职业性致癌因素.ppt

职业性致癌因素与职业肿瘤,在工作环境中长期接触致癌因素，经过较长的潜伏期，而患某种特定的肿瘤，称职业性肿瘤（occupationaltumor）。能引起职业性肿瘤的致癌因素，称职业性致癌因素（occupationalcarcinogen）。,1.职业性肿瘤的发病特点1.1好发部位多在致癌因素作用最强烈、最经常的部位发生或直接作用的靶器官。职业性癌的好发部位见下表。,职业性癌的好发部位（摘自FischmanM.L.等，1990，略有修改）职业接触发癌部位4-氨基联苯膀胱砷及砷化合物肺、皮肤？肝、血管肉瘤石棉胸膜与腹膜（间皮瘤）、肺、喉、胃肠道，肾苯骨髓（白血病）联苯胺膀胱双氯甲醚肺六价化合物肺煤焦油沥青皮肤、阴囊、肺、膀胱煤焦油皮肤、阴囊、肺、？膀胱电离辐射白血病、皮肤、其它,职业接触发癌部位未处理或轻度处理的矿物油肺芥子气肺萘胺膀胱镍和镍化合物肺、鼻窦镭骨（肉瘤）氡肺页岩油皮肤、阴囊煤烟、焦油和油类皮肤、肺、？膀胱含石棉纤维的滑石肺、？间皮瘤紫外线皮肤氯乙烯肝（血管肉瘤）、脑、肺,1.2发病条件第一所接触物质的化学结构第二接触途径第三接触剂量和时间1.3发病年龄平均42年，但有长有短，如苯致白血病，最短者仅需4个月。潜伏期多在10年以上，发病年龄以40-50最多见，较非职业性的早10-15年。,致癌因素肿瘤部位潜伏期（年）沥青、煤焦油皮肤20-24矿物油皮肤50-54粗石蜡油皮肤15-18无机砷酸盐皮肤20-24肺25-48电离辐射皮肤20-30肺15-23骨髓（白血病）11-17骨骼（骨肉瘤）10-15石棉肺25-40胸腹膜20-40氯甲醚肺10-24切削油阴囊40-50芳香胺膀胱11-15,职业性肿瘤的潜伏期,1.4病理类型物不同而各具有一定的病理类型，例如铀矿工肺癌大部分为未分化小细胞癌，铬多致鳞癌、未分化小细胞癌。,1.5高危职业有致癌危险的职业（据IARC资料，1987，略加整理）工业过程可能致癌因素铝生产多环芳烃金胺制造金胺靴、鞋制造及修理苯煤气制造、焦炭生产多环芳烃铸铁及铸钢多环芳烃、SiO2、金属烟异丙醇制造（强酸法）二异丙基硫酸酯、二丙基油品红制造品红、前身（即甲土立丁）镍冶炼氧化镍、低硫化镍橡胶工业芳香胺赤铁矿地下开采（氡）氡,2.职业性肿瘤的识别和确认,2.1临床观察阴囊癌与扫烟囱工作；家具制造与鼻窦癌；品红染料与膀胱癌等。2.2实验研究用可疑致癌物作动物诱变实验，观察能否诱发与人类相似的肿瘤，是证明职业因素致癌的重要依据之一。但动物与人有种属差异。,2.3流行病调查（1）病因联系强度足够大；（2）接触后果呈一致性；（3）存在接触水平反应关系；（4）有其佐证资料；（5）肿瘤发病的性别比例异常根据流行病学调查和动物实验研究结果，职业致癌物可分为三类：确认致癌物；可疑致癌物；潜在致癌物。,确认的主要职业性致癌物,致癌物致癌部位致癌物致癌部位煤焦油唇、皮肤、鼻砷皮肤、肺、喉等苯并a芘肺、皮肤-萘胺、-萘胺膀胱、肾盂等沥青皮肤联苯胺、4-氨基泌尿系统页岩油皮肤芥子气肺、气管、喉、鼻矿物油皮肤、喉氯甲醚、双氯甲醚肺石蜡皮肤异丙基油鼻窦、喉、肺碳黑皮肤氯乙烯肝木馏油皮肤、唇氯丁二烯皮肤、肺石棉肺、胸膜苯白血病铬酸盐鼻腔、喉、肺硬木尘鼻镍及其盐类鼻腔、鼻窦、肺、喉放射性物质肺、皮肤、白血病、骨瘤,某些疑似职业性致癌物，但缺乏证据（据1987IARC资料，略有修改）,职业接触发癌部位动物人乙醛鼻粘膜1,3-丁二烯淋巴瘤、肺、胃、肝四氯化碳肝三氯甲烷肝、肾氯酚及苯氧基乙酸软组织肉瘤及淋巴瘤除草剂DDT肝、肺、淋巴瘤1,2-二溴-3-氯丙烷鼻腔、肺、胃对-二氯苯肝、肾二氯甲烷肺、肝,职业接触发癌部位动物人1,4-二恶烷肝、鼻腔表氯醇鼻腔、前胃呼吸道二溴化乙烯前胃、皮肤、肺乙烯硫脲甲状腺六六六（六氯化笨）肝白血病肼肺、肝、乳腺、鼻腔铅化合物（无机）肾4,4-甲撑双氯苯胺肺、肝、乳腺膀胱多溴化联苯肝TCDD肝、肺、其他软组织肉瘤、淋巴瘤四氯乙烯肝、白血病,3.化学致癌机制3.1化学致癌机制（1）体细胞突变学说（2）非遗传机制学说（3）癌基因学说（癌基因和抗癌基因），癌基因如：ras基因、ras与myc基因；抗癌基因如p53，HSPs（4）近来肿瘤与细胞凋亡（apoptosis）的研究颇受重视。细胞凋亡或称程序性细胞死亡（programmedcelldeath）热应激蛋白（heatstressproteins，HSPs）,3.2致癌机制研究的实际应用（1）检测致癌物和促癌物短期实验的建立；（2）促进抗癌的研究；（3）癌基因蛋白用于癌症早期诊断；,4.我国八种法定职业性肿瘤4.1石棉所致肺癌、间皮瘤4.2联苯胺所致膀胱癌4.3苯所致白血病4.4氯甲醚所致肺癌4.5砷所致肺癌及皮肤癌4.6氯乙烯所致肝血管肉瘤4.7焦炉工人肺癌4.8铬酸盐制造工人肺癌,5.职业性肿瘤的预防原则5.1加强对职业性致癌因素的控制和管理5.2对致癌剂的限制与使用定出规程5.3加强宣传教育讲究个人卫生5.4逐渐建立致癌危险性预测制度,cancer,Neoplasmsarediseasescharacterizedbyabnormalproliferationofcells.Iftheproliferatingcellsdonotinvadesurroundingtissues,theresultoftumorisbenign;iftheydo,itismalignant.Somebenignneoplasmsmaybefatal,includinghistologicallybenignbraintumorsthatgrowanddisplacenormalbraintissueintheconfinedspaceoftheskull,andhepatocellularadenomasthatruptureandcausebleedingintotheperitonealcavity.,DESCRIPTIVEEPIDEMIOLOGY,ClassificationCancersareclassifiedaccordingtotheirorganortissueoforigin(siteortopographycode)andhistologicalfeatures(morphologycode).ICD-9SourcesofincidenceandMortalityRatesMagnitudeoftheCancerProblemRelativeImportanceofSpecificNeoplasms,Age-adjustedincidence,mortality,and5-yearsurvivalratesinmenandwomenintheUnitedStates,Rates(per100,000)IncidenceMortality5-yearRelativeSurvival(%)SitemalefemalemalefemalemalefemaleBuccalcavityandpharynx16.26.24.61.748.460.2Digestivesystem96.761.852.331.342.045.0Respiratorysystem92.244.077.632.217.517.7Bonesandjoints1.00.80.50.357.968.2Skin21.210.94.41.953.189.9Breast0.9109.60.227.183.983.2Femalegenitalsystem48.014.967.6Malegenitalsystem146.926.586.3Urinarysystem43.114.110.84.175.766.0Brainandnervoussystem7.55.25.13.528.129.9Endocrinesystem3.37.10.70.685.693.4Lymphomas21.514.38.65.552.960.7Leukemias13.47.88.44.941.038.7Allsites485.0345.0219.6141.552.360.1,AgeSexANNUALINCIDENCEOFSELECTEDCANCERSINCHILDRENUNDERAGE151980TO1992Ages014SiteMaleFemaleAllsites15.012.9Boneandjoint0.60.8Brainandothernervous3.63.0Hodgkinsdisease0.70.5Kidneyandrenalpelvis0.80.8Leukemias4.63.8Acutelymphocytic3.72.9Non-Hodgkinslymphomas1.20.4Softtissue0.80.8,CriteriaforCausalityGeneralEtiologicalConsiderationTobaccoAlcoholIndustrialExposuresEnvironmentalPollutionNonionizingRadiationIonizingRadiationExogenousSexHormonesInfectiousAgentsNutritionandPhysicalActivityReproductiveFactorsGeneticFactors,ETIOLOGYANDPRIMARYPREVENTION,ReductioninMortalityifFactorGoalGoalMet(%)SmokingReduceprevalenceto1516%by1990by20008DietReducefatto30%ofcaloriesand8increasefiberto20to30g/dayScreeningMammogramsin80%of5070yearoldsPapsmearsin90%of20-39yearolds;80%of40-70yearolds3treatmentincreaseuseofstate-of-the-arttherapy10-26,NATIONALCANCERINSTITUTESGOALSFORIMPROVEDCANCERMORTALITYBYTHEYEAR2000,Smoking1994DeathsCancerRelativeAttributableDuetoSiteRiskRisk%SmokingLung10.085.1130,163Larynx8.080.93,074Oralcavity4.079.06,259Esophagus3.075.47,845Bladder2.040.14,252Pancreas2.028.57,386Stomach1.835.75,000Kidney1.532.93,722,ASSOCIATIONOFCIGARETTESMOKINGWITHCANCERSATSELECTEDSITES,SpecificExposuresSiteorTumorType4-AminobiphenylBladderArsenicandarseniccompoundsLung,skinAsbestosLung,mesotheliomaBenzeneLeukemiaBenzidineBladderBerylliumandberylliumcompoundsLungCadmiumandcadmiumcompoundsLungChromiumcompoundsLung,sinonasalCoaltarpitchesSkin,lung,bladderCoaltarsSkinErioniteMesotheliomaEthyleneoxideLeukemia,lymphomaMineraloils,untreatedandSkinmildlytreated2-NaphthylamineBladderNickelandnickelcompoundsSinonasal,lung,OCCUPATIONALCAUSESOFCANCER,IndustrialprocessSiteorTumorTypeAluminumproductionLung,bladder,lympho-sarcomasandreticulosarcomasManufactureofauramineBladderBootandshoemanufactureNose,bladderandrepairCoalgasificationLung,bladder,skinCokeproductionLung,bladder,skinFurnitureandcabinetmakingNoseHematitemining,underground,withexposuretoradonLungOccupationalexposuretostrong-inorganic-acidLung,larynx,nasalsinusIronandsteelfoundingLungManufactureofmagentaBladderPaintersLung,larynx,esophagus,stomach,bladder,leukemia,lymphomaRubberindustryBladder,leukemia,lymphoma,OCCUPATIONALCAUSESOFCANCER,PERECENTAGEOFU.S.CANCERCASESANDDEATHSMOSTPROBABLYATTRIBUTABLETOVARIOUSACCEPTEDCAUSESOFCANCER,NewCasesTotalCancerCauseMaleFemaleDeathsTobacco302030Alcoholandtobacco423Occupation524Drugs111Ionizingradiation111Sunlight10102Infectiousagents355Totalpercentage544146,SCREENINGANDSECONDARYPREVENTION,PlanningaScreeningProgram1.Thesensitivityandspecificityoftestsorproceduresusedforscreening2.Thetargetspopulation3.Theprevalenceofthediseaseinthetargetpopulation4.Thepredictivevalueofapositivetest5.Theconsequencesoffalse-positivetests6.Consequencesofafalse-negativetest7.Applicabilityofthetest8.Acceptabilityofthetest9.Adverseconsequencesofthetest10.theevaluabilityoftheprogram,WorksofMylabrelatedtothisfield,InducingFactorsofHeatshockproteins,Environmentalstresses:heat,ultravioletradiation,heavymetals,andcarbonmonoxide,BaPetalVerycommoninlivingandworkingenvironmentsPathologicalstimuli:viral,bacterialandparasiticinfections,fever,inflammation,malignancyandautoimmunityPhysiologicalstimuli:cellgrowth,celldifferentiation,hormonalstimulationortissuedevelopment,TheImportantBiologicalFunctionsofHsps,ThermotoleranceandTolerancetomanyharmfulchemicalsChaperonesTheprotectionofDNAGrowthandDevelopment,Stresses,Diseases,Hsps(anti-Hsps),Mechanisms?,Biomarkers?,Others?,?,Signaltransductionofstressresponse：StressesHSFgene(heatshockfactor,HSF)HSF(proteins)HSE(heatshockelement，HSE)HSPs(proteins)HSPsmRNAHSPs,BaP影响HSP70基因表达可能的模式图,HSP70mRNAHSP70,ERK1/2JNK1/2P38,NOS,HSF1,维生素,凋亡,InvitrostudyontheroleofHsp70expressioninDNAdamageinhumanembryoniclungcellsexposedtobenzo(a)pyrene,GaoY,ChenS,XiaoC,WangR,HeH,TanguayRM,WuT*BiomedEnvironSci,2003(inPress),Bezeneapyrene,BaP,BaP(Benzo(a)Pyrene)isthoughttobeprocarcinogensandtoxicantswhichcommonlyandwidelyexistinlivingandworkingenvironmentsEpidemiologicaldatahavealsoshownanassociationbetweenBaPexposureandanincreasedincidenceofcertaincancersinhumansBaPanditsreactivemetabolitesareconsideredtobeprototypecompoundsthatexhibitmanyofthecytotoxic,mutagenicandcarcinogeniceffectscharacteristicofPAHs,EffectsofBaPonDNAtaillength/totallengthratioinHELcells(n=25),Environmentalworkingconditionsinsixgroupsofworkers,ValuesaremeanS.D.*P0.05,comparedwithgroup6(control).,IncidenceofantibodiesagainstHsp70inplasmaofworkers,*P0.05,*P0.01comparedwithgroup6.,Univariatelogisticregressionanalysisofriskfactorsinhypertension,OR:Oddsratio,Multivariatelogisticregressionanalysisoftheriskfactorsofhypertension(160/95mmHg),OR,oddsratio.,MultivariatelogisticregressionanalysisoftheassociationofantibodiestoHsp70withhypertension,OR:Oddsratio,MultivariatelogisticregressionanalysisoftheassociationofantibodiestoHsp70withharshworkingcondi