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Breast cancer is one of the most worrisome diagnoses a woman can get, and now women know that they can get a heads-up if they have an extra-high risk by getting a genetic test.
Mutations in dozens of different genes can raise the risk of breast cancer, but the two best-known risk genes are BRCA1 and BRCA2. Everyone carries these genes. When breast cancer, ovarian cancer or prostate cancer runs in a family, doctors often advise getting a test to assess whether a patient carries a risky version of one of them.
Now there are home tests for common BRCA1 and BRCA2 mutations. Some clearly raise a woman's risk of cancer, and she can get more regular mammograms or, as actress Angelie Jolie opted to do, have her breasts surgically removed.
However, many people have mutations called variants of uncertain significance. It’s not known whether they raise cancer risk.
Mutations are mistakes in the genetic code, represented by the letters A, T, C and G repeated over and over again. Big mistakes in the code mean that the BRCA genes don’t work right and don’t fix the damage in cells that can lead to cancer.
But the BRCA1 gene is 10,000 letters long. A lot of little mistakes can turn up in a sequence that long, and not all of them mean cancer.
How can you tell which ones do?
Jay Shendure at the University of Washington and colleagues think they’ve come up with a way to tell. They painstakingly created mutations one by one in a batch of cancer cells that die when they carry mutations that affect a gene’s function.
To do this, they used a precision DNA editing method called CRISPR. They created nearly 4,000 single-letter mutations, one by one, in their dishes of cells and found that they could predict which mutations might raise the risk of cancer.
They won’t be able to say precisely how those mistakes would affect development of cancer in a living human being, but when they compared their findings with known cancer-causing mutations, they aligned.
The method might be used to help tell people with so-called variants of uncertain significance whether they should worry.
“We predict that these results will be immediately useful for the clinical interpretation of BRCA1 variants,” they wrote in their report, published Wednesday in the journal Nature.
Breast cancer is the second-biggest cancer killer of American women, after lung cancer. The American Cancer Society says that every year, it's diagnosed in 260,000 women and a few men, and kills around 40,000.
BRCA mutations are among dozens of other genetic mutations that raise the risk of breast or ovarian cancer. BRCA1 and BRCA2 are DNA repair genes, which find and fix cancer-causing mistakes elsewhere in the DNA code. When they carry mistakes themselves, the repair isn’t made, or it’s made improperly.
About 55 percent to 65 percent of women with a known cancer-causing BRCA1 mutation will develop breast cancer by age 70, the National Cancer Institute says. About 45 percent of women with faulty BRCA2 genes will.
This new approach might add to the list of risky mutations, and it may also eventually be used to predict the effects of other genetic mutations, the researchers said.
"If such a variant were present in a family member of mine, would I use this information? Absolutely," Shendure said in a statement.