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Gastric Cancer pp 91–109Cite as

Pathophysiology of Hereditary Diffuse Gastric Cancer

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Abstract

Hereditary diffuse gastric cancer (HDGC) is an autosomal dominant disorder, characterised by early onset diffuse gastric cancer (DGC). Approximately 30 % of families that meet current clinical criteria for genetic testing are found to have mutations in the cadherin 1 (CDH1) gene, which encodes E-cadherin, a glycoprotein with roles in cell adhesion and cell signalling. The lifetime risk or disease penetrance is variable and has been estimated between 60 and 80 %. Patients usually first develop intramucosal signet ring cell carcinomas (SRCCs), which are often multifocal and difficult to identify via routine white light endoscopy. Current guidelines recommend prophylactic total gastrectomy, under the care of a multidisciplinary team with experience in management of HDGC. The environmental and genetic factors that influence the penetrance of HDGC in mutation carriers are unknown, and further research is needed in this area.

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Abbreviations

DGC:

Diffuse gastric cancer

EMT:

Epithelial to mesenchymal transition

EPIC:

European Prospective Investigation into Cancer and Nutrition

FAP:

Familial adenomatous polyposis

FDG—fluoro:

2-deoxy-D-glucose

FDGC:

Familial diffuse gastric cancer

GC:

Gastric cancer

GI:

Gastrointestinal tract

HDGC:

Hereditary diffuse gastric cancer

HNPCC:

Hereditary non-polyposis colorectal cancer

IGCLC:

International Gastric Cancer Linkage Consortium

LBC:

Lobular breast cancer

PET:

Positron emission tomography

SRC:

Signet ring cell

SRCC:

Signet ring cell carcinoma

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Acknowledgments

The authors would like to acknowledge Dr Bill Murray for preparing the gastrectomy specimen stomach map and H&E images appearing in this manuscript.

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Authors and Affiliations

  1. Department of Medicine, Royal Melbourne Hospital, East Melbourne, Australia

    Sharon Pattison MBChB, BMedSc, FRACP & Alex Boussioutas MBBS, FRACP, PhD

  2. Sir Peter MacCallum Department of Oncology, University of Melbourne, East Melbourne, Australia

    Sharon Pattison MBChB, BMedSc, FRACP & Alex Boussioutas MBBS, FRACP, PhD

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  1. Sharon Pattison MBChB, BMedSc, FRACP
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  2. Alex Boussioutas MBBS, FRACP, PhD
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Correspondence to Alex Boussioutas MBBS, FRACP, PhD .

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  1. Gastric and Mixed Tumor Service, Memorial Sloan-Kettering Cancer Center, New York, New York, USA

    Vivian E. Strong

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Pattison, S., Boussioutas, A. (2015). Pathophysiology of Hereditary Diffuse Gastric Cancer. In: Strong, V. (eds) Gastric Cancer. Springer, Cham. https://doi.org/10.1007/978-3-319-15826-6_6

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