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The Sidney Kimmel Comprehensive Cancer Center

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Hereditary Diffuse Gastric Cancer (HDGC)

An estimated 1 percent to 3 percent of cases of stomach (gastric) cancers are hereditary diffuse gastric cancer (HDGC), an inherited cancer syndrome that leads to an increased risk for both diffuse stomach cancer and lobular breast cancer. Patients who inherit the genetic mutation for HDGC are at high risk for developing stomach cancer at a young age.

Diffuse (Stomach) Gastric Cancer

HDGC results in a cancer marked by the appearance of signet-ring shaped cells in the lining of the stomach, which occurs 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 (a procedure that uses a small camera to see into the stomach). For this reason, most cases of diffuse stomach cancer are diagnosed at late stages.

Identification of HDGC Family Members

People from HDGC families are at an increased risk of developing diffuse-type stomach cancer. It is estimated that the lifetime risk of developing stomach cancer is 80 percent. Additionally, female carriers have an estimated 60 percent lifetime risk of developing lobular breast cancer.

Hereditary diffuse stomach cancer is 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 this criteria, it is estimated that 25 percent to 40 percent 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 HDGC families, as well as patients diagnosed with diffuse stomach cancer before age 40, are referred for genetic counseling and testing for CDH1 gene mutations. They should also be followed by a medical team.

The current screening recommendations are upper endoscopy with biopsies on an annual basis. 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.

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 increased risk for other cancers, including breast cancer. The disorder is caused by mutation in the CDH1 gene. Our Cancer Risk Assessment Clinic evaluates patients and families for this disorder, provides management recommendations and when appropriate, genetically tests patients for a CDH1 gene mutation.