Identification of six new susceptibility loci for invasive epithelial ovarian cancer.
Karoline B KuchenbaeckerSusan J RamusJonathan TyrerAndrew LeeHoward C ShenJonathan BeesleyKate LawrensonLesley McGuffogSue HealeyJanet M LeeTassja J SpindlerYvonne G LinTanja PejovicYukie BeanQiyuan LiSimon CoetzeeDennis HazelettAlexander MironMelissa SoutheyMary Beth TerryDavid E GoldgarSaundra S BuysRamunas JanaviciusCecilia M DorflingElizabeth J van RensburgSusan L NeuhausenYuan Chun DingThomas V O HansenLars JønsonAnne-Marie GerdesBent EjlertsenDaniel BarrowdaleJoe G DennisJavier BenitezAna OsorioMaria Jose GarciaIan KomenakaJeffrey N WeitzelPamela GanschowPaolo PeterlongoLoris BernardAlessandra VielBernardo BonanniBernard PeisselSiranoush ManoukianPaolo RadiceLaura PapiLaura OttiniFlorentia FostiraIrene KonstantopoulouJudy GarberDebra FrostJo PerkinsRadka PlatteSteve Ellisnull nullAndrew K GodwinRita Katharina SchmutzlerAlfons MeindlChristoph EngelChristian SutterOlga M Sinilnikovanull nullFrancesca DamiolaSylvie MazoyerDominique Stoppa-LyonnetKathleen ClaesKim De LeeneerJudy KirkGustavo C RodriguezMarion PiedmonteDavid M O'MalleyMiguel de la HoyaTrinidad CaldesKristiina AittomäkiHeli NevanlinnaJ Margriet ColléeMatti A RookusJan C Oosterwijknull nullLaima TihomirovaNadine TungUte HamannClaudine IsaccsMarc TischkowitzEvgeny N ImyanitovMaria A CaligoIan G CampbellFrans B L Hogervorstnull nullEdith OlahOrland DiezIgnacio BlancoJoan BrunetConxi LazaroMiquel Angel PujanaAnna JakubowskaJacek GronwaldJan LubinskiGrzegorz SukiennickiRosa B BarkardottirMarie PlanteJacques SimardPenny SoucyMarco MontagnaSilvia TognazzoManuel R Teixeiranull nullVernon S PankratzXianshu WangNoralane LindorCsilla I SzaboNoah KauffJoseph VijaiCarol A AghajanianGeorg PfeilerAndreas BergerChristian F SingerMuy-Kheng TeaCatherine M PhelanMark H GreenePhuong L MaiGad RennertAnna Marie MulliganSandrine TchatchouIrene L AndrulisGord GlendonAmanda Ewart TolandUffe Birk JensenTorben A KruseMads ThomassenAnders BojesenJamal ZidanEitan FriedmanYael LaitmanMaria SollerAnnelie LiljegrenBrita ArverZakaria EinbeigiMarie Stenmark-AskmalmOlufunmilayo I OlopadeRobert L NussbaumTimothy R RebbeckKatherine L NathansonSusan M DomchekKaren H LuBeth Y KarlanChristine WalshJenny Lesternull nullnull nullAlexander HeinArif Bülent EkiciMatthias W BeckmannPeter A FaschingDiether LambrechtsEls Van NieuwenhuysenIgnace VergoteSandrina LambrechtsEd DicksJennifer A DohertyKristine G WicklundMary Anne RossingAnja RudolphJenny Chang-ClaudeShan Wang-GohrkeUrsula EilberKirsten B MoysichKunle OdunsiLara SuchestonShashi LeleLynne R WilkensMarc T GoodmanPamela J ThompsonYurii B ShvetsovIngo B RunnebaumMatthias DürstPeter HillemannsThilo DörkNatalia AntonenkovaNatalia BogdanovaArto LeminenLiisa M PelttariRalf ButzowFrancesmary ModugnoJoseph L KelleyRobert P EdwardsRoberta B NessAndreas du BoisFlorian HeitzIra SchwaabPhilipp HarterKeitaro MatsuoSatoyo HosonoSandra OrsulicAllan JensenSusanne Kruger KjaerEstrid HogdallHanis Nazihah HasmadMat Adenan Noor AzmiSoo-Hwang TeoYin-Ling WooBrooke L FridleyEllen L GoodeJulie M CunninghamRobert A VierkantFiona BruinsmaGraham G GilesDong LiangMichelle A T HildebrandtXifeng WuDouglas A LevineMaria BisognaAndrew BerchuckEdwin S IversenJoellen M SchildkrautPatrick ConcannonRachel Palmieri WeberDaniel W CramerKathryn L TerryElizabeth M PooleShelley T TworogerElisa V BanderaIrene OrlowSara H OlsonCamilla KrakstadHelga B SalvesenIngvild L TangenLine BjorgeAnne M van AltenaKatja K H AbenLambertus A KiemeneyLeon F A G MassugerMelissa KellarAngela Brooks-WilsonLinda E KelemenLinda S CookNhu D LeCezary CybulskiHannah YangJolanta LissowskaLouise A BrintonNicolas WentzensenClaus HogdallLene LundvallLotte NedergaardHelen BakerHonglin SongDiana EcclesIan McNeishJames PaulKaren CartyNadeem SiddiquiRosalind GlasspoolAlice S WhittemoreJoseph H RothsteinValerie McGuireWeiva SiehBu-Tian JiWei ZhengXiao-Ou ShuYu-Tang GaoBarry RosenHarvey A RischJohn R McLaughlinSteven A NarodAlvaro N A MonteiroAnn ChenHui-Yi LinJenny Permuth-WeyThomas A SellersYa-Yu TsaiZhihua ChenArgyrios ZiogasHoda Anton-CulverAleksandra Gentry-MaharajUsha MenonPatricia HarringtonAlice W LeeAnna H WuCeleste L PearceGerry CoetzeeMalcolm C PikeAgnieszka Dansonka-MieszkowskaAgnieszka TimorekIwona K RzepeckaJolanta KupryjanczykMatt FreedmanHoutan NoushmehrDouglas F EastonKenneth OffitFergus J CouchSimon GaytherPaul P PharoahAntonis C AntoniouGeorgia Chenevix-Trenchnull nullPublished in: Nature genetics (2015)
Genome-wide association studies (GWAS) have identified 12 epithelial ovarian cancer (EOC) susceptibility alleles. The pattern of association at these loci is consistent in BRCA1 and BRCA2 mutation carriers who are at high risk of EOC. After imputation to 1000 Genomes Project data, we assessed associations of 11 million genetic variants with EOC risk from 15,437 cases unselected for family history and 30,845 controls and from 15,252 BRCA1 mutation carriers and 8,211 BRCA2 mutation carriers (3,096 with ovarian cancer), and we combined the results in a meta-analysis. This new study design yielded increased statistical power, leading to the discovery of six new EOC susceptibility loci. Variants at 1p36 (nearest gene, WNT4), 4q26 (SYNPO2), 9q34.2 (ABO) and 17q11.2 (ATAD5) were associated with EOC risk, and at 1p34.3 (RSPO1) and 6p22.1 (GPX6) variants were specifically associated with the serous EOC subtype, all with P < 5 × 10(-8). Incorporating these variants into risk assessment tools will improve clinical risk predictions for BRCA1 and BRCA2 mutation carriers.