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Disease Profile

Hereditary diffuse gastric cancer

Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.


US Estimated

Europe Estimated

Age of onset






Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease.


Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype.


dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.


recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.


Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.


Not applicable


Other names (AKA)

HDGC; Gastric cancer, hereditary diffuse; Gastric cancer, familial diffuse;


Congenital and Genetic Diseases; Digestive Diseases; Hereditary Cancer Syndromes;


Hereditary diffuse gastric cancer (HDGC) leads to an increased risk (predisposition) of developing a specific form of stomach cancer called diffuse gastric cancer. Women with HDGC also have an increased risk for lobular breast cancer. Cancers associated with HDGC generally occur at earlier ages than those seen in people who do not have a hereditary predisposition to cancer. HDGC is caused by genetic variants in the CDH1 gene and the CTNNA1 gene. It is inherited in an autosomal dominant pattern. Diagnosis of HDGC is based on the symptoms, family history, and may be confirmed by the results of genetic testing. Treatment is focused on reducing the risk to develop cancer and includes increased screening for gastric cancer (endoscopy) and breast cancer in women (mammography). In some cases, surgery is done to remove the stomach before cancer develops (prophylactic surgery).[1][2][3]


The following list includes the most common signs and symptoms in people with hereditary diffuse gastric cancer (HDGC). These features may be different from person to person. Some people may have more symptoms than others, and they can range from mild to severe. This list does not include every symptom that has been described in the condition.

Signs and symptoms may include:[1][3]

  • Personal history of diffuse gastric cancer
  • Family history of diffuse gastric cancer
  • Personal or family history of cleft lip/palate and diffuse gastric cancer
  • Personal or family history of lobular breast cancer

People with HDGC have an increased risk of developing gastric cancer compared to people without HDGC. The average age at diagnosis is in the late 30s or early 40s. Symptoms of gastric cancer can be difficult to recognize until it's in the advanced stages. These may include abdominal pain, nausea, and loss of appetite.[1]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
Percent of people who have these symptoms is not available through HPO
Autosomal dominant inheritance
Chronic atrophic gastritis
Stomach cancer


Hereditary diffuse gastric cancer (HDGC) occurs when the CDH1 or the CTNNA1 gene is not working correctly. DNA changes known as pathogenic variants are responsible for making genes work incorrectly or sometimes, not at all.[2][3]


Diagnosis of hereditary diffuse gastric cancer (HDGC) is based on the symptoms, the family history, and the features of the cancer cells when viewed under the microscope. The diagnosis may be confirmed by the results of genetic testing.[1][3]

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.


    Treatment for hereditary diffuse gastric cancer (HDGC) is focused on frequent screening for gastric and breast cancer. Screening involves imaging studies such as endoscopy and mammography. In some cases, surgery is done to remove the stomach before cancer develops (prophylactic surgery).[2][3]

    Specialists involved in the care of someone with HDGC may include:

    • Oncologist
    • Medical geneticist
    • Gastroenterologist
    • Surgeon
    • Nutritionist

    FDA-Approved Treatments

    The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition. Learn more orphan products.


    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Social Networking Websites

        Organizations Providing General Support

          Learn more

          These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

          Where to Start

          • Cancer.net provides oncologist-approved cancer information from the American Society of Clinical Oncology and has information about Hereditary diffuse gastric cancer.
          • Genetics Home Reference (GHR) contains information on Hereditary diffuse gastric cancer. This website is maintained by the National Library of Medicine.

            In-Depth Information

            • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
            • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
            • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
            • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
            • PubMed is a searchable database of medical literature and lists journal articles that discuss Hereditary diffuse gastric cancer. Click on the link to view a sample search on this topic.


              1. Kaurah P, Huntsman DG. Hereditary Diffuse Gastric Cancer. GeneReviews. Updated Mar, 2018; https://www.ncbi.nlm.nih.gov/books/NBK1139/.
              2. van der Post RS, Oliveira C, Guilford P, Carneiro F. Hereditary gastric cancer: what's new? Update 2013-2018. Fam Cancer. Jul 2019; 18(3):363-367. https://pubmed.ncbi.nlm.nih.gov/30989426/.
              3. Blair VR, McLeod M, Carneiro F, Coit DG, D'Addario JL, van Dieren JM, et al. Hereditary diffuse gastric cancer: updated clinical practice guidelines. Lancet Oncol. Aug 2020; 21(8):e386-e397.. https://pubmed.ncbi.nlm.nih.gov/32758476/.
              4. Shenoy S.. CDH1 (E-Cadherin) Mutation and Gastric Cancer: Genetics, Molecular Mechanisms and Guidelines for Management.. Cancer Manag Res. Dec 13, 2019; 11:10477-10486. https://pubmed.ncbi.nlm.nih.gov/31853199/.

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