In the Ashkenazi Jewish population, the mutation profile of BRCA1 and BRCA2 is distinctive, with three ancient founder mutations in these two genes. Combined, these three mutations are responsible for 10% of invasive breast cancer among Ashkenazi Jewish women.
The relatively high frequency of the Ashkenazi Jewish founder mutations in BRCA1 and BRCA2 has enabled the effective use of cancer genetics services by Jewish women, according to research published online July 20, 2017, in JAMA Oncology.
For Ashkenazi Jewish patients with breast cancer who do not carry one of these three founder mutations, the chance of carrying some other pathogenic mutation in BRCA1 or BRCA2, or a pathogenic mutation in a different breast cancer gene, is not known. This information, however, would be valuable to patients and their families for cancer prevention and treatment.
A group of researchers, led by Mary-Claire King, PhD, Department of Medicine, University of Washington in Seattle, conducted a study to determine the frequency of cancer-predisposing mutations other than the BRCA1 and BRCA2 founder mutations among patients of Ashkenazi Jewish ancestry with breast cancer.
Should Ashkenazi Jewish women with breast or ovarian cancer who have negative results for the three founder mutations obtain complete sequencing of BRCA1 and BRCA2 so as not to miss some other mutation? Should these patients also be tested for mutations in other breast cancer genes?
“We addressed these questions by sequencing all known breast and ovarian cancer genes in genomic DNA, which was provided by participants of the New York Breast Cancer Study (NYBCS), a longstanding cohort of Ashkenazi Jewish women with a primary diagnosis of invasive breast cancer,” the authors said.
The result, they said, is that Ashkenazi Jewish patients with breast cancer can benefit from genetic testing for all breast cancer genes. Comprehensive sequencing would provide complete relevant genetic information.