CDH1 Gene Mutations

Hereditary Diffuse Gastric Cancer Syndrome (HDGC)




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Additional Information

CDH1 gene

Associated Syndrome Name: Hereditary Diffuse Gastric Cancer (HDGC) Syndrome

CDH1 Summary Cancer Risk Table

Cancer Genetic Cancer Risk
Female BreastHigh Risk
GastricHigh Risk
ColorectalElevated Risk

CDH1 gene Overview

Hereditary Diffuse Gastric Cancer (HDGC) Syndrome 1, 2, 3, 4, 5
  • Individuals with mutations in CDH1 have a condition called Hereditary Diffuse Gastric Cancer syndrome (HDGC).
  • Patients with HDGC have a high risk for the diffuse form of gastric cancer, which is less common than intestinal type gastric cancer. Diffuse gastric cancer is more difficult to detect with endoscopic screening because it typically forms without a distinct mass. The majority of gastric cancers in individuals with HDGC are diagnosed under age 40, with some diagnoses occurring in the mid-teens.
  • Estimates of gastric cancer risk for men and women with mutations in CDH1 are currently based on studies of families with multiple people affected by gastric cancer, often at very young ages. Recent studies suggest that the risk of gastric cancer may be lower, and less likely to occur at young ages, in individuals with CDH1 mutations who do not have a family history of gastric cancer.
  • Women with HDGC have a risk for lobular breast cancer that is significantly increased over the 12.5% lifetime breast cancer risk for women in the general population of the United States. The risk for male breast cancer is not thought to be increased.
  • It is currently not certain that patients with HDGC have an increased risk for colorectal cancer, but there is enough suspicion of an increased risk to recommend special screening.
  • Guidelines for the medical management of patients with HDGC have been developed by the International Gastric Cancer Linkage Consortium (IGCLC) and the National Comprehensive Cancer Network (NCCN). These are listed below. Due to the complexity of this condition, it is recommended that patients with CDH1 mutations and a diagnosis of HDGC be managed by a multidisciplinary team with expertise in medical genetics, gastric surgery, gastroenterology, pathology and nutrition.

CDH1 gene Cancer Risk Table

Cancer Type Age Range Cancer Risk Risk for General Population
Gastric (male)To age 801, 5, 6, 767%-70%0.6%
Gastric (female)To age 801, 5, 6, 756%-83%0.6%
Female BreastTo age 505, 710%1.9%
To age 801, 5, 6, 739%-52%10.2%
ColorectalTo age 801, 3, 5, 7Possibly elevated risk3.0%

CDH1 Cancer Risk Management Table

The overview of medical management options provided is a summary of professional society guidelines. The most recent version of each guideline should be consulted for more detailed and up-to-date information before developing a treatment plan for a particular patient.

This overview is provided for informational purposes only and does not constitute a recommendation. While the medical society guidelines summarized herein provide important and useful information, medical management decisions for any particular patient should be made in consultation between that patient and his or her healthcare provider and may differ from society guidelines based on a complete understanding of the patient’s personal medical history, surgeries and other treatments.

Cancer Type Procedure Age to Begin Frequency
(Unless otherwise indicated by findings)
GastricGastrectomy818 to 40 years, or individualized to a younger age if a relative was diagnosed under age 25NA
Baseline endoscopy prior to gastrectomy. Upper endoscopies with random biopsies may be appropriate for patients delaying or declining gastrectomy.3, 8IndividualizedEvery 6 to 12 months
Consider testing and treating for Helicobacter pylori infection if present.3IndividualizedNA
Female BreastBreast awareness - Women should be familiar with their breasts and promptly report changes to their healthcare provider. Periodic, consistent breast self-examination (BSE) may facilitate breast awareness.8, 918 yearsNA
Clinical breast examination8, 9, 1025 yearsEvery 6 months
Mammography with consideration of tomosynthesis and consideration of breast MRI with contrast3, 10, 1130 to 35 yearsAnnually
ColorectalConsider colonoscopy for patients with a family history of colorectal cancer.3, 10IndividualizedIndividualized

Information for Family Members

The following information for Family Members will appear as part of the MMT for a patient found to have a mutation in the CDH1 gene.

A major potential benefit of myRisk genetic testing for hereditary cancer risk is the opportunity to prevent cancer in relatives of patients in whom clinically significant mutations are identified. Healthcare providers have an important role in making sure that patients with clinically significant mutations are informed about the risks to relatives, and ways in which genetic testing can guide lifesaving interventions.

There is an increased risk for children who inherit a CDH1 mutation to be born with Blepharocheilodontic syndrome or isolated cleft lip/palate. This risk may be higher in families in which clefts have occurred previously.4, 12, 13


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  3. van der Post RS, et al. Hereditary diffuse gastric cancer: updated clinical guidelines with an emphasis on germline CDH1 mutation carriers. J Med Genet. 2015 52:361-74. PMID: 25979631.
  4. Kluijt I, et al. Dutch Working Group on Hereditary Gastric Cancer. CDH1-related hereditary diffuse gastric cancer syndrome: clinical variations and implications for counseling. Int J Cancer. 2012 131:367-76. PMID: 22020549.
  5. Pharoah PD, et al. International Gastric Cancer Linkage Consortium. Incidence of gastric cancer and breast cancer in CDH1 (E-cadherin) mutation carriers from hereditary diffuse gastric cancer families. Gastroenterology. 2001 121:1348-53. PMID: 11729114.
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  7. Fast Stats: An interactive tool for access to SEER cancer statistics. Surveillance Research Program, National Cancer Institute. (Accessed on 1-2-2017)
  8. Ajani JA, et al. NCCN Clinical Practice Guidelines in Oncology®: Gastric Cancer. V 4.2019. Dec 20. Available at
  9. Bevers TB, et al. NCCN Clinical Practice Guidelines in Oncology®: Breast Cancer Screening and Diagnosis. V 1.2019. May 17. Available at
  10. Syngal S, et al. ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes. Am J Gastroenterol. 2015 110:223-62. PMID: 25645574.
  11. Daly M et al. NCCN Clinical Practice Guidelines in Oncology®: Genetic/Familial High-Risk Assessment: Breast, Ovarian and Pancreatic. V 1.2020. Dec 4. Available at
  12. Figueiredo J, et al. Clinical spectrum and pleiotropic nature of CDH1 germline mutations. J Med Genet. 2019 56:199-208. PMID: 30661051.
  13. Obermair F, et al. Cleft lip/palate and hereditary diffuse gastric cancer: report of a family harboring a CDH1 c.687+1G>A germline mutation and review of the literature. Fam Cancer. 2019 18:253-260. PMID: 30306390.
Last Updated on 10-Dec-2020