Identification of nine new susceptibility loci for endometrial cancer.
Tracy A O'MaraDylan M GlubbFrederic AmantDaniela AnnibaliKatie AshtonJohn Richard AttiaPaul L AuerMatthias W BeckmannAmanda BlackManjeet K BollaHiltrud B BrauchHermann BrennerLouise BrintonDaniel D BuchananBarbara BurwinkelJenny Chang-ClaudeStephen J ChanockChu ChenMaxine M ChenTimothy H T ChengChristine L ClarkeMark ClendenningLinda S CookFergus J CouchAngela CoxMarta Crous-BousKamila CzeneFelix R DayJoe G DennisJeroen DepreeuwJennifer Anne DohertyThilo DörkSean C DowdyMatthias DürstArif B EkiciPeter Andreas FaschingBrooke L FridleyChristine M FriedenreichLin FritschiJenny FungMontserrat García-ClosasMia M GaudetGraham G GilesEllen L GoodeMaggie GormanChristopher A HaimanPer HallSusan E HankisonCatherine S HealeyAlexander HeinPeter HillemannsShirley HodgsonErling A HoivikElizabeth G HollidayJohn L HopperDavid J HunterAngela JonesCamilla KrakstadVessela N KristensenDiether LambrechtsLoic Le MarchandXiaolin LiangAnnika LindblomJolanta LissowskaJirong LongChangquan LingAnthony M MaglioccoLynn MartinMark McEvoyAlfons MeindlKyriaki MichailidouJonathan BeesleyMiriam MintsGrant W MontgomeryRami NassirHåkan OlssonIrene OrlowGeoffrey OttonClaire PallesJohn R B PerryJulian PetoLoreall PoolerJennifer PrescottTony ProiettoTimothy R RebbeckHarvey A RischPeter A W RogersMatthias RübnerIngo RunnebaumCarlotta SacerdoteGloria E SartoFredrick SchumacherRodney J ScottV Wendy SetiawanMitul ShahXin ShengXiao-Ou ShuMelissa C SoutheyAnthony J SwerdlowEmma ThamJone TrovikConstance TurmanJonathan P TyrerCeline VachonDavid VanDen BergAdriaan VandersticheleZhaoming WangPenelope M WebbNicolas WentzensenHenrica M J WernerStacey J WinhamAlicja WolkLucy XiaYong-Bing XiangHannah P YangHerbert YuQuan LongPaul David Peter PharoahAlison M DunningPeter KraftImmaculata De VivoIan P M TomlinsonDouglas F EastonAmanda B SpurdleDeborah J ThompsonPublished in: Nature communications (2018)
Endometrial cancer is the most commonly diagnosed cancer of the female reproductive tract in developed countries. Through genome-wide association studies (GWAS), we have previously identified eight risk loci for endometrial cancer. Here, we present an expanded meta-analysis of 12,906 endometrial cancer cases and 108,979 controls (including new genotype data for 5624 cases) and identify nine novel genome-wide significant loci, including a locus on 12q24.12 previously identified by meta-GWAS of endometrial and colorectal cancer. At five loci, expression quantitative trait locus (eQTL) analyses identify candidate causal genes; risk alleles at two of these loci associate with decreased expression of genes, which encode negative regulators of oncogenic signal transduction proteins (SH2B3 (12q24.12) and NF1 (17q11.2)). In summary, this study has doubled the number of known endometrial cancer risk loci and revealed candidate causal genes for future study.
Keyphrases
- endometrial cancer
- genome wide
- genome wide association
- genome wide association study
- dna methylation
- copy number
- systematic review
- poor prognosis
- transcription factor
- signaling pathway
- case control
- high resolution
- gene expression
- machine learning
- squamous cell carcinoma
- oxidative stress
- randomized controlled trial
- immune response
- cell proliferation
- young adults