Pancreatic Cancer Susceptibility Loci and Their Role in Survival 英文参考文献.docVIP

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Pancreatic Cancer Susceptibility Loci and Their Role in Survival 英文参考文献.doc

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Pancreatic Cancer Susceptibility Loci and Their Role in Survival 英文参考文献

PancreaticCancerSusceptibilityLociandTheirRolein Survival CosmeriRizzato1.,DanieleCampa1.,NathaliaGiese2,JensWerner2,P.SivaramakrishnaRachakonda1, RajivKumar1,MichaelaSchanne′1,WilliamGreenhalf3,EithneCostello3,Kay-teeKhaw4,TimJ.Key5, AfshanSiddiq6,JustoLorenzo-Bermejo7,BarbaraBurwinkel1,8,JohnP.Neoptolemos3,MarkusW. Bu¨chler2,Jo¨rgD.Hoheisel1,AndreaBauer1,FedericoCanzian1* 1GermanCancerResearchCenter(DKFZ),Heidelberg,Germany,2ClinicforGeneral,VisceralandTransplantationSurgery,UniversityofHeidelberg,Heidelberg,Germany, 3Pancreas Biomedical Research Unit and the Liverpool Experimental Cancer Medicine Centre, National Institute for Health Research, Liverpool, United Kingdom, 4UniversityofCambridgeSchoolofClinicalMedicine,Cambridge,UnitedKingdom,5CancerEpidemiologyUnit,UniversityofOxford,Oxford,UnitedKingdom,6Imperial College,London,UnitedKingdom,7InstituteofMedicalBiometryandInformatics,UniversityHospitalHeidelberg,Heidelberg,Germany,8DivisionMolecularBiologyof BreastCancer,DepartmentofGynecologyandObstetrics,UniversityofHeidelberg,Heidelberg,Germany Abstract Pancreaticcancerhasoneoftheworstmortalityratesofallcancers.Littleisknownaboutitsetiology,particularlyregarding inheritedrisk.ThePanScanproject,agenome-wideassociationstudy,identifiedseveralcommonpolymorphismsaffecting pancreaticcancersusceptibility.Singlenucleotidepolymorphisms(SNPs)inABO,sonichedgehog(SHH),telomerasereverse transcriptase(TERT),nuclearreceptorsubfamily5,groupA,member2(NR5A2)werefoundtobeassociatedwithpancreatic cancer risk. Moreover the scan identified loci on chromosomes 13q22.1 and 15q14, to which no known genes or other functionalelements aremapped.We soughttoreplicatethese observations intwoadditional, independentpopulations (fromGermanyandtheUK),andalsoevaluatethepossibleimpactoftheseSNPsonpatientsurvival.Wegenotyped15SNPs in690casesofpancreaticductaladenocarcinoma(PDAC)andin1277healthycontrols.Wereplicatedseveralassociations between SNPs and PDAC risk. Furthermore we found that SNP rs802