Association between polygenic risk scores and cardiovascular events in prostate cancer patients receiving androgen deprivation therapy in Han Chinese

INTRODUCTION: Cardiovascular disease (CVD) remains one of the leading non-cancer causes of mortality in prostate cancer patients, with previous studies indicating that androgen deprivation therapy (ADT) may increase cardiovascular risk. In this study, we aimed to predict cardiovascular events by incorporating polygenic risk scores (PRS). METHODS: Data were collected from 24,778 men, including 903 prostate cancer patients at Taichung Veterans General Hospital. Genotyping was performed using the Affymetrix Genome-Wide TWB 2.0 SNP Array. Four PRSs (PGS000337, PGS002262, PGS002725, and PGS003727) associated with coronary artery disease were utilized for analysis. Patients were stratified into quartiles based on their risk levels. Cox proportional hazards models were applied to assess the association between PRSs and the incidence of cardiovascular disease, adjusting for age, androgen deprivation therapy use, and comorbidities. RESULTS: PGS003727 demonstrated the highest predictive performance, with an area under curve (AUC) of 0.5550. Among ADT-treated patients, those in the highest PRS quartile (Q4) of PGS003727 had a significantly higher risk of CVD compared to those in the lowest quartile (Q1) (HR = 1.892, p = 0.0056). However, this Q4-to-Q1 risk difference was not significant in non-ADT patients (HR = 1.244, p = 0.3951). Kaplan-Meier analysis revealed significant risk variation across Q1 to Q4 in the ADT-treated group (p = 0.028) but not in the non-ADT group. Among Q4 prostate cancer patients, ADT treatment significantly increased CVD risk compared to non-ADT treatment (HR = 1.625, p = 0.0428). Kaplan-Meier analysis further confirmed that ADT treatment was associated with a higher cumulative incidence of CVD in Q4 prostate cancer patients (p = 0.033). CONCLUSION: This hospital-based cohort study demonstrated that the PRS effectively predicted CVD risk in prostate cancer patients receiving ADT. Integrating this model into clinical practice could enable more precise cardiovascular risk assessment to aid treatment decisions and improving disease prevention strategies.