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Hereditary Diffuse Gastric Cancer and Other Gastric Cancers Associated with Hereditary Predisposition Syndromes

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Molecular Pathology of Neoplastic Gastrointestinal Diseases

Part of the book series: Molecular Pathology Library ((MPLB,volume 7))

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Abstract

Gastric cancer is a heterogeneous and highly prevalent disease, being the fourth most common cancer and the second leading cause of cancer-associated death worldwide. Most cases of gastric cancer are sporadic, and familial aggregation occurs in about 10 % of the cases. In 1998, Guilford et al identified the first inherited gastric cancer syndrome, which was designated as Hereditary Diffuse Gastric Cancer (HDGC) and shown to be caused by germline alterations at the E-cadherin/CDH1 gene. In HDGC families, penetrance of gastric cancer is >80 % at the age of 80 in both genders, and lobular breast cancer is 60 % in women by age 80. To date, 120 families/probands have been described to harbor 99 different germline CDH1 alterations, mainly point mutations and large deletions. A third of all HDGC families described so far carry recurrent CDH1 alterations. Full screening of the CDH1 gene (genetic testing) is recommended in families/patients fulfilling the HDGC criteria. Total gastrectomy is the only reliable intervention and therefore is recommended for carriers of CDH1 pathogenic alterations. In this chapter, we will discuss the currently accepted definition and clinical criteria for HDGC syndrome, as well as the guidelines for genetic counseling and molecular screening. Moreover, molecular pathology, frequency and type of CDH1 germline alterations, other candidate genes and CDH1 associated syndromes, as well as available animal models and cell culture models of disease will be presented. Finally, treatment options, prophylactic gastrectomy, and potential molecular targets for therapy will be discussed in light of the knowledge obtained so far from patients/families and from basic research experiments.

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Authors and Affiliations

  1. Department of Pathology and Cancer Genetics Group, Institute of Molecular Pathology and Immunology of the University of Porto and Centro Hospitalar São João/Medical Faculty of the University of Porto, Porto, Portugal

    Fátima Carneiro M.D., Ph.D.

  2. Cancer Genetics Group, Institute of Molecular Pathology and Immunology of the University of Porto and Medical Faculty of the University of Porto, Porto, Portugal

    Carla Oliveira Ph.D. & Raquel Seruca M.D., Ph.D.

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  1. Fátima Carneiro M.D., Ph.D.
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  2. Carla Oliveira Ph.D.
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  3. Raquel Seruca M.D., Ph.D.
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Correspondence to Fátima Carneiro M.D., Ph.D. .

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  1. Department of Pathology & Cell Biology, Columbia University, New York, 10032, New York, USA

    Antonia R. Sepulveda

  2. Division of Gastroenterology, University of Pennsylvania, Philadelphia, 19104, Pennsylvania, USA

    John P. Lynch

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Carneiro, F., Oliveira, C., Seruca, R. (2013). Hereditary Diffuse Gastric Cancer and Other Gastric Cancers Associated with Hereditary Predisposition Syndromes. In: Sepulveda, A., Lynch, J. (eds) Molecular Pathology of Neoplastic Gastrointestinal Diseases. Molecular Pathology Library, vol 7. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-6015-2_6

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