啟東肝癌發(fā)生機理的病例對照研究.pdf

1、復(fù)旦大學(xué)碩士學(xué)位論文啟東肝癌發(fā)生機理的病例對照研究姓名：羅海濤申請學(xué)位級別：碩士專業(yè)：流行病學(xué)指導(dǎo)教師：錢耕蓀2001.4.15星呈查堂坌莖里圭蘭墮圭墮史壁墮塹窒墮堡圭嬰塑生蘭垡堡奎Case—controlStudiesfortheMechanismofHepatocellularcarcinogenesisinQidongAreaAbstractHepatocellula書arcinogenesisisalongprocesswith

2、multiplephasesinvolvingman。yfactorsmV，AFB1，andMCarethe3majorenvironmentalriskfactorstoHCC，whilethepeople’SsusceptibilitytoHCCalsoaccountsQidongiSanareawithahighHCCincidenceofmorethan50／105formanyyearsandrecentlyreachedaH

3、CCincidenceof60／105_70／10’，withmostpatientsbeingmaleToexplorewhichfactorsaremoreimportantinQidong’ShepatocellularcarcinogenesisthisstudyinvestigatedmanyriskfactorsinvolvedintheHCCrelatedtoHBVandAFB1Weconductedcase—contr0

4、1studiestoresearchthediffeFencesinAFB1exposure，HBxAgexpressioninhepatictissues，phaseIIdetoxificationenzymeGSTgenepolymorphism，andp53overexpressioninhepatictissuesbetweenHCCpatientsandnormalcontrolsOurstudyrevealedsignifi

5、cantlyhigherexpressionsofcytoplasmicHBsAgandcytoplasmicp53inHCC—adjacenttissuesthanHCCtissues，withthe2expressionshavingasignificantcorrelationinHCCadjacenttissuesAndwealsevealedasignificantlyhigherexpressionofnuclearp53i

6、nHCCthanHCC—aajacenttissuesTheseresultssuggestthatinQidong’ShepatocellularcarcinogenesisHBVmayfunctionallyinactivatethetumorsuppressorgenep53byacombinationofHBsAgtOp53proteininthecytoplasm，andputthe1ivercelltomoreriskofh

7、epatocellularcarcinogenesisbecauseofthelostofp53’SprotectionAndintheHCCtissues，thenuclearp53mayhavemutatedbecauseoftheattackofcarcinogenssuchasAFB1andalsolostthetumorsuppressorfunctionThisiSthefunctionallyinactivationoft

8、hetumorsuppressorgenep53byHBVontheproteinlevelandbycarcinogensfAFB11ontheDNAlevelThecombinationofthe2riskfactorsmaycausethehighincidenceofHCCinOidongarea0urstudyalsorevealedasignificantdifferenceinAFBlexposurebetweenHCCp

9、atientsandnormalcontrolsBecauseweadoptedaprospectivecase—contr01(nestedcase—contr01)studytheserausedherecouldreflectthereallongtermexposuretoAFB1ofthepatientsandweovercamethelimitsofretrospective(case—contr01)studyandpro

10、spectivecohortstudy，verifiedagaintherelationshipbetweentheexposuretoAFB1andhepatocellularcarcinogenesisinOidongareawithlargersamplesizeOurstudydidnotfindthesignificantdifferenceofGSTgenepolymorphismbetweenHCCpatientsandn