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EPIDEMIOLOGYFactorsinfluencingtheassociationbetweenCYP17T34Cpolymorphismandtheriskofbreastcancer:meta-regressionandsubgroupanalysisYunChen•JianpingPeiReceived:11December2009/Accepted:12December2009/Publishedonline:31December2009�SpringerScience+BusinessMedia,LLC.2009AbstractAnumberofstudieshavebeeninvestigatedtheassociationbetweenCYP17T34Cpolymorphismandtheriskofbreastcancer;theresultsofthesestudiesareinconsistent,however.ThisfactimpliesthattheeffectofCYP17T34Cpolymorphismonsusceptibilitytobreastcancermaybemodifiedbyotherriskfactors.Inordertoprovideamoredefinitiveconclusion,afullmeta-analysiscombiningandsummarizing24studieswasfirstper-formed.BothtraditionalmethodandBayesianapproachwereapplied.Oddsratiowasestimatedusingadominantmodeofinheritanceafterabiologicaljustificationforthechoiceofgeneticmodel.Theresultsofhomogeneityanalysis(H=1.16,I2=25.4%,andP=0.127)sug-gestedthepresenceofheterogeneityacrossthestudies.Thus,randomeffectsmodelssimulatedbytheDerSimo-nian–Lairdmethodwereemployed.ThecapabilityofaBayesianapproachwashighlightedintheestimationofapooledoddsratioand95%confidenceinterval.Theresultsofmeta-analysis(OR=1.001,CI=0.832–1.208)suggestnosignificantassociationinthecombinedpopulations.Furthermore,Bayesianmeta-regressionandsubgroupanalysiswereconductedtoinvestigatethesourcesofhet-erogeneity.Theriskfactorsevaluatedinthestudyweremenopausalstatus,ethnicity,ageatmenarche,ageatfirstbirth,parity,useoforalcontraceptives,bodymassindex(BMI),anduseofhormonerepairtherapy(HRT).Afterthesepopulationstratifications,therewasevidenceindi-catingthatapossibleimpactofmenopausalstatus,ageatmenarche,andBMIontheassociationbetweenCYP17T34Cpolymorphismandtheriskofbreastcancer.KeywordsCYP17�Polymorphism�Breastcancer�Bayesianmeta-regression�Subgroupmeta-analysisIntroductionBreastcanceristhesecondleadingcauseofcancerdeathsinwomentoday.Exposuretocirculatingestrogenhasbeenwidelyacceptedasanimportantfactorfortheriskofbreastcancer.Sinceestrogenbiosynthesisandmetabolismconsistofmanytranslationandtranscriptionsteps,thegenesinvolvedintheseprocessesmaycontributetothelevelofestrogen,therebytheinherentvariabilityinsusceptibilitytobreastcancer[1,2].Amongthegenesidentified,BRCA1andBRCA2havebeenassociatedwithadominantlyinheritedincreasedriskofthedisease[3,4].However,theyonlyaccountforabout5%ofbreastcanceroccurrences[5].Thisfactleavesthepossibilitythatlow-penetrancegeneticfactorsarelikelytoexplainmostofdiseasecases[6].OnesuchcandidateisCYP17.Itencodescytochromep450c17A,whichmediatesactivitiesessentialfortheproductionofendogenoussteroidhormones,likeandrogenandestrogen[7,8].Todate,muchattentionhasbeenfocusedonasinglenucleotidepolymorphism(SNP)inCYP17gene,aT(A1)?C(A2)substitutionat34basepairupstreamofthetranslationinitiationsite(T34C)ofCYP17(rs743572)[9].ThesubstitutionwasthoughttocreateanadditionalSP1-type(CCACCbox)bindingsiteinElectronicsupplementarymaterialTheonlineversionofthisarticle(doi:10.1007/s10549-009-0690-9)containssupplementarymaterial,whichisavailabletoauthorizedusers.Y.Chen(&)DepartmentofPharmacology,NanjingMedicalUniversity,140HanzhongRoad,Nanjing210029,Chinae-mail:ychen@njmu.edu.cn;yun.chen.chem@gmail.comJ.PeiJiangsuProvincialJiaotongPlanningandDesignInstitute,Nanjing210005,China123BreastCancerResTreat(2010)122:471–481DOI10.1007/s10549-009-0690-9promoterregion,enhanceCYP17transcription,a...