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dc.contributor.authorSchumacher, Fredrick R
dc.contributor.authorAl Olama, Ali Amin
dc.contributor.authorBerndt, Sonja I
dc.contributor.authorBenlloch, Sara
dc.contributor.authorAhmed, Mahbubl
dc.contributor.authorSaunders, Edward J
dc.contributor.authorDadaev, Tokhir
dc.contributor.authorLeongamornlert, Daniel
dc.contributor.authorAnokian, Ezequiel
dc.contributor.authorCieza-Borrella, Clara
dc.contributor.authorGoh, Chee
dc.contributor.authorBrook, Mark N
dc.contributor.authorSheng, Xin
dc.contributor.authorFachal Vilar, Laura
dc.contributor.authorDennis, Joe
dc.contributor.authorTyrer, Jonathan
dc.contributor.authorMuir, Kenneth
dc.contributor.authorLophatananon, Artitaya
dc.contributor.authorStevens, Victoria L
dc.contributor.authorGapstur, Susan M
dc.contributor.authorCarter, Brian D
dc.contributor.authorTangen, Catherine M
dc.contributor.authorGoodman, Phyllis J
dc.contributor.authorThompson, Ian M
dc.contributor.authorBatra, Jyotsna
dc.contributor.authorChambers, Suzanne
dc.contributor.authorMoya, Leire
dc.contributor.authorClements, Judith
dc.contributor.authorHorvath, Lisa
dc.contributor.authorTilley, Wayne
dc.contributor.authorRisbridger, Gail P
dc.contributor.authorGronberg, Henrik
dc.contributor.authorAly, Markus
dc.contributor.authorNordström, Tobias
dc.contributor.authorPharoah, Paul
dc.contributor.authorPashayan, Nora
dc.contributor.authorSchleutker, Johanna
dc.contributor.authorTammela, Teuvo LJ
dc.contributor.authorSipeky, Csilla
dc.contributor.authorAuvinen, Anssi
dc.contributor.authorAlbanes, Demetrius
dc.contributor.authorWeinstein, Stephanie
dc.contributor.authorWolk, Alicja
dc.contributor.authorHåkansson, Niclas
dc.contributor.authorWest, Catharine ML
dc.contributor.authorDunning, Alison
dc.contributor.authorBurnet, Neil
dc.contributor.authorMucci, Lorelei A
dc.contributor.authorGiovannucci, Edward
dc.contributor.authorAndriole, Gerald L
dc.contributor.authorCussenot, Olivier
dc.contributor.authorCancel-Tassin, Géraldine
dc.contributor.authorKoutros, Stella
dc.contributor.authorBeane Freeman, Laura E
dc.contributor.authorSorensen, Karina Dalsgaard
dc.contributor.authorOrntoft, Torben Falck
dc.contributor.authorBorre, Michael
dc.contributor.authorMaehle, Lovise
dc.contributor.authorGrindedal, Eli Marie
dc.contributor.authorNeal, David E
dc.contributor.authorDonovan, Jenny L
dc.contributor.authorHamdy, Freddie C
dc.contributor.authorMartin, Richard M
dc.contributor.authorTravis, Ruth C
dc.contributor.authorKey, Tim J
dc.contributor.authorHamilton, Robert J
dc.contributor.authorFleshner, Neil E
dc.contributor.authorFinelli, Antonio
dc.contributor.authorIngles, Sue Ann
dc.contributor.authorStern, Mariana C
dc.contributor.authorRosenstein, Barry S
dc.contributor.authorKerns, Sarah L
dc.contributor.authorOstrer, Harry
dc.contributor.authorLu, Yong-Jie
dc.contributor.authorZhang, Hong-Wei
dc.contributor.authorFeng, Ninghan
dc.contributor.authorMao, Xueying
dc.contributor.authorGuo, Xin
dc.contributor.authorWang, Guomin
dc.contributor.authorSun, Zan
dc.contributor.authorGiles, Graham G
dc.contributor.authorSouthey, Melissa C
dc.contributor.authorMacInnis, Robert J
dc.contributor.authorFitzGerald, Liesel M
dc.contributor.authorKibel, Adam S
dc.contributor.authorDrake, Bettina F
dc.contributor.authorVega, Ana
dc.contributor.authorGómez-Caamaño, Antonio
dc.contributor.authorSzulkin, Robert
dc.contributor.authorEklund, Martin
dc.contributor.authorKogevinas, Manolis
dc.contributor.authorLlorca, Javier
dc.contributor.authorCastaño-Vinyals, Gemma
dc.contributor.authorPenney, Kathryn L
dc.contributor.authorStampfer, Meir
dc.contributor.authorPark, Jong Y
dc.contributor.authorSellers, Thomas A
dc.contributor.authorLin, Hui-Yi
dc.contributor.authorStanford, Janet L
dc.contributor.authorCybulski, Cezary
dc.contributor.authorWokolorczyk, Dominika
dc.contributor.authorLubinski, Jan
dc.contributor.authorOstrander, Elaine A
dc.contributor.authorGeybels, Milan S
dc.contributor.authorNordestgaard, Børge G
dc.contributor.authorNielsen, Sune F
dc.contributor.authorWeischer, Maren
dc.contributor.authorBisbjerg, Rasmus
dc.contributor.authorRøder, Martin Andreas
dc.contributor.authorIversen, Peter
dc.contributor.authorBrenner, Hermann
dc.contributor.authorCuk, Katarina
dc.contributor.authorHolleczek, Bernd
dc.contributor.authorMaier, Christiane
dc.contributor.authorLuedeke, Manuel
dc.contributor.authorSchnoeller, Thomas
dc.contributor.authorKim, Jeri
dc.contributor.authorLogothetis, Christopher J
dc.contributor.authorJohn, Esther M
dc.contributor.authorTeixeira, Manuel R
dc.contributor.authorPaulo, Paula
dc.contributor.authorCardoso, Marta
dc.contributor.authorNeuhausen, Susan L
dc.contributor.authorSteele, Linda
dc.contributor.authorDing, Yuan Chun
dc.contributor.authorDe Ruyck, Kim
dc.contributor.authorDe Meerleer, Gert
dc.contributor.authorOst, Piet
dc.contributor.authorRazack, Azad
dc.contributor.authorLim, Jasmine
dc.contributor.authorTeo, Soo-Hwang
dc.contributor.authorLin, Daniel W
dc.contributor.authorNewcomb, Lisa F
dc.contributor.authorLessel, Davor
dc.contributor.authorGamulin, Marija
dc.contributor.authorKulis, Tomislav
dc.contributor.authorKaneva, Radka
dc.contributor.authorUsmani, Nawaid
dc.contributor.authorSinghal, Sandeep
dc.contributor.authorSlavov, Chavdar
dc.contributor.authorMitev, Vanio
dc.contributor.authorParliament, Matthew
dc.contributor.authorClaessens, Frank
dc.contributor.authorJoniau, Steven
dc.contributor.authorVan den Broeck, Thomas
dc.contributor.authorLarkin, Samantha
dc.contributor.authorTownsend, Paul A
dc.contributor.authorAukim-Hastie, Claire
dc.contributor.authorGago-Dominguez, Manuela
dc.contributor.authorCastelao, Jose Esteban
dc.contributor.authorMartinez, Maria Elena
dc.contributor.authorRoobol, Monique J
dc.contributor.authorJenster, Guido
dc.contributor.authorvan Schaik, Ron HN
dc.contributor.authorMenegaux, Florence
dc.contributor.authorTruong, Thérèse
dc.contributor.authorKoudou, Yves Akoli
dc.contributor.authorXu, Jianfeng
dc.contributor.authorKhaw, Kay-Tee
dc.contributor.authorCannon-Albright, Lisa
dc.contributor.authorPandha, Hardev
dc.contributor.authorMichael, Agnieszka
dc.contributor.authorThibodeau, Stephen N
dc.contributor.authorMcDonnell, Shannon K
dc.contributor.authorSchaid, Daniel J
dc.contributor.authorLindstrom, Sara
dc.contributor.authorTurman, Constance
dc.contributor.authorMa, Jing
dc.contributor.authorHunter, David J
dc.contributor.authorRiboli, Elio
dc.contributor.authorSiddiq, Afshan
dc.contributor.authorCanzian, Federico
dc.contributor.authorKolonel, Laurence N
dc.contributor.authorLe Marchand, Loic
dc.contributor.authorHoover, Robert N
dc.contributor.authorMachiela, Mitchell J
dc.contributor.authorCui, Zuxi
dc.contributor.authorKraft, Peter
dc.contributor.authorAmos, Christopher I
dc.contributor.authorConti, David V
dc.contributor.authorEaston, Douglas
dc.contributor.authorWiklund, Fredrik
dc.contributor.authorChanock, Stephen J
dc.contributor.authorHenderson, Brian E
dc.contributor.authorKote-Jarai, Zsofia
dc.contributor.authorHaiman, Christopher A
dc.contributor.authorEeles, Rosalind A
dc.contributor.authorProfile Study
dc.contributor.authorAustralian Prostate Cancer BioResource (APCB)
dc.contributor.authorIMPACT Study
dc.contributor.authorCanary PASS Investigators
dc.contributor.authorBreast and Prostate Cancer Cohort Consortium (BPC3)
dc.contributor.authorPRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium
dc.contributor.authorCancer of the Prostate in Sweden (CAPS)
dc.contributor.authorProstate Cancer Genome-wide Association Study of Uncommon Susceptibility Loci (PEGASUS)
dc.contributor.authorGenetic Associations and Mechanisms in Oncology (GAME-ON)/Elucidating Loci Involved in Prostate Cancer Susceptibility (ELLIPSE) Consortium
dc.date.accessioned2018-02-12T15:42:03Z
dc.date.accessioned2018-07-10T09:20:53Z
dc.date.available2018-02-12T15:42:03Z
dc.date.available2018-07-10T09:20:53Z
dc.date.issued2018-07
dc.identifier.issn1061-4036
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/277937
dc.description.abstractGenome-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.
dc.format.mediumPrint-Electronic
dc.languageeng
dc.publisherSpringer Science and Business Media LLC
dc.relation.replaceshttps://www.repository.cam.ac.uk/handle/1810/273150
dc.relation.replaces1810/273150
dc.subjectProfile Study
dc.subjectAustralian Prostate Cancer BioResource (APCB)
dc.subjectIMPACT Study
dc.subjectCanary PASS Investigators
dc.subjectBreast and Prostate Cancer Cohort Consortium (BPC3)
dc.subjectPRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium
dc.subjectCancer of the Prostate in Sweden (CAPS)
dc.subjectProstate Cancer Genome-wide Association Study of Uncommon Susceptibility Loci (PEGASUS)
dc.subjectGenetic Associations and Mechanisms in Oncology (GAME-ON)/Elucidating Loci Involved in Prostate Cancer Susceptibility (ELLIPSE) Consortium
dc.subjectHumans
dc.subjectProstatic Neoplasms
dc.subjectGenetic Predisposition to Disease
dc.subjectRisk
dc.subjectCase-Control Studies
dc.subjectGenotype
dc.subjectPolymorphism, Single Nucleotide
dc.subjectMale
dc.subjectGenome-Wide Association Study
dc.subjectGenetic Loci
dc.titleAssociation analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci.
dc.typeArticle
prism.endingPage936
prism.issueIdentifier7
prism.publicationDate2018
prism.publicationNameNat Genet
prism.startingPage928
prism.volume50
dc.identifier.doi10.17863/CAM.18848
dc.identifier.doi10.17863/CAM.25271
dcterms.dateAccepted2018-04-05
rioxxterms.versionofrecord10.1038/s41588-018-0142-8
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2018-07
dc.contributor.orcidSchumacher, Fredrick R [0000-0002-3073-7463]
dc.contributor.orcidFachal Vilar, Laura [0000-0002-7256-9752]
dc.contributor.orcidDennis, Joe [0000-0003-4591-1214]
dc.contributor.orcidTyrer, Jonathan [0000-0003-3724-4757]
dc.contributor.orcidPharoah, Paul [0000-0001-8494-732X]
dc.contributor.orcidDunning, Alison [0000-0001-6651-7166]
dc.contributor.orcidKhaw, Kay-Tee [0000-0002-8802-2903]
dc.contributor.orcidEaston, Douglas [0000-0003-2444-3247]
dc.identifier.eissn1546-1718
rioxxterms.typeJournal Article/Review
pubs.funder-project-idNational Institutes of Health (NIH) (via University of Southern California) (1 U19 CA148537-01)
pubs.funder-project-idCancer Research UK (16565)
pubs.funder-project-idMedical Research Council (G0401527)
pubs.funder-project-idMedical Research Council (G1000143)
pubs.funder-project-idMedical Research Council (MR/N003284/1)
pubs.funder-project-idNational Cancer Institute (U19CA148537)
pubs.funder-project-idNational Cancer Institute (U19CA148065)
pubs.funder-project-idNational Cancer Institute (R01CA128978)
pubs.funder-project-idEuropean Commission (223175)
pubs.funder-project-idCancer Research UK (A16563)
pubs.funder-project-idCancer Research UK (A12014)
pubs.funder-project-idCancer Research UK (A10118)
cam.issuedOnline2018-06-11
rioxxterms.freetoread.startdate2018-12-11


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