Background: Heritable risk factors account for a significant proportion of prostate cancer (PrCa) risk, of which only a minority are high risk Mendelian traits. Men of Black African and African Caribbean ancestry are at higher risk of developing PrCa in their lifetime (1 in 4) compared with the general population in the United Kingdom (1 in 8). PROFILE is a multi-cohort study of targeted screening for groups of men at higher risk of developing PrCa: 1) men of European ancestry with family history of PrCa, 2) men of black African and African Caribbean ancestry regardless of family history and 3) men with known rarer higher risk gene mutations for PrCa. This abstract concentrates on group 2. The aim is to investigate the role of targeted PrCa screening in men at higher genetic risk and its association with specific genetic profiles and biomarkers. Methods: Healthy men aged 40-69 are invited to participate. Inclusion Criteria: Both parents and all four grandparents must be of either black African or African Caribbean ancestry. Arm 1: PSA only – once PSA is below an age-related threshold (aged 40-49 and PSA ≥0ng/ml, aged 50-69 PSA >/= 2ng/ml) they continue on the study with annual PSA, only triggering a prostate MRI and Biopsy if the PSA is above the threshold. Arm 2: Regardless of PSA men opt for prostate mpMRI and biopsy. Polygenic risk score (PRS) calculated based on 230 SNPs including latest AA specific variants. Results: Arm 1: 121 enrolled PSA only (this has triggered 8 biopsies with 3 cancers). Arm 2: 58 enrolled MRI and biopsy, 58 MRIs and 36 biopsies carried out, PrCa detected in 15 men (42%). 22% are Gleason score ≥7. Association between PRS and MRI/Biopsy results will be presented. Conclusions: We will continue to perform MRI and biopsies on men, we will also carry out polygenic risk scores on these men to verify whether a genetic PRS can help guide enhanced screening for certain men in the population. Although data are early, a significant proportion of biopsies are positive for PrCa that needs radical treatment. Clinical trial information: NCT02543905.