Hereditary diffuse gastric cancer (HDGC) syndrome is an inherited condition that increases a person’s risk of developing diffuse type stomach cancer, which tends to affect much more of the stomach than other types of stomach cancer. It is also linked to an increased risk of a type of breast cancer called lobular type.
HDGC syndrome is caused by a mutation in the CDH1 gene. The mutation can be passed from a mother or father to a son or daughter. People with a first-degree relative (a parent, sibling, or child) with HDGC syndrome have a 50% chance of having inherited the CDH1 mutation.
Having a mutation in the CDH1 gene does not mean that you will definitely develop cancer; it means that your risk is higher. The age at diagnosis and type of cancer can vary among people with HDGC syndrome, even within the same family.
What can a person do to manage their CDH1-associated cancer risk?
People who inherit a CDH1 mutation are at an increased risk of developing diffuse gastric cancer and lobular breast cancer.
Some people choose to have risk-reducing surgery to remove their stomach. This operation is called a gastrectomy. While this surgery is the best way to prevent diffuse gastric cancer for people with a CDH1 mutation, there are risks to consider as well.
Some people with a CDH1 mutation may opt for an examination of the stomach, called an upper endoscopy. Samples of tissue, or biopsies, may be taken during this procedure.
We recommend that women who have a CDH1 genetic mutation pursue increased breast surveillance with more frequent and specialized exams. Women may also consider pursuing a risk-reducing bilateral mastectomy to address their risk of breast cancer.
Individualized medical management recommendations should be discussed with a genetic counselor or doctor who is experienced in the care of people with HDGC syndrome.
Are there other genes associated with hereditary diffuse gastric cancer?
Mutations in the CTNNA1 gene also have been linked to hereditary diffuse gastric cancer. The exact risk for diffuse gastric cancer and potentially for other types of cancer in the setting of a CTNNA1 gene mutation is not yet well established. A CTNNA1 mutation can be passed from a mother or father to a son or daughter. People with a first-degree relative (a parent, sibling, or child) with a CTNNA1 mutation have a 50% chance of having also inherited the CTNNA1 mutation.