biostudies-literatureHuynh-Le MPNIBIB NIH HHSCancer Research UKNational Institute for Health Research (NIHR)NCI NIH HHS755-761https://www.ebi.ac.uk/biostudies/studies/S-EPMC9372232biostudies-literatureUnknown25(4)<h4>Background</h4>Prostate cancer risk stratification using single-nucleotide polymorphisms (SNPs) demonstrates considerable promise in men of European, Asian, and African genetic ancestries, but there is still need for increased accuracy. We evaluated whether including additional SNPs in a prostate cancer polygenic hazard score (PHS) would improve associations with clinically significant prostate cancer in multi-ancestry datasets.<h4>Methods</h4>In total, 299 SNPs previously associated with prostate cancer were evaluated for inclusion in a new PHS, using a LASSO-regularized Cox proportional hazards model in a training dataset of 72,181 men from the PRACTICAL Consortium. The PHS model was evaluated in four testing datasets: African ancestry, Asian ancestry, and two of European Ancestry-thProstate cancer and prostatic diseasesProstate cancer risk stratification improvement across multiple ancestries with new polygenic hazard score.PMC9372232NIHR201620K08 EB026503UG1 CA18997429017UM1 CA18288318504Gamulin MAbraham AAPCB (Australian Prostate Cancer BioResource)Huff CDBerndt SITeixeira MRLu YJRosenstein BSLophatananon AHuynh-Le MPGrindedal EMKoutros SNordestgaard BGUKGPCS collaboratorsAndreassen OAMuir KRPashayan NNeal DEWiklund FPetrovics GWolk ACrawford DCKote-Jarai ZMacInnis RJEeles RAIngles SAMartinez MENC-LA PCaP InvestigatorsClaessens FZheng WRazack AStanford JLOst PNielsen SFMucci LABrenner HNeuhausen SLTravis RCBlot WJLeach RJMills IGHu JJSeibert TMCussenot OTangen CMKibel ASSorensen KDvan Schaik RHNVega AKarunamuni RFan CCThompson WKPark JYNewcomb LFWest CMLWatya SProfile Study Steering CommitteeHaiman CAJohn EMFowke JHSchleutker JTownsend PALogothetis CJKogevinas MMultigner LMenegaux FGronberg HDe Ruyck KAlbanes DIMPACT Study Steering Committee and CollaboratorsBatra JMaier CCastelao JEDale AMParent MEHamilton RJPenney KLKaneva RCanary PASS InvestigatorsAsona LPRACTICAL ConsortiumCybulski CfalseProstate cancer risk stratification improvement across multiple ancestries with new polygenic hazard score.<h4>Background</h4>Prostate cancer risk stratification using single-nucleotide polymorphisms (SNPs) demonstrates considerable promise in men of European, Asian, and African genetic ancestries, but there is still need for increased accuracy. We evaluated whether including additional SNPs in a prostate cancer polygenic hazard score (PHS) would improve associations with clinically significant prostate cancer in multi-ancestry datasets.<h4>Methods</h4>In total, 299 SNPs previously associated with prostate cancer were evaluated for inclusion in a new PHS, using a LASSO-regularized Cox proportional hazards model in a training dataset of 72,181 men from the PRACTICAL Consortium. The PHS model was evaluated in four testing datasets: African ancestry, Asian ancestry, and two of European Ancestry-th2022-01-01T00:00:00Z2022 Apr2026-06-03T18:36:22.521Z2026-04-30T03:11:17.056ZS-EPMC93722323515227110.1038/s41391-022-00497-7