NAT2 slow acetylation and bladder cancer in workers exposed to benzidine.
Carreón T; Ruder AM; Schulte PA; Hayes RB; Rothman N; LeMasters GK; Waters M; Grant DJ; Boissy R; Bell DA; Kadlubar FF; Hemstreet GP; Yin S; Li G; Feng P
Proceedings of the 93rd American Association for Cancer Research Annual Meeting, April 6-10, 2002, San Francisco, California. Philadelphia, PA: American Association for Cancer Research, 2002 Apr; 43:938
The slow NAT2 N-acetylation genotype inhibits detoxification of a range of monoarylamines and has been associated with increased risk for bladder cancer in cigarette smokers and workers in arylamine dye production. The diarylamine, benzidine, is also a strong bladder carcinogen, however, NAT2 N-acetylation is not key to its detoxification. The purpose of this study was to expand on a previous study that evaluated the impact of NAT2 polymorphisms on bladder cancer in male subjects exposed only to benzidine. The combined analysis included 68 cases and 107 controls from a cohort of benzidine dye producers in China exposed occupationally to benzidine, of which 30 cases and 67 controls had not been previously studied. NAT2 enzymatic activity phenotype was characterized by measuring urinary caffeine metabolite ratios. Polymerase chain reaction (PCR)-based methods were used to identify genotypes for the NAT2 gene. A protective association was observed for the slow NAT2 genotype (bladder cancer odds ratio (OR)=0.3, 95% confidence interval (CI) 0.11-0.99) after adjustment for cumulative benzidine exposure and lifetime smoking. The interaction between NAT2 polymorphism and benzidine exposure was evaluated: compared to rapid acetylators with high exposure, the respective risks were OR=0.5 (95% CI 0.26-1.05) for rapid acetylators with low exposure, OR=0.4 (95% CI 0.12-1.57) for slow acetylators with high exposure, and OR=0.1 (95% CI 0.03-0.61) for slow acetylators with low exposure (test for multiplicative interaction, p=0.58). NAT2 phenotype results were consistent with NAT2 genotype data. Study findings confirm that slow acetylators are not at increased risk of developing benzidine-induced bladder cancer, in contrast to slow acetylators who smoke cigarettes or are exposed to monoarylamine dyes. The data actually suggest decreased risk for bladder cancer among NAT2 slow acetylators, although the mechanism for risk reduction is not clearly understood.
Cancer; Bladder-cancer; Urogenital-system-disorders; Benzidines; Solvents; Bladder-disorders; Bladder-disease; Dyes; Carcinogenicity; Carcinogens; Humans; Epidemiology; Case-studies
Abstract; Conference/Symposia Proceedings
Research Tools and Approaches: Cancer Research Methods
Proceedings of the 93rd American Association for Cancer Research Annual Meeting, April 6-10, 2002, San Francisco, California