The BRCA1 gene

Most breast cancer arises from genetic changes in breast cells during life, but some families pass a strong susceptibility down the generations. In 1974 Mary-Claire King began studying families of women with breast cancer, eventually drawing on more than 1,500 families of women diagnosed before 55. Her team at the University of California, Berkeley, analysed DNA from 329 relatives in 23 families, among whom there were 146 cases of invasive breast cancer, often in young women, and searched marker after marker across the chromosomes.

In December 1990 the group reported in Science that susceptibility in families with early-onset disease was linked to a region of chromosome 17, 17q21, with a lod score of 5.98 for one marker. Families with late-onset breast cancer showed no such linkage, evidence that inherited breast cancer had more than one genetic cause. King named the locus BRCA1.

On 7 October 1994 researchers at the University of Utah Medical Center in Salt Lake City and at Myriad Genetics, with Yoshio Miki as first author, reported a strong candidate found by positional cloning. It encoded a protein of 1,863 amino acids, and likely disease-causing mutations turned up in five of eight families thought to carry BRCA1 susceptibility. A second gene, BRCA2, was found by Michael Stratton and colleagues at the Institute of Cancer Research in Britain.

Myriad obtained patents based on its discovery of BRCA1 and BRCA2 and developed tests for mutations in them. The Association for Molecular Pathology and others sued, and on 13 June 2013 the Supreme Court held, in an opinion by Justice Thomas, that a naturally occurring DNA segment was a product of nature and could not be patented merely because it had been isolated, although synthetic cDNA could be. The opinion noted that the average American woman has a 12 to 13 percent risk of developing breast cancer, while some BRCA mutations raise it to between 50 and 80 percent, with a 20 to 50 percent risk of ovarian cancer.