Chapter 19. Hereditary Gastric Cancer

  1. Prof. Dr. Heike Allgayer PhD3,
  2. Prof. Dr. Helga Rehder4 and
  3. Prof. Dr. Simone Fulda5
  1. Holger Vogelsang1 and
  2. Gisela Keller2

Published Online: 21 AUG 2009

DOI: 10.1002/9783527627523.ch19

Hereditary Tumors: From Genes to Clinical Consequences

Hereditary Tumors: From Genes to Clinical Consequences

How to Cite

Vogelsang, H. and Keller, G. (2008) Hereditary Gastric Cancer, in Hereditary Tumors: From Genes to Clinical Consequences (eds H. Allgayer, H. Rehder and S. Fulda), Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, Germany. doi: 10.1002/9783527627523.ch19

Editor Information

  1. 3

    University of Heidelberg and DKFZ (German Cancer Research Center) Heidelberg, Medical Faculty Mannheim, Chair of Experimental Surgery, Theodor-Kutzer-Ufer 1–3, 68167 Mannheim, Germany

  2. 4

    Medical University Vienna, Department of Medical Genetics, Währinger Strasse 10, 1090 Wien, Austria

  3. 5

    Ulm University Children's Hospital, Eythstrasse 24, 89075 Ulm, Germany

Author Information

  1. 1

    Klinikum Garmisch-Partenkirchen, Abteilung für Allgemein-, Viszeral-, Thorax-, Gefäss- und endokrine Chirurgie, Auenstrasse 6, 82467 Garmisch-Partenkirchen, Germany

  2. 2

    Technische Universität München, Institut für Pathologie, Trogerstrasse 18, 81675 München, Germany

Publication History

  1. Published Online: 21 AUG 2009
  2. Published Print: 17 DEC 2008

ISBN Information

Print ISBN: 9783527320288

Online ISBN: 9783527627523

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Keywords:

  • E-cadherin gene;
  • endoscopic surveillance familial gastric cancer;
  • hereditary non-polyposis colorectal cancer;
  • Helicobacter pylori

Summary

Familial gastric cancer (FGC) aggregation with at least two first- or second-degree gastric cancer cases can be observed in 15 to 20% of the patients. Five percent of the families even show up with three or more gastric cancer cases. Finally, less than 2% of gastric cancer cases can be identified as mutation positive hereditary gastric cancer. Therefore strong FGC aggregation without identifiable mutational background represents the majority of families that have to be considered as potentially hereditary. This group cannot be dissected by genetic characteristics but by certain phenotypic characteristics, such as familial pattern, gastric cancer subtype, age of manifestation, and associated tumors. Germline mutation has been identified for three categories of hereditary gastric cancer: hereditary diffuse type gastric cancer (HDGC – E-cadherin gene), hereditary colorectal cancer (HNPCC – mismatch repair genes), and particularly rare syndromes (Li–Fraumeni – p53 gene; polyposis syndromes – various genes). For all of these syndromes, at least some specific phenotypic-characteristics of single gastric cancer cases as well as the familial pattern can be described.

Mutation screening is stratified according to the number of gastric cancer cases, age of manifestation, histological subtype of gastric cancer observed, and associated family pattern of other tumor diseases. As the life-time risk for gastric cancer is particularly high in E-cadherin mutation carriers (HDGC) at 60 to 80%, and endoscopic surveillance for diffuse type gastric cancer instead of difficult prophylactic gastrectomy has been offered and performed. In all other syndromes there is no option of prophylactic therapy but only surveillance and extended radicality in cases of gastric cancer manifestation, as limited endoscopic or surgical therapy has to calculate the risk of synchronous multifocal or metachronous recurrent disease of the same organ. Predictive testing in first-degree relatives of germline mutation carriers can detect persons at risk for gastric cancer or other tumors and exclude non-mutation carriers from surveillance programs. In families with strong gastric cancer aggregation without identifiable germline mutation, at least all first-degree relatives have to be considered as persons at risk and surveillance has to be offered according to the clinical phenotype observed (age of manifestation, gastric cancer subtype, and associated tumor disease). Additional macroscopic and histological potential risk factors (atrophic gastritis, metaplasia, neoplasia) assessed by endoscopy may help to stratify surveillance programs. The Munich Hereditary Gastric Cancer Registry at the University of Technology (www.tumorgen.de) collected data and performed mutation screening over a period of almost 15 years. Participants of an international interdisciplinary group working on hereditary and FGC, the International Gastric Cancer Linkage Consortium (IGCLC), have been performing studies on new candidate genes, establishing functional tests for missense mutations, analyzing mutation detection rates in cohorts of FGC cases, and publishing guidelines for the management of hereditary and FGC.