CDH1 Gene: Hereditary Diffuse Gastric Cancer and What to Do
Medically reviewed by LifeShield Medical Team, Board-Certified Genetic Counselors & Clinical Advisors
Last updated February 20, 2026
Key Takeaways
- CDH1 makes E-cadherin, a protein that acts as cellular glue keeping cells properly organized. Mutations cause hereditary diffuse gastric cancer (HDGC) syndrome.
- CDH1 mutation carriers face a 37–70% lifetime risk of diffuse gastric cancer, a type of stomach cancer that is difficult to detect with standard endoscopy.
- Women with CDH1 mutations also face a 39–55% lifetime risk of lobular breast cancer.
- Prophylactic total gastrectomy (preventive stomach removal) is often recommended because diffuse gastric cancer is difficult to detect early through screening alone.
- CDH1 mutations are rare but highly actionable, making genetic testing and cascade family testing essential.
CDH1 In Plain English
The CDH1 gene provides instructions for making a protein called E-cadherin. Think of E-cadherin as the glue that holds your cells together in an organized structure. In healthy tissue, cells stick to each other in orderly patterns. When CDH1 is mutated, this cellular glue does not work properly. Cells can become disorganized, detach from their neighbors, and invade surrounding tissues, which is a defining characteristic of cancer.
CDH1 mutations are specifically linked to a type of stomach cancer called diffuse gastric cancer. Unlike the more common intestinal-type gastric cancer, diffuse gastric cancer does not form a visible mass. Instead, cancer cells infiltrate the stomach wall in a scattered pattern, making it extremely difficult to detect with standard endoscopy until it is advanced. This is why preventive surgery is often recommended for CDH1 carriers. Women with CDH1 mutations also face a significant risk of lobular breast cancer, and screening recommendations overlap with those for BRCA1 and BRCA2 carriers, including annual breast MRI. For a broader understanding of hereditary cancer genes and when testing is recommended, see our guide on hereditary cancer screening.
If you receive a positive CDH1 result, see our guide on what to do after a positive genetic test result for recommended next steps. For help interpreting different result types, see our resource on understanding genetic test results. Because CDH1-associated gastric cancer is difficult to detect through screening and carries a high mortality when diagnosed late, cascade testing for family members is especially important and can be life-saving. For guidance on working with a genetics professional, see what to expect from genetic counseling. To learn more about the role of genetic counseling in hereditary cancer management, see our genetic counseling for cancer guide.
Cancer Risks Associated with CDH1 Mutations
| Cancer Type | Lifetime Risk | General Population | Source |
|---|---|---|---|
| Diffuse gastric cancer | 37–70% | < 1% | NCCN v3.2025; Hansford et al., J Med Genet 2015 |
| Lobular breast cancer (women) | 39–55% | 12.9% (all types) | NCCN v3.2025; Hansford et al., J Med Genet 2015 |
| Colorectal cancer (signet ring type) | Slightly elevated | 4.1% | NCCN v3.2025 |
Who Should Consider CDH1 Testing?
NCCN recommends CDH1 testing for individuals from families meeting HDGC criteria: two or more cases of gastric cancer in the family with at least one diffuse type, diffuse gastric cancer before age 50, or a personal or family history of diffuse gastric cancer and lobular breast cancer. Testing is also recommended when a known CDH1 mutation exists in the family.
Should You Get Tested?
Free 60-second screener based on NCCN guidelines — no account needed
Check Your Eligibility →Questions to Ask Your Genetic Counselor About CDH1
- What is my specific CDH1 variant, and is it definitively associated with HDGC?
- What is the recommended timing for prophylactic gastrectomy in my case?
- What does life after total gastrectomy look like day to day?
- If I choose surveillance over surgery, how effective is the Cambridge endoscopy protocol?
- As a woman, how should I manage my lobular breast cancer risk?
- Which family members should be tested for this CDH1 mutation?
- Are there specialized centers for prophylactic gastrectomy that you recommend?
What a CDH1 Result Means for Your Family
CDH1 mutations follow autosomal dominant inheritance. Each first-degree relative of a carrier has a 50% chance of carrying the mutation. Because CDH1-associated gastric cancer is difficult to detect through screening and carries a high mortality rate when diagnosed late, identifying carriers through cascade testing is potentially life-saving. Carriers can make informed decisions about prophylactic gastrectomy or enhanced surveillance before cancer develops. Testing is recommended for at-risk relatives starting in late adolescence or early adulthood.
Inheritance Pattern: Autosomal dominant
Prevalence: Rare; exact population prevalence unknown. CDH1 mutations are found in approximately 30–50% of families meeting HDGC clinical criteria.
Management Options If Positive:
- Discussion of prophylactic total gastrectomy (typically age 20–30)
- Annual endoscopy with Cambridge protocol biopsies (if gastrectomy deferred)
- Annual breast MRI starting at age 30 (women)
- Annual mammogram starting at age 30 (women)
- Discussion of risk-reducing mastectomy (women)
- Lifelong nutritional support post-gastrectomy (B12, iron, calcium)
Medical Disclaimer: This content is for informational purposes only and does not constitute medical advice. It is based on published NCCN clinical guidelines and peer-reviewed research. Always consult a qualified healthcare provider for medical decisions. LifeShield content is reviewed by board-certified genetic counselors.