N-Acetyltransferase 2 (NAT2) and Glutathione S-Transferase μ (GSTM1) in Bladder-cancer Patients in a Highly Industrialized Area

Abstract

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 (PARs) 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% slowacetylators) and GSTMI (54% GSTMI negative) were normal in businessmen and administrative officers among the occupationally non-exposed bladder-cancer patients. The results are consistent with the view that as low-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 also dyes and in coke-oven workers. PAHs may also contribute to elevated bladder-cancer risks in coke-oven workers and in underground coal miners.

Keywords:

• bladder cancer
• N-acetyltrans-ferase 2
• glutathione S-transferase μ
• occupational risk factors
• aromatic amines
• polycyclic aromatic hydrocarbons
• genetic predisposition