CDH1

The CDH1 gene provides instructions for making a protein called epithelial cadherin or E-cadherin. Cadherins are a group of proteins on the surface of cells that help neighboring cells stick to one another (cell adhesion). These proteins bind cells together to form organized tissues.

E-cadherin is one of the best-understood cadherin proteins. In addition to its role in cell adhesion, E-cadherin is involved in transmitting chemical signals within cells, controlling cell movement, and regulating the activity of certain genes. Researchers believe that E-cadherin also acts as a tumor suppressor gene, preventing cells from growing and dividing in an uncontrolled way to form a cancerous tumor. Because this protein helps cells stick together, it may keep cancer cells from detaching from a tumor, traveling through the bloodstream, and invading other tissues (metastasizing).

breast cancer - increased risk from variations of the CDH1 gene

Inherited mutations in the CDH1 gene increase a woman's risk of developing a form of breast cancer that begins in the milk-producing glands (lobular breast cancer). In many cases, this increased risk occurs as part of a cancer syndrome called hereditary diffuse gastric cancer (HDGC). This condition is characterized by a very high risk of developing cancer of the stomach lining as well as an increased risk of lobular breast cancer.

Some gene mutations are acquired during a person's lifetime and are present only in certain cells. These changes, which are called somatic mutations, are not inherited. Studies have shown that somatic CDH1 mutations occur commonly in cases of lobular breast cancer in women without a family history of the disease. Some of these genetic changes occur within the gene itself, while others inactivate a region of nearby DNA that controls the gene's activity. Researchers believe that the resulting loss of E-cadherin may allow cells to grow and divide unchecked. A lack of this protein, which is critical for cell adhesion, may also make it easier for cancer cells to detach from a primary tumor and metastasize to other parts of the body.

other cancers - increased risk from variations of the CDH1 gene

More than 50 mutations in the CDH1 gene have been identified in people with an inherited cancer syndrome called hereditary diffuse gastric cancer. This disorder greatly increases the chance of developing cancer of the stomach lining, most often in a person's late thirties or early forties. This disorder also increases the risk of other forms of cancer, particularly lobular breast cancer in women. Most inherited CDH1 mutations lead to the production of an abnormally short, nonfunctional version of the E-cadherin protein. Researchers have not yet determined why a loss of E-cadherin is more likely to be associated with stomach cancer and lobular breast cancer than other types of tumors.