Hereditary diffuse gastric cancer (HDGC) is an inherited genetic syndrome most often caused by an inactivating mutation in the E-cadherin gene (CDH1) located on chromosome 16.

[4] Hereditary diffuse gastric cancer is inherited as an autosomal dominant mutation of the E-cadherin gene (CDH1), which is located on chromosome 16q22.1.

Therefore, HDGC is developed through a loss of heterozygosity, in which the one unmutated copy of the CDH1 gene undergoes mutation or inactivation in some cells during the lifetime of the individual.

In addition, all individuals testing positive receive an initial endoscopy, at which any lesion is biopsied, as gastric cancer frequently begins without symptoms.

Due to the mild risk that may be associated, individuals often receive screening colonoscopies at age 40, five years prior to the recommendation in the general population.

[4] HDGC was originally discovered through studies of Maori families in New Zealand that were noted to have increased incidences of gastric cancer.

[2] Detection of CDH1 mutations causing HDGC is highest in countries with low incidences of gastric cancer, such as the United States and Canada.

Conversely, detection of CDH1 mutations is lowest in countries with high rates of gastric cancer, such as Portugal, Italy, and Japan.