Hereditary diffuse gastric cancer


Hereditary diffuse gastric cancer

HDGC causes signet-ring shaped cells to form in the lining of the stomach. These abnormal cells can grow either one by one or in small clusters (a formation known as diffuse). The diffuse type of stomach cancer associated with HDGC is difficult to diagnose because the cancer is not visible on upper endoscopy. For this reason, most cases of diffuse stomach cancer are diagnosed at late stages.

Identification of family members

People from families that carry the HDGC gene are at an increased risk of developing diffuse-type stomach cancer. The lifetime risk of developing stomach cancer is about 80%. Females who have the gene are also at an estimated 60% lifetime risk of developing lobular breast cancer.

Stomach Cancer CDH1 Screening

Patients from families with the HDGC gene, as well as patients diagnosed with diffuse stomach cancer before age 40, are referred for genetic counseling and testing for CDH1 gene mutations and should also be followed by a medical team. 

The current screening recommendations are upper endoscopy with biopsies each year. Because hereditary diffuse stomach cancer is nearly impossible to detect at an early stage, however, the recommended procedure to prevent stomach cancer is a total gastrectomy, or complete removal of the stomach. Although this procedure is complicated and commonly leads to weight loss, diarrhea, altered eating habits and vitamin deficiency, it is possibly the only method to prevent stomach cancer. 


HDGC is an inherited genetic condition that is rare. This means that the cancer risk and other features of HDGC can be passed from generation to generation in a family. The gene most commonly associated with HDGC is called CDH1. A mutation (alteration) in the CDH1 gene gives a person an increased risk of developing gastric cancer and other cancers associated with HDGC. Researchers believe that other genes, including CTNNA1, may be associated with HDGC. Studies are ongoing to learn more about all of these genes, and testing for inherited genetic mutations in these newer genes is currently not recommended except in clinical trials.


Families with 2 or more cases of stomach cancer, with at least 1 being diffuse gastric cancer

A person diagnosed with diffuse gastric cancer before age 40

Personal or family history of both diffuse gastric cancer and lobular breast cancer, if at least 1 person was diagnosed before age 50

Families with 2 or more cases of lobular breast cancer diagnosed before age 50

A person diagnosed with multiple different lobular breast cancers before age 50

A person with diffuse gastric cancer and a personal or family history of a cleft lip or cleft palate


Not everyone who inherits a gene mutation for HDGC will develop cancer. In people who have a mutation in the CDH1 gene, the lifetime risk for diffuse gastric cancer is estimated to be 67% to 70% for men and 56% to 83% for women by age 80. Women with a mutation in the CDH1 gene have about a 39% to 52% risk of developing lobular breast cancer by age 80. Although some earlier studies suggested a possible link to risks of colon and/or rectal cancer, the current findings suggest that there is likely no increased risk for these cancers in people with an inherited CDH1 mutation.