Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction.
David V ContiBurcu F DarstLilit C MossEdward J SaundersXin ShengAlisha J ChouFredrick R SchumacherAli Amin Al OlamaSara BenllochTokhir DadaevMark N BrookAli SahimiThomas J HoffmannAtsushi TakahashiKoichi MatsudaYukihide MomozawaMasashi FujitaKenneth Ross MuirArtitaya LophatananonPeggy WanLoic Le MarchandLynne R WilkensVictoria L StevensSusan M GapsturBrian D CarterJohanna SchleutkerTeuvo L J TammelaCsilla SipekyAnssi AuvinenGraham G GilesMelissa C SoutheyRobert J MacInnisCezary CybulskiDominika WokołorczykJan LubińskiDavid E NealJenny L DonovanFreddie C HamdyRichard M MartinBørge Grønne NordestgaardSune F NielsenMaren WeischerStig Egil BojesenMartin Andreas RøderPeter IversenJyotsna BatraSuzanne ChambersLeire MoyaLisa HorvathJudith A ClementsWayne D TilleyGail P RisbridgerHenrik GronbergMarkus AlyRobert SzulkinMartin EklundTobias NordströmNora PashayanAlison M DunningMaya GhoussainiRuth C TravisTim J KeyElio RiboliJong Y ParkThomas A SellersHui-Yi LinDemetrius AlbanesStephanie J WeinsteinLorelei A MucciEdward GiovannucciSara LindstromPeter KraftDavid J HunterKathryn L PenneyConstance TurmanCatherine M TangenPhyllis J GoodmanIan M ThompsonRobert J HamiltonNeil E FleshnerAntonio FinelliMarie-Élise ParentJanet L StanfordElaine A OstranderMilan S GeybelsStella KoutrosLaura E Beane FreemanMeir StampferAlicja WolkNiclas HåkanssonGerald L AndrioleRobert N HooverMitchell J MachielaKarina Dalsgaard SørensenMichael BorreWilliam J BlotQuan LongEdward D YeboahJames Edward MensahYong-Jie LuHong-Wei ZhangNinghan FengXueying MaoYudong WuShan-Chao ZhaoZan SunStephen N ThibodeauShannon K McDonnellDaniel J SchaidCatharine M L WestNeil BurnetGill BarnettChristiane MaierThomas SchnoellerManuel LuedekeAdam S KibelBettina F DrakeOlivier CussenotGeraldine Cancel-TassinFlorence MenegauxThérèse TruongYves Akoli KoudouEsther M JohnEli Marie GrindedalLovise MaehleKay-Tee KhawSue A InglesMariana C SternAna VegaAntonio Gómez-CaamañoLaura FachalBarry S RosensteinSarah L KernsHarry OstrerManuel R TeixeiraPaula PauloAndreia BrandãoStephen WatyaAlexander LubwamaJeannette T BensenElizabeth T H FonthamJames MohlerJack A TaylorManolis KogevinasJavier LlorcaGemma Castaño-VinyalsLisa Anne Cannon-AlbrightCraig C TeerlinkChad D HuffSara S StromLuc MultignerPascal BlanchetLaurent BrureauRadka KanevaChavdar SlavovVanio MitevRobin J LeachBrandi WeaverHermann BrennerKatarina CukBernd HolleczekKai-Uwe SaumEric E KleinAnn W HsingRick A KittlesBernice OforiChristopher J LogothetisJeri KimSusan L NeuhausenLinda SteeleYuan Chun DingWilliam B IsaacsBarbara NemesureAnselm J M HennisJohn CarptenHardev PandhaAgnieszka MichaelKim De RuyckGert De MeerleerPiet OstJianfeng XuAzad RazackJasmine LimSoo-Hwang TeoLisa F NewcombDaniel W LinJay H FowkeChristine Neslund-DudasBenjamin A RybickiMarija GamulinDavor LesselTomislav KulisNawaid UsmaniSandeep SinghalMatthew ParliamentFrank ClaessensSteven JoniauThomas Van den BroeckManuela Gago-DominguezJose Esteban CastelaoMaria Elena MartinezSamantha LarkinPaul A TownsendClaire Aukim-HastieWilliam S BushMelinda C AldrichDana C CrawfordShiv SrivastavaJennifer C CullenGyorgy PetrovicsGraham CaseyMonique J RoobolGuido W JensterRon H N van SchaikJennifer J HuMaureen SandersonRohit VarmaRoberta McKean-CowdinMina TorresNicholas MancusoSonja I BerndtStephen K Van den EedenDouglas F EastonStephen J ChanockMichael B CookFredrik WiklundHidewaki NakagawaJohn S WitteRosalind A EelesZsofia Kote-JaraiChristopher A HaimanPublished in: Nature genetics (2021)
Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction.