Association of a Polygenic Risk Score With Breast Cancer Among Women Carriers of High- and Moderate-Risk Breast Cancer Genes

Key Points Question Are polygenic risk scores associated with changes in breast cancer risks for individuals with a pathogenic variant in moderate-risk breast cancer genes? Findings In this case-control study of 9802 women carrying pathogenic variants of breast cancer genes, an 86–single-nucleotide variation score was associated with breast cancer risk in each of the tested carrier populations. Stratification was more pronounced for noncarriers and CHEK2 pathogenic variant carriers than for BRCA1 or BRCA2 pathogenic variant carriers, with ATM and PALB2 pathogenic variant carriers being intermediate between those groups. Meaning Theses findings suggest that the 86–single-nucleotide variation score may modify risk for carriers of BRCA1, BRCA2, CHEK2, ATM, and PALB2 pathogenic variants.