Lesser-known Gene Mutations May Boost Breast Cancer Risk in Jewish Women

By Andrew M. Seaman

July 25, 2017

(Reuters Health) - Jewish women of European descent may be at risk for additional genetic mutations that increase their risk of breast cancer, according to a new study.

Researchers from University of Washington in Seattle found that around 4 percent of Ashkenazi Jewish women without well-known founder mutations in BRCA1 and BRCA2 genes have other mutations that may increase their risk for breast cancer.

Founder mutations in BRCA1 and BRCA2 are responsible for about 10 percent of invasive breast cancers among Ashkenazi Jewish women, lead author Mary-Claire King and colleagues note in JAMA Oncology July 20.

According to the National Cancer Institute, between 1 in 400 and 1 in 800 people in the general U.S. population has one of these founders mutations - but that number increases to about 1 in 40 among Ashkenazi Jews.

In women who don't carry one of these mutations, the risk of having another mutation that increases their risk of breast cancer is unknown, King's team writes.

For the new study, the researchers analyzed blood samples collected between 1996 and 2000 from 1,007 Ashkenazi Jewish women who were diagnosed with invasive breast cancer and were being treated at one of 12 cancer centers near New York City.

Genetic testing showed 903 women did not have founder mutations in their BRCA1 or BRCA2 genes.

But seven of these women - nearly 1 percent - carried another pathogenic mutation in BRCA1 or BRCA2 and 31 women - nearly 3.5 percent - had mutations in other genes that might have increased their risk for breast cancer.

The researchers point out that about half of the women with these genetic mutations did not have a family history of breast cancer. So, making genetic counseling available only to women with a family history of breast cancer might miss about half of the women with mutations.

Ashkenazi Jewish women who have not been tested for genetic mutations tied to an increased risk of breast cancer should be offered testing for all mutations, they write.

"Given that complete sequencing of all breast cancer genes is now straightforward and inexpensive, its use as the primary testing tool offers a uniform approach for women of all ancestries and precludes the need to consider additional testing for Ashkenazi Jewish women with negative results for only BRCA1 and BRCA2 founder allies," they add.

The hope is that such testing would allows healthcare providers to prevent cancer or find it early, said Leigha Senter, a licensed genetics counselor at The Ohio State University Comprehensive Cancer Center in Columbus.

"That is a clear pathway to action," said Senter, who wasn't involved in the new study.

She said a positive finding could lead to women getting more screenings, for example.

"If we’re going to look for the founding mutations, it’s no more difficult to look for these other mutations," said Senter.

She cautioned that some of these other mutations don't increase the risk of breast cancer to the same extent as the founder mutations, however.

SOURCE: http://bit.ly/2uQTcwu

JAMA Oncol 2017.