Golka K, Reckwitz T, Kempkes M, Cascorbi I, Blaskewicz M, Reich SE, Roots I, Soekeland J, Schulze H, Bolt HM
Institut fuer Arbeitsphysiologie an der Universitaet Dortmund, Ardeystrasse 67, D-44139 Dortmund, Germany.
Int J Occup Environ Health. 1997 Apr;3(2):105-110. doi: 10.1179/107735297800407686.
The study was designed to assess occupational and non-occupational risk factors in patients with urothelial carcinomas in an area of former coal, iron, and steel industries, with special regard to the impacts of polymorphic enzymes involved in the metabolism of aromatic amines (N-acetyltransferase 2, NAT2) and of polycyclic aromatic hydrocarbons (glutathione S-transferase µ, GSTM1). Inpatients with bladder cancer (n = 179) were interviewed for occupations ever engaged in for more than six months, and for bladder cancer risk factors in general. NAT2 was phenotyped by high-pressure liquid chromatography of caffeine metabolites in urine. The NAT2 status was additionally evaluated by genotyping 88 of these patients. Eighty-nine patients were genotyped for GSTM1. Of the 179 bladder-cancer patients, 115 (64%) were slow acetylators. In 70% of the subgroup of 89 patients, GSTM1 was negative, suggesting an impact of polycyclic aromatic hydrocarbons (PAHs) in bladder-cancer carcinogenesis in the general population in this area. Contrary to an ordinary distribution of the acetylator status in underground coal miners (18 slow acetylators out of 32), GSTM1 was negative in 16 of 19 of these coal miners. Five of six coke-oven workers were slow acetylators; GSTM1 was negative in all four genotyped coke-oven workers. Twelve of 17 patients formerly exposed to colorants were slow acetylators. Distributions of NAT2 (59% slow acetylators) and GSTM1 (54% GSTM1 negative) were normal in businessmen and administrative officers among the occupationally non-exposed bladder-cancer patients. The results are consistent with the view that a slow-acetylator status and lack of the GSTM1 gene are individual risk factors for bladder cancer in persons occupationally exposed to aromatic amines and PAHs. Aromatic amines may be connected with induction of bladder cancer in persons who have been in contact with azo dyes and in coke-oven workers. PAHs may also contribute to elevated bladder-cancer risks in coke-oven workers and in underground coal miners.
该研究旨在评估前煤炭、钢铁工业区尿路上皮癌患者的职业和非职业风险因素，特别关注参与芳香胺（N - 乙酰转移酶2，NAT2）和多环芳烃（谷胱甘肽S - 转移酶μ，GSTM1）代谢的多态性酶的影响。对膀胱癌住院患者（n = 179）进行访谈，了解其从事超过六个月的职业以及一般膀胱癌风险因素。通过尿液中咖啡因代谢物的高压液相色谱法对NAT2进行表型分析。另外对其中88例患者进行基因分型以评估NAT2状态。对89例患者进行GSTM1基因分型。在179例膀胱癌患者中，115例（64%）为慢乙酰化者。在89例患者的亚组中，70%的GSTM1为阴性，表明多环芳烃（PAHs）对该地区普通人群膀胱癌致癌作用有影响。与地下煤矿工人中乙酰化状态的正常分布情况相反（32例中有18例慢乙酰化者），这些煤矿工人中有19例中的16例GSTM1为阴性。六名焦炉工人中有五名是慢乙酰化者；在所有四名进行基因分型的焦炉工人中GSTM1均为阴性。17名曾接触过着色剂的患者中有12名是慢乙酰化者。在职业未接触膀胱癌患者中的商人及行政人员中，NAT2（59%慢乙酰化者）和GSTM1（54% GSTM1阴性）的分布是正常的。这些结果与以下观点一致，即慢乙酰化状态和GSTM1基因缺失是职业接触芳香胺和PAHs人群患膀胱癌的个体风险因素。芳香胺可能与接触偶氮染料的人和焦炉工人患膀胱癌有关。PAHs也可能导致焦炉工人和地下煤矿工人患膀胱癌风险升高。
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