碱基切除修复基因ape1 ogg1 xrcc1多态性与肺癌遗传易感性研究-study on polymorphism of ape 1 ogg 1 xr cc1 gene and genetic susceptibility of lung cancer.docxVIP

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碱基切除修复基因ape1 ogg1 xrcc1多态性与肺癌遗传易感性研究-study on polymorphism of ape 1 ogg 1 xr cc1 gene and genetic susceptibility of lung cancer.docx

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碱基切除修复基因ape1 ogg1 xrcc1多态性与肺癌遗传易感性研究-study on polymorphism of ape 1 ogg 1 xr cc1 gene and genetic susceptibility of lung cancer

GeneticpolymorphismofDNAbase-excisionrepairgenes(APE1,OGG1andXRCC1)andtheircorrelationwithriskoflungcancerAbstractLungcancerisamongthemostandlife-threateningmalignanciesworldwide,withthehighestincidenceandmortalityratesandoverall5-yearsurvivalrateof15%.Smokingisthemajorcauseoflungcancer,whichaccountsforabout80-90%oflungcancerincidentcases;nonetheless,only10-15%ofsmokersdeveloplungcancer,andafractionoflifelongnon-smokerswilldiefromlungcancer,suggestingthatlungcancerisamultifactorialdiseasethatresultsfromcomplexinteractionwithmanygeneticandenvironmentalfactors.Genepolymorphismisdecidedtoindividualdiseasesusceptibility,phenotypeanddifferenceoftreatreactive,oneofthemostimportantandthemostcommonisthesinglenucleotidepolymorphis(SNP).SNPinindividualshaverecentlybeenimplicatedtoaccountforsomeoftheobserveddifferencesinlungcancersusceptibility.Reactiveoxygenspecies(ROS)producedbycigarettesmokingandmanyothercarcinogenscaninducevarioustypesofDNAdamage,inwhichthe8-oxo-Gisthemostcommonoxidativebasedamagehappenedtoaguaninebase.AsoneoftheDNArepairpathways,theDNAbaseexcisionrepair(BER)pathwayrepairstheDNAbasedamagecausedbyoxidativereagentsandalkylationandthusprotectscellsagainstthetoxiceffectsofendogenousandexogenousagents.BERgenepolymorphismasmoleculargeneticsbasisofDNArepairability,maybeimportanttolungcancerrisk.8-oxoguanineglycosylase-1(OGG1),X-rayrepaircross-complementing-1(XRCC1)andapurinic/apyimidinicendonuclease1(APE1)genesarethreekeyenzymesinBERpathway.AndtherearesomestudiesinvolvingrelationbetweenOGG1,XRCC1andAPE1polymorphismsandcancerriskfocusedoncancersofthebladder,breast,esophagusandcervixuteri.ThelungcancerriskwasgenerallycorrelatedwithpolymorphismsofoneortwoofthesethreeDNArepairgenes,whilethejointeffectsofthesethreegeneswerenotreportedyet.Therefore,weassumedthatthepolymorphismsofDNABERgenesOOG1,XRCC1andAPE1mayhaveajointeffectandcontributetotheriskoflungcancertogether.Inthisstudy,wetestedthishypothesisinahospital-basedstudyof455patientswithincidentlungcancerand443cancer