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dc.contributor.authorMavaddat, Nasim
dc.contributor.authorMichailidou, Kyriaki
dc.contributor.authorDennis, Joe
dc.contributor.authorLush, Michael
dc.contributor.authorFachal, Laura
dc.contributor.authorLee, Andrew
dc.contributor.authorTyrer, Jonathan P
dc.contributor.authorChen, Ting-Huei
dc.contributor.authorWang, Qin
dc.contributor.authorBolla, Manjeet K
dc.contributor.authorYang, Xin
dc.contributor.authorAdank, Muriel A
dc.contributor.authorAhearn, Thomas
dc.contributor.authorAittomäki, Kristiina
dc.contributor.authorAllen, Jamie
dc.contributor.authorAndrulis, Irene L
dc.contributor.authorAnton-Culver, Hoda
dc.contributor.authorAntonenkova, Natalia N
dc.contributor.authorArndt, Volker
dc.contributor.authorAronson, Kristan J
dc.contributor.authorAuer, Paul L
dc.contributor.authorAuvinen, Päivi
dc.contributor.authorBarrdahl, Myrto
dc.contributor.authorBeane Freeman, Laura E
dc.contributor.authorBeckmann, Matthias W
dc.contributor.authorBehrens, Sabine
dc.contributor.authorBenitez, Javier
dc.contributor.authorBermisheva, Marina
dc.contributor.authorBernstein, Leslie
dc.contributor.authorBlomqvist, Carl
dc.contributor.authorBogdanova, Natalia V
dc.contributor.authorBojesen, Stig E
dc.contributor.authorBonanni, Bernardo
dc.contributor.authorBørresen-Dale, Anne-Lise
dc.contributor.authorBrauch, Hiltrud
dc.contributor.authorBremer, Michael
dc.contributor.authorBrenner, Hermann
dc.contributor.authorBrentnall, Adam
dc.contributor.authorBrock, Ian W
dc.contributor.authorBrooks-Wilson, Angela
dc.contributor.authorBrucker, Sara Y
dc.contributor.authorBrüning, Thomas
dc.contributor.authorBurwinkel, Barbara
dc.contributor.authorCampa, Daniele
dc.contributor.authorCarter, Brian D
dc.contributor.authorCastelao, Jose E
dc.contributor.authorChanock, Stephen J
dc.contributor.authorChlebowski, Rowan
dc.contributor.authorChristiansen, Hans
dc.contributor.authorClarke, Christine L
dc.contributor.authorCollée, J Margriet
dc.contributor.authorCordina-Duverger, Emilie
dc.contributor.authorCornelissen, Sten
dc.contributor.authorCouch, Fergus J
dc.contributor.authorCox, Angela
dc.contributor.authorCross, Simon S
dc.contributor.authorCzene, Kamila
dc.contributor.authorDaly, Mary B
dc.contributor.authorDevilee, Peter
dc.contributor.authorDörk, Thilo
dc.contributor.authorDos-Santos-Silva, Isabel
dc.contributor.authorDumont, Martine
dc.contributor.authorDurcan, Lorraine
dc.contributor.authorDwek, Miriam
dc.contributor.authorEccles, Diana M
dc.contributor.authorEkici, Arif B
dc.contributor.authorEliassen, A Heather
dc.contributor.authorEllberg, Carolina
dc.contributor.authorEngel, Christoph
dc.contributor.authorEriksson, Mikael
dc.contributor.authorEvans, D Gareth
dc.contributor.authorFasching, Peter A
dc.contributor.authorFigueroa, Jonine
dc.contributor.authorFletcher, Olivia
dc.contributor.authorFlyger, Henrik
dc.contributor.authorFörsti, Asta
dc.contributor.authorFritschi, Lin
dc.contributor.authorGabrielson, Marike
dc.contributor.authorGago-Dominguez, Manuela
dc.contributor.authorGapstur, Susan M
dc.contributor.authorGarcía-Sáenz, José A
dc.contributor.authorGaudet, Mia M
dc.contributor.authorGeorgoulias, Vassilios
dc.contributor.authorGiles, Graham G
dc.contributor.authorGilyazova, Irina R
dc.contributor.authorGlendon, Gord
dc.contributor.authorGoldberg, Mark S
dc.contributor.authorGoldgar, David E
dc.contributor.authorGonzález-Neira, Anna
dc.contributor.authorGrenaker Alnæs, Grethe I
dc.contributor.authorGrip, Mervi
dc.contributor.authorGronwald, Jacek
dc.contributor.authorGrundy, Anne
dc.contributor.authorGuénel, Pascal
dc.contributor.authorHaeberle, Lothar
dc.contributor.authorHahnen, Eric
dc.contributor.authorHaiman, Christopher A
dc.contributor.authorHåkansson, Niclas
dc.contributor.authorHamann, Ute
dc.contributor.authorHankinson, Susan E
dc.contributor.authorHarkness, Elaine F
dc.contributor.authorHart, Steven N
dc.contributor.authorHe, Wei
dc.contributor.authorHein, Alexander
dc.contributor.authorHeyworth, Jane
dc.contributor.authorHillemanns, Peter
dc.contributor.authorHollestelle, Antoinette
dc.contributor.authorHooning, Maartje J
dc.contributor.authorHoover, Robert N
dc.contributor.authorHopper, John L
dc.contributor.authorHowell, Anthony
dc.contributor.authorHuang, Guanmengqian
dc.contributor.authorHumphreys, Keith
dc.contributor.authorHunter, David J
dc.contributor.authorJakimovska, Milena
dc.contributor.authorJakubowska, Anna
dc.contributor.authorJanni, Wolfgang
dc.contributor.authorJohn, Esther M
dc.contributor.authorJohnson, Nichola
dc.contributor.authorJones, Michael E
dc.contributor.authorJukkola-Vuorinen, Arja
dc.contributor.authorJung, Audrey
dc.contributor.authorKaaks, Rudolf
dc.contributor.authorKaczmarek, Katarzyna
dc.contributor.authorKataja, Vesa
dc.contributor.authorKeeman, Renske
dc.contributor.authorKerin, Michael J
dc.contributor.authorKhusnutdinova, Elza
dc.contributor.authorKiiski, Johanna I
dc.contributor.authorKnight, Julia A
dc.contributor.authorKo, Yon-Dschun
dc.contributor.authorKosma, Veli-Matti
dc.contributor.authorKoutros, Stella
dc.contributor.authorKristensen, Vessela N
dc.contributor.authorKrüger, Ute
dc.contributor.authorKühl, Tabea
dc.contributor.authorLambrechts, Diether
dc.contributor.authorLe Marchand, Loic
dc.contributor.authorLee, Eunjung
dc.contributor.authorLejbkowicz, Flavio
dc.contributor.authorLilyquist, Jenna
dc.contributor.authorLindblom, Annika
dc.contributor.authorLindström, Sara
dc.contributor.authorLissowska, Jolanta
dc.contributor.authorLo, Wing-Yee
dc.contributor.authorLoibl, Sibylle
dc.contributor.authorLong, Jirong
dc.contributor.authorLubiński, Jan
dc.contributor.authorLux, Michael P
dc.contributor.authorMacInnis, Robert J
dc.contributor.authorMaishman, Tom
dc.contributor.authorMakalic, Enes
dc.contributor.authorMaleva Kostovska, Ivana
dc.contributor.authorMannermaa, Arto
dc.contributor.authorManoukian, Siranoush
dc.contributor.authorMargolin, Sara
dc.contributor.authorMartens, John WM
dc.contributor.authorMartinez, Maria Elena
dc.contributor.authorMavroudis, Dimitrios
dc.contributor.authorMcLean, Catriona
dc.contributor.authorMeindl, Alfons
dc.contributor.authorMenon, Usha
dc.contributor.authorMiddha, Pooja
dc.contributor.authorMiller, Nicola
dc.contributor.authorMoreno, Fernando
dc.contributor.authorMulligan, Anna Marie
dc.contributor.authorMulot, Claire
dc.contributor.authorMuñoz-Garzon, Victor M
dc.contributor.authorNeuhausen, Susan L
dc.contributor.authorNevanlinna, Heli
dc.contributor.authorNeven, Patrick
dc.contributor.authorNewman, William G
dc.contributor.authorNielsen, Sune F
dc.contributor.authorNordestgaard, Børge G
dc.contributor.authorNorman, Aaron
dc.contributor.authorOffit, Kenneth
dc.contributor.authorOlson, Janet E
dc.contributor.authorOlsson, Håkan
dc.contributor.authorOrr, Nick
dc.contributor.authorPankratz, V Shane
dc.contributor.authorPark-Simon, Tjoung-Won
dc.contributor.authorPerez, Jose IA
dc.contributor.authorPérez-Barrios, Clara
dc.contributor.authorPeterlongo, Paolo
dc.contributor.authorPeto, Julian
dc.contributor.authorPinchev, Mila
dc.contributor.authorPlaseska-Karanfilska, Dijana
dc.contributor.authorPolley, Eric C
dc.contributor.authorPrentice, Ross
dc.contributor.authorPresneau, Nadege
dc.contributor.authorProkofyeva, Darya
dc.contributor.authorPurrington, Kristen
dc.contributor.authorPylkäs, Katri
dc.contributor.authorRack, Brigitte
dc.contributor.authorRadice, Paolo
dc.contributor.authorRau-Murthy, Rohini
dc.contributor.authorRennert, Gad
dc.contributor.authorRennert, Hedy S
dc.contributor.authorRhenius, Valerie
dc.contributor.authorRobson, Mark
dc.contributor.authorRomero, Atocha
dc.contributor.authorRuddy, Kathryn J
dc.contributor.authorRuebner, Matthias
dc.contributor.authorSaloustros, Emmanouil
dc.contributor.authorSandler, Dale P
dc.contributor.authorSawyer, Elinor J
dc.contributor.authorSchmidt, Daniel F
dc.contributor.authorSchmutzler, Rita K
dc.contributor.authorSchneeweiss, Andreas
dc.contributor.authorSchoemaker, Minouk J
dc.contributor.authorSchumacher, Fredrick
dc.contributor.authorSchürmann, Peter
dc.contributor.authorSchwentner, Lukas
dc.contributor.authorScott, Christopher
dc.contributor.authorScott, Rodney J
dc.contributor.authorSeynaeve, Caroline
dc.contributor.authorShah, Mitul
dc.contributor.authorSherman, Mark E
dc.contributor.authorShrubsole, Martha J
dc.contributor.authorShu, Xiao-Ou
dc.contributor.authorSlager, Susan
dc.contributor.authorSmeets, Ann
dc.contributor.authorSohn, Christof
dc.contributor.authorSoucy, Penny
dc.contributor.authorSouthey, Melissa C
dc.contributor.authorSpinelli, John J
dc.contributor.authorStegmaier, Christa
dc.contributor.authorStone, Jennifer
dc.contributor.authorSwerdlow, Anthony J
dc.contributor.authorTamimi, Rulla M
dc.contributor.authorTapper, William J
dc.contributor.authorTaylor, Jack A
dc.contributor.authorTerry, Mary Beth
dc.contributor.authorThöne, Kathrin
dc.contributor.authorTollenaar, Rob AEM
dc.contributor.authorTomlinson, Ian
dc.contributor.authorTruong, Thérèse
dc.contributor.authorTzardi, Maria
dc.contributor.authorUlmer, Hans-Ulrich
dc.contributor.authorUntch, Michael
dc.contributor.authorVachon, Celine M
dc.contributor.authorvan Veen, Elke M
dc.contributor.authorVijai, Joseph
dc.contributor.authorWeinberg, Clarice R
dc.contributor.authorWendt, Camilla
dc.contributor.authorWhittemore, Alice S
dc.contributor.authorWildiers, Hans
dc.contributor.authorWillett, Walter
dc.contributor.authorWinqvist, Robert
dc.contributor.authorWolk, Alicja
dc.contributor.authorYang, Xiaohong R
dc.contributor.authorYannoukakos, Drakoulis
dc.contributor.authorZhang, Yan
dc.contributor.authorZheng, Wei
dc.contributor.authorZiogas, Argyrios
dc.contributor.authorABCTB Investigators
dc.contributor.authorkConFab/AOCS Investigators
dc.contributor.authorNBCS Collaborators
dc.contributor.authorDunning, Alison M
dc.contributor.authorThompson, Deborah J
dc.contributor.authorChenevix-Trench, Georgia
dc.contributor.authorChang-Claude, Jenny
dc.contributor.authorSchmidt, Marjanka K
dc.contributor.authorHall, Per
dc.contributor.authorMilne, Roger L
dc.contributor.authorPharoah, Paul DP
dc.contributor.authorAntoniou, Antonis C
dc.contributor.authorChatterjee, Nilanjan
dc.contributor.authorKraft, Peter
dc.contributor.authorGarcía-Closas, Montserrat
dc.contributor.authorSimard, Jacques
dc.contributor.authorEaston, Douglas F
dc.date.accessioned2018-12-22T00:31:37Z
dc.date.available2018-12-22T00:31:37Z
dc.date.issued2019-01-03
dc.identifier.issn0002-9297
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/287410
dc.description.abstractStratification of women according to their risk of breast cancer based on polygenic risk scores (PRSs) could improve screening and prevention strategies. Our aim was to develop PRSs, optimized for prediction of estrogen receptor (ER)-specific disease, from the largest available genome-wide association dataset and to empirically validate the PRSs in prospective studies. The development dataset comprised 94,075 case subjects and 75,017 control subjects of European ancestry from 69 studies, divided into training and validation sets. Samples were genotyped using genome-wide arrays, and single-nucleotide polymorphisms (SNPs) were selected by stepwise regression or lasso penalized regression. The best performing PRSs were validated in an independent test set comprising 11,428 case subjects and 18,323 control subjects from 10 prospective studies and 190,040 women from UK Biobank (3,215 incident breast cancers). For the best PRSs (313 SNPs), the odds ratio for overall disease per 1 standard deviation in ten prospective studies was 1.61 (95%CI: 1.57-1.65) with area under receiver-operator curve (AUC) = 0.630 (95%CI: 0.628-0.651). The lifetime risk of overall breast cancer in the top centile of the PRSs was 32.6%. Compared with women in the middle quintile, those in the highest 1% of risk had 4.37- and 2.78-fold risks, and those in the lowest 1% of risk had 0.16- and 0.27-fold risks, of developing ER-positive and ER-negative disease, respectively. Goodness-of-fit tests indicated that this PRS was well calibrated and predicts disease risk accurately in the tails of the distribution. This PRS is a powerful and reliable predictor of breast cancer risk that may improve breast cancer prevention programs.
dc.format.mediumPrint-Electronic
dc.languageeng
dc.publisherElsevier BV
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectABCTB Investigators
dc.subjectkConFab/AOCS Investigators
dc.subjectNBCS Collaborators
dc.subjectHumans
dc.subjectBreast Neoplasms
dc.subjectGenetic Predisposition to Disease
dc.subjectReceptors, Estrogen
dc.subjectMedical History Taking
dc.subjectRisk Assessment
dc.subjectReproducibility of Results
dc.subjectAge Factors
dc.subjectMultifactorial Inheritance
dc.subjectPolymorphism, Single Nucleotide
dc.subjectAdult
dc.subjectAged
dc.subjectAged, 80 and over
dc.subjectMiddle Aged
dc.subjectFemale
dc.titlePolygenic Risk Scores for Prediction of Breast Cancer and Breast Cancer Subtypes.
dc.typeArticle
prism.endingPage34
prism.issueIdentifier1
prism.publicationDate2019
prism.publicationNameAm J Hum Genet
prism.startingPage21
prism.volume104
dc.identifier.doi10.17863/CAM.34714
dcterms.dateAccepted2018-11-03
rioxxterms.versionofrecord10.1016/j.ajhg.2018.11.002
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2019-01
dc.contributor.orcidMavaddat, Nasim [0000-0003-0307-055X]
dc.contributor.orcidDennis, Joe [0000-0003-4591-1214]
dc.contributor.orcidFachal Vilar, Laura [0000-0002-7256-9752]
dc.contributor.orcidLee, Andrew [0000-0003-0677-0252]
dc.contributor.orcidTyrer, Jonathan [0000-0003-3724-4757]
dc.contributor.orcidWang, Jean [0000-0002-9139-0627]
dc.contributor.orcidAllen, Jamie [0000-0002-8677-2225]
dc.contributor.orcidRhenius, Valerie [0000-0003-4215-3235]
dc.contributor.orcidDunning, Alison [0000-0001-6651-7166]
dc.contributor.orcidThompson, Deborah [0000-0003-1465-5799]
dc.contributor.orcidPharoah, Paul [0000-0001-8494-732X]
dc.contributor.orcidAntoniou, Antonis [0000-0001-9223-3116]
dc.contributor.orcidEaston, Douglas [0000-0003-2444-3247]
dc.identifier.eissn1537-6605
rioxxterms.typeJournal Article/Review
pubs.funder-project-idCancer Research Uk (None)
pubs.funder-project-idMedical Research Council (MR/P012930/1)
pubs.funder-project-idNational Cancer Institute (U19CA148065)
pubs.funder-project-idEuropean Commission (223175)
pubs.funder-project-idEuropean Commission Horizon 2020 (H2020) Societal Challenges (634935)
pubs.funder-project-idEuropean Commission Horizon 2020 (H2020) Societal Challenges (633784)
pubs.funder-project-idCancer Research UK (A10710)
pubs.funder-project-idCancer Research UK (A16563)
pubs.funder-project-idCancer Research UK (A10118)
cam.issuedOnline2018-12-13


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Attribution-NonCommercial-NoDerivatives 4.0 International
Except where otherwise noted, this item's licence is described as Attribution-NonCommercial-NoDerivatives 4.0 International