The BRCA1 and BRCA2 genes were among the first cancer genes to be identified in the 1990’s. Alterations in these genes, otherwise known as mutations, increase the risk of breast, ovarian and prostate cancer (these mutations are also known to increase the risk of pancreatic cancer, melanoma and some other cancers, though all at a low level of risk). Whilst the majority of cases of these cancers occur without any identifiable underlying genetic cause, in the UK population, approximately 5-10% of all breast and 10-15% of all ovarian cancer cases are thought to be caused by inheritance of a BRCA mutation. Not all families with a strong history of breast, ovarian and prostate cancers have mutations in BRCA genes, as many other genes can also lead to an increased risk of these cancers.
People with mutations in a BRCA gene are often referred to as being BRCA positive, although the term BRCA carrier is also widely used. It is important to remember that someone who is BRCA positive will not definitely develop cancer, however they do have a greater risk of developing it at some point in their lives relative to the general population.
As we go through life, we accumulate damage to our DNA known as mutations. BRCA genes are responsible for repairing this damage. Usually a cell needs to develop multiple mutations before it becomes cancerous, but in most cases the BRCA1/2 proteins repair these faults as they occur, which prevents the development of cancer.
In people who are BRCA positive, the gene doesn’t function as it should. These people are therefore less able to repair DNA damage as it occurs and so are more likely to develop cancer at a younger age. For more information, see The Role of The BRCA Gene at the BRCA Alliance website.
BRCA genes are inherited in an autosomal dominant manner. This means that a person who has a mutation in either of the BRCA1 or BRCA2 genes has a 50% chance of passing on that mutation to each of their children. Men as well as women can be BRCA positive so a mutation can be passed from father to child as well as mother to child.
BRCA genes, though dominant, have incomplete penetrance . This means that someone that is BRCA positive is more likely, but not guaranteed, to develop cancer relative to someone in the general population.
Approximately 1 in 300-400 people in the UK have a mutation in their BRCA1 or BRCA2 genes. Certain people, however, are at greater risk of having BRCA mutations than others. Individuals with several close blood relatives (e.g. sister, mother, grandmother, aunt) affected with breast or ovarian cancers, and where the diagnoses of cancer occurred before the age of 50, are at greater risk.
Individuals of Ashkenazi Jewish origin are also at greater risk than the general population. It is estimated that 1 in 40 people of Ashkenazi Jewish ancestry have a mutation in a BRCA gene (see section on BRCA and Ashkenazi Jews).
If you have a blood relative with a known mutation in a BRCA gene and would like to understand more about your risk, talk to your GP about your family’s cancer history. If appropriate, they will refer you to your regional genetics clinic where a genetic counsellor will provide you with support and information and will discuss with you whether genetic testing is an appropriate option. This will be dependent on how closely related you are to the family members with known BRCA mutations and whether any of your family members have been affected by cancer.
Being BRCA positive means that your lifetime risk of developing certain forms of cancer is higher than the general population. The table below illustrates the increased risk for these cancers for individuals who possess mutations in the BRCA1 and BRCA2 genes.
|Cancer type||General population||BRCA1 carrier||BRCA2 carrier|
Although being BRCA positive increases the risk, it does not guarantee that cancer will develop. It is not yet known why some carriers develop cancer and others do not. It is also worth noting that the risk of developing cancer is not the same as the risk of dying from cancer, as there is a good chance that the disease can be managed if detected at an early stage and treated effectively.
Written by Jnetics.
Approved by Professor Rosalind Eeles Professor of Oncogenetics at The Institute of Cancer Research, The Royal Marsden Hospital London
Last review: 10.09.2016