biostudies-literatureJee YHNational Cancer InstituteNCI NIH HHSNational Institutes of Health796-805https://www.ebi.ac.uk/biostudies/studies/S-EPMC10244045biostudies-literatureUnknown52(3)<h4>Background</h4>Polygenic risk scores (PRSs) for breast cancer, developed using European and Asian genome-wide association studies (GWAS), have been shown to have good discrimination in Asian women. However, prospective calibration of absolute risk prediction models, based on a PRS or PRS combined with lifestyle, clinical and environmental factors, in Asian women is limited.<h4>Methods</h4>We consider several PRSs trained using European and/or Asian GWAS. For each PRS, we evaluate the discrimination and calibration of three absolute risk models among 41 031 women from the Korean Cancer Prevention Study (KCPS)-II Biobank: (i) a model using incidence, mortality and risk factor distributions (reference inputs) among US women and European relative risks; (ii) a recalibrated model, using Korean reference but European relative risks; and (iii) a fully Korean-based model using Korean reference and relative risk estimates from KCPS.<h4>Results</h4>All Asian and European PRS improved discrimination over lifestyle, clinical and environmental (Qx) factors in Korean women. US-based absolute risk models overestimated the risks for women aged ≥50 years, and this overestimation was larger for models that only included PRS (expected-to-observed ratio E/O = 1.2 for women <50, E/O = 2.7 for women ≥50). Recalibrated and Korean-based risk models had better calibration in the large, although the risk in the highest decile was consistently overestimated. Absolute risk projections suggest that risk-reducing lifestyle changes would lead to larger absolute risk reductions among women at higher PRS.<h4>Conclusions</h4>Absolute risk models incorporating PRS trained in European and Asian GWAS and population-appropriate average age-specific incidences may be useful for risk-stratified interventions in Korean women.International journal of epidemiologyPolygenic risk scores for prediction of breast cancer in Korean women.PMC10244045U01 CA261339U01 CA249866Jee YHHo WKEaston DFJung KJKraft PPark STeo SHfalsePolygenic risk scores for prediction of breast cancer in Korean women.<h4>Background</h4>Polygenic risk scores (PRSs) for breast cancer, developed using European and Asian genome-wide association studies (GWAS), have been shown to have good discrimination in Asian women. However, prospective calibration of absolute risk prediction models, based on a PRS or PRS combined with lifestyle, clinical and environmental factors, in Asian women is limited.<h4>Methods</h4>We consider several PRSs trained using European and/or Asian GWAS. For each PRS, we evaluate the discrimination and calibration of three absolute risk models among 41 031 women from the Korean Cancer Prevention Study (KCPS)-II Biobank: (i) a model using incidence, mortality and risk factor distributions (reference inputs) among US women and European relative risks; (ii) a recalibrated model, using Korean reference but European relative risks; and (iii) a fully Korean-based model using Korean reference and relative risk estimates from KCPS.<h4>Results</h4>All Asian and European PRS improved discrimination over lifestyle, clinical and environmental (Qx) factors in Korean women. US-based absolute risk models overestimated the risks for women aged ≥50 years, and this overestimation was larger for models that only included PRS (expected-to-observed ratio E/O = 1.2 for women <50, E/O = 2.7 for women ≥50). Recalibrated and Korean-based risk models had better calibration in the large, although the risk in the highest decile was consistently overestimated. Absolute risk projections suggest that risk-reducing lifestyle changes would lead to larger absolute risk reductions among women at higher PRS.<h4>Conclusions</h4>Absolute risk models incorporating PRS trained in European and Asian GWAS and population-appropriate average age-specific incidences may be useful for risk-stratified interventions in Korean women.2023-01-01T00:00:00Z2023 Jun2025-04-21T17:24:31.161Z2025-04-05T16:23:48.406ZS-EPMC102440453634301710.1093/ije/dyac206