What Is Hereditary Diffuse Gastric Cancer (HDGC) Syndrome?

Hereditary diffuse gastric (stomach) cancer (HDGC) is a genetic cancer susceptibility syndrome characterized by a high risk for stomach and lobular breast cancer. HDGC is inherited in an autosomal dominant pattern, therefore several generations of relatives with stomach or lobular breast cancer are often seen clustering on one side of the family. Gastric cancers that occur in this syndrome are of the "diffuse" type (as opposed to "intestinal") and often have "signet ring" cells through the stomach wall causing thickening ("linitis plastica") without forming a discrete mass.

The average age of onset of gastric cancer in HDGC is 38 years old, with individuals as young as 14 having been diagnosed. The estimated lifetime risk of developing gastric cancer by age 80 is 67% for men and 83% for women. Women with HDGC also have an elevated risk of breast cancer, predominantly of the lobular type, with a 20-40% lifetime risk. Most of these women are over 50 at diagnosis.

Mutations in the E-cadherin (CDH1) gene have been identified in SOME families with this syndrome and genetic testing is now available. However, CDH1 mutations cause only 1-3% of all gastric cancers and in families with a strong history of diffuse gastric cancer, only one-third to one-half are due to CDH1 mutations. Therefore, genetic testing for CDH1 should be undertaken in partnership with a genetics professional who can assess the likelihood that CDH1 testing would be useful for a particular family and is able to interpret test results appropriately. CDH1 testing should be considered in any of the following situations:

  1. Two or more cases of diffuse gastric cancer in a family, with at least one diffuse gastric cancer diagnosed before the age of 50 years.
  2. Three or more cases of diffuse gastric cancer in a family diagnosed at any age.
  3. An individual diagnosed with diffuse gastric cancer before 35 years of age.
  4. An individual diagnosed with both diffuse gastric cancer and lobular breast cancer.
  5. One family member with diffuse gastric cancer and another with either lobular breast cancer OR signet ring colon cancer.

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