The glutathione S-transferase M1 (GSTM1) null genotype and benzidine- associated bladder cancer, urine mutagenicity, and exfoliated urothelial cell DNA adducts

Nathaniel Rothman, Richard B. Hayes, Terry V. Zenser, David M. DeMarini, Wenfang Bi, Ari Hirvonen, Glenn Talaska, Vijay K. Bhatnagar, Neil E. Caporaso, Lance R. Brooks, Vijaya M. Lakshmi, Peiwen Feng, Sri K. Kashyap, Xiejun You, Brent T. Eischen, Rekha Kashyap, Melissa L. Shelton, Fong F. Hsu, Marione Jaeger, Dinesh J. ParikhBernard B. Davis, Songnian Yin, Douglas A. Bell

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31 Scopus citations

Abstract

Multiple studies in the general population have suggested that subjects with the glutathione S-transferase M1 (GSTM1)-null genotype, who lack functional GSTM1, are at higher risk for bladder cancer. To evaluate the impact of the GSTM1-null genotype on bladder cancer caused by occupational exposure to benzidine and to determine its influence on benzidine metabolism, we carried out three complementary investigations: a case-control study of bladder cancer among workers previously exposed to benzidine in China, a cross-sectional study of urothelial cell DNA adducts and urinary mutagenicity in workers currently exposed to benzidine in India, and a laboratory study of the ability of human GSTM1 to conjugate benzidine and its known metabolites in vitro. There was no overall increase in bladder cancer risk for the GSTM1- null genotype among 38 bladder cancer cases and 43 controls (odds ratio, 1.0; 95% confidence interval, 0.42.7), although there was some indication that highly exposed workers with the GSTM1-null genotype were at greater risk of bladder cancer compared to similarly exposed workers without this allele. However, the GSTM1 genotype had no impact on urothelial cell DNA adduct and urinary mutagenicity levels in workers currently exposed to benzidine. Furthermore, human GSTM1 did not conjugate benzidine or its metabolites. These results led us to conclude that the GSTM1-null genotype does not have an impact on bladder cancer caused by benzidine, providing a contrast to its association with elevated bladder cancer risk in the general population.

Original languageEnglish
Pages (from-to)979-983
Number of pages5
JournalCancer Epidemiology Biomarkers and Prevention
Volume5
Issue number12
StatePublished - Dec 1 1996
Externally publishedYes

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    Rothman, N., Hayes, R. B., Zenser, T. V., DeMarini, D. M., Bi, W., Hirvonen, A., Talaska, G., Bhatnagar, V. K., Caporaso, N. E., Brooks, L. R., Lakshmi, V. M., Feng, P., Kashyap, S. K., You, X., Eischen, B. T., Kashyap, R., Shelton, M. L., Hsu, F. F., Jaeger, M., ... Bell, D. A. (1996). The glutathione S-transferase M1 (GSTM1) null genotype and benzidine- associated bladder cancer, urine mutagenicity, and exfoliated urothelial cell DNA adducts. Cancer Epidemiology Biomarkers and Prevention, 5(12), 979-983.