Cancer Risks Associated with Inherited CDH1 Mutations

People with a CDH1 mutation have an increased risk for breast and stomach cancer. However, research published in 2024 suggests that the lifetime risk for stomach cancer in CDH1 mutation carriers may be lower than previously reported.

If you have tested positive for an inherited CDH1 mutation, we recommend that you speak with a genetics expert who can look at your personal and family history of cancer and help you decide on a plan for managing your cancer risk. 

It is important to note that cancer risks are estimates over the course of a person's lifetime. Your risk will vary, depending on your:

• current age
• sex assigned at birth
• specific mutation
• personal and family health history
• diet, exercise, lifestyle and other factors

Note that when we refer to "men" and "women" we are referring to the sex you were assigned at birth.

Breast cancer

Women with a CDH1 gene mutation have an increased risk of developing lobular breast cancer. Their estimated lifetime risk for this specific type of breast cancer is 26-63 percent. In the new study published in 2024, two people who developed breast cancer were men with CDH1 mutations. 

Stomach cancer

People with an inherited CDH1 mutation have an increased risk of developing a type of stomach (gastric) cancer called diffuse hereditary gastric cancer (DHGC). 

Current NCCN guidelines quote the following risks of stomach cancer identified in older studies:

• an estimated lifetime risk of up to 67% for men and 83% for women
• an average age of diagnosis of 37 years 

A newer study published in 2024 suggests a much lower lifetime risk of stomach cancer:

• an average lifetime risk of 10% for men and 6.5% for women for advanced stomach cancer 
• an average lifetime risk between 13-19% for any stage of stomach cancer
• the risks increased to about 38% in people with three first-degree relatives (parent, child, sibling) with stomach cancer 
• the average age of gastric cancer in the study was 49 years 

People in the general population have a 1 percent lifetime risk for stomach cancer. The average age of diagnosis is 68 years. 

Other cancers

Researchers are studying whether CDH1 mutations increase the risk for other cancers. To date, these studies are not conclusive, and the risks for other cancers are unclear. For this reason, genetics experts often look at a family’s history of cancer to help people with CDH1 mutations understand their risk for additional cancers.