Certain mutations in the CDH1 gene have been linked to a rare hereditary syndrome that can increase your risk for diffuse stomach cancer and lobular breast cancer.

The human body is thought to contain more than 20,000 genes. Genes are short sections of DNA inherited from your parents that carry all the genetic information that makes you uniquely you.

Some diseases are caused by gene mutations present from birth. A gene mutation is an abnormal change in the DNA building blocks that makes up a gene.

Certain mutations in the CDH1 gene have been linked to a condition called hereditary diffuse gastric cancer (HDGC) syndrome. HDGC syndrome is estimated to occur in about 5 to 10 people per 100,000.

Research suggests that people with HDGC syndrome have as high as an 80% chance of developing diffuse stomach cancer in their lifetime. As many as 60% of females with HDGC syndrome develop lobular breast cancer.

In this article, we take a deeper look at CDH1 gene mutations and how they relate to cancer.

CDH1, or cadherin 1, is a gene found on chromosome 16 that tells your cells to make a protein called epithelial cadherin. This protein has many important roles including helping your cells stick together to create tissues.

Some people have mutations in their CDH1 gene that predisposes them to HDGC syndrome. These harmful changes are known as pathogenic mutations. A parent with a CDH1 mutation that causes HDGC syndrome has a 50% chance of passing on the gene to a child.

In a 2022 study, researchers analyzed the genetic information of 30,223 people. They found that six people, or about 1 in 5,000, carried pathogenic CDH1 mutations. All six people self-reported their ethnicity as non-European and one person was female.

It’s thought that pathogenic CDH1 mutations are particularly common among the Māori population in New Zealand. The Māori people have very high rates of stomach cancer and diffuse stomach cancer.

People with CDH1 mutations associated with HDGC syndrome are at an increased risk of developing diffuse stomach cancer. Females are at an increased risk of lobular breast cancer.

Diffuse stomach cancer

Diffuse stomach cancer is characterized by a thickening of the wall of your stomach, as opposed to an isolated tumor. HDGC syndrome accounts for about 1% to 3% of stomach cancers.

In a 2019 study, researchers estimated that the chances of somebody with HDGC syndrome developing stomach cancer by age 80 were 42% for men and 33% for women. Previous studies have estimated the risk may be as high as 70% for men and 83% for women.

Signs and symptoms of diffuse stomach cancer

Diffuse stomach cancer often doesn’t cause symptoms in the early stages. Cancer has often spread to distant body parts by the time it’s diagnosed. When symptoms do appear, they can include:

Lobular breast cancer

Lobular breast cancer is the second most common type of breast cancer. It starts in the glands that produce milk. About 3% of people with lobular breast cancer carry CDH1 mutations. People who have CDH1 mutations linked to HDGC syndrome have about a 39% to 55% chance of developing breast cancer.

Signs and symptoms of lobular breast cancer

Lobular breast cancer tends to cause similar symptoms as other breast cancers, but it can be harder to detect during a breast exam. You may not have symptoms in the early stages. When symptoms do appear, they can include:

  • a hardened area inside your breast or under your arm
  • dimpling or puckering of skin on your breast
  • fullness or swelling of your breast
  • changes to your nipple, such as new inversion
  • changes in the size or shape of your breast

Other cancers

Researchers are still investigating if there’s a connection between CDH1 mutations and other types of cancer like colorectal cancer or appendix cancer. Some studies have uncovered a potential link while others haven’t.

In a 2019 study, researchers didn’t find an increased risk of developing colorectal cancer among 238 people from 75 families with pathogenic CDH1 variations compared with people in the general population.

Doctors can test for CDH1 gene mutations with a blood test. You may consider genetic counseling and screening for a CDH1 mutation if a member of your immediate family has had gastric cancer, or if you’ve been diagnosed with stomach cancer before the age of 40.

Other screening criteria include:

  • having diffuse stomach cancer and a personal or family history of a cleft lip or cleft palate
  • receiving a diagnosis of multiple lobular breast cancers before age 50
  • having a family history of two or more cases of lobular breast cancer diagnosed before age 50
  • having a personal or family history of diffuse stomach cancer and lobular breast cancer if at least one person received the diagnosis before age 50

If you’re carrying a pathogenic CDH1 gene mutation, your doctor will likely want to start screening you for cancer at a young age. They may also recommend surgically removing your stomach before cancer develops. However, this is a major surgery and it’s important to weigh the pros and cons carefully with your medical team.

The American College of Gastroenterology recommends the following for people with HDGC syndrome:

  • removing the stomach after age 20 before stomach cancer forms to reduce the risk of future cancer
  • breast cancer screening in women starting at age 35 with a yearly mammogram as well as a breast MRI and a clinical breast exam every 6 months
  • colonoscopy starting at age 40 if you have a family history of colon cancer

Can you live without a stomach?

Yes, a person can live without a stomach. In people who have had their stomach removed, food moves directly from their esophagus to their small intestines.

What’s the outlook for people with diffuse gastric cancer?

The 5-year survival rate for people with diffuse gastric cancer is above 90% if it’s caught while it’s still contained in your stomach. The 5-year survival rate is less than 20% if cancer spreads to other body parts.

What’s the outlook for people with lobular breast cancer?

In a 2022 study, researchers found the 5-year survival rate among people with lobular breast cancer was 93.6%. The survival rate drops significantly if cancer spreads to distant tissues. It’s not clear if having a CDH1 mutation affects the survival rate of people with lobular breast cancer.

People with certain mutations in their CDH1 gene are at an increased risk of developing HDGC syndrome.

The majority of people with this syndrome develop diffuse stomach cancer in their lifetime. Females have a significant risk of developing lobular breast cancer.

Some studies have found a potential link between CDH1 mutations and colorectal cancer, but more research is needed to understand if there’s a connection.

If you have a CDH1 mutation associated with cancer, your doctor may recommend the removal of your stomach before cancer forms. They may also recommend aggressive screening for breast cancer or colorectal cancer.