Study Highlights Importance of Ethnic Calibration for Breast Cancer Polygenic Risk Scores

Polygenic risk scores (PRSs) for breast cancer that are calibrated for white European women are not as effective in women of Ashkenazi Jewish descent, according to a new Genetics in Medicine study. The finding highlights the importance of ethnic accuracy when using breast cancer risk prediction algorithms. In some commercially available breast cancer PRSs, Ashkenazi Jewish individuals are assumed to be of white European origin despite differing effect allele frequencies. To assess the validity of two such PRSs in Ashkenazi Jewish women, a team led by University of Manchester investigators conducted a case-control study of white European and Ashkenazi Jewish women from a cohort study and a regional genetics database, using a large Israeli case-control population to validate their findings. All women in the study underwent Illumina Oncoarray SNP analysis. The researchers find that, as previously observed in Black and Asian women, the PRSs overestimate risks in the Ashkenazi Jewish population and require calibration. "Failure to calibrate appropriately for women of self-reported Ashkenazi Jewish heritage, which coupled with risk prediction models that also overestimate risk, will result in significant over prediction of [breast cancer] risk, and potentially lead to harms through the delivery of enhanced screening and preventive measures including risk reducing mastectomies," the study's authors write.