女性肺癌——流行病学，生物学和治疗上的

776LenoThomas,MD;L.AustinDoyle,MD;andMartinJ.Edelman,MDDNA(DNArepair);(estrogenreceptor);(humanpapillomavirus);(non-smallcelllungcancer);(smallcelllungcancer)1.2.200417370013%29%[1]30y4(1)2010[2](relativerisksRRs)FromtheUniversityofMarylandGreenebaumCancerCenter,Baltimore,MD.Correspondenceto:MartinJ.Edelman,MD,UniversityofMarylandGreenebaumCancerCenter,22SouthGreeneSt,Baltimore,MD21201;e-mail:[e-mail]777(1)85%~90%22[3]20407022%[4]RRZang[5]1.2~1.7(10-y)CT(OR2.7)[6]Bain[7]6[7]RR(environmentaltobaccosmoke,ETS)300024%[8]ETS4-()-1-(3-)-(NNK)1HPVDRCK-ras,10000040200193019401950196019701980199020001Ahmedin[1]778(NNAL-Gluc)[9][10]ETS22y(OR2.495%CI1.1~5.4)[11]30%(P=0.03)[12~14][15][16](OR2.78)(OR4.14P=0.07)[12,17]Schwartz[12](ORs1.70.5)[18]50.4(95%CI0.2~0.8)[18][19]10y4692427512y772835194~8y(RR0.68;95%CI0.49~0.94)63%[20][21][22](humanpapillomavirusHPV)HPV611HPV1618(polymerasechainreactionPCR)()49%HPVDNA[23][24]HPVDNA(1618)HPVYousem[25]HPV6/116/1831/33/35[26,27]HPVDNA(6111618)HPV[28~30]3215PCRHPV1512HPV[30]HPVETS100N-779(P450)()DNADNADNA[31,32]DNAP4501A1(CYP1A1)()[33]159DNA-y(22.935.0P=9.410-5)(56.262.2P=0.034)DNA(15.3912.08108DNAP=0.047)-PCRGAPDHCYP1A1(494334CYP1A1mRNA/106GAPDHmRNA210208P=0.016)[32]Dresler[34]CYP1A1(OR4.981.37)SM1(glutathioneS-transferaseM1GSM1)GSM1[35]()CYP1A1(OR6.542.36)GSM1ETSETSGSM1GSM1OR2.6ETS[36][37]p53[90%(smallcelllungcancersSCLCs)]40%~70%(non-smallcelllungcancers,NSCLCs)](K-ras)p53DNAG1G2DNAp53DNADNAp53DNA[38]RasK-rasp53DNA[39]K-ras3[40,41][42,43]RasK-ras[44~50](gastrinreleasingpeptidereceptorGRPR)NSCLC[51,52]GRPRXX[53]ERBB2(HER-2/neu)4ERB-B25%~30%HER-2/neu780NSCLC27%~63%[54]NSCLC[55]HER-2/neu(7.110.9moP=0.004)[56,57]HER-2/neuHER-2/neu[58]trastuzamb(HER-2/neu)[59]DNADNA(DNArepaircapaci-ty,DRC)DNAWei[60]DNA(316)(316)1DNA()(60)DRC[60]764677[61]DRCDNADRC(DNAERCCI)NSCLC[62]RNA[63]Stabile[64](estrogenreceptoER)ERα();ERαERERββ-173.8DNA[65,66]-α-1[67]ERERp29[68]Yang[69]ER5yER(72.5%8.8%)(hormonereplacementtherapyHRT)Adami[70]HRT(RR1.26)Taioli[71]HRT(ORs1.732.4)(OR0.3)DNAETSERs[72]HRT499781(OR0.5995%CI0.38~0.92)[73]Moore[74]5114676(P0.0001)(58%48%P0.0001)()(23)2070Edmonson[75]312262NSCLC(1)//MSTHRP%O'Connell[85]/MSKCC19861978198637830~(2)12.48.80.710.001Mitsudomi[78]/Kyushu19891974198849227~60380.630.00036Sorenson/Finsen19891981198525946~(3)6.86.81.00.5Ferguson[80]/(4)199019741989299()45~12.19.10.750.044244()2411.17.10.640.08Shinkai/19921982198919229~(2)14.69.10.620.02Albain[90]/SWOG199119741988253123~(5)NSNS0.770.00005Paesmans[89]/ELCWP199519801991105210~(2)NSNS0.70(RR)0.03(1)HRNSMS(2)(3)(4)(5)772(SCLC)3SCLC//MSTHRP%Johnson[88]/19881973198637828LDED,/13100.770.002Albain[90]/SWOG199019761988136332LD/NSNS0.77(RR)0.0001121728EDNANA0.91(RR)0.35Paesmans[89]/ELCWP20001982199376311LDED11.110.20.91(1)0.16(1)(1)CoxHR0.71(P=0.02)MST78250[76][77]1995199820561RR11.21(P=0.001)(5023.3%12%P0.001)(21.6%96%P0.001)SCLC(26.6%19.9%P0.001)(18.8%2.4%P0.001)RR(1.15P=0.001)NSCLC()NSCLCNSCLC[76](P=0.0234)(P=0.0036Minami[79]1242(79.6%85.2%)(510y69%51%)6060[79]Ferguson[80]19801990451(41.8mo26.9mo)(109.8mo50.3moP=0.0008)coxFEV1[80]Werner-Wasik[81]1983199491999()11.49.9mo3()(SouthwestOncologyGroupSWOG)[81]ABNSCLC/21mo12mo(P=0.08)Albain[83]1974198713SWOG25310.77[83]/5.7/4.81y19%14%(P0.01)(EuropeanLungCancerWorkingPartyELCWP)19801991NSCLC1052[84]238RR0.7(P=0.03)O’Connell[85]378Karnofsky80(lactatedehydrogenaseLDH)0-1[86](35mo41moP=0.12)(P0.01)91(21)NSCLC[87]ERCC1Her2RXRβ-2783[88]2.5yELCWP7635y(80%69%)(P=0.16)(OR1.82;95%CI1.00~3.34P=0.05)(10%)[89]10SWOGSCLC2580(limiteddiseaseLD)(extensive-stagediseaseED)6SWOGLD(01)70LDH(P0.00124.4mo17.7mo)[90]SWOGED[90]LDH(bronchio-lalveolarcarcinomaBAC)()/BAC[91][92]NSCLC[93]BACgefinitiberlotinibgefinitib(IRESSA)(IRESSADoseEvaluationinAdvancedLungCancerIDEAL)1IDEAL2NSCLC[94,95]()[95,96]IDEAL2[95]50%31%(P=0.006)19%3%(P=0.001)gefinitiberlotinibNSCLC23[97]1~2015y1.62115y4ORsSCLC[98]14ySCLC19%(12%)10ySCLC65%47%SCLC784(gefitniberlotinib)1AhmedinJA,etal.CACancerJClin2004;54:8−292PatelJD,etal.JAMA2004;291:1763−17683UnitedStatesSurgeonGeneral.Reducingthehealthconsequences:25yearsofprogress.Washington,DC:USGovernmentPrintingOffice,19894Areportofthesurgeongeneral:womenandsmoking.MMWRMorbMortalWklyRep2002.Availableat::183−1926HenschkeCI,etal.LungCancer2004;43:1−57BainC,etal.JNatlCancerInst2004;96:826−8348HackshawAK,etal.BMJ1997;315:980−9889AndersonKE,etal.JNatlCancerInst2001;93:378−38110StockwellHG,etal.JNatlCancerInst1992;84:1417−142211FonthamET,etal.JAMA1994;271:1752−175912SchwartzAG,etal.AmJEpidemiol1996;144:554−56213OoiWL,etal.JNatlCancerInst1986;76:217−22214WuAH,etal.CancerRes1988;48:7279−728415TokuhataGK,etal.JNatlCancerInst1963;30:289−31216MayneST,etal.CancerEpidemiolBiomarkersPrev1999;8:1065−106917WuAH,etal.AmJEpidemiol1996;143:535−54218Sp