CDH1 Gene Mutations
Hereditary Diffuse Gastric Cancer Syndrome (HDGC)
What does it mean to have a CDH1 gene mutation and a diagnosis of Hereditary Diffuse Gastric Cancer syndrome (HDGC)?
People with mutations in the CDH1 gene have a condition called Hereditary Diffuse Gastric Cancer syndrome, or HDGC. Men and women with HDGC have a high risk for stomach cancer. Women also have a high risk for breast cancer. These cancers can occur at young ages.
People with HDGC often get a kind of stomach cancer called “diffuse gastric cancer.” This type of stomach cancer is hard to find at early stages, because it does not form a noticeable tumor that can be easily seen with screening. For this reason, it is sometimes recommended that people with HDGC have their stomach removed before cancer can form. This may be the best choice for someone who has a CDH1 gene mutation and has one or more close relatives who have had stomach cancer in the past.
Women with HDGC have a high risk for a type of breast cancer that forms in the lobules of the breast. This is different than the more common type of breast cancer that starts in the milk ducts. It is recommended that women with CDH1 mutations start their breast screening at age 35 or earlier if they have relatives who had breast cancer at younger ages. It is also recommended that this screening include MRIs in addition to mammograms.
What can be done to protect people with HDGC from cancer?
Because people with HDGC have a high risk for the diffuse type of stomach cancer, screening may start in the teenage years. Stomach cancer screening is usually done by endoscopy, which involves putting a tube down the throat with a light and a camera so that doctors can look at the inside of the stomach for signs of cancer. However, the diffuse type of stomach cancer that occurs in people with HDGC is hard to see in this way, so it is recommended that the screening also include taking small tissue samples (biopsies) from the stomach to be examined under the microscope for signs of cancer.
Studies have shown that many stomach cancers are still missed, even with screening. For this reason, it is usually recommended that the stomach be removed completely as people with HDGC get older. Removing the stomach is a serious operation, but studies have shown that people can live long and healthy lives after the procedure.
Finally, there is concern that people with HDGC might have a higher than average risk for colon cancer. For this reason, it is recommended that people with HDGC start having colonoscopies at young ages.
We are still learning about CDH1 mutations and HDGC. Anyone who knows that they have a CDH1 gene mutation can benefit from being under the care of doctors and other health professionals who are knowledgeable about HDGC so that they can take steps to prevent cancer or find it as early as possible as well as have access to the most up-to-date information on HDGC and associated cancer risks.
Associated Syndrome Name: Hereditary Diffuse Gastric Cancer (HDGC) Syndrome
CDH1 Summary Cancer Risk Table
|Cancer||Genetic Cancer Risk|
|Female Breast||High Risk|
CDH1 gene Overview
- 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
|Cancer Type||Age Range||Cancer Risk||Risk for General Population *|
|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.
|Cancer Type||Procedure||Age to Begin||Frequency|
|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
- Kaurah P, Huntsman DG. Hereditary Diffuse Gastric Cancer. 2014 Jul 31. In: Pagon RA, et al., editors. GeneReviews® [Internet]. Available from http://www.ncbi.nlm.nih.gov/books/NBK1139/ PMID: 20301318.
- 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.
- 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.
- 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.
- 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.
- Surveillance Research Program, National Cancer Institute SEER*Stat software (seer.cancer.gov/seerstat) V 8.0.1, Nov 19, 2012.
- 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 http://www.nccn.org.
- Ajani JA, et al. NCCN Clinical Practice Guidelines in Oncology®: Gastric Cancer. V 3.2016. August 3. Available at http://www.nccn.org.