Polygenic hazard score is associated with prostate cancer in multi-ethnic populations.
Minh-Phuong Huynh-LeChun-Chieh FanRoshan KarunamuniWesley K ThompsonMaria Elena MartinezRosalind A EelesZsofia Kote-JaraiKenneth Ross MuirJohanna SchleutkerNora PashayanJyotsna BatraHenrik GronbergDavid E NealJenny L DonovanFreddie C HamdyRichard M MartinSune F NielsenBørge Grønne NordestgaardFredrik WiklundCatherine M TangenGraham G GilesAlicja WolkDemetrius AlbanesRuth C TravisWilliam J BlotQuan LongMaureen SandersonJanet L StanfordLorelei A MucciCatharine M L WestAdam S KibelOlivier CussenotSonja I BerndtStella KoutrosKarina Dalsgaard SørensenCezary CybulskiEli Marie GrindedalFlorence MenegauxKay-Tee KhawJong Y ParkSue A InglesChristiane MaierRobert J HamiltonStephen N ThibodeauBarry S RosensteinYong-Jie LuStephen WatyaAna VegaManolis KogevinasKathryn L PenneyChad HuffManuel R TeixeiraLuc MultignerRobin J LeachLisa Anne Cannon-AlbrightHermann BrennerEsther M JohnRadka KanevaChristopher J LogothetisSusan L NeuhausenKim De RuyckHardev PandhaAzad RazackLisa F NewcombJay H FowkeMarija GamulinNawaid UsmaniFrank ClaessensManuela Gago-DominguezPaul A TownsendWilliam S BushMonique J RoobolMarie-Élise ParentJennifer J HuIan G MillsOle Andreas AndreassenAnders M DaleTyler M Seibertnull nullnull nullnull nullnull nullnull nullnull nullnull nullPublished in: Nature communications (2021)
Genetic models for cancer have been evaluated using almost exclusively European data, which could exacerbate health disparities. A polygenic hazard score (PHS1) is associated with age at prostate cancer diagnosis and improves screening accuracy in Europeans. Here, we evaluate performance of PHS2 (PHS1, adapted for OncoArray) in a multi-ethnic dataset of 80,491 men (49,916 cases, 30,575 controls). PHS2 is associated with age at diagnosis of any and aggressive (Gleason score ≥ 7, stage T3-T4, PSA ≥ 10 ng/mL, or nodal/distant metastasis) cancer and prostate-cancer-specific death. Associations with cancer are significant within European (n = 71,856), Asian (n = 2,382), and African (n = 6,253) genetic ancestries (p < 10-180). Comparing the 80th/20th PHS2 percentiles, hazard ratios for prostate cancer, aggressive cancer, and prostate-cancer-specific death are 5.32, 5.88, and 5.68, respectively. Within European, Asian, and African ancestries, hazard ratios for prostate cancer are: 5.54, 4.49, and 2.54, respectively. PHS2 risk-stratifies men for any, aggressive, and fatal prostate cancer in a multi-ethnic dataset.