Identifying the Genetic Basis for
Gastric Cancer Risk and Development

The potentially most powerful way of eliminating gastric cancer is to prevent its occurrence in the first place. One approach to this strategy is to identify individuals or families with a particularly high risk of developing gastric cancer due to hereditary factors, and provide intensive screening for early detection. However, the genetic basis for gastric cancer risk and progression is poorly understood. Researchers at Stanford have recently identified and collected clinical samples from a number of families with a rare, highly penetrant hereditary diffuse gastric cancer syndrome (HDGC) due to germline DNA mutations in the E-cadherin gene (CDH1 gene), including normal gastric tissue, early occult gastric malignancies, and invasive gastric cancers. However, inherited mutations in this gene account for only a fraction of familial gastric cancers and even less of very young individuals with gastric cancer but no family history. Therefore, a major goal of the registry is to collect blood samples from these families for genome-wide studies to identify other genes conferring gastric cancer risk. The DNA sequencing technologies described above now allow powerful approaches to identifying candidate genes for familial cancer risk. Ultimately, this genetic approach to risk assessment will be used together with advances in clinical screening and prevention of gastric cancer.