Researchers from clinical genetics testing company Ambry Genetics (Ambry) and Mayo Clinic, report that they have documented significant differences in the prevalence of hereditary genetic mutations, also called germline mutations, linked to breast cancer among racial and ethnic populations compared to non-Hispanic White women.
“The prevalence of germline mutations and associated germline genetic drivers of breast cancer risk in racial and ethnic populations is largely unknown, and much of the known risk that is cited in the literature has been studied in non-Hispanic White populations,” stated Dr. Siddhartha Yadav, Hematology/Oncology Fellow at the Mayo Clinic working in the lab of Fergus Couch, PhD, Zbigniew and Anna M. Scheller Professor of Medical Research Chair, Division of Experimental Pathology and Laboratory Medicine Mayo Clinic. “That’s a clinical ‘blind spot’ that needs to be addressed because a better understanding of racial or ethnicity-specific genetic risk for breast cancer is key to improved targeting of genetic testing and more informed management of patients in these populations.”
A population of 77,900 women with breast cancer, comprised of 57,003 non-Hispanic White, 6,722 Black, 4,183 Asian, 5,194 Hispanic and 4,798 Ashkenazi-Jewish subjects, underwent germline multigene panel testing of cancer genes. The prevalence of gene mutations in racial and ethnic populations relative to non-Hispanic Whites was assessed.
Results revealed numerous differences between populations that may have important clinical implications. The frequency of pathogenic mutations in known breast cancer genes was 7.5 percent for Asians and Ashkenazi-Jews, 8.7 percent for non-Hispanic Whites, compared to 9.7 percent for Blacks, and 9.9 percent for Hispanics.
Distribution of variants of uncertain significance (VUS), a variant classification indicating unknown relevance to disease, also differed, being most frequent among Asians (29 percent), followed by Blacks (27 percent), Hispanics (21 percent), non-Hispanic Whites (16 percent) and Ashkenazi-Jews (14 percent). However, across all ethnicities and races, mutations in BRCA1, BRCA2, and PALB2 were significantly associated with a four-times higher risk of breast cancer.
