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Effect of metabolic polymorphisms on benzidine-induced bladder cancer in Chinese workers: a nested case-control study.
Carreon T; Ruder AM; Schulte PA; Hayes RB; Rothman N; Lemasters GK; Grant DJ; Boissy R; Bell DA; Kadlubar FF; Hemstreet GP; Yin S; Li G; Feng P
Am J Epidemiol 2001 Jun; 153(11)(Suppl):S199
Slow acetylation activity and its associated NAT2 genotype are generally associated with increased risk for bladder cancer in general populations and in workers exposed to arylamine mixtures. For workers exposed to benzidine, a borderline protective association has been reported. The purpose of this study was to evaluate the impact that metabolic polymorph isms have on bladder cancer in Chinese workers exposed only to benzidine. This nested case-control study included 30 cases with transitional cell carcinoma of the urinary bladder, diagnosed after 1991. Sixty seven controls, frequency-matched by decade of birth, were selected. NAT2 and CYP 1 A2 enzymatic activities were characterized by measuring urinary caffeine metabolite ratios as phenotypic function markers. Polymerase chain reaction-based methods were used to identify genotypes for the following genes: NAT2, NAT1, GSTM1, GSTT1, GSTP1, and UGTIA1. Crude analysis of bladder cancer risk shows an odds ratio of 0.1 (95% confidence interval: 0.01 - 0.92) for workers with the NAT2 slow genotype. Adjustment for lifetime smoking, age, and NATI genotype did not alter the findings. A protective but not significant association was found for slow acetylation phenotype. NATl, GSTMl, and GSTTI polymorphisms showed no association with bladder cancer risk; frequencies of the rare alleles for GSTP 1 and UGT1A1 were too low for analysis. These findings suggest that the risk of bladder cancer from benzidine exposure is due to activation by N-acetylation.
Benzidines; Bladder cancer; Bladder disorders; Endocrine system disorders; Arylamines; Occupational exposure; Exposure assessment; Exposure levels; Risk analysis
Issue of Publication
American Journal of Epidemiology
Page last reviewed: June 15, 2021
Content source: National Institute for Occupational Safety and Health Education and Information Division