Hereditary Diffuse Gastric Cancer

Inherited syndromes cause an estimated 1-3% of cases of stomach cancer. Hereditary Diffuse Gastric Cancer (HDGC) is an inherited cancer syndrome that increases the risk of both diffuse gastric and lobular breast cancer. Patients who inherit the genetic mutation for HDGC are at high risk of developing stomach cancer at a young age.

History of Hereditary Diffuse Gastric Cancer

Walk Photo AfAmer family

In 1964, stomach cancer was noted in a Maori tribal family in New Zealand, following an autosomal dominant pattern of inheritance. CDH1 gene mutations were first described in patients from three Maori families in 1998. The International Gastric Cancer Linkage Consortium (IGCLC) was formed, and the name “Hereditary Diffuse Gastric Cancer” was introduced. Families with multiple cases of diffuse gastric cancer, lobular breast cancer, or both may be affected by hereditary diffuse gastric cancer syndrome.

Diffuse Gastric Cancer

HDGC leads to cancer called diffuse-type, signet ring cell gastric adenocarcinoma. These signet ring cells appear as isolated cells or in small clusters in the stomach lining. Unfortunately, the diffuse type of gastric cancer associated with HDGC is challenging to diagnose because the tumor is not visible on upper endoscopy (looking into the stomach with a tiny camera). For this reason, most cases of diffuse gastric cancer are diagnosed at late stages (III or IV) and are associated with a lower survival rate.

In 2023, No Stomach For Cancer partnered with the NIH and NCI to create a library of comprehensive guidelines for patients and families who carry the CDH1 gene mutation. Each in-depth resource is viewable online and available as a PDF to share and print. We also have printed booklets containing all the patient guides for shipping to your home, clinic, or practice.

National Cancer Institute Patient Resources for Hereditary Diffuse Gastric Cancer

National Library of Medicine Genetics Home Reference for HDGC

Hereditary Diffuse Gastric Cancer Syndrome and the Role of CDH1 – A Review (2021)

Lobular Breast Cancer

Oncologists or breast surgeons should follow women from HDGC families and have clinical breast exams regularly performed on those who are CDH1 positive. Screening with yearly breast MRI and mammograms is recommended starting at age 30. There is a possible role for preventive hormone-blocking medications to reduce lobular breast cancer risk in CDH1 mutation carriers. If there are many breast cancer cases in the family, prophylactic mastectomy may also be considered, but mastectomy is not routinely recommended.

Future of HDGC Research and Treatment

Research on the genetics, diagnosis, and treatment of HDGC is ongoing. Centers of Excellence have been established worldwide, and experts from the International Gastric Cancer Linkage Consortium continue to work together to develop new guidelines and recommendations for patients and families affected by HDGC. The next IGCLC HDGC Guidelines Meeting to discuss updates to the guidelines will take place June 13-15, 2024, in Porto, Portugal. You can contact Dr. Parry Guilford at the University of Otago to inquire about attending.

The Save Our Stomachs campaign has been created and driven by the Save Our Stomachs (SOS) Advocacy Group, also called Parry’s Angels. NSFC has chosen to support this vital campaign with a $250,000 grant and by helping spread the word and encouraging others to support this critical and worthy campaign. For questions or more information about the campaign, you may visit

Clinical Guidelines for Hereditary Stomach Cancer Syndromes

The American College of Gastroenterology Clinical Guideline: Genetic Testing and Management of Hereditary Gastrointestinal Cancer Syndromes.

Hereditary Diffuse Gastric Cancer: Updated clinical guidelines with an emphasis on germline CDH1 mutation carriers.

Other Inherited Cancer Syndromes

Establishing a Center of Excellence for hereditary diffuse gastric cancer syndrome

Published January 3, 2019, in the Journal of Surgical Oncology. You may request access to the article from one of the co-authors, Dr. Jeremy Davis.

Medical Centers for the treatment and care of Hereditary Diffuse Gastric Cancer

Clinical Trials and Research Studies for Hereditary Stomach Cancer

Researchers at the National Institutes of Health (NIH) seek individuals with hereditary stomach (gastric) cancer or who are at risk for developing stomach cancer because of a genetic (inherited) condition. Hereditary stomach cancers run in families, meaning they are passed down from one generation to the next.

View and download more information on this study.

Researchers at Penn University seek individuals with a CTNNA1 gene variant and should be referred to the CTNNA1 Familial Expansion Study (CAFÉ) research study as they need better risk estimates.

Click here for more information on this study.

Ford JM. Inherited susceptibility to gastric cancer: advances in genetics and guidelines for clinical management. American Society of Clinical Oncology Educational Sessions. 2002:116-125.

Huntsman DG, Carneiro F, Lewis FR, MacLeod PM, Hayashi A, Monaghan KG, et al. Early gastric cancer in young, asymptomatic carriers of germline E-cadherin mutations. The New England Journal of Medicine. June 2001;344(25):1904-1909.

Francis WP, Rodrigues DM, Perez NE, Lonardo F, Weaver D, Webber JD. Prophylactic laparoscopic-assisted total gastrectomy for hereditary diffuse gastric cancer. Journal of the Society of Laparoendoscopic Surgeons. 2007;11:142-147.

Caldas C, Carneiro F, Lynch HT, Yokota J, Wiesner GL, et al. Familial gastric cancer: overview and management guidelines. Journal of Medical Genetics. 1999;36:873-880.