The CDH1 gene provides instructions for how cells are organized, particularly in forming tissues and organs. It plays a role in maintaining the structure and integrity of cellular arrangements.
The Role of the CDH1 Gene
The CDH1 gene contains instructions for creating E-cadherin, a protein that functions like cellular “glue,” helping cells adhere to form organized tissues. E-cadherin is found in the membrane surrounding epithelial cells, which line the body’s surfaces and cavities. Beyond its adhesive role, E-cadherin also participates in cell signaling. Because it helps regulate cell growth and prevents cells from detaching, the CDH1 gene is classified as a tumor suppressor gene. Its normal function helps control cell division and prevent uncontrolled cell proliferation.
CDH1 Gene Mutations and Associated Cancers
A mutation in the CDH1 gene means the E-cadherin protein does not function correctly. This compromises the cellular “glue,” allowing cells to grow abnormally and potentially spread. This loss of function contributes to rapid cell growth and the ability of cells to invade tissues.
The primary cancer linked to this mutation is Hereditary Diffuse Gastric Cancer (HDGC). In diffuse gastric cancer, abnormal cells spread throughout the stomach lining rather than forming a single tumor, making early detection challenging. Men with a CDH1 mutation have a lifetime risk of diffuse gastric cancer ranging from 40% to 70%, while women have a risk between 30% and 56%. The average age of diagnosis is around 38 years.
Women with a CDH1 mutation also face an increased risk of lobular breast cancer, with lifetime risks between 23% and 68%. This breast cancer can also be difficult to detect early due to its diffuse growth pattern. Other cancer risks associated with CDH1 mutations include colorectal, thyroid, ovarian, endometrial, and prostate cancers.
Genetic Testing and Carrier Identification
Discovering a CDH1 mutation involves genetic testing. This testing should be considered based on clinical guidelines based on personal and family history.
Criteria for testing include:
A personal diagnosis of diffuse gastric cancer at any age (especially before 50).
A family history of two or more cases of diffuse gastric cancer.
A personal or family history of both diffuse gastric cancer and lobular breast cancer.
Bilateral lobular breast cancer before age 70.
Two cases of lobular breast cancer in close family members before age 50.
A positive result means the individual carries the gene change and increased cancer risk. Genetic counseling is an important step before and after testing, providing information about the results, risks, and implications for family members.
Medical Management for Mutation Carriers
Individuals identified as carriers of a CDH1 mutation benefit from medical management strategies to reduce cancer risks. These strategies are tailored to gastric and breast cancer risks. A multidisciplinary team, including surgeons, gastroenterologists, and genetic counselors, guides these decisions.
For gastric cancer, two management paths exist. One option involves heightened surveillance through frequent upper endoscopies with extensive random biopsies. This approach attempts to detect early signs of cancer, though diffuse gastric cancer is challenging to identify early due to its infiltrative growth pattern. Risk-reducing total gastrectomy, the surgical removal of the entire stomach, is recommended. This procedure is considered between the ages of 20 and 30 years for individuals with a strong family history of HDGC.
For women with a CDH1 mutation, breast cancer management focuses on increased surveillance. This includes annual mammograms and breast MRIs. These imaging techniques help monitor for lobular breast cancer, which can also be difficult to detect early. Risk-reducing (prophylactic) mastectomy can also be discussed. It may be considered, especially with a strong family history of breast cancer.