Hereditary Diffuse Gastric Cancer Syndrome (HDGC)



Additional Information

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

CDH1 Summary Cancer Risk Table

Female Breast High Risk
Gastric High Risk
Colorectal Elevated Risk

CDH1 gene Overview

Hereditary Diffuse Gastric Cancer (HDGC) Syndrome 1, 2, 3, 4

  • 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.
  • 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. 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

Gastric (male) To age 801, 3, 5 67%-70% 0.6%
Gastric (female) To age 801, 3, 5 56%-83% 0.6%
Female Breast To age 503 10% 1.9%
To age 801, 3, 5 39%-52% 10.2%
Colorectal To age 801, 2, 3 Possibly elevated risk 3.4%

CDH1 Cancer Risk Management Table

The overview of medical management options provided is a summary of professional society guidelines as of the last Myriad update shown on this page. The specific reference provided (e.g., NCCN guidelines) should be consulted for more details 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.

Gastric Gastrectomy8 18 to 40 years, or individualized to a younger age if a relative was diagnosed under age 25 NA
Baseline endoscopy prior to gastrectomy. Endoscopies with targeted biopsies may be appropriate for patients delaying or declining gastrectomy.2, 8 Individualized Every 6 to 12 months
Treat for Helicobacter pylori infection if present.2 Individualized NA
Female Breast Breast 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.7, 8 18 years NA
Clinical breast examination7, 8 25 years Every 6 to 12 months
Mammography and consideration of breast MRI with contrast7 Age 30, or modified to a younger age based on family history Annually
Consider investigational screening studies within clinical trials.7, 8 Individualized NA
Consider risk-reducing mastectomy.7, 8 Individualized NA
Consider options for breast cancer risk-reduction agents (i.e. tamoxifen).7, 8 Individualized NA
Colorectal Consider colonoscopy for patients with a family history of colorectal cancer.2 Individualized Individualized

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 a cleft lip and/or palate. This risk may be higher in families in which clefts have occurred previously.4


  1. Kaurah P, Huntsman DG. Hereditary Diffuse Gastric Cancer. 2014 Jul 31. In: Pagon RA, et al., editors. GeneReviews® [Internet]. Available from PMID: 20301318.
  2. 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.
  3. 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.
  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. Hansford S, et al. Hereditary Diffuse Gastric Cancer Syndrome: CDH1 Mutations and Beyond. JAMA Oncol. 2015 1:23-32 doi: 10.1001/jamaoncol.2014.168.
  6. Surveillance Research Program, National Cancer Institute SEER*Stat software ( V 8.0.1, Nov 19, 2012.
  7. Daly M et al. NCCN Clinical Practice Guidelines in Oncology®: Genetic/Familial High-Risk Assessment: Breast and Ovarian. V 1.2017. September 19. Available at
  8. Ajani JA, et al. NCCN Clinical Practice Guidelines in Oncology®: Gastric Cancer. V 3.2016. August 3. Available at
Last Updated on 01-Jun-2017