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J Med Genet. 2015 Jun;52(6):361-74. doi: 10.1136/jmedgenet-2015-103094. Epub 2015 May 15.

Hereditary diffuse gastric cancer: updated clinical guidelines with an emphasis on germline CDH1 mutation carriers.

Author information

1
Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands.
2
Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
3
Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal Department of Pathology and Oncology, Medical Faculty of the University of Porto, Porto, Portugal Centro Hospitalar São João, Porto, Portugal.
4
Department of Biochemistry, University of Otago, Dunedin, New Zealand.
5
British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
6
Department of Oncology, University of Cambridge, Cambridge, UK.
7
No Stomach For Cancer, Inc., Madison, Wisconsin, USA.
8
Department of Oesophago-Gastric Surgery, Addenbrooke's Hospital, Cambridge, UK.
9
Department of Medical Genetics, University Medical Centre Utrecht, Utrecht, The Netherlands.
10
Department of Surgical Gastroenterology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
11
Department of Medical Oncology, Institut Gustave Roussy, Villejuif, France.
12
Department of Gastroenterology, Radboud University Medical Center, Nijmegen, The Netherlands.
13
Vinery Lane Surgery, Whangarei, New Zealand.
14
Division of Psychosocial Research and Epidemiology/Family Cancer Clinic, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
15
Sir Peter MacCallum Department of Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Melbourne, Victoria, Australia.
16
Department of Gastroenterology and Hepatology, Netherlands Cancer Institute/ Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
17
Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
18
The DeGregorio Family Foundation for Stomach and Esophageal Cancer Research, Pleasantville, New York, USA.
19
Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.
20
Division of Oncology, Stanford University School of Medicine, Stanford, California, USA.
21
Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
22
Scientific Institute for Quality of Healthcare, Radboud University Medical Center, Nijmegen, The Netherlands.
23
Division of Surgical Research, University of Zurich, Zurich, Suisse.
24
Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.
25
Institute of Pathology, Technische Universität, Munich, Germany.
26
Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
27
Department of Histopathology, Cambridge University Hospitals NHS Trust, Cambridge, UK.
28
Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal Department of Pathology and Oncology, Medical Faculty of the University of Porto, Porto, Portugal.
29
NIHR Biomedical Research Unit, Nottingham Digestive Diseases Centre, Queens Medical Centre campus, Nottingham University Hospitals NHS Trust, Nottingham, UK.
30
Patient representative, The Netherlands.
31
Department of Oncology, Familial Gastric Cancer Registry, Cambridge University Hospital, Cambridge, UK.
32
Department of General Surgery and Surgical Oncology, University of Siena, Siena, Italy.
33
Department of Surgical Research, Technical University Dresden, Dresden, Germany.
34
Cambridge University Hospital, Cambridge, UK.
35
Stichting CDH1, The Netherlands.
36
Department of Medical Genetics, University of Cambridge, Cambridge, UK.
37
Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
38
Department of Surgical Oncology, University Medical Centre Utrecht, Utrecht, The Netherlands.
39
Department of Surgery, Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
40
Radboud University Medical Center, Nijmegen, The Netherlands.
41
Cambridge NIHR Biomedical Research Centre, University of Cambridge NHS Foundation Trust MRC Cancer Unit, Hutchison/MRC Research Centre, Cambridge, UK Department Gastroenterology, Cambridge University Hospitals, UK.

Abstract

Germline CDH1 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 CDH1 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, CDH1 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 CDH1 mutations. Breast cancer surveillance with annual breast MRI starting at age 30 for women with a CDH1 mutation is recommended. Standardised endoscopic surveillance in experienced centres is recommended for those opting not to have gastrectomy at the current time, those with CDH1 variants of uncertain significance and those that fulfil hereditary DGC criteria without germline CDH1 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.

KEYWORDS:

Cancer: breast; Cancer: gastric; Clinical genetics; Diagnostics; Stomach and duodenum

PMID:
25979631
PMCID:
PMC4453626
DOI:
10.1136/jmedgenet-2015-103094
[Indexed for MEDLINE]
Free PMC Article

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