Genetic screening for hereditary diffuse gastric cancer

Knowledge regarding the genetic basis of hereditary diffuse gastric cancer has greatly increased in the past 4 years, namely due to the discovery of segregating germline mutations in the gene coding for E-cadherin, within families with this cancer predisposing syndrome. Members of hereditary diffuse gastric cancer families have predominantly high predisposition to develop diffuse carcinomas of the stomach but can also be associated with an elevate risk for other types of cancer, namely lobular breast carcinoma. In this review, we focus on the epidemiology, pathology and genetics of gastric cancer, describe families, E-cadherin mutations, and suggest alternative candidate genes underlying the hereditary diffuse gastric cancer syndrome. This knowledge is a fundamental step towards accurate genetic counselling, in which a highly specialized presymptomatic therapeutic intervention should be offered.