In May 2013, Angelina Jolie,1 the actress and director, announced in an op-ed in the New York Times that she carried a BRCA1 mutation and had had a preventive double mastectomy. Jolie’s message was striking—by identifying a mutation in a cancer susceptibility gene, one of the most famous actresses of our generation dramatically reduced her risk of dying from cancer.
Widely available for more than a decade, clinical testing for mutations in the breast and ovarian cancer genes, BRCA1 and BRCA2, remains the most prominent example of the use of human genetic variation to reduce disease risk. BRCA1 and BRCA2 are tumor suppressor genes involved in DNA repair, and therefore a defective copy of either gene sensitizes cells to mutations and cancer development. BRCA1/2 mutations substantially increase the risks of breast and ovarian cancer. The average US woman has a 12% lifetime risk of breast cancer, whereas BRCA1/2 mutation carriers have a 50% to 60% lifetime risk. The increase in ovarian cancer risk is even greater—from a 1.4% lifetime risk without the mutations to over 40% among BRCA1 carriers and nearly 20% among BRCA2 carriers.2