Genetic Screening for Familial Gastric Cancer

Hereditary Cancer in Clinical Practice

Raquel Seruca²  José Carlos Machado²  David Huntsman³  Gisela Keller¹  Fátima Carneiro²  Céu Figueiredo²  Maria José Oliveira⁴  António C Ferreira⁴  Ana Ferreira⁴  Rita Mateus⁴  Pardeep Kaurah³  Paulo Canedo⁴  Paulo Ferreira⁴  Gianpaolo Suriano⁴  Carla Oliveira⁴ 

[1] Institute of Pathology, Klinikum rechts der Isar, Technische Universität München, Germany;Faculdade de Medicina da Universidade do Porto, Porto, Portugal;Hereditary Cancer Program, British Columbia Cancer Agency, Vancouver BC, Canada;Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Porto, Portugal

关键词: functional analysis;    genetic counselling;    early onset;    TNFα;    IL1;    low penetrance genes;    Helicobacter pylori;    missense mutation;    germline mutation;    inheritance;    hereditary diffuse gastric cancer;    HDGC;    CDH1;    E-cadherin;    familial gastric cancer;    gastric cancer;   

Others  :  825533
DOI  :  10.1186/1897-4287-2-2-51

 received in 2004-05-14, accepted in 2004-05-16,  发布年份 2004

【 摘 要 】

Approximately 10% of gastric cancer cases show familial clustering but only 1-3% of gastric carcinomas arise as a result of inherited gastric cancer predisposition syndromes. Direct proof that Hereditary Gastric Cancer a genetic disease with a germline gene defect has come from the demonstration of co-segregation of germline E-cadherin (CDH1) mutations with early onset diffuse gastric cancer in families with an autosomal dominant pattern of inheritance (HDGC). E-cadherin is a transmembrane calcium-dependent cell-adhesion molecule involved in cell-junction formation and the maintenance of epithelial integrity. In this review, we describe frequency and type of CDH1 mutations in sporadic and familial gastric cancer. Further we demonstrate the functional significance of some CDH1 germline missense mutations found in HDGC. We also discuss the CDH1 polymorphisms that have been associated to gastric cancer. We report other types of malignancies associated to HDGC, besides diffuse gastric cancer. Moreover, we review the data available on putative alternative candidate genes screened in familial gastric cancer. Finally, we briefly discuss the role of low-penetrance genes and Helicobacter pylori in gastric cancer. This knowledge is a fundamental step towards accurate genetic counselling, in which a highly specialised pre-symptomatic therapeutic intervention should be offered.

   

【 图 表 】

Figure 1.

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