Familial gastric carcinoma

Most cases of gastric cancer are sporadic and familial clustering is observed in about 10% of cases. Hereditary gastric cancer accounts for a very low percentage of cases (1–3%), encompassing: hereditary diffuse gastric cancer (HDGC) and gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS). Furthermore, gastric cancer can develop in the setting of other hereditary cancer syndromes such as Li–Fraumeni syndrome, Familial Adenomatous Polyposis, Peutz–Jeghers syndrome, Lynch syndrome, MUTYH-associated adenomatous polyposis, Juvenile Polyposis syndrome, and Cowden syndrome. HDGC is caused by alterations of the CDH1 gene that encodes for e-cadherin and the model of development encompasses non-atrophic gastritis, in situ signet ring cell carcinoma, pagetoid spread of signet ring cells and invasive carcinoma. GAPPS is characterized by proximal fundic gland polyposis, with areas of dysplasia or intestinal-type gastric cancer, without evidence of colorectal polyposis or other heritable gastrointestinal cancer syndromes. The genetic cause of GAPPS has not been identified yet.