Hereditary Diffuse Gastric Cancer (HDGC) is a hereditary condition causing an increased risk for diffuse gastric (stomach) cancer and lobular breast cancer. Diffuse gastric cancer is sometimes called signet ring gastric cancer. This type of cancer gets into the stomach wall, causing thickening of the wall without forming a mass or tumor. CDH1 is the only gene known to be associated with hereditary diffuse gastric cancer. 30-50% of HDGC is caused by mutations in the CDH1 gene.
The lifetime risk for gastric cancer in a person with HDGC is approximately 67% for men and 83% for women. The average age of onset of hereditary diffuse gastric cancer is 38 years, with a range of 14-69 years. The majority of the cancers in individuals with CDH1 mutations occur before the age of 40 years. Women also have between a 39-52% lifetime risk for lobular breast cancer. In addition there may be an increase in colon cancers in the families with CDH1 mutations.
A family can be diagnosed with HDGC either based on their family history or by a genetic test. A diagnosis of HDGC via family history would include the presence of two or more documented cases of diffuse gastric cancer in first- or second-degree relatives with at least one case diagnosed prior to age 50 years OR three or more documented cases of diffuse gastric cancer in first- or second-degree relatives, at any age. Mutations in CDH1 are inherited in an autosomal dominant manner, meaning each first degree relative (parent, child, and sibling) of an individual with this condition has a 50% chance of inheriting the disease causing mutation.
- Breast cancer screening: Annual mammogram and consider breast MRI with contrast starting at age 30.
- Breast cancer prevention: Risk reducing mastectomies may be considered based on family history of breast cancer.
- Stomach cancer screening: Endoscopy with multiple random biopsies.
- Stomach cancer prevention: Gastrectomy (removal of the stomach) is recommended between ages 18-40 for mutation carriers.
- No Stomach for Cancer
- Stanford Cancer Institute: Hereditary Diffuse Gastric Cancer Syndrome
- American Society of Clinical Oncology
Screening recommendations based on National Comprehensive Cancer Network Guidelines Version 1.2017 Genetic/Familial High Risk Assesment: Breast and Ovarian Cancer and National Comprehensive Cancer Network Guidelines Version 3.2016 Gastric Cancer.