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couple undergoing genetic screening
couple undergoing genetic screening

Hereditary Diffuse Gastric Cancer (HDGC)

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About 1% to 3% of stomach (gastric) cancers are hereditary diffuse gastric cancers (HDGC). The disorder is caused by mutation in the CDH1 gene. HDGC is an inherited cancer syndrome that leads to an increased risk for both diffuse stomach cancer and lobular breast cancer. People who inherit the genetic mutation for HDGC are at high risk for developing stomach cancer at a young age. 

Diffuse Stomach (Gastric) Cancer

HDGC causes signet-ring shaped cells to form in the lining of the stomach. These abnormal cells can grow either one by one or in small clusters (a formation known as diffuse). The diffuse type of stomach cancer associated with HDGC is difficult to diagnose because the cancer is not visible on upper endoscopy. For this reason, most cases of diffuse stomach cancer are diagnosed at late stages. 

Identification of HDGC Family Members

People from families that carry the HDGC gene are at an increased risk of developing diffuse-type stomach cancer. The lifetime risk of developing stomach cancer is about 80%. Females who have the gene are also at an estimated 60% lifetime risk of developing lobular breast cancer. 

Hereditary diffuse stomach cancer is often diagnosed in families with:

  • Two or more cases of diffuse stomach cancer in first- or second-degree relatives, where at least one case was diagnosed before the age of 50, OR 
  • Three or more cases of diffuse stomach cancer in first- or second-degree relatives, regardless of the age at diagnosis. 

Among families that fit these conditions, about 25% to 40% will have a CDH1 gene mutation. Families with multiple cases of diffuse stomach cancer, as well as patients diagnosed with diffuse stomach cancer before age 40, are referred for genetic counseling and testing for CDH1 gene mutations.

Stomach Cancer CDH1 Screening 

Patients from families with the HDGC gene, as well as patients diagnosed with diffuse stomach cancer before age 40, are referred for genetic counseling and testing for CDH1 gene mutations and should also be followed by a medical team. 

The current screening recommendations are upper endoscopy with biopsies each year. Because hereditary diffuse stomach cancer is nearly impossible to detect at an early stage, however, the recommended procedure to prevent stomach cancer is a total gastrectomy, or complete removal of the stomach. Although this procedure is complicated and commonly leads to weight loss, diarrhea, altered eating habits and vitamin deficiency, it is possibly the only method to prevent stomach cancer. 

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Stomach Cancer Screening at Johns Hopkins

Those with hereditary diffuse stomach cancer are at high lifetime risk for the development of stomach cancer that occurs at a young age. In addition, these patients are at an increased risk for other cancers, including breast cancer. 


Our cancer risk assessment clinic evaluated patients and families for this disorder, provides management recommendations, and when appropriate, genetically tests patients for a CDH1 gene mutation. 

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