Allelic Variation at the 8q23.3 Colorectal Cancer Risk Locus Functions as a Cis-Acting Regulator of EIF3H 英文参考文献.docVIP

Allelic Variation at the 8q23.3 Colorectal Cancer Risk Locus Functions as a Cis-Acting Regulator of EIF3H 英文参考文献.doc

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Allelic Variation at the 8q23.3 Colorectal Cancer Risk Locus Functions as a Cis-Acting Regulator of EIF3H 英文参考文献

AllelicVariationatthe8q23.3ColorectalCancerRisk LocusFunctionsasaCis-ActingRegulatorofEIF3H AlanM.Pittman1,SilviaNaranjo2,SanniE.Jalava3,PhilipTwiss1,YussanneMa1,BiancaOlver1 ,Amy Lloyd1,JayaramVijayakrishnan1,MobshraQureshi1,PeterBroderick1,TomvanWezel4,HansMorreau4, SariTuupanen5,LauriA.Aaltonen5,M.EvaAlonso6,MiguelManzanares6,AngelaGavila′n7 ,Tapio Visakorpi3,Jose′ LuisGo′mez-Skarmeta2,RichardS.Houlston1* 1SectionofCancerGenetics,InstituteofCancerResearch,Sutton,UnitedKingdom,2CentroAndaluzdeBiolog?′adelDesarrollo,CSIC-UPO,Seville,Spain,3Instituteof MedicalTechnology,UniversityofTampereandTampereUniversityHospital,Tampere,Finland,4DepartmentofPathology,LeidenUniversityMedicalCenter,Leiden,The Netherlands,5DepartmentofMedicalGenetics,UniversityofHelsinki,Helsinki,Finland,6CentroNacionaldeInvestigacionesCardiovasculares,Madrid,Spain,7Centro NacionaldeInvestigacionesBiome′dica enRedEnfermedadesRaras(CIBERER),UniversidadPablodeOlavide-CSIC,Seville,Spain Abstract Commongeneticvariationathuman8q23.3issignificantlyassociatedwithcolorectalcancer(CRC)risk.Toelucidatethe basisofthisassociationwecomparedthefrequencyofcommonvariantsat8q23.3in1,964CRCcasesand2,081healthy controls. Reporter gene studies showed that the single nucleotide polymorphism racts as an allele-specific transcriptional repressor. Chromosome conformation capture (3C) analysis demonstrated that the genomic region harboringrnteractswiththepromoterofgeneforeukaryotictranslationinitiationfactor3,subunitH(EIF3H) .We show that increased expression of EIF3H gene increases CRC growth and invasiveness thereby providing a biological mechanismforthe8q23.3association.Thesedataprovideevidenceforafunctionalbasisforthenon-codingriskvariant rt8q23.3andprovidesnovelinsightintotheetiologicalbasisofCRC. Citation: Pittman AM, Naranjo S,Jalava SE, Twiss P, Ma Y, et al.(2010) Allelic Variation at the 8q23.3 Colorectal Cancer Risk Locus Functions asa Cis-Acting RegulatorofEIF3H.PLoSGenet6(9):e100

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