Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci.
Fredrick R SchumacherAli Amin Al OlamaSonja I BerndtSara BenllochMahbubl AhmedEdward J SaundersTokhir DadaevDaniel LeongamornlertEzequiel AnokianClara Cieza-BorrellaChee GohMark N BrookXin ShengLaura FachalJoe DennisJonathan TyrerKenneth MuirArtitaya LophatananonVictoria L StevensSusan M GapsturBrian D CarterCatherine M TangenPhyllis J GoodmanIan M ThompsonJyotsna BatraSuzanne ChambersLeire MoyaJudith ClementsLisa HorvathWayne TilleyGail P RisbridgerHenrik GronbergMarkus AlyTobias NordströmPaul PharoahNora PashayanJohanna SchleutkerTeuvo L J TammelaCsilla SipekyAnssi AuvinenDemetrius AlbanesStephanie WeinsteinAlicja WolkNiclas HåkanssonCatharine M L WestAlison M DunningNeil BurnetLorelei A MucciEdward GiovannucciGerald L AndrioleOlivier CussenotGéraldine Cancel-TassinStella KoutrosLaura E Beane FreemanKarina Dalsgaard SorensenTorben Falck OrntoftMichael BorreLovise MaehleEli Marie GrindedalDavid E NealJenny L DonovanFreddie C HamdyRichard M MartinRuth C TravisTim J KeyRobert J HamiltonNeil E FleshnerAntonio FinelliSue Ann InglesMariana C SternBarry S RosensteinSarah L KernsHarry OstrerYong-Jie LuHong-Wei ZhangNinghan FengXueying MaoXin GuoGuomin WangZan SunGraham G GilesMelissa C SoutheyRobert J MacInnisLiesel M FitzGeraldAdam S KibelBettina F DrakeAna VegaAntonio Gómez-CaamañoRobert SzulkinMartin EklundManolis KogevinasJavier LlorcaGemma Castaño-VinyalsKathryn L PenneyMeir StampferJong Y ParkThomas A SellersHui-Yi LinJanet L StanfordCezary CybulskiDominika WokolorczykJan LubinskiElaine A OstranderMilan S GeybelsBørge G NordestgaardSune F NielsenMaren WeischerRasmus BisbjergMartin Andreas RøderPeter IversenHermann BrennerKatarina CukBernd HolleczekChristiane MaierManuel LuedekeThomas SchnoellerJeri KimChristopher J LogothetisEsther M JohnManuel R TeixeiraPaula PauloMarta CardosoSusan L NeuhausenLinda SteeleYuan Chun DingKim De RuyckGert De MeerleerPiet OstAzad RazackJasmine LimSoo-Hwang TeoDaniel W LinLisa F NewcombDavor LesselMarija GamulinTomislav KulisRadka KanevaNawaid UsmaniSandeep SinghalChavdar SlavovVanio MitevMatthew ParliamentFrank ClaessensSteven JoniauThomas Van den BroeckSamantha LarkinPaul A TownsendClaire Aukim-HastieManuela Gago-DominguezJose Esteban CastelaoMaria Elena MartinezMonique J RoobolGuido JensterRon H N van SchaikFlorence MenegauxThérèse TruongYves Akoli KoudouJianfeng XuKay-Tee KhawLisa Cannon-AlbrightHardev PandhaAgnieszka MichaelStephen N ThibodeauShannon K McDonnellDaniel J SchaidSara LindstromConstance TurmanJing MaDavid J HunterElio RiboliAfshan SiddiqFederico CanzianLaurence N KolonelLoic Le MarchandRobert N HooverMitchell J MachielaZuxi CuiPeter KraftChristopher I AmosDavid V ContiDouglas F EastonFredrik WiklundStephen J ChanockBrian E HendersonZsofia Kote-JaraiChristopher A HaimanRosalind A Eelesnull nullnull nullnull nullnull nullnull nullnull nullnull nullnull nullnull nullPublished in: Nature genetics (2018)
Genome-wide association studies (GWAS) and fine-mapping efforts to date have identified more than 100 prostate cancer (PrCa)-susceptibility loci. We meta-analyzed genotype data from a custom high-density array of 46,939 PrCa cases and 27,910 controls of European ancestry with previously genotyped data of 32,255 PrCa cases and 33,202 controls of European ancestry. Our analysis identified 62 novel loci associated (P < 5.0 × 10-8) with PrCa and one locus significantly associated with early-onset PrCa (≤55 years). Our findings include missense variants rs1800057 (odds ratio (OR) = 1.16; P = 8.2 × 10-9; G>C, p.Pro1054Arg) in ATM and rs2066827 (OR = 1.06; P = 2.3 × 10-9; T>G, p.Val109Gly) in CDKN1B. The combination of all loci captured 28.4% of the PrCa familial relative risk, and a polygenic risk score conferred an elevated PrCa risk for men in the ninetieth to ninety-ninth percentiles (relative risk = 2.69; 95% confidence interval (CI): 2.55-2.82) and first percentile (relative risk = 5.71; 95% CI: 5.04-6.48) risk stratum compared with the population average. These findings improve risk prediction, enhance fine-mapping, and provide insight into the underlying biology of PrCa1.