The announcement that Angelia Jolie has undergone a double mastectomy to reduce her chances of developing breast cancer has many people wondering what BRCA1 is and how it relates to breast cancer.
It is important to realize that technically, BRCA1 (breast cancer susceptibility gene 1 - sometimes also called breast cancer predisposition gene 1), is not a cancer gene. Often in human genetics, genes are named for what happens when something, such as mutation, causes the gene to malfunction. They do not always indicate the true function of the gene in the body. Such is the case with BRCA1.
BRCA1 belongs to a class of genes called tumor-supressor genes. Tumor-supressor genes are involved in regulating how fast a cell divides. Normally, cell division involves a orderly series of events commonly called the cell cycle (see below).
So lets take a quick look at what is happening in this diagram. The cell cycle represents the life cycle of a cell. After cell division, cells are in the the first growth phase (G1) of the cell cycle. In order to divide again, cells need to progress through a phase where its DNA is replicated (S), then a second period of growth (G2). When these are complete, the cell can proceed into nuclear division (mitosis) and division of the cyoplasm (cytokinesis). The rate at which a cell can move through these phases and divide is based on a number of factors, including the presence of checkpoints (red lines in the diagram below). Checkpoints are not physical locations, but rather times within the cell cycle when special proteins monitor the condition of the cell.
The tumor-suppressor genes, such as BRCA1, are responsible for producing one set of these control proteins. BRCA1 is a gene whose protein is active in the tissues of the breast (and other tissues). The role of the proteins produce by BRCA1 is to monitor the condition of the DNA in the cell, mostly at the G1/S boundary. If the DNA is damaged, or mutated, then the cell is prevented from proceeding into the next phase of the cell cycle. However, if the BRCA1 gene itself is mutated, then the cell can proceed in the cell cycle even if it has damage to the DNA. If this damage causes the cell to develop cancer-like characteristics, then the constant division of this cell may form a mass of cells called a tumor. This is why BRCA1 is called a tumor-suppressor gene – it slows the rate of division and suppresses the formation of tumors. But note that its function is to check the DNA damage of all cells in the body, and slow the process of cell division.
So, the BRCA1 gene does not actually cause cancer, if it is defective allows cells that contain cancer-causing genes to divide rapidly. In other words, tumor-suppressor genes act like the breaks on a car. They slow how fast the cell moves through the cell cycle, and therefore divides. There are other genes, called proto-oncogenes, that act like gas pedals, they allow the cell to move more quickly through the cell cycle.
Normally, each cell of our body has two copies of BRCA1. One copy you inherited from mom, the other from dad. Only one copy needs to remain operational to keep control of the cell cycle. If a person inherits a defective copy of BRCA1, then they still have one good copy. In fact, almost 1 in 800 individuals have a defective copy of BRCA1. These individuals are susceptible to cancer, including breast cancer, because any mutation that causes the loss of the second BRCA1 gene would result in complete loss of control of the cell cycle – a characteristic of a cancer cell.
It is possible to use genetic testing to determine if you carry a defective BRCA1 gene, and thus a susceptibility for breast cancer. This appears to be the case for Angelia Jolie. She did not have breast cancer, but her family has a history of breast cancer, and a genetic test indicated the presence of a mutated BRCA1. This news that a celebrity such as Angelina has undergone a genetic test is going to lead to increase awareness that these tests exist. It is important to recognize that genetic testing is not only expensive, but it is still a relatively new science. This excellent video from Vanderbilt Health outlines some aspects of genetic testing that women should be aware of. We have posted some additional links below.