The CDH1 gene, located on chromosome 16, normally encodes for a protein called E-cadherin. The normal function of E-cadherin is to allow cells and tissues to adhere to one another.
When there is a mutation in the CDH1 gene, the function of the E-cadherin protein is disrupted, and cancer often results. The exact mechanism by which the CDH1 gene mutation ultimately causes gastric cancer is not entirely known.
Inheritance of the CDH1 gene mutation follows an autosomal dominant pattern, meaning that offspring of mutation carriers have a 50% chance of inheriting the mutant gene. It is estimated that up to three out of every four CDH1 gene mutation carriers will go on to develop gastric cancer.
It is important to note, however, that not all HDGC families have a mutation in the CDH1 gene. Other genes that may lead to HDGC (Hereditary Diffuse Gastric Cancer) are currently being studied.
Families with a history of stomach cancer may qualify for diagnostic or predictive testing. Learn more on HDGC in families and the criteria for genetic testing. Read about DNA banking and why it’s important.
For assistance in locating a genetic counseling service in the US and Canada, you can search the National Society of Genetic Counselors database.
Huntsman DG, Carneiro F, Lewis FR, MacLeod PM, Hayashi A, Monaghan KG, et al. Early gastric cancer in young, asymptomatic carriers of germ-line E-cadherin mutations. The New England Journal of Medicine. June 2001;344(25):1904-1909.
Francis WP, Rodrigues DM, Perez NE, Lonardo F, Weaver D, Webber JD. Prophylactic laparoscopic-assisted total gastrectomy for hereditary diffuse gastric cancer. Journal of the Society of Laparoendoscopic Surgeons. 2007;11:142-147.
Caldas C, Carneiro F, Lynch HT, Yokota J, Wiesner GL, et al. Familial gastric cancer: overview and guidelines for management. Journal of Medical Genetics. 1999;36:873-880.
Kaurah P, MacMillan A,Boyd N, Senz J, De Luca A, et al. Founder and recurrent CDH1 mutations in families with hereditary diffuse gastric cancer. Journal of the American Medical Association. 2007;297(21):2360-2372.
Vogelaar IP, van der Post RS, Carneiro F, Guilford P, Huntsman D, et al. Hereditary diffuse gastric cancer: updated clinical guidelines with an emphasis on germline CDH1 mutation carriers. J Med Genet. 2015;00:1-14.