CDH1 gene

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

CDH1 Summary Cancer Risk Table

Cancer Genetic Cancer Risk
BreastHigh Risk
GastricHigh Risk

CDH1 gene Overview

Hereditary Diffuse Gastric Cancer (HDGC) Syndrome 1, 2, 3, 4, 5, 6, 7
  • Individuals with mutations in CDH1 have 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.
  • There have been reports of an increased risk for colorectal cancer in patients with HDGC, but recent studies have not shown an increased risk. Currently, most experts in HDGC do not provide any recommendations for medical management of colorectal cancer risk.
  • 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 summarized below. These groups differ in the details of their recommendations, including whether gastrectomy or screening is the best choice for some patients. Due to the complexity of this condition, it is recommended that patients with CDH1 mutations 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 802, 6, 7, 867%-70%0.6%
Gastric (female)To age 802, 6, 7, 856%-83%0.6%
Female BreastTo age 507, 810%2.0%
To age 802, 6, 7, 839%-52%10.6%

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)
GastricGastrectomy, after baseline endoscopy1, 418 to 40 yearsNA
Surveillance with endoscopies including targeted and random biopsies is recommended for patients delaying or declining gastrectomy, and may be appropriate for those with no family history of diffuse gastric cancer1, 4IndividualizedEvery 6 to 12 months
Treat Helicobacter pylori infection if present1IndividualizedNA
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.1, 918 yearsNA
Clinical breast examination1, 925 yearsAnnually
Annual mammogram with consideration of tomosynthesis1, 530 to 40 yearsAnnually
Consider breast MRI with contrast1, 530 yearsAnnually
Consider risk-reducing mastectomy.1, 5Between 30 and 60 yearsNA

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.

This patient's relatives are at risk for carrying the same mutation(s) and associated cancer risks as this patient. Cancer risks for females and males who have this/these mutation(s) are provided below.

Family members should talk to a healthcare provider about genetic testing. Close relatives such as parents, children, brothers and sisters have the highest chance of having the same mutation(s) as this patient. Other more distant relatives such as cousins, aunts, uncles, and grandparents also have a chance of carrying the same mutation(s). Testing of at-risk relatives can identify those family members with the same mutation(s) who may benefit from surveillance and early intervention.

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.3, 10, 11

Parents who are concerned about the possibility of passing on a CDH1 mutation to a future child may want to discuss options for prenatal testing and assisted reproduction techniques, such as pre-implantation genetic diagnosis (PGD).1


  1. Blair VR, et al. Hereditary diffuse gastric cancer: updated clinical practice guidelines. Lancet Oncol. 2020 21:e386-e397. PMID: 32758476.
  2. Hansford S, et al. Hereditary Diffuse Gastric Cancer Syndrome: CDH1 Mutations and Beyond. JAMA Oncol. 2015 1:23-32. PMID: 26182300.
  3. 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.
  4. Ajani JA, et al. NCCN Clinical Practice Guidelines in Oncology®: Gastric Cancer. V 4.2021. Aug 3. Available at
  5. Daly M et al. NCCN Clinical Practice Guidelines in Oncology®: Genetic/Familial High-Risk Assessment: Breast, Ovarian and Pancreatic. V 1.2022. Aug 11. Available at
  6. Kaurah P, Huntsman DG. Hereditary Diffuse Gastric Cancer. 2018 Mar 22. In: Pagon RA, et al., editors. GeneReviews® [Internet]. Available from PMID: 20301318.
  7. 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.
  8. SEER*Explorer: An interactive website for SEER cancer statistics [Internet]. Surveillance Research Program, National Cancer Institute. [Cited 2020 Sep 14]. Available from
  9. Bevers TB, et al. NCCN Clinical Practice Guidelines in Oncology®: Breast Cancer Screening and Diagnosis. V 1.2021. May 6. Available at
  10. Figueiredo J, et al. Clinical spectrum and pleiotropic nature of CDH1 germline mutations. J Med Genet. 2019 56:199-208. PMID: 30661051.
  11. 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 29-Sep-2022