E-钙黏蛋白基因多态性与胃癌关系的流行病学研究

华中科技大学硕士学位论文E-钙黏蛋白基因多态性与胃癌关系的流行病学研究姓名：甘秀敏申请学位级别：硕士专业：流行病与卫生统计学指导教师：聂绍发;陆云霞20080501IE-1202E-3E--160C/A12021997120082MedlinePubmedCNKIE-ReviewManager4.2.10Stata8.0MetaBeggEggerMeta3883578262TaqmanPCRE--160C/ALogisticOR95%119832002771725.110.77.0:1(P0.05)4417.695.520II2Meta30E--160C/A80368189AC/A+A/AC/C17OR1.1795CI1.061.30AOR0.8595CI0.720.99-347G/GA12151595GAG/G43OR1.4395CI1.051.94Meta3Logistic-160C/AAP0.051202E--160C/AA3E--160C/AAE-MetaIIITheAssociationbetweentheGeneticPolymorphismsofE-cadherinGeneandGastricCancer:AnEpidemiologicalStudyAbstractObjective:1ToestimatethepathologicaldistributionandseculartrendofdetectionofuppergastrointestinaldisordersinanoccupationalpopulationinWuhanfrom1983to2002.2TosystematicallyreviewtheassociationbetweenthepolymorphismsintheE-cadheringenepromoterandtheriskofcancer.3TostudytherelationshipbetweentheC-160ApolymorphismintheE-cadheringenepromoterandtheriskofcancerintheoccupationalpopulation,soastoprovideepidemiologicalevidencesfortheetiologicalmechanismsofgastriccancer.Methods:1RetrospectiveinvestigationwasperformedonthedataofpathologicalrecordsinthehospitalsofWISCO.Chi-squaretestwasusedtoanalyzethedetectioncharacteristicsandtheseculartrendofuppergastrointestinaldisorders.2AcomputerizedliteraturesearchwasperformedintheMedline,PubMed,CNKI(Chinese)etal.DigitalDissertationsDatabaseduringJanuary,1997toFebruary,2008.PaperswereincludediftheymettheinclusioncriteriathatinvestigatedtheassociationbetweenCDH1polymorphismsandtheriskofcancer.Meta-analysiswasconductedbyusingReviewManager4.2.10software,selectingfixedorrandommodelbasedontheheterogeneitytest.CumulativeMeta-analysisandsensitivityanalysisweredonetofurtheranalyzethesourceoftheheterogeneity.ThepublicationbiaswasevaluatedbyBegg’sfunnelplotsanditsasymmetrywastestedbyEgger’slinearregression.3Inthisstudybasedonapopulationsourcecase-controldesign,weincluded88gastriccancer,35atypicalhyperplasia,78intestinalmetaplasiapatientsand262chronicIVsuperficialgastritiscontrolsfrequencymatchedonsampleageandgenotypedanovelC-to-Atransitionatthepromoterregion(-160C/A)ofCDH1byTaqmanPCRmethod.TheassociationsbetweenCDH1variantsandtheriskofdifferentoutcomeswereestimatedbycalculatingtheORsand95%CIsfromLogisticregressionanalysesusingSPSS13.0software.Results:1Therewere7717pathologicalrecordsofuppergastrointestinaldisordersduringthese20years.Theproportionsofpathologicaldetectionofchronicsuperficialgastritisandgastriculcerwerethehighestwith25.1%and10.7%respectively.Thegenderratiosofgastriculcerandduodenalulcerwerebothgreaterthan7.0:1withstatisticalsignificance(P0.05).Forty-fourcasesofesophagealadenocarcinomawerefoundinthetotalcasesofesophagealcancer,95.5%ofthemoccurredinthemiddleandlowthirdoftheesophagus.Theproportionsofatrophicgastritisandgastriccancerweregraduallyincreasingasyearswentby.Theseculartrendsofratesofpathologicaldetectionofesophagealandgastriccancerinthispopulationshowednosignificantchangesduring20years(P0.05).2Ourmeta-analysisontotalof8036cancercasesand8189controlsubjectsfrom30publishedcase-controlstudiesabouttheCDH1-160C/Apolymorphismshowedthatthe-160Aallelecarriers(C/A+A/A),comparedwithnoncarriers,had17%increasedriskofcancer(OR,1.17;95%CI,1.06~1.30).Thestratifiedanalysesrevealedthat,inEuropeans,carriersofthe-160Awithgastriccancerwerefoundtosufferasignificantlyincreasedrisk,whichwasincontrastintheAsians(OR,0.85;95%CI,0.72~0.99).ThecombinedanalysesontheCDH1-347G/GApolymorphismcomprised1215cancercasesand1595controls.Thepooledoddsratioforthevariantgenotypes(G/GA+GA/GA),comparedwiththewild-typehomozygote(G/G),was1.43(95%CI,1.12~1.44)forgastriccancer.Sensitivityanalysesshowedthattheresultsofthissystematicreviewwerenotaffectedbyanystudyordifferentstatisticalmodels.TheBegg’sfunnelplotsdidnotshowevidenceofpublicationbias,neitherbystatisticalanalyseswithEgger’slinearregression.V3Noevidencewasfoundthatthevariantgenotypes(C/A+A/A)wereassociatedwithsignificantlyincreasedriskofgastriccancer,atypicalhyperplasiaandintestinalmetaplasiacomparedwiththe-160C/Cwild-typehomozygote(P0.05).Butduetolowstatisticalpowerofthisstudy,westillneedepidemiologicalstudieswithlargersamplesizetofurtherevaluatethepotentialassociationbetweenCDH1-160C/Apolymorphismandtheriskofgastriccancer.Conclusion:1Therearesignificantdifferencesinagegroupsandgendersfordiseasesofuppergastrointestinaldisorders.Theseculartrendsofesophagealandgastriccancersseemtokeepstable,whichsuggeststhattheriskfactorsofthesecancershaven’tchangedobviouslyin20years.Themostlikelyexplanationsfortheincreaseinproportionofgastriccancermaybetheaccumulationofcasesandthechangesofthemedicalbehaviors.2TheMeta-analysisfindingsindicatethat-160AoftheE-cadheringenepromoterisemergingasalow-penetrancetumorsusceptibilityalleleforthedevelopmentofgastric,prostateandurothelialcancers.3Thisstudyindicatesthatcarriersof-160Aarenotatincreasedriskofgastriccancer.ButwestillneedepidemiologicalstudieswithlargersamplesizetofurtherevaluatethepotentialassociationbetweenCDH1-160C/Apolymorphismandtheriskofgastriccancer.Keywords:Diseasesofuppergas