Associations between Gene Expression Variations and Ovarian Cancer Risk Alleles Identified from Genome Wide Association Studies 英文参考文献.docVIP

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Associations between Gene Expression Variations and Ovarian Cancer Risk Alleles Identified from Genome Wide Association Studies 英文参考文献.doc

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Associations between Gene Expression Variations and Ovarian Cancer Risk Alleles Identified from Genome Wide Association Studies 英文参考文献

AssociationsbetweenGeneExpressionVariationsand OvarianCancerRiskAllelesIdentifiedfromGenome WideAssociationStudies HuaZhao1*,JieShen1,DanWang2,StevenGregory1,LeonardoMedico1,QiangHu2,LiYan2, KunleOdunsi3,ShashikantLele3,SongLiu2* 1DepartmentofCancerPreventionandControls,RoswellParkCancerInstitute,Buffalo,NewYork,UnitedStatesofAmerica,2DepartmentofBiostatistics,RoswellPark CancerInstitute,Buffalo,NewYork,UnitedStatesofAmerica,3DepartmentofGynecologicOncology,RoswellParkCancerInstitute,Buffalo,NewYork,UnitedStatesof America Abstract Functionalgeneticvariationsplayimportantrolesinshapingphenotypicdifferencesamongindividualsthroughaffecting geneexpression,andthus,verylikelytoinfluencediseasesusceptibility,suchascancersusceptibility.Onecriticalquestion in this era of post-genome wide association studies (GWAS) is how to assess the functional significance of the genetic variationsidentifiedfromGWAS.Inthecurrentstudy,withlymphoblastoidcelllines(LCLs)from74non-relatedwomenwith familialovariancancerand47unrelatedcontrolsmatchedongenderandrace,weexploredtheassociationsbetweenseven ovariancancerriskvariantsidentifiedfromGWAS(rs3814113on9p22.2,rs2072590on2q31,rs2665390on3q25,r rs1516982,rn8q24.21,andrs2363956on19p13)andwholegenomemRNAexpressionprofiles.Weobserved95 significanttrans-associations atapermutationlevelof0.001.Comparedtotheotherriskvariants, rrs1516982, andrn8q24.21hadthegreatestnumberofsignificantassociations(25,16,and38,respectively).Twopossible cis-associationswereobservedbetweenrndc-Myc,andrs2072590andHS.565379(PermutatedP=0.0198and 0.0399, respectively). Pathway enrichment analysis showed that several key biological pathways, such as cell cycle (P=2, etc, were significantly overrepresented. Further characterization of significant associations between mRNAsandriskallelesmightfacilitateunderstandingthefunctionsofGWASdiscoveredriskallelesinthegeneticetiology ofovariancancer. Citation:ZhaoH,ShenJ,Wa