Early Life Exposure to Famine and Colorectal Cancer Risk A Role for Epigenetic Mechanisms 英文参考文献.docVIP

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Early Life Exposure to Famine and Colorectal Cancer Risk A Role for Epigenetic Mechanisms 英文参考文献.doc

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Early Life Exposure to Famine and Colorectal Cancer Risk A Role for Epigenetic Mechanisms 英文参考文献

EarlyLifeExposuretoFamineandColorectalCancerRisk: ARoleforEpigeneticMechanisms LauraA.E.Hughes1,PietA.vandenBrandt1,AdriaanP.deBru?¨ne2,KimA.D.Wouters2 ,Sarah Hulsmans2,AngelaSpiertz3,R.AlexandraGoldbohm3,AntonF.P.M.deGoeij2,JamesG.Herman4, MattyP.Weijenberg1,ManonvanEngeland2* 1DepartmentofEpidemiology,GROWSchoolforOncologyandDevelopmentalBiology,MaastrichtUniversityMedicalCenter,Maastricht,TheNetherlands,2Department ofPathology,GROWSchoolforOncologyandDevelopmentalBiology,MaastrichtUniversityMedicalCenter,Maastricht,TheNetherlands,3DepartmentofPreventionand Health,TNOQualityofLife,Leiden,TheNetherlands,4SidneyKimmelComprehensiveCancerCenter,JohnHopkinsUniversitySchoolofMedicine,Baltimore,Maryland, UnitedStatesofAmerica Abstract Background:Exposuretoenergyrestrictionduringchildhoodandadolescenceisassociatedwithalowerriskofdeveloping colorectal cancer (CRC). Epigenetic dysregulation during this critical period of growth and development may be a mechanism to explain such observations. Within the Netherlands Cohort Study on diet and cancer, we investigated the association between early life energyrestriction andrisk ofsubsequent CRC characterized by the(promoter) CpG island methylationphenotype(CIMP). Methodology/PrincipalFindings:Informationondietandriskfactorswascollectedbybaselinequestionnaire(n=120,856). Threeindicatorsofexposurewereassessed:placeofresidenceduringtheHungerWinter(1944–45)andWorldWarIIyears (1940–44),andfather’semploymentstatusduringtheEconomicDepression(1932–40).MethylationspecificPCR(MSP)on DNA from paraffin embedded tumor tissue was performed to determine CIMP status according to the Weisenberger markers.After7.3yearsoffollow-up,603casesand4631sub-cohortmemberswereavailableforanalysis.Coxregression was used to calculate hazard ratios (HR) and 95% confidence intervals for CIMP+ (27.7%) and CIMP- (72.3%) tumors accordingtothethreetimeperiodsofenergyrestriction,adjustedforageandgender.Individualsexposedtoseverefamine during the Hunger Winter had a