate, and those with precursor lesions for signet ring cell carcinoma. Given the high mortality associated with invasive disease, prophylactic total gastrectomy at a centre of expertise is advised for individuals with pathogenic <jats:italic>CDH1<\/jats:italic> mutations. Breast cancer surveillance with annual breast MRI starting at age 30 for women with a <jats:italic>CDH1<\/jats:italic> mutation is recommended. Standardised endoscopic surveillance in experienced centres is recommended for those opting not to have gastrectomy at the current time, those with <jats:italic>CDH1<\/jats:italic> variants of uncertain significance and those that fulfil hereditary DGC criteria without germline <jats:italic>CDH1<\/jats:italic> mutations. Expert histopathological confirmation of (early) signet ring cell carcinoma is recommended. The impact of gastrectomy and mastectomy should not be underestimated; these can have severe consequences on a psychological, physiological and metabolic level. Nutritional problems should be carefully monitored.<\/jats:p>","DOI":"10.1136\/jmedgenet-2015-103094","type":"journal-article","created":{"date-parts":[[2015,5,15]],"date-time":"2015-05-15T23:06:15Z","timestamp":1431731175000},"page":"361-374","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":476,"title":["Hereditary diffuse gastric cancer: updated clinical guidelines with an emphasis on germline <i>CDH1<\/i> mutation carriers"],"prefix":"10.1136","volume":"52","author":[{"given":"Rachel S","family":"van der Post","sequence":"first","affiliation":[{"name":"Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands"}]},{"given":"Ingrid P","family":"Vogelaar","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands"}]},{"given":"F\u00e1tima","family":"Carneiro","sequence":"additional","affiliation":[{"name":"Institute of 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