Risk Management for People with Inherited CDH1 Mutations

If you have tested positive for a 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 to manage your risk. This is particularly important when considering risk management options for stomach cancer. Research published in 2024 suggests that the risks for hereditary diffuse gastric cancer (HDGC) may be lower than previously reported, especially in CDH1 families where there have been no cases or few cases of stomach cancer.

Gastric cancer screening and prevention options

HDGC is an aggressive type of cancer that can be hard to detect, as these cancers spread through the lining of the stomach rather than forming a mass. 

There are two main options for managing HDGC risk in people with CDH1 mutations. 

Preventive gastrectomy

• Preventive gastrectomy (also known as prophylactic or risk-reducing gastrectomy) involves surgery to remove the entire stomach before cancer can develop. The procedure is effective at lowering risk for stomach cancer, but can have a large impact on lifestyle, (such as eating habits, symptoms that happen with eating, and the ability to maintain your weight). It can also have an impact on overall health, (such as increased risk of vitamin and mineral deficiencies, increased risk of bone disease and other effects).

Upper endoscopy and random gastric biopsy

• The goal of upper endoscopy with both targeted and random gastric biopsies is to try to find evidence of diffuse gastric cancer at its earliest and most curable stage. This screening is done under anesthesia. The endoscopist passes a scope with a video camera through the mouth into the stomach in order to get a close look. The endoscopist then passes a tiny instrument through the scope to take tissue samples from different spots within the stomach. These samples are sent to a pathologist to check them for cancer. 
• Experts do not all agree on how well this screening works for finding HDGC cancer in its earliest and most treatable stage. 

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Expert guidelines

Based on new research, some experts are changing how they counsel people with CDH1 mutations on managing their stomach cancer risk. In the past, all people who tested positive for a CDH1 mutation were recommended to have risk-reducing surgery, regardless of their family history of gastric cancer. The International Gastric Cancer Linkage Consortium (IGCLC) is a panel of experts that published guidelines in 2020 recommending the following for people who test positive for a CDH1 mutation: 

• People from families with members diagnosed with HDGC should consider risk-reducing gastrectomy (surgery to remove their stomach to prevent cancer), ideally between the ages of 20-30.
• People from families with no family members diagnosed with HDGC should speak with genetics and gastrointestinal experts to understand their risk for cancer, and compare the benefits, limitations, risks, side effects and costs related to risk-reducing gastrectomy versus screening.  
• People who have not had their stomachs removed should have annual screening with endoscopy and biopsy. 
• All people should be tested for the bacteria H. Pylori and treated if they are positive. 

Researchers are continuing to study the best way to manage cancer risk in people with CDH1 mutations. It's important for people with CDH1 mutations to choose a healthcare team with experience managing people at high risk for HDGC. 

Breast cancer risk management for women and people assigned female at birth

Other cancer screening and prevention

There has not been enough research to show a benefit from screening and prevention for other cancers in people who have a CDH1 mutation. For this reason, experts recommend managing these risks based on family history of cancer. You may also qualify for clinical trials looking for more effective screening or prevention for cancer.