联苯胺接触人群中谷胱甘肽S-转移酶基因型的多态性分布

为了探讨与膀胱癌发生危险有关的谷胱甘肽Ｓ－转移酶（ＧＳＴｓ）Ｍ１和Ｔ１基因型的多态性在有联苯胺接触的膀胱癌高危人群中的分布状况,对上海市染料化工行业的联苯胺接触人群与上海市某制造行业的健康对照人群作各种基因型构成比的比较,在接触人群中进行工种和工龄的职业因素分层分析。结果表明,接触人群中Ｔ１０／０型、Ｍ１０／０型、和Ｔ１０／０－Ｍ１０／０型的构成比均高于对照人群,在Ｔ１０／０－Ｍ１０／０型的构成比上出现统计学意义（ＯＲ＝１．５８,χ＾２＝５．４１）。职业因素分层分析未发现显著的趋势或差异。结果中,职业性膀胱癌高危人群中ＧＳＴｓ０／０基因型的构成比向高比例方向移动可以理解。但研究中该人群虽是一个特殊职业人群,可从根本上说仍应属于健康人群,而健康人群中ＧＳＴｓ０／０基因型的构成比会产生漂移,在过去的研究中尚未见过。     

核有丝分裂器蛋白22在联苯胺接触人群医学监护中的应用

[目的]研究联苯胺接触人群中核有丝分裂器蛋白22（NMP22）的表达情况。[方法]用酶联免疫吸附实验（ELISA）法测定联苯胺接触人群尿液中的NMP22，以巴氏分级法对尿脱落细胞进行分级。[结果]联苯胺接触人群中巴氏分级Ⅰ级组NMP22的测定值显著低于6U／ml的诊断标准（P〈0．05）；巴氏分级〉Ⅰ级组NMP22的测定值显著高于6U／ml（P〈0．01）。巴氏分级〉Ⅰ级组NMP22的测定值虽高于巴氏分级Ⅰ级组，但两组间NMP22测定值的差异不具有统计学意义（P＝0．909）。[结论]尿液中NMP22可作为联苯胺接触人群常规医学监护的生物指标，但尿中NMP22的测定尚不能替代尿脱落细胞巴氏染色检查法作为职业性膀胱癌高危人群医学监护的指标。     

联苯胺接触人群尿细胞学监护的一些特点

目的 对上海联苯胺接触人群中医学监护１６年（１９８３～１９９８年）作初步总结。方法 监护人群为联苯胺职业接触者,采用巴氏分级法作尿脱落细胞检查。巴氏分级为５级,介于相邻两级之间的结果以０．５表达,受监护５次以上者列入统计范围,采用平均级数和出现过２．５次以上者的构成比两个指标,以ｔ检验和卡方试验进行分析。结果 监护中发生８例膀胱癌,诊断前监护中出现过２．５级以上者４例（５０％）,不同工种和不同吸烟     

天津市职业性膀胱癌危险因素的病例对照研究

目的探讨天津市联苯胺职业接触人群膀胱癌的主要危险因素,以确定高危人群。方法对天津市联苯胺职业接触人群中106例膀胱癌和同时期、同车间的未发生膀胱癌的106人进行成组病例-对照研究,通过单因素和多因素非条件Logistic回归分析筛选职业人群中膀胱癌的主要危险因素,同时分析病例组与对照组尿中脱落细胞检查情况,为职业肿瘤的早期发现及高危人群的确定提供参考依据。结果单因素及多因素分析结果显示,联苯胺职业接触人群膀胱癌危险因素包括接触联苯胺浓度、专业工龄、吸烟(P0.05);多因素分析结果表明,联苯胺职业接触人群膀胱癌的主要危险因素为高接触浓度(OR=4.752,95%CI=2.458~9.190)、专业工龄(OR=2.557,95%CI=1.394~4.692)、吸烟(OR=2.011,95%CI=1.020~3.966)。病例组巴氏分级Ⅱ级及以上和定量荧光影像分析(QFIA)阳性检出均高于对照组,P0.05。结论高浓度接触、专业工龄超过5年、吸烟是联苯胺职业接触人群发生膀胱癌的主要危险因素,应以此确定高危人群;尿脱落细胞检查巴氏分级Ⅱ级及以上和QFIA阳性者,也应加强监护。     

停止接触联苯胺35年后作业人员尿脱落细胞学3年监护结果分析

目的 分析天津市所属染料行业的7家企业联苯胺接触人群的3年监护结果,以便及早预防联苯胺作业人员膀胱癌发生。 方法 以停止接触联苯胺35年后作业人员尿脱落细胞学3年监护结果作为主要分析指标。 结果 2011-2013年发现新发阳性病例4例。 结论 在停止接触联苯胺35年之后,仍有职业性膀胱癌的发生。建议对离岗后接触联苯胺人员的健康行终生监护。     

NQO1和GSTT1基因多态性与慢性苯中毒的危险性

目的 探讨NQO1和GSTT1的基因多态性和苯中毒易感性的关系。方法 采用病例－对照研究，以152名苯中毒工人为病例组，152名接触苯而没有中毒表现的工人为对照组。采用名聚酶链反应（PCR）、变性高效液相色谱（DHPLC）和测序检测NQO1基因的启动子和全部编码区的单核苷酸多态性（single mucleotide polymorphism,SNP)，以多重PCR检测GSTT1的基因型。结果 在经常吸烟的人群中，携带NQO1c.609T/T基因型的个体接触苯时发生慢性苯中毒的危险性是C／C和C／T基因型的7．73倍（95％CI：1．71－34．97，P＝0．010）。在经常饮酒的人群中，携带NQO1第6外显子T／T突变纯合子的个体在接触苯时发生慢性苯中毒的危险性是C／C和C／T基因型的11．00倍（95％CI：1．89－63．83，P=0．005）。结论 携带NQO1c.609T/T基因型而又同时吸烟或饮酒的个体对苯中毒可能易感。     

联苯胺代谢酶的基因多态性和膀胱癌生物标志物

在我国泌尿系统肿瘤中，膀胱癌的发病率和死亡率均占首位。膀胱癌的发生与大多数肿瘤一样是遗传与环境共同作用的结果，但环境因素的作用更为明显，25％-27％的膀胱癌患者可能因接触芳香族化合物如联苯胺、β-萘胺等引发。在同等接触联苯胺的条件下，接触个体是否易发膀胱癌，取决于其自身的遗传易感性。膀胱癌的生物标志物是在职业接触人群中进行医学监护的生物指标，用于识别膀胱癌的早期患者。     

尿脱落细胞检查在联苯胺作业工人健康监护中的作用

目的研究通过在职业性膀胱癌高发人群中进行尿脱落细胞检查,以早期发现、早期治疗膀胱肿瘤,说明其在健康监护中的作用.方法对染化行业在职和退休职工,有联苯胺接触史1年以上的男性,进行尿脱落细胞病理学检查.结果对联苯胺作业人群进行20年的尿脱落细胞健康监护工作,并已取得肯定效果.结论通过尿脱落细胞检查可以检出尚无临床症状的早期患者,可使患者早期发现早期治疗膀胱肿瘤,所以尿脱落细胞学检查对于联苯胺作业人群的职业健康监护有着重要的意义.     

天津市联苯胺制造与使用作业人员膀胱癌前瞻性流行病学调查

化学致癌物是膀胱肿瘤发病的主要原因之一,染料工业中的中间体——联苯胺是人类膀胱癌的强致癌物,已为国际公认。流行病学调查资料表明我国联苯胺接触者膀胱癌的发病率高达167.84/10万。天津是我国重要的染料工业基地之一,有30余年生产联苯胺和使用联苯胺生产直接染料的历史。该人群中膀胱癌的发病和死亡水平均在全国同     

Calpain10基因多态性与昆明地区人群2型糖尿病相关性研究

目的 探讨Calpain10基因多态性与昆明地区人群2型糖尿病遗传易感性的关系。方法采用病例-对照研究设计，以聚合酶链式反应-等位基因特异性扩增法（PCR-ASA），检测Calpain10基因单核苷酸多态性（SNP）43G／A位点和SNP44T／C位点基因型，并进行关联分析。结果 对131例2型糖尿病患者和131例正常对照进行了Calpain10基因SNP43和SNP44基因分型，与对照组相比，SNP43的G等位基因频率和SNP44的C等位基因频率在昆明地区2型糖尿病人群中显著升高（分别为93．13％，86．26％，P=0．0097；18．70％，9．92％，P=0．004）。结论 Calpain10基因SNP43位点G等位基因和SNP44位点C等位基因可能与昆明地区人群2型糖尿病的发病相关。     

p53蛋白在联苯胺接触人群和膀胱癌患者血清中的表达

目的研究职业性联苯胺接触者和膀胱癌患者突变型p53蛋白的表达。方法用免疫PCR法测定职业性联苯胺接触人群和膀胱癌患者血中突变型p53蛋白,用巴氏分级法对尿脱落细胞进行分级。结果随着联苯胺接触强度指数的增高,人群突变型p53蛋白的阳性率不断增加,膀胱癌患者组突变型p53蛋白的阳性率(83.3%)高于接触强度指数1组(33.3%)。PCR扩增条带经扫描积分后,膀胱癌患者组和接触强度指数2组的平均扫描积分(24016.11±2979.99、12960.79±903.27)高于1组(9231.58±1140.74),差异有统计学意义(P<0.01,P<0.05)。在联苯胺接触人群的各组中以巴氏分级作为组内分层因素,接触强度指数2组中,巴氏2、3级层PCR扩增条带平均扫描积分(12960.79±903.27、13612.78±1697.38)高于1级层(9231.58±1140.74),差异有统计学意义(P<0.05)。接触强度指数3组中,巴氏3级层的突变型p53蛋白的阳性率(46.9%)高于1级层(33.3%),差异有统计学意义(P<0.05)。结论在联苯胺接触强度较低的范围内,随着接触强度的增加,接触工人血清中p53突变蛋白的阳性表达不但更频繁,而且更加强烈;但接触强度超过了这个范围,工人血中p53突变蛋白的阳性率以及表达量将不再随着接触强度的上升而增高,而尿脱落细胞病变程度在联苯胺接触强度较高的情况下与p53基因突变率     

医学监护在联苯胺作业膀胱癌高发人群中应用的意义

本文报道了对联苯胺作业膀胱癌高发人群实行医学监护的方法和结果。指出定期进行尿液脱落细胞检查,并对其中巴氏分级Ⅲ级以上者做膀胱镜检查,不但可以早期发现膀胱肿瘤,同时也可以对尿路粘膜上皮组织炎症及增生等病变作出一定的诊断。有利于早期治疗。尿液脱落细胞检查方法简便易行,对病人安全无痛苦,并可重复检验,诊断肿瘤的阳性率较高,可以作为普查和职业人群医学监护的主要手段。     

接触联苯胺工人及膀胱癌患者染色体研究

报道了联苯胺接触者及其膀胱癌患者和正常对照者淋巴细胞染色体畸变和膀胱癌发病的关系。观察对象包括三组，Ａ组为联苯胺接触者发生膀胱癌的病人（１５例）Ｂ组为联苯胺接触者（１５人），Ｃ组为正常对照工人（１４人）。三组中淋巴细胞畸变的人数分别占６０．０％，５８．３％及１４．０％，其淋巴细胞畸变率分别为１．１％，０．７％及０．３％。Ａ、Ｂ组显著高于Ｃ组，且膀胱癌组比非膀胱癌组细胞畸变率高。Ａ组有４例发现有２个以上的淋巴细胞畸变，Ｂ组仅有２例，其中１例在染色体畸变检验后１年发生了膀胱癌。对有染色体畸变者作Ｇ带分析的结果表明主要是缺失、易位、断裂和插入，其中多数在９号、８号、６号染色体，且Ａ组至少牵涉３次。表明具有较高畸变的个体可能有较高的膀胱癌危险性。外周血淋巴细胞染色体畸变及／或先天的遗传缺陷（通称为染色体不稳定性）反映了癌症的易感性。作者认为联苯胺工人淋巴细胞染色体畸变率增高可与其它生物学标记相结合作为膀胱癌早期监测的指标。     

Detection of mutant p53 protein in workers occupationally exposed to benzidine

To investigate the expression of mutant p53 protein in workers occupationally exposed to benzidine, we detected mutant p53 protein by immuno-PCR assay in the serum of 331 benzidine-exposed healthy workers, while we classified exfoliated urothelial cells in urine samples with Papanicoloau's grading (PG). The Papanicoloau's grading classified exfoliated urothelial cells of the subjects from grade I (normal cells) to grade III (suspicious malignant cells). The subjects were also divided into high, medium and low exposure groups according to the exposure intensity index. The results revealed that mutant p53 protein in the medium and high exposure groups were significantly higher than the in low exposure group (p<0.05), and in PG II and III were significantly higher than in the PG I (p<0.05). There was no significant differences among Papanicoloau's gradings strata in the low exposure group on the incidence and quantity of mutant p53 protein. In the medium and high exposure groups, the incidence and/or quantity of mutant p53 protein in the stratum of PG II and/or III were significantly higher than that of PG I (p<0.05). Detection of mutant p53 protein in conjunction with benzidine exposure level and Papanicoloau's gradings of exfoliated urothelial cells could provide more information to help us elevate surveillance efficiency and diagnose bladder cancer in the early period.     

联苯胺致膀胱癌88例临床及预后分析

目的 探讨联苯胺所致职业性膀胱癌与普通人群膀胱癌的区别及终生监护的意义。方法 以尿脱落细胞检查及定量荧光影像分析作为早期诊断指标。根据膀胱癌确诊前是否进入监护网分组观察。结果 监护组39/53例通过定期普查,尿脱落细胞阳性后进一步确诊,需经腹手术者仅占29.4%,有41.2%可经尿道电切治疗;非监护组几乎全部因血尿就医,需经腹手术者占65.7%,可经尿道电切治疗者仅占14.3%,职业性膀胱癌临床分期高,具有明显的肿瘤多发性和再发性。88例膀胱癌中有11例患多原癌。结论 对有联苯胺接触史的人群进行医学监护可以早期发现,早期期诊断膀胱癌;对职业性膀胱癌应进行终身监护,多原癌病因是否与接触致癌物有关,有待进一步研究。     

Periodic urine cytology surveillance of bladder tumor incidence in dyestuff workers

The validity of urine cytology surveillance of occupational bladder tumor incidence was evaluated by reviewing the clinical history of nine bladder tumor cases found in dyestuff plant workers. A bladder tumor surveillance system has been organized for workers (179 active and 65 retired) who had been exposed to benzidine or beta-naphthylamine in the plant. The system consists of two-stage tests: periodic urine cytology as the first-stage screening test, followed by, in suspicious cases, urological examinations as second-stage tests. The urine cytology surveillance was found to be useful for two reasons: first, it detected tumors in five out of six cases surveyed by the system, and second, four cases screened by cytology had tumors curable by transurethral operation, while other cases underwent cystectomy. Calculated average latent periods from the first and last exposure was 26.4 years (SD = 6.0) and 14.0 years (SD = 6.2), respectively. This time period indicates that the surveillance system should continue to be used for the exposed group even after workers have ceased being exposed.     

Studies on the relation between bladder cancer and benzidine or its derived dyes in Shanghai

Shanghai is the largest industrial centre in China and has a history of about 50 years in producing and applying benzidine derived dyes. A series of epidemiological studies on the carcinogenicity of benzidine and its derived dyes have been performed since 1979. This report describes three such studies. A case-control study was carried out on 344 cases of bladder cancer, each matched for age and sex, with a person without bladder cancer. Factors studied were occupational exposure, smoking, drinking, medical histories, and family history of bladder cancer and other carcinomas. The correlation between bladder cancer and occupational exposures (relative risk (RR) 5.71) was greater than that between bladder cancer and smoking (RR 1.53). A retrospective cohort study was conducted in seven dyestuffs factories where benzidine had served as an intermediate in the manufacture of dyes before 1976. The cohort was made up of 550 men and 186 women. The men were divided into two groups according to job; 354 were assigned to a presynthesis group and 196 to a postsynthesis group. Those in the presynthesis group were thought to have been exposed to benzidine and the subjects in the postsynthesis group were exposed mainly to its derived dyes. The 15 cases of bladder cancer diagnosed were all in the presynthesis group, although an excess of bladder cancer was also seen in the whole cohort. The standardised incidence ratio (SIR) of bladder cancer was 1918 in the whole cohort and 3500 in the presynthesis group. Moreover, the SIR of bladder cancer in a subgroup working directly with the assignment, transport, and mixing of benzidine was as high as 7500. A further retrospective cohort study was made on incidence of cancer among 1420 workers who used benzidine derived dyes in 43 textile printing and dyeing factories. No excess carcinoma was found. These results suggest that, in Shanghai, the main cause of bladder cancer is occupational exposure, especially to benzidine. The risk of bladder cancer, however, existed only in the presynthesis stage of dye manufacture.     

Studies on the relation between bladder cancer and benzidine or its derived dyes in Shanghai.

Shanghai is the largest industrial centre in China and has a history of about 50 years in producing and applying benzidine derived dyes. A series of epidemiological studies on the carcinogenicity of benzidine and its derived dyes have been performed since 1979. This report describes three such studies. A case-control study was carried out on 344 cases of bladder cancer, each matched for age and sex, with a person without bladder cancer. Factors studied were occupational exposure, smoking, drinking, medical histories, and family history of bladder cancer and other carcinomas. The correlation between bladder cancer and occupational exposures (relative risk (RR) 5.71) was greater than that between bladder cancer and smoking (RR 1.53). A retrospective cohort study was conducted in seven dyestuffs factories where benzidine had served as an intermediate in the manufacture of dyes before 1976. The cohort was made up of 550 men and 186 women. The men were divided into two groups according to job; 354 were assigned to a presynthesis group and 196 to a postsynthesis group. Those in the presynthesis group were thought to have been exposed to benzidine and the subjects in the postsynthesis group were exposed mainly to its derived dyes. The 15 cases of bladder cancer diagnosed were all in the presynthesis group, although an excess of bladder cancer was also seen in the whole cohort. The standardised incidence ratio (SIR) of bladder cancer was 1918 in the whole cohort and 3500 in the presynthesis group. Moreover, the SIR of bladder cancer in a subgroup working directly with the assignment, transport, and mixing of benzidine was as high as 7500. A further retrospective cohort study was made on incidence of cancer among 1420 workers who used benzidine derived dyes in 43 textile printing and dyeing factories. No excess carcinoma was found. These results suggest that, in Shanghai, the main cause of bladder cancer is occupational exposure, especially to benzidine. The risk of bladder cancer, however, existed only in the presynthesis stage of dye manufacture.     

对氧磷酶和谷胱甘肽S转移酶基因多态性与农药暴露花卉种植者的健康关系研究

目的 探讨花卉种植者(花农)对氧磷酶及谷胱甘肽S转移酶基因多态性的分布情况,并分析基因多态性与健康的关系.方法 选择云南省某村136名从事花卉种植的花农作为暴露组(男性74名,女性62名);41名不使用农药的同村居民作为对照组(男性16名,女性25名);进行问卷调查和体格检查,并采集血液样本,分析血常规、肝功能、激素水平、免疫球蛋白(IgM、IgG、IgA)和全血乙酰胆碱酯酶活性.采用聚合酶链反应-限制性片段长度多态性方法(PCR-RFLP)检测PON1-107、PON1 192、GST M1、T1基因型.结果 (1)对照组球蛋白高于暴露组(β=-0.16,t=-2.30,P=0.02),而白蛋白与球蛋白的比(白球比)低于暴露组(β=0.14,t=2.09,P=0.04);(2)PON1 192位点分析显示,QQ基因型个体症状积分高于RR基因型个体(t=-2.78,P=0.006);(3)GSTT1-的个体分析显示,球蛋白高于GSTT1+的个体(β=-0.20,t=-3.01,P=0.00),IgG高于GST T1+的个体(β=-0.15,t=-2.15,P=0.03),而白球比低于GST T1+的个体(β=0.17,t=2.54,P=0.01);(4)农药暴露者心电图异常情况增加(β=1.147,P=0.042).结论 PON1 192和GST T1位点与农药暴露后的花农健康状况相关.