Understanding Hereditary Diffuse Gastric Cancer (HDGC)

HDGC is a rare hereditary cancer syndrome that increases your risk of diffuse stomach cancer and lobular breast cancer.

Hereditary cancer syndromes are disorders that increase your risk of developing certain cancers due to mutations in one or more genes inherited from your parents.

HDGC goes by other names, such as:

• familial diffuse cancer of stomach
• hereditary diffuse gastric adenocarcinoma
• familial diffuse gastric cancer
• hereditary diffuse cancer of stomach

Mutations in the CDH1 gene are most associated with HDGC. The average age of onset for HDGC is 38 years. Most people are diagnosed before age 40.

The estimated risk of developing gastric cancer by age 80 is 70% for men and 56% for women. Women with this mutation also have an estimated 42% chance of developing lobular breast cancer by age 80.

Diffuse stomach cancer is a type of stomach cancer that tends to cause a thickening of the stomach wall without causing a distinct tumor. It’s also called gastric signet-ring-cell adenocarcinoma or linitis plastica.

HDGC leads to the development of diffuse stomach cancer in most people who carry a CDH1 mutation. However, HDGC is thought to make up less than 3% of stomach cancers, while diffuse stomach cancer makes up about 17%.

The majority of diffuse stomach cancers aren’t associated with HDGC.

People with HDGC often don’t have symptoms in the early stages.

Late stage symptoms of HDGC

Late stage symptoms of diffuse stomach cancer can include:

• abdominal pain
• nausea
• vomiting
• trouble swallowing
• prolonged fullness after eating (postprandial fullness)
• loss of appetite
• unintentional weight loss

Late stage symptoms of lobular breast cancer

Lobular breast cancer often doesn’t cause noticeable symptoms in the beginning. As the cancer grows larger, you may have symptoms in your breast such as:

• thickening or hardening
• swelling or fullness
• change in texture or skin appearance
• newly developed inverted nipple
• changes in size or shape

HDGC is inherited from your parents.

The most common gene mutation associated with HDGC occurs in CDH1. It’s autosomal dominant, meaning that you only need to receive the gene from one parent to develop HDGC. If one of your parents has a mutation in this gene, you have a 50% chance of having it too.

Mutations in other genes such as CTNNA1may also be associated with HDGC. Researchers are continuing to examine the role these genes play.

Both men and women can develop HDGC. Mutations in the CDH1 gene have been identified in many different ethnic groups. The first case of HDGC was described in a Māori family in New Zealand in 1998.

In a 2017 study, researchers found that historically marginalized groups had a 40% to 50% higher risk of developing stomach cancer in general than people who were non-Hispanic white.

People with family members with genes linked to HDGC can receive a genetic test to see if they carry the same gene.

Testing for the CDH1 gene should be considered in people who:

• have two or more relatives with a history of stomach cancer and at least one with diffuse stomach cancer
• are diagnosed with diffuse stomach cancer before age 40
• have a personal or family history of stomach cancer and lobular breast cancer if at least one relative was diagnosed before age 50
• have two or more relatives with lobular breast cancer diagnosed before age 50
• were diagnosed with multiple lobular breast cancers before age 50
• have diffuse stomach cancer and a personal or family history of a cleft lip or palate

If you have symptoms of HDGC, your doctor may order imaging tests such as:

• ultrasound
• computed tomography (CT) scan
• positron emission tomography (PET) scan

Doctors can differentiate HDGC from other stomach cancers with a biopsy, where a small cell sample is extracted with a thin needle for lab analysis.

Intense surveillance is generally recommended for people with a CDH1 mutation linked to HDGC. The optimal surveillance regime remains controversial.

According to the National Cancer Institute, people with a CDH1 mutation linked to HDGC have the option of having their stomach removed before they develop cancer. This can potentially be lifesaving but can cause life-long problems with digestion.

The American College of Gastroenterology recommends the removal of the stomach after age 20 before cancer forms. They also recommend an annual mammogram in women after age 35 as well as MRI and clinical breast examination every 6 months.

Treatment for diffuse stomach cancer primarily consists of surgery to remove the stomach and chemotherapy when surgery isn’t possible or if cancer has spread beyond the stomach. Immunotherapy is also currently under investigation.

Treatment options for lobular breast cancer include:

• surgery
• chemotherapy
• hormone therapy
• radiation therapy

The majority of people with HDGC will develop cancer at some point in their life. Catching diffuse stomach cancer before it spreads to distant organs is critical for improving your outlook.

The 5-year survival rate is above 90% if the cancer is diagnosed and removed before it invades your stomach wall. The survival rate drops below 30% if it’s diagnosed in the late stages, primarily due to the spread of cancer to distant tissues.

HDGC is a cancer syndrome that predisposes you to diffuse stomach cancer and lobular breast cancer. The majority of people with HDGC develop stomach cancer at some point in their life.

Mutations in the CDH1 gene are most associated with HDGC. Doctors usually recommend aggressive screening or stomach removal for people with this mutation.

People with early stage diffuse stomach cancer have a good outlook when it’s caught early but a much poorer outlook if it advances to the late stages.