CDH1 gene- Hereditary Diffuse Gastric Cancer

Hereditary Diffuse Gastric Cancer (HDGC)

HDGC is a hereditary condition causing an increased risk for diffuse or signet ring gastric (stomach) cancer. This type of cancer gets into the stomach wall causing thickening of the wall (linitis plastica) without forming a mass or tumor.  HDGC is defined clinically as 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, regardless of age of onset. 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. The estimated cumulative risk of gastric cancer by age 80 years is 67% for men and 83% for women. Women also have between a 39-52% lifetime risk for lobular breast cancer. In addition there is an increase in colon cancers in the families with CDH1 mutations. CDH1 is the only gene known to be associated with hereditary diffuse gastric cancer and sequence analysis of the CDH1 gene is available on a clinical basis. Mutations in CDH1 account for approximately one-half of hereditary diffuse gastric cancers and 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.


Screening recommendations*

  1. Breast cancer screening: Annual mammogram and consider breast MRI with contrast starting at age 30.
  2. Breast cancer prevention: Risk reducing mastectomies may be considered based on family history of breast cancer.
  1. Stomach cancer screening: Endoscopy with multiple random biopsies.
  2. Stomach cancer prevention: Gastrectomy (removal of the stomach) is recommended between ages 18-40 for mutation carriers.

Resources

No Stomach for Cancer http://www.nostomachforcancer.org/gastric-cancer/hereditary-diffuse-gastric-cancer

Stanford Cancer Institute: Hereditary Diffuse Gastric Cancer Syndrome http://cancer.stanford.edu/patient_care/services/geneticCounseling/HDGC.html

American Society of Clinical Oncology  http://www.cancer.net/cancer-types/hereditary-diffuse-gastric-cancer

* 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.