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Genetics Home Reference: your guide to understanding genetic conditions     A service of the U.S. National Library of Medicine®

Hereditary diffuse gastric cancer

Reviewed January 2014

What is hereditary diffuse gastric cancer?

Hereditary diffuse gastric cancer (HDGC) is an inherited disorder that greatly increases the chance of developing a form of stomach (gastric) cancer. In this form, known as diffuse gastric cancer, there is no solid tumor. Instead cancerous (malignant) cells multiply underneath the stomach lining, making the lining thick and rigid. The invasive nature of this type of cancer makes it highly likely that these cancer cells will spread (metastasize) to other tissues, such as the liver or nearby bones.

Symptoms of diffuse gastric cancer occur late in the disease and can include stomach pain, nausea, vomiting, difficulty swallowing (dysphagia), decreased appetite, and weight loss. If the cancer metastasizes to other tissues, it may lead to an enlarged liver, yellowing of the eyes and skin (jaundice), an abnormal buildup of fluid in the abdominal cavity (ascites), firm lumps under the skin, or broken bones.

In HDGC, gastric cancer usually occurs in a person's late thirties or early forties, although it can develop anytime during adulthood. If diffuse gastric cancer is detected early, the survival rate is high; however, because this type of cancer is hidden underneath the stomach lining, it is usually not diagnosed until the cancer has become widely invasive. At that stage of the disease, the survival rate is approximately 20 percent.

Some people with HDGC have an increased risk of developing other types of cancer, such as a form of breast cancer in women that begins in the milk-producing glands (lobular breast cancer); prostate cancer; and cancers of the colon (large intestine) and rectum, which are collectively referred to as colorectal cancer. Most people with HDGC have family members who have had one of the types of cancer associated with HDGC. In some families, all the affected members have diffuse gastric cancer. In other families, some affected members have diffuse gastric cancer and others have another associated form of cancer, such as lobular breast cancer. Frequently, HDGC-related cancers develop in individuals before the age of 50.

How common is hereditary diffuse gastric cancer?

Gastric cancer is the fourth most common form of cancer worldwide, affecting 900,000 people per year. HDGC probably accounts for less than 1 percent of these cases.

What genes are related to hereditary diffuse gastric cancer?

It is likely that 30 to 40 percent of individuals with HDGC have a mutation in the CDH1 gene. The CDH1 gene provides instructions for making a protein called epithelial cadherin or E-cadherin. This protein is found within the membrane that surrounds epithelial cells, which are the cells that line the surfaces and cavities of the body. E-cadherin helps neighboring cells stick to one another (cell adhesion) to form organized tissues. E-cadherin has many other functions including acting as a tumor suppressor protein, which means it prevents cells from growing and dividing too rapidly or in an uncontrolled way.

People with HDGC caused by CDH1 gene mutations are born with one mutated copy of the gene in each cell. These mutations cause the production of an abnormally short, nonfunctional version of E-cadherin or alter the protein's structure. For diffuse gastric cancer to develop, a second mutation involving the other copy of the CDH1 gene must occur in the cells of the stomach lining during a person's lifetime. People who are born with one mutated copy of the CDH1 gene have a 80 percent chance of acquiring a second mutation in the other copy of the gene and developing gastric cancer in their lifetimes.

When both copies of the CDH1 gene are mutated in a particular cell, that cell cannot produce any functional E-cadherin. The loss of this protein prevents it from acting as a tumor suppressor, contributing to the uncontrollable growth and division of cells. A lack of E-cadherin also impairs cell adhesion, increasing the likelihood that cancer cells will not come together to form a tumor but will invade the stomach wall and metastasize as small clusters of cancer cells into nearby tissues.

These CDH1 gene mutations also lead to a 40 to 50 percent chance of lobular breast cancer in women, a slightly increased risk of prostate cancer in men, and a slightly increased risk of colorectal cancer. It is unclear why CDH1 gene mutations primarily occur in the stomach lining and these other tissues.

About 60 to 70 percent of individuals with HDGC do not have an identified mutation in the CDH1 gene. The cancer-causing mechanism in these individuals is unknown.

Related Gene(s)

Changes in this gene are associated with hereditary diffuse gastric cancer.

  • CDH1

How do people inherit hereditary diffuse gastric cancer?

HDGC is inherited in an autosomal dominant pattern, which means one copy of the altered CDH1 gene in each cell is sufficient to increase the risk of developing cancer.

In most cases, an affected person has one parent with the condition.

Where can I find information about diagnosis or management of hereditary diffuse gastric cancer?

These resources address the diagnosis or management of hereditary diffuse gastric cancer and may include treatment providers.

  • American Cancer Society: How is Stomach Cancer Diagnosed? (
  • Gene Review: Hereditary Diffuse Gastric Cancer (
  • Genetic Testing Registry: Hereditary diffuse gastric cancer (
  • MedlinePlus Encyclopedia: Gastric Cancer (
  • Memorial Sloan-Kettering Cancer Center: Early Onset and Familial Gastric Cancer Registry (
  • National Cancer Institute: Gastric Cancer Treatment Option Overview (

You might also find information on the diagnosis or management of hereditary diffuse gastric cancer in Educational resources and Patient support.

General information about the diagnosis ( and management ( of genetic conditions is available in the Handbook. Read more about genetic testing (, particularly the difference between clinical tests and research tests (

To locate a healthcare provider, see How can I find a genetics professional in my area? ( in the Handbook.

Where can I find additional information about hereditary diffuse gastric cancer?

You may find the following resources about hereditary diffuse gastric cancer helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for hereditary diffuse gastric cancer?

  • E-cadherin-associated hereditary gastric cancer
  • familial diffuse gastric cancer
  • FDGC
  • HDGC
  • hereditary diffuse gastric adenocarcinoma

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines ( and How are genetic conditions and genes named? ( in the Handbook.

What if I still have specific questions about hereditary diffuse gastric cancer?

Ask the Genetic and Rare Diseases Information Center (

What glossary definitions help with understanding hereditary diffuse gastric cancer?

adenocarcinoma ; ascites ; autosomal ; autosomal dominant ; cancer ; carcinoma ; cell ; cell adhesion ; colon ; colorectal ; difficulty swallowing ; dysphagia ; epithelial ; familial ; gastric ; gene ; hereditary ; inherited ; intestine ; jaundice ; metastasize ; mutation ; prostate ; protein ; rectum ; stage ; stomach ; tumor

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.


  • Carneiro P, Fernandes MS, Figueiredo J, Caldeira J, Carvalho J, Pinheiro H, Leite M, Melo S, Oliveira P, Simões-Correia J, Oliveira MJ, Carneiro F, Figueiredo C, Paredes J, Oliveira C, Seruca R. E-cadherin dysfunction in gastric cancer--cellular consequences, clinical applications and open questions. FEBS Lett. 2012 Aug 31;586(18):2981-9. doi: 10.1016/j.febslet.2012.07.045. Epub 2012 Jul 25. Review. (
  • Figueiredo J, Söderberg O, Simões-Correia J, Grannas K, Suriano G, Seruca R. The importance of E-cadherin binding partners to evaluate the pathogenicity of E-cadherin missense mutations associated to HDGC. Eur J Hum Genet. 2013 Mar;21(3):301-9. doi: 10.1038/ejhg.2012.159. Epub 2012 Aug 1. (
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  • Kluijt I, Sijmons RH, Hoogerbrugge N, Plukker JT, de Jong D, van Krieken JH, van Hillegersberg R, Ligtenberg M, Bleiker E, Cats A; Dutch Working Group on Hereditary Gastric Cancer. Familial gastric cancer: guidelines for diagnosis, treatment and periodic surveillance. Fam Cancer. 2012 Sep;11(3):363-9. doi: 10.1007/s10689-012-9521-y. (
  • Oliveira C, Pinheiro H, Figueiredo J, Seruca R, Carneiro F. E-cadherin alterations in hereditary disorders with emphasis on hereditary diffuse gastric cancer. Prog Mol Biol Transl Sci. 2013;116:337-59. doi: 10.1016/B978-0-12-394311-8.00015-7. Review. (
  • Oliveira C, Seruca R, Hoogerbrugge N, Ligtenberg M, Carneiro F. Clinical utility gene card for: Hereditary diffuse gastric cancer (HDGC). Eur J Hum Genet. 2013 Aug;21(8). doi: 10.1038/ejhg.2012.247. Epub 2013 Feb 27. (
  • Simões-Correia J, Figueiredo J, Lopes R, Stricher F, Oliveira C, Serrano L, Seruca R. E-cadherin destabilization accounts for the pathogenicity of missense mutations in hereditary diffuse gastric cancer. PLoS One. 2012;7(3):e33783. doi: 10.1371/journal.pone.0033783. Epub 2012 Mar 21. (
  • Vogelaar IP, van der Post RS, Bisseling TM, van Krieken JH, Ligtenberg MJ, Hoogerbrugge N. Familial gastric cancer: detection of a hereditary cause helps to understand its etiology. Hered Cancer Clin Pract. 2012 Dec 12;10(1):18. doi: 10.1186/1897-4287-10-18. (


The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? ( in the Handbook.

Reviewed: January 2014
Published: February 1, 2016