Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer.
Jonathan BeesleyKaroline B KuchenbaeckerKyriaki MichailidouJonathan BeesleySiddhartha KarSara LindströmShirley HuiAudrey LemaçonPenny SoucyJoe DennisXia JiangAsha RostamianfarHilary FinucaneManjeet K BollaLesley McGuffogQin WangCora M Aalfsnull nullMarcia AdamsJulian AdlardSimona AgataShahana AhmedHabibul AhsanKristiina AittomäkiFares Al-EjehJamie AllenChristine B AmbrosoneChristopher I AmosIrene L AndrulisHoda Anton-CulverNatalia N AntonenkovaVolker ArndtNorbert ArnoldKristan J AronsonBernd AuberPaul L AuerMargreet G E M AusemsJacopo AzzolliniFrançois BacotJudith BalmañaMonica BarileLaure BarjhouxRosa B BarkardottirMyrto BarrdahlDaniel BarnesDaniel BarrowdaleCaroline BaynesMatthias W BeckmannJavier BenitezMarina BermishevaLeslie BernsteinYves-Jean BignonKathleen R BlazerMarinus J BlokCarl BlomqvistWilliam BlotKristie BobolisBram BoeckxNatalia V BogdanovaAnders BojesenStig E BojesenBernardo BonanniAnne-Lise Børresen-DaleAniko BozsikAngela R BradburyJudith S BrandHiltrud BrauchHermann BrennerBrigitte Bressac-de PailleretsCarole BrewerLouise BrintonPer BrobergAngela Brooks-WilsonJoan BrunetThomas BrüningBarbara BurwinkelSaundra S BuysJinyoung ByunQiuyin CaiTrinidad CaldésMaria A CaligoIan CampbellFederico CanzianOlivier CaronAngel CarracedoBrian D CarterJ Esteban CastelaoLaurent CasteraVirginie Caux-MoncoutierSalina B ChanJenny Chang-ClaudeStephen J ChanockXiaoqing ChenTing-Yuan David ChengJocelyne ChiquetteHans ChristiansenKathleen B M ClaesChristine L ClarkeThomas ConnerDon M ConroyJackie CookEmilie Cordina-DuvergerSten CornelissenIsabelle CoupierAngela CoxDavid G CoxSimon S CrossKatarina CukJulie M CunninghamKamila CzeneMary B DalyFrancesca DamiolaHatef DarabiRosemarie DavidsonKim De LeeneerPeter DevileeEd DicksOrland DiezYuan Chun DingNina DitschKimberly F DohenySusan M DomchekCecilia M DorflingThilo DörkIsabel Dos-Santos-SilvaStéphane DuboisPierre-Antoine DuguéMartine DumontAlison M DunningLorraine DurcanMiriam DwekBernd DworniczakDiana EcclesRos EelesHans EhrencronaUrsula EilberBent EjlertsenArif B EkiciA Heather Eliassennull nullChristoph EngelMikael ErikssonLaura FachalLaurence FaivrePeter A FaschingUlrike FaustJonine FigueroaDieter Flesch-JanysOlivia FletcherHenrik FlygerWilliam D FoulkesEitan FriedmanLin FritschiDebra FrostMarike GabrielsonPragna GaddamMarilie D GammonPatricia A GanzSusan M GapsturJudy GarberVanesa Garcia-BarberanJosé A García-SáenzMia M GaudetMarion Gauthier-VillarsAndrea Gehrignull nullVassilios GeorgouliasAnne-Marie GerdesGraham G GilesGord GlendonAndrew K GodwinMark S GoldbergDavid E GoldgarAnna González-NeiraPaul GoodfellowMark H GreeneGrethe I Grenaker AlnæsMervi GripJacek GronwaldAnne GrundyDaphne Gschwantler-KaulichPascal GuénelQi GuoLothar HaeberleEric HahnenChristopher A HaimanNiclas HåkanssonEmily HallbergUte HamannNathalie HamelSusan HankinsonThomas V O HansenPatricia HarringtonSteven N HartJaana M HartikainenCatherine S Healeynull nullAlexander HeinSonja HelbigAlex HendersonJane HeyworthBelynda HicksPeter HillemannsShirley HodgsonFrans B HogervorstAntoinette HollestelleMaartje J HooningBob HooverJohn L HopperChunling HuGuanmengqian HuangPeter J HulickKeith HumphreysDavid J HunterEvgeny N ImyanitovClaudine IsaacsMotoki IwasakiLouise IzattAnna JakubowskaPaul JamesRamunas JanaviciusWolfgang JanniUffe Birk JensenEsther M JohnNichola JohnsonKristine JonesMichael JonesArja Jukkola-VuorinenRudolf KaaksMaria KabischKatarzyna KaczmarekDaehee KangKarin Kastnull nullRenske KeemanMichael J KerinCarolien M KetsMachteld KeupersSofia KhanElza KhusnutdinovaJohanna I KiiskiSung-Won KimJulia A KnightIrene KonstantopoulouVeli-Matti KosmaVessela N KristensenTorben A KruseAva KwongAnne-Vibeke LænkholmYael LaitmanFiona LallooDiether LambrechtsKeren LandsmanChristine LassetConxi LazaroLoic Le MarchandJulie LecarpentierAndrew LeeEunjung LeeJong Won LeeMin Hyuk LeeFlavio LejbkowiczFabienne LesueurJingmei LiJenna LilyquistAnne LincolnAnnika LindblomJolanta LissowskaWing-Yee LoSibylle LoiblJirong LongJennifer T LoudJan LubinskiCraig LuccariniMichael LushRobert J MacInnisTom MaishmanEnes MakalicIvana Maleva KostovskaKathleen E MaloneSiranoush ManoukianJoAnn E MansonSara MargolinJohn W M MartensMaria Elena MartinezKeitaro MatsuoDimitrios MavroudisSylvie MazoyerCatriona McLeanHanne Meijers-HeijboerPrimitiva MenéndezJeffery MeyerHui MiaoAustin MillerNicola MillerGillian MitchellMarco MontagnaKenneth MuirAnna Marie MulliganClaire MulotSue NadesanKatherine L Nathansonnull nullSusan L NeuhausenHeli NevanlinnaInes NevelsteenDieter NiederacherSune F NielsenBørge G NordestgaardAaron NormanRobert L NussbaumEdith OlahOlufunmilayo I OlopadeJanet E OlsonCurtis OlswoldKai-Ren OngJan C OosterwijkNick OrrAna OsorioV Shane PankratzLaura PapiTjoung-Won Park-SimonYlva Paulsson-KarlssonRachel LloydInge Søkilde PedersenBernard PeisselAna PeixotoJose I A PerezPaolo PeterlongoJulian PetoGeorg PfeilerCatherine M PhelanMila PinchevDijana Plaseska-KaranfilskaBruce PoppeMary E PorteousRoss PrenticeNadege PresneauDarya ProkofievaElizabeth PughMiquel Angel PujanaKatri PylkäsBrigitte RackPaolo RadiceNazneen RahmanJohanna RantalaChristine Rappaport-FuerhauserGad RennertHedy S RennertValerie RheniusKerstin RhiemAndrea RichardsonGustavo C RodriguezAtocha RomeroJane RommMatti A RookusAnja RudolphThomas RuedigerEmmanouil SaloustrosJoyce SandersDale P SandlerSuleeporn SangrajrangElinor J SawyerDaniel F SchmidtMinouk J SchoemakerFredrick SchumacherPeter SchürmannLukas SchwentnerChristopher ScottRodney J ScottSheila SealLeigha SenterCaroline SeynaeveMitul ShahPriyanka SharmaChen-Yang ShenXin ShengHermela ShimelisMartha J ShrubsoleXiao-Ou ShuLucy E SideChristian F SingerChristof SohnMelissa C SoutheyJohn J SpinelliAmanda B SpurdleChrista StegmaierDominique Stoppa-LyonnetGrzegorz SukiennickiHarald SurowyChristian SutterAnthony SwerdlowCsilla I SzaboRulla M TamimiYen Y TanJack A TaylorMaria-Isabel TejadaMaria TengströmSoo H TeoMary B TerryDaniel C TessierAlex TeuléKathrin ThöneDarcy L ThullMaria Grazia TibilettiLaima TihomirovaMarc TischkowitzAmanda E TolandRob A E M TollenaarIan TomlinsonLing TongDiana TorresMartine TranchantThérèse TruongKathy TuckerNadine TungJonathan TyrerHans-Ulrich UlmerCeline VachonChristi J van AsperenDavid Van Den BergAns M W van den OuwelandElizabeth J van RensburgLiliana VarescoRaymonda Varon-MateevaAna VegaAlessandra VielJoseph VijaiDaniel VincentJason VollenweiderLisa WalkerZhaoming WangShan Wang-GohrkeBarbara WappenschmidtClarice R WeinbergJeffrey N WeitzelCamilla WendtJelle WesselingAlice S WhittemoreJuul T WijnenWalter WillettRobert WinqvistAlicja WolkAnna H WuLucy XiaXiaohong R YangDrakoulis YannoukakosDaniela ZaffaroniWei ZhengBin ZhuArgyrios ZiogasElad ZivKristin K ZornManuela Gago-DominguezArto MannermaaHåkan OlssonManuel R TeixeiraJennifer StoneKenneth OffitLaura OttiniSue K ParkMads ThomassenPer HallAlfons MeindlRita K SchmutzlerArnaud DroitGary D BaiderPaul David Peter PharoahFergus J CouchDouglas F EastonPeter KraftGeorgia Chenevix-TrenchMontserrat García-ClosasMarjanka K SchmidtAntonis C AntoniouJacques SimardPublished in: Nature genetics (2017)
Most common breast cancer susceptibility variants have been identified through genome-wide association studies (GWAS) of predominantly estrogen receptor (ER)-positive disease. We conducted a GWAS using 21,468 ER-negative cases and 100,594 controls combined with 18,908 BRCA1 mutation carriers (9,414 with breast cancer), all of European origin. We identified independent associations at P < 5 × 10-8 with ten variants at nine new loci. At P < 0.05, we replicated associations with 10 of 11 variants previously reported in ER-negative disease or BRCA1 mutation carrier GWAS and observed consistent associations with ER-negative disease for 105 susceptibility variants identified by other studies. These 125 variants explain approximately 16% of the familial risk of this breast cancer subtype. There was high genetic correlation (0.72) between risk of ER-negative breast cancer and breast cancer risk for BRCA1 mutation carriers. These findings may lead to improved risk prediction and inform further fine-mapping and functional work to better understand the biological basis of ER-negative breast cancer.