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Precision healthcare aims to tailor disease prevention and early detection to individual risk. Prostate cancer screening may benefit from genomics-informed approaches. We developed and validated the P-CARE model, a prostate cancer risk prediction tool combining a polygenic score, family history and genetic ancestry, using data from over 585,000 male participants in the Million Veteran Program. The model was externally validated in diverse cohorts and implemented via a blended genome-exome assay for clinical use. Here we show that the P-CARE model identifies clinically meaningful gradients of prostate cancer risk among men, with higher scores associated with increased risk of any, metastatic and fatal prostate cancer. The model is now being used in a clinical trial of precision prostate cancer screening. This work demonstrates the potential for genomics-enabled health systems to improve prostate cancer screening and prevention in men. ClinicalTrials.gov registration: NCT05926102 .

Genomic risk model to implement precision prostate cancer screening in clinical care: the ProGRESS study.

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