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
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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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