Lesser-known gene mutations may boost breast cancer risk in Ashkenazi women

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 found that around 4% of Ashkenazi women without three well-known mutations in their BRCA1 and BRCA2 genes have other mutations that may increase their risk for breast cancer.

The well-known mutations are called “founders” since they’ve been inherited from the women’s ancestors in Europe. Lead author Mary-Claire King and colleagues write in JAMA Oncology that those mutations are responsible for about 10% of invasive breast cancers among Ashkenazi women.

According to the US National Cancer Institute, between 1 in 400 and 1 in 800 people in the general US 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 those mutations, the risk of having another mutation that increases their risk of breast cancer is unknown, King’s team writes.

For the 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 those founder mutations in their BRCA1 or BRCA2 genes.

But seven of these women – nearly 1% – had a different mutation in those genes and 31 women – nearly 3.5% – 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 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 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.

Senter said women should be proactive and tell their doctors about any history of breast cancer on either side of their family. Additionally, she said, it’s important to keep checking on the current screening recommendations.

“Those screening recommendations as we know them now, might be very different a couple of years from now as we learn more,” she said. (Reuters)