What the genes do
BRCA1 and BRCA2 produce proteins that help repair damaged DNA. Everyone has two copies of each gene, one inherited from each parent, and one working copy usually protects cells at first, but alteration or loss of the remaining copy can allow cancer to develop. A person who inherits a harmful change in one copy has a higher risk of cancer. Because the change is inherited, it may also be present in parents, brothers, sisters and children, so a result in one person can be relevant to relatives.
Cancer risks
The United States National Cancer Institute (NCI) estimates that about 13% of women in the general population will develop breast cancer during their lifetime, compared with more than 60% of women who inherit a harmful change in BRCA1 or BRCA2. Lifetime ovarian cancer risk is about 1.1% in the general population, compared with about 39% to 58% for women with a harmful BRCA1 change and 13% to 29% for women with a harmful BRCA2 change. Carriers also have a raised risk of pancreatic cancer. Men with harmful changes have higher risks of breast cancer and prostate cancer; NCI reports that 19% to 61% of men with a harmful BRCA2 change will develop prostate cancer by age 80.
Fanconi anaemia is a separate condition
People who inherit harmful changes in both copies of BRCA1 or BRCA2 develop subtypes of Fanconi anaemia, a rare inherited condition that NCI associates with solid tumours and acute myeloid leukaemia, often in childhood. Fanconi anaemia should not be confused with Fanconi syndrome, which is an unrelated disorder of kidney tubule function.
Who may consider testing
Testing is most useful for people with a higher likelihood of carrying a harmful change. The CDC lists features that suggest increased risk, including:
- breast cancer before age 50, triple-negative breast cancer, breast cancer more than once, or breast cancer in a man
- ovarian, fallopian tube or primary peritoneal cancer at any age
- relatives with breast cancer before 50, cancer in both breasts, ovarian cancer, or male breast cancer
- Ashkenazi Jewish ancestry with a personal or family history of breast or ovarian cancer
- a relative with a known harmful BRCA change
Genetic counselling and understanding results
Testing uses a blood or saliva sample and is usually preceded by a risk assessment and genetic counselling, so that the benefits and possible downsides are discussed first. NCI notes that professional groups do not recommend testing children under 18. A positive result shows increased risk but cannot predict whether or when cancer will develop. A negative result is most informative when a specific variant is already known in the family. A variant of uncertain significance is managed according to personal and family history until it is reclassified. Options for carriers, such as breast MRI with mammography, risk-reducing surgery and medicines, are discussed with a specialist.