BRCA2

The BRCA2 gene belongs to a class of genes known as tumor suppressor genes. Like many other tumor suppressors, the protein produced from the BRCA2 gene helps prevent cells from growing and dividing too rapidly or in an uncontrolled way.

The BRCA2 gene provides instructions for making a protein that is directly involved in the repair of damaged DNA. In the nucleus of many types of normal cells, the BRCA2 protein interacts with several other proteins, including the proteins produced from the RAD51 and PALB2 genes, to mend breaks in DNA. These breaks can be caused by natural and medical radiation or other environmental exposures, and also occur when chromosomes exchange genetic material in preparation for cell division. By helping repair DNA, BRCA2 plays a role in maintaining the stability of a cell's genetic information.

Researchers suspect that the BRCA2 protein may have additional functions within cells. For example, the protein may help regulate cytokinesis, which is the step in cell division when the fluid surrounding the nucleus (the cytoplasm) divides to form two separate cells. Researchers are investigating the protein's other potential activities.

breast cancer - increased risk from variations of the BRCA2 gene

Researchers have identified more than 800 mutations in the BRCA2 gene, many of which are associated with an increased risk of breast cancer. Many BRCA2 mutations insert or delete a small number of DNA building blocks (nucleotides) in the gene. Most of these genetic changes disrupt protein production from one copy of the gene in each cell, resulting in an abnormally small, nonfunctional version of the BRCA2 protein. Researchers believe that the defective BRCA2 protein is unable to help repair damaged DNA or fix mutations that occur in other genes. As these defects accumulate, they can allow cells to grow and divide uncontrollably and form a tumor.

other disorders - caused by mutations in the BRCA2 gene

A condition known as Fanconi anemia type D1 (FA-D1) results when two faulty copies of the BRCA2 gene are present in each cell. These mutations reduce the amount of the BRCA2 protein to very low levels. Without enough of this protein, breaks in DNA are not repaired normally and genetic damage can accumulate. As a result, people with Fanconi anemia are prone to several types of cancer, including cancers of blood-forming tissue (leukemias). They are also at an increased risk of developing solid tumors, particularly of the head, neck, skin, and reproductive organs. Additionally, people with Fanconi anemia experience bone marrow suppression, which causes an abnormal reduction in the number of red blood cells, white blood cells, and blood platelets made by the bone marrow. The reduced production of red blood cells causes the anemia characteristic of this disorder.

other cancers - increased risk from variations of the BRCA2 gene

In addition to female breast cancer, mutations in one copy of the BRCA2 gene can lead to an increased risk of ovarian cancer, prostate cancer, pancreatic cancer, fallopian tube cancer, male breast cancer, and an aggressive form of skin cancer called melanoma. Mutations in the central part of the gene have been associated with a higher risk of ovarian cancer and a lower risk of prostate cancer than mutations in other parts of the gene.