July 27, 2017 – Jewish women of Ashkenazi descent may be at risk for additional genetic mutations that increase their risk of breast cancer, according to a new study just published in JAMA Oncology. 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, 2017.
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 Jewish women of Ashkenazi descent. In women who don’t carry one of these mutations, the risk of having another mutation that increases their risk of breast cancer was unknown so far.
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, who were being treated at one of 12 cancer centers near New York City, and who were participants off the New York Breast Cancer Study (NYBCS), a longstanding cohort of Ashkenazi Jewish women with a primary diagnosis of invasive breast cancer.
In fact, genetic testing showed 903 women did not have founder mutations in their BRCA1 or BRCA2 genes. while 31women (3.4%) carried a pathogenic mutation in another breast cancer gene (29 in the CHEK2 gene, and 1 each in the BRIP1 gene and the NBN gene). Of all inherited predispositions to breast cancer in the NYBCS, 73.8% (104 of 142) were due to a BRCA1 or BRCA2 founder allele, 4.9% (7 of 142) to another BRCA1 or BRCA2 mutation, and 21.8% (31 of 142) to a mutation in another gene. Overall, 14.1% (142 of 1007) of Ashkenazi Jewish women with breast cancer in the NYBCS carried a germline mutation responsible for their disease: 11.0% (111 of 1007) in BRCA1 or BRCA2, and 3.1% (31 of 1007) in CHEK2 or another breast cancer gene. Of the 111 patients with BRCA1 or BRCA2 mutations, 57 (51.4%) had a mother or sister with breast or ovarian cancer and 54 patients (48.6%) did not.