Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer.
Alison P KleinBrian M WolpinHarvey A RischRachael Z Stolzenberg-SolomonEvelina MocciMingfeng ZhangFrederico CanzianErica J ChildsJason W HoskinsAshley JermusykJun ZhongFei ChenDemetrius AlbanesGabriella AndreottiAlan A ArslanAna BabicWilliam R BamletLaura Beane-FreemanSonja I BerndtAmanda BlackfordMichael BorgesAyelet BorgidaPaige M BracciLauren BraisPaul BrennanHermann BrennerBas Bueno-de-MesquitaJulie BuringDaniele CampaGabriele CapursoGiulia Martina CavestroKari G RabeCharles C ChungSean ClearyMichelle CotterchioFrederike DijkEric J DuellLenka ForetovaCharles FuchsNiccola FunelSteven GallingerJ Michael M GazianoMaria GazouliGraham G GilesEdward GiovannucciMichael GogginsGary E GoodmanPhyllis J GoodmanThilo HackertChristopher HaimanPatricia HartgeManal HasanPeter HegyiKathy J HelzlsouerJoseph HermanIvana HolcatovaElizabeth A HollyRobert HooverRayjean J HungEric J JacobsKrzysztof JamroziakVladimir JanoutRudolf KaaksKay-Tee KhawEric E KleinManolis KogevinasCharles KooperbergMatthew H KulkeJuozas KupcinskasRobert J KurtzDaniel LaheruStefano LandiRita T LawlorI-Min LeeLoic LeMarchandChangquan LingNúria MalatsAndrea MambriniSatu MannistoJonathan BeesleyBeatrice Mohelníková-DuchoňováRachel E NealeJohn P NeoptolemosAnn L ObergSara H OlsonIrene OrlowClaudio PasqualiAlpa V PatelUlrike PetersRaffaele PezzilliMiquel PortaFrancisco X RealNathaniel RothmanGhislaine SceloHoward D SessoGianluca SeveriXiao-Ou ShuDebra SilvermanJill P SmithPavel SoucekMalin SundRenata Talar-WojnarowskaFrancesca TavanoMark D ThornquistGeoffrey S TobiasStephen K Van den EedenYogesh VashistKala VisvanathanPavel VodickaJean Wactawski-WendeZhaoming WangNicolas WentzensenEmily WhiteHerbert YuKai YuAnne Zeleniuch-JacquotteQuan LongPeter KraftDonghui LiStephen ChanockOfure ObazeeGloria M PetersenLaufey T AmundadottirPublished in: Nature communications (2018)
In 2020, 146,063 deaths due to pancreatic cancer are estimated to occur in Europe and the United States combined. To identify common susceptibility alleles, we performed the largest pancreatic cancer GWAS to date, including 9040 patients and 12,496 controls of European ancestry from the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4). Here, we find significant evidence of a novel association at rs78417682 (7p12/TNS3, P = 4.35 × 10-8). Replication of 10 promising signals in up to 2737 patients and 4752 controls from the PANcreatic Disease ReseArch (PANDoRA) consortium yields new genome-wide significant loci: rs13303010 at 1p36.33 (NOC2L, P = 8.36 × 10-14), rs2941471 at 8q21.11 (HNF4G, P = 6.60 × 10-10), rs4795218 at 17q12 (HNF1B, P = 1.32 × 10-8), and rs1517037 at 18q21.32 (GRP, P = 3.28 × 10-8). rs78417682 is not statistically significantly associated with pancreatic cancer in PANDoRA. Expression quantitative trait locus analysis in three independent pancreatic data sets provides molecular support of NOC2L as a pancreatic cancer susceptibility gene.
Keyphrases
- genome wide
- end stage renal disease
- dna methylation
- systematic review
- chronic kidney disease
- newly diagnosed
- ejection fraction
- copy number
- case control
- peritoneal dialysis
- genome wide association study
- prognostic factors
- poor prognosis
- randomized controlled trial
- machine learning
- immune response
- electronic health record
- single molecule