Abstract
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.
Highlights
Gastric cancer is one of the most common gastrointestinal malignancies world-wide, in recent decades a decline has been observed in its incidence and associated mortality [1, 2]
In formulating a definition of familial gastric cancer syndromes, a distinction must be made between the histopathological subtypes which segregate within families [8]
The identification of the germline gene defect underlying hereditary diffuse gastric cancer (HDGC) came from segregation studies in early onset diffuse gastric cancer families [9-12]
Summary
Carla Oliveira1, Gianpaolo Suriano1, Paulo Ferreira1, Paulo Canedo1, Pardeep Kaurah2, Rita Mateus1, Ana Ferreira1, António C. Ferreira1, Maria José Oliveira1, Céu Figueiredo1, 3, Fátima Carneiro1, 3, Gisela Keller4, David Huntsman2, José Carlos Machado1, 3, Raquel Seruca1, 3 Key words: gastric cancer, familial gastric cancer, E-cadherin, CDH1, HDGC, hereditary diffuse gastric cancer, inheritance, germline mutation, missense mutation, Helicobacter pylori, low penetrance genes, IL1, TNFα, early onset, genetic counselling, functional analysis
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
