What is the breast cancer gene, and what are the issues with DNA testing for cancer?

Angelina Jolie’s public announcement that she had elected to have her breasts removed in light of her cancer gene mutations attracted worldwide interest. In fact, the phrase “mutation” had never been so popular on internet search engines! Requests for BRCA1 testing from worried women have increased dramatically. Two issues have arisen: who should be tested, and who should perform the test? Because breast cancer is relatively common (women have about a 10 percent lifetime chance of having it), having several relatives who have had the disease is not unusual. Medical geneticists have come up with several criteria for defining when BRCA1 DNA analysis is warranted. These include having several close relatives who had or have the disease, with early onset (typically before age 50) and the presence of multiple tumors.

Even when a test shows no BRCA1 mutations in a woman with a family history of breast or ovarian cancer, we cannot say that breast or ovarian cancer may not arise. It turns out that BRCA1 mutations only account for about one in five hereditary breast cancer cases. Other genes are involved; we just don’t know what they are, so we can’t analyze their DNA. Remember: hereditary breast cancer (a germ line mutation) accounts for only one case in ten. The other 90 percent arise from somatic mutation of breast cells.

As to who does the test, the BRCA1 gene was isolated by a private company that patented the DNA sequence. Until recently, that company was the only lab that could do BRCA1 analysis, and not surprisingly, the price was high. In 2013, the U.S. Supreme Court invalidated the patent, and now more labs can do it, and more cheaply.

Future directions

Are there genetic tests for other hereditary cancers? About 10 percent of all cancers are caused by inheritance of mutated oncogenes or tumor suppressor genes (as opposed to mutations that occur after birth). As with the situation in breast cancer, a person who inherits a cancer-causing mutation has a much higher chance of developing cancer than one who does not have that mutation. As whole genome DNA sequencing is developed (see Chapter 18), mutations involved with other types of hereditary cancer are being identified and screening of relatives with a propensity for cancer is on the horizon.