Performance of different polygenic risk scores for breast cancer risk prediction: in-depth evaluations across large UK and Australian cohorts.

ABSTRACT: Polygenic risk scores (PGS) have the potential to support enhanced, risk-based screening for breast cancer. Previous studies for many diseases found that genome-wide PGS (GW-PGS) outperform PGS derived by applying hard GWAS significance thresholds. To support future breast cancer risk predictions, we compared the predictive performance of two existing PGS (including PGS313, a leading hard-thresholding PGS) and five newly developed GW-PGS (applying different methods to recent GWAS). We evaluated the performance of PGS Z-scores and of predicted 5-year absolute breast cancer risks based on age alone or age and PGS, across three large cohorts from the UK (UK Biobank) and Australia (QSkin, Melbourne Collaborative Cohort Study). Performance was assessed using discrimination (AUC) and calibration

SUBMITTER: Tanha HM 

PROVIDER: S-EPMC12858958 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature