Polygenic Risk Scores for Breast Cancer in African Ancestry Populations: Transferability, Calibration, and Decision Thresholds

Ssenkayi Julius

Department of Pharmacy Kampala International University Uganda

Email:Julius.ssenkayi@studwc.kiu.ac.ug

ABSTRACT

Polygenic risk scores (PRS) have emerged as promising tools for stratifying breast cancer risk and informing screening and prevention strategies. However, their clinical utility in African ancestry populations remains limited due to poor transferability, miscalibration, and uncertainty surrounding appropriate decision thresholds. Most existing PRS are derived from genome-wide association studies (GWAS) conducted predominantly in European ancestry populations, resulting in reduced predictive accuracy and systematic over- or underestimation of risk when applied to individuals of African ancestry. This review examines the current evidence on the transferability of breast cancer PRS to African ancestry populations, with particular emphasis on population-specific genetic architecture, methodological challenges, calibration performance, and threshold derivation strategies. Empirical findings consistently demonstrate diminished predictive performance and substantial miscalibration of European-derived PRS in African ancestry cohorts, raising concerns for equitable clinical implementation. We further explore calibration methods, decision-curve analysis, and ancestry-sensitive thresholding approaches, highlighting their implications for risk stratification, screening eligibility, and preventive interventions. Finally, we identify key evidence gaps, including underrepresentation in GWAS, limited biobank infrastructure, and heterogeneity in phenotype definitions, and propose future directions emphasizing multi-ancestry GWAS, integrative multi-omics models, standardized reporting, and equity-centered implementation frameworks. Addressing these challenges is essential to ensure that PRS-based breast cancer risk prediction contributes meaningfully and ethically to precision medicine for African ancestry populations.

Keywords: Polygenic risk scores, Breast cancer, African ancestry populations, Risk calibration, and Decision thresholds.

CITE AS: Ssenkayi Julius (2026). Polygenic Risk Scores for Breast Cancer in African Ancestry Populations: Transferability, Calibration, and Decision Thresholds. IAA Journal of Biological Sciences 14(1):125-132. https://doi.org/10.59298/IAAJB/2026/141125132