Several studies hi subjects occupational^ exposed to arylamine carcinogens have shown increased risks for bladder cancer associated with the slow acetylator phenotype. To follow up these reports, a case-control study of N-acetylation and bladder cancer risk was carried out among subjects occupational^ exposed to benzidine, in benzidine dye production and use faculties hi China. Thirty-eight bladder cancer cases and 43 controls from these factories were included for study of acetylation phenotype, by dapsone administration, and for polymorphisms in the NAT2 gene, by a polymerase chain reaction (PCR)-based test. In contrast to previous studies, no increase in bladder cancer risk was found for the slow iV-acetylation phenotype (OR = 0.3; 95% CI = 0.1-1.3) or for slow /V-acetylation-associated double mutations in NAT2 (OR = 0.5; 95% CI = 0.1-1.8). Examination of specific mutations and adjustment for age, weight, city and tobacco use did not alter the results. When examined by level of benzidine exposure hi the cases, the bladder cancer risks associated with low (OR= 0.3, 95% CI = 0.0-2.2), medium (OR = 0.7, 95% CI = 0.1-4.5) and high (OR = 0.6, 95% CI = 0.1-3.5) exposure showed no interaction between genotype and benzidine exposure, within the range of exposures experienced by subjects hi this study. This study, which is the first to incorporate phenotypic and genotypic analyses, provides evidence that the iVA72-related slow iV-acetylation polymorphism is not associated with an increased risk of bladder cancer hi workers exposed to benzidine, and may have a protective effect.

Occupationally exposed workers at risk for bladder cancer can be individually stratified, screened, monitored, and diagnosed based on predefined molecular biomarker profiles.

We examined bladder cancer mortality and incidence to 1981 in 1,972 workers employed in benzidine-exposed jobs in Tianjin, Shanghai, and Jilin, China, between 1972 and 1977, and in 1,974 unexposed workers employed during the same time period. In comparison to general population rates, in the benzidine-exposed group the ratio of observed to expected deaths (SMR) was 17.5 (95% C.I.: 7.5-34.5) and the ratio of observed to expected incident cases (SIR) was 25.0 (95% C.I.: 16.9-35.7). No excess was noted in the unexposed group. The 25-fold increase in bladder cancer incidence in the exposed group was related to level of exposure, with the SIR rising from 4.8 for low exposure to 36.2 for medium exposure, and 158.4 for high exposure. Risks were elevated both for producers of benzidine (SIR = 45.7; 95% C.I.: 20.9-86.8) and for users (SIR = 20.9; 95% C.I.: 12.9-32.0) of benzidine dyes. Benzidine-exposed workers who smoked tobacco had a 31-fold risk (95% C.I.: 20.4-46.4), while non-smoking workers had an 11-fold risk (95% C.I.: 3.6-25.8), suggestive of a multiplicative relationship between these two carcinogens.

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