Relationship between glutathione S-transferase M1 deficiency and urothelial cancer in dye workers exposed to aromatic amines.

PURPOSE

It is speculated that the susceptibility to urothelial cancer in dye workers who are exposed to aromatic amines is affected not only by occupational environmental factors but by host specific factors. We evaluated the interaction between glutathione S-transferase M1 gene deficiency and the occupational environmental factors associated with urothelial cancer.

MATERIALS AND METHODS

The study included 137 workers who had prior exposure to dyestuff intermediates, of whom 36 had urothelial cancer. The prevalence of a glutathione S-transferase M1 gene polymorphism was investigated using polymerase chain reaction. The relationship between the glutathione S-transferase M1 0/0 gene and occupational environmental factors in the onset of urothelial cancer was examined by multivariate analysis.

RESULTS

The prevalence of glutathione S-transferase M1 gene deficiency did not differ significantly between the urothelial cancer (21 cases, 58.3%) group and the cancer-free (47, 46.3%) group. It was estimated that 29.6% of the urothelial cancers in these dye workers was attributable to the glutathione S-transferase M1 0/0 gene. Analysis using multiple logistic models showed low predictive ability for urothelial cancer due to glutathione S-transferase M1 gene deficiency (p = 0.084, odds ratio 2.260, 95% confidence interval [CI] 0.904 to 5.652). A history of working in small factories (p = 0.000, odds ratio 7.404, 95% CI 2.854 to 19.206) and a long period of exposure (p = 0.016, odds ratio 5.051, 95% CI 1.371 to 18.612) significantly predicted cancer.

CONCLUSIONS

We demonstrated a strong trend using the multiple logistic analysis of the contribution of glutathione S-transferase M1 gene polymorphism and occupational environmental factors. Therefore, the glutathione S-transferase M1 enzyme might have an important role in the detoxification of aromatic amine derived carcinogens. Occupational environmental factors, however, might contribute more than a glutathione S-transferase M1 gene deficiency to the occurrence of urothelial cancer among individuals exposed to aromatic amines, because of the extremely potent carcinogenicity of some occupational environmental factors.