6533b86dfe1ef96bd12ca95e

RESEARCH PRODUCT

Genome-wide association studies identify four ER negative-specific breast cancer risk loci

M. Rosario AlonsoMinh BuiGianluca SeveriGianluca SeveriHanne Meijers-heijboerLorna GibsonPascal GuénelPascal GuénelHidemi ItoKee Seng ChiaDavid Van Den BergMichael P. LuxMichael F. PressChristopher A. HaimanChristine D. BergMagdalena LochmannAnne Sophie DieudonneSune F. NielsenKyriaki MichailidouAns M.w. Van Den OuwelandSue GertyPeter LichtnerWilliam BlotWilliam J. TapperVessela N. KristensenNazneen RahmanDiana EcclesAnnegien BroeksPriyanka SharmaPierre KerbratJonine D. FigueroaAndreas SchneeweissMalcolm W.r. ReedThilo DörkFederico CanzianElisa V. BanderaFrancois BacotKatarzyna JaworskaYon KoMitul ShahMatthias W. BeckmannNichola JohnsonFleur HammetDaniel F. SchmidtDaehee KangMattias JohanssonNicholas G. MartinMartha J. ShrubsoleKatri PylkäsWei ZhengPeter KraftJavier BenitezKay-tee KhawIrene KonstantopoulouDaniel VincentAntoinette HollestelleAndré G. UitterlindenSarah Stewart-brownJianjun LiuJaana M. HartikainenAnja RudolphArto MannermaaElinor J. SawyerGord GlendonDouglas F. EastonClaudia RauhHoda Anton-culverFoluso O. AdemuyiwaVeli-matti KosmaRudolf KaaksPeterlongo PaoloKristen N. StevensArif B. EkiciGrant W. MontgomeryCarolien H.m. Van DeurzenChen-yang ShenChen-yang ShenAndrew H. BeckHelen R. WarrenIan TomlinsonEd DicksThérèse TruongThérèse TruongJacques SimardJ. DennisSuleeporn SangrajrangPetra H.m. PeetersCurtis OlswoldChristine B. AmbrosoneEnes MakalicAnna Marie MulliganHui MiaoWilliam J. HowatFredrick R. SchumacherKirsimari AaltonenW. Ryan DiverWalter C. WillettXiao-ou ShuJennifer StoneRobert PilarskiQin WangMarjanka K. SchmidtIsabel Dos Santos SilvaMelissa C. SoutheyGraham G. GilesGraham G. GilesSimon S. CrossOlivia FletcherDaniel C. TessierJanet E. OlsonKristiina AittomäkiDimitrios TrichopoulosDimitrios TrichopoulosPierre Laurent-puigNils SchoofBertram Müller-myhsokSebastian M. JudPer HallRadice PaoloNorbert DahmenJoellen WeaverFederick MarmeHui CaiChing Wan ChanJorge L. Rodriguez-gilNicola MillerChing-yu ChengRobert N. HooverPei Ei WuRobert WinqvistAlison M. DunningSabapathy P. BalasubramanianRosario TuminoRosemary L. BalleineNick OrrNevanlinna HeliLeslie BernsteinJenny Chang-claudeFergus J. CouchKenneth MuirKenneth MuirMartine DumontJose Ignacio Arias PerezKeitaro MatsuoMia M. GaudetJulia A. KnightJolanta LissowskaLaura J. Van't VeerStefan NickelsAlan AshworthSaila KauppilaSandra Deming-halversonRobert M. MillikanJakubowska AnnaSoo Hwang TeoPaul D.p. PharoahRita K. SchmutzlerJulian PetoYe FengDaniel J. ParkUte HamannGerhard A. CoetzeeBørge G. NordestgaardGary K. ChenPrimitiva MenéndezLoris BernardJulie E. BuringBarbara BurwinkelBarbara BurwinkelChristina JustenhovenChristina JustenhovenGuillermo PitaLars BeckmannR.a.e.m. TollenaarDaniel O. StramStephen J. ChanockAndrew K. GodwinFrançoise Clavel-chapelonFrançoise Clavel-chapelonManjeet K. BollaSue A. InglesMark N. BrookStig E. BojesenStig E. BojesenDieter Flesch-janysC. BlomqvistTuomas HeikkinenIrene L. AndrulisMark S. GoldbergDario GrecoAngela CoxLorraine DurcanYu Tang GaoDennis J. SlamonS. MargolinXianshu WangSusan L. SlagerMichael J. KerinJane CarpenterMaartje J. HooningHeather Spencer FeigelsonLoic Le MarchandCheng Har YipHelen TsimiklisClare TurnbullKamila CzeneFernando RivadeneiraVolker ArndtKarin LeunenTaru A. MuranenCatriona Mclean Georgia Chenevix TrenchAnnika LindblomMieke KriegeYasushi YatabePornthep SiriwanarangsanNur Aishah TaibJennifer J. HuDavid J. HunterHermann BrennerChristof SohnSarah J. NyanteJohn L. HopperMichael G. SchrauderRoger L. MilneHarsh B. PathakPatrick NevenRegina G. ZieglerVesa KatajaConstance ChenPeter DevilleePeter DevilleeChia-ni HsiungHenrik FlygerMichael JonesEsther M. JohnEsther M. JohnQuinten WaisfiszDaniele CampaRebecca HeinRebecca HeinChrista StegmaierAstrid IrwantoHiroji IwataDiether LambrechtsDiether LambrechtsCaroline M. SeynaevePenelope MironSara LindströmAnna González-neiraEmiel J. Th. RutgersLisa B. SignorelloKatarzyna DurdaSusan E. HankinsonSusan E. HankinsonAlfons MeindlLaura BagliettoLaura BagliettoElisabete WeiderpassPeissel BernardQiuyin CaiJan LubinskiRuth C. TravisDaniel I. ChasmanBrian E. HendersonSuhn K. RhieMontserrat Garcia-closasLaurence N. KolonelHiltrud BrauchHiltrud BrauchElio RiboliCeline M. VachonThomas BrüningMikael HartmanNatalia BogdanovaAnna H. WuHeiko MüllerJyh Cherng YuMark E. ShermanNatalia AntonenkovaJirong LongAnthony J. SwerdlowChiu-chen TsengArtitaya LophatananonArja Jukkola-vuorinenWei LuPeter A. FaschingPeter A. Fasching

subject

Oncologygenetic associationbody-mass indexEstrogen receptorGenome-wide association studycancer riskBioinformaticssusceptibilitychromosome 1q0302 clinical medicineRisk Factorssingle nucleotide polymorphismGenotypeestrogenCooperative Behaviorcomparative studyOligonucleotide Array Sequence Analysis0303 health scienceschromosome 16q3. Good healthReceptors Estrogenpriority journal030220 oncology & carcinogenesisFemalecancer invasionsignal transductionbreast cancer; cancer invasion; cancer risk; chromosome 1; chromosome 16q; chromosome 1q; chromosome 2p; comparative study; follow up; gene locus; genetic association; genetic susceptibility; human; nucleotide sequence; priority journal; signal transduction; single nucleotide polymorphismmedicine.medical_specialtyGenotypegene locusBreast NeoplasmsSingle-nucleotide polymorphismBiologyPolymorphism Single NucleotideArticle03 medical and health sciencesBreast cancerbreast cancerMeta-Analysis as TopicSDG 3 - Good Health and Well-beingInternal medicineexpressionGeneticsmedicineGenetic predispositionHumansfollow upGenetic Predisposition to Diseasehumanchromosome 1gene030304 developmental biologyCase-control studyCancernucleotide sequencemedicine.diseasechromosome 2pGenetic LociCase-Control Studiescommon variantGenome-Wide Association Studygenetic susceptibility

description

Estrogen receptor (ER)-negative tumors represent 20-30% of all breast cancers, with a higher proportion occurring in younger women and women of African ancestry. The etiology and clinical behavior of ER-negative tumors are different from those of tumors expressing ER (ER positive), including differences in genetic predisposition. To identify susceptibility loci specific to ER-negative disease, we combined in a metaanalysis 3 genome-wide association studies of 4,193 ER-negative breast cancer cases and 35,194 controls with a series of 40 follow-up studies (6,514 cases and 41,455 controls), genotyped using a custom Illumina array, iCOGS, developed by the Collaborative Oncological Gene-environment Study (COGS). SNPs at four loci, 1q32.1 (MDM4, P= 2.1 x 10(-12) and LGR6, P = 1.4 x 10(-8)), 2p24.1 (P = 4.6 x 10(-8)) and 16q12.2 (FTO, P = 4.0 x 10(-8)), were associated with ER-negative but not ER-positive breast cancer (P> 0.05). These findings provide further evidence for distinct etiological pathways associated with invasive ER-positive and ER-negative breast cancers.

yearjournalcountryeditionlanguage
2013-04-30Nature Genetics
10.1038/ng.2561http://dx.doi.org/10.1038/ng.2561