Genetic Variation in Telomere Maintenance Genes, Telomere Length and Breast Cancer Risk 英文参考文献.docVIP

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Genetic Variation in Telomere Maintenance Genes, Telomere Length and Breast Cancer Risk 英文参考文献.doc

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Genetic Variation in Telomere Maintenance Genes, Telomere Length and Breast Cancer Risk 英文参考文献

GeneticVariationinTelomereMaintenanceGenes, TelomereLengthandBreastCancerRisk JingShen1*,MaryBethTerry2,YuyanLiao2,IrinaGurvich1,QiaoWang1,RubyT.Senie2, ReginaM.Santella1 1DepartmentofEnvironmentalHealthSciences,MailmanSchoolofPublicHealth,ColumbiaUniversity,NewYork,NewYork,UnitedStatesofAmerica,2Departmentof Epidemiology,MailmanSchoolofPublicHealth,ColumbiaUniversity,NewYork,NewYork,UnitedStatesofAmerica Abstract Background:Telomeresattheendsofeukaryoticchromosomesplayacriticalroleinmaintainingtheintegrityandstability ofthegenomeandparticipateintheinitiationofDNAdamage/repairresponses. Methods:Weperformedacase-controlstudytoevaluatetheroleofthreeSNPs(TERT-07,TERT-54andPOT1-03)intelomere maintenance genes previously found to be significantly associated with breast cancer risk. We used sister-sets obtained fromtheNewYorksiteoftheBreastCancerFamilyRegistry(BCFR).Amongthe313sister-sets,therewere333breastcancer cases and 409 unaffected sisters who were evaluated in the current study. We separately applied conditional logistic regressionandgeneralizedestimatingequations(GEE)modelstoevaluateassociationsbetweenthethreeSNPsandbreast cancer risk within sister-sets. We examined the associations between genotype, covariates and telomere length among unaffectedsistersusingaGEEmodel. Results:WefoundnosignificantassociationsbetweenthethreeSNPsintelomeremaintenancegenesandbreastcancer riskbybothconditionallogisticregressionandGEEmodels,norweretheseSNPssignificantlyrelatedtotelomerelength. Amongunaffectedsisters,shortenedtelomereswerestatisticallysignificantlycorrelatedwithneverhormonereplacement therapy(HRT)use.IncreaseddurationofHRTusewassignificantlyassociatedwithreducedtelomerelength.Themeansof telomerelengthwere0.77(SD=0.35)forneverHRTuse,0.67(SD=0.29)forHRTuse,5yrsand0.59(SD=0.24)forHRTuse $5yrsafteradjustingforageofblooddonationandraceandethnicity. Conclusions:Wefoundthatexogenoushormonalexposurewasinverselyassociatedwithtelomerelength.Nosignificant associations between ge