RESUMO
PURPOSE: Several occupational carcinogens are metabolized by polymorphic enzymes. The distribution of the polymorphic enzymes N-acetyltransferase 2 (NAT2; substrates: aromatic amines), glutathione S-transferase M1 (GSTM1; substrates: e. g., reactive metabolites of polycyclic aromatic hydrocarbons), and glutathione S-transferase T1 (GSTT1; substrates: small molecules with 1 - 2 carbon atoms) were investigated. MATERIAL AND METHODS: At the urological department in Lutherstadt Wittenberg, 136 patients with a histologically proven transitional cell cancer of the urinary bladder were investigated for all occupations performed for more than 6 months. Several occupational and non-occupational risk factors were asked. The genotypes of NAT2, GSTM1, and GSTT1 were determined from leucocyte DNA by PCR. RESULTS: Compared to the general population in Middle Europe, the percentage of GSTT1 negative persons (22.1 %) was ordinary; the percentage of slow acetylators (59.6 %) was in the upper normal range, while the percentage of GSTM1 negative persons (58.8 %) was elevated in the entire group. Shifts in the distribution of the genotypes were observed in subgroups who had been exposed to asbestos (6/6 GSTM1 negative, 5/6 slow acetylators), rubber manufacturing (8/10 GSTM1 negative), and chlorinated solvents (9/15 GSTM1 negative). CONCLUSIONS: The overrepresentation of GSTM1 negative bladder cancer patients also in this industrialized area and more pronounced in several occupationally exposed subgroups points to an impact of the GSTM1 negative genotype in bladder carcinogenesis.
Assuntos
Carcinoma de Células de Transição/epidemiologia , Exposição Ocupacional/efeitos adversos , Neoplasias da Bexiga Urinária/epidemiologia , Acetiltransferases/genética , Adulto , Amianto/efeitos adversos , Carcinoma de Células de Transição/induzido quimicamente , Carcinoma de Células de Transição/enzimologia , Carcinoma de Células de Transição/genética , Genótipo , Alemanha/epidemiologia , Glutationa Transferase/genética , Humanos , Ocupações , Reação em Cadeia da Polimerase , Polimorfismo Genético , Fatores de Risco , Borracha/efeitos adversos , Solventes/efeitos adversos , Fatores de Tempo , Neoplasias da Bexiga Urinária/induzido quimicamente , Neoplasias da Bexiga Urinária/enzimologia , Neoplasias da Bexiga Urinária/genéticaRESUMO
Genotype distributions for GSTP1, GSTM1, and GSTT1 were determined in 91 patients with prostatic carcinoma and 135 patients with bladder carcinoma and compared with those in 127 abdominal surgery patients without malignancies. None of the genotypes differed significantly with respect to age or sex among controls or cancer patients. In the group of prostatic carcinoma patients, GSTT1 null allele homozygotes were more prevalent (25% in carcinoma patients vs. 13% in controls, Fisher P =0.02, chi2 P=0.02, OR=2.31, CI = 1.17-4.59) and the combined M1-/T1 -null genotype was also more frequent (9% vs. 3%, chi2 P=0.02, Fisher P = 0.03). Homozygosity for the GSTM1 null allele was more frequent among bladder carcinoma patients (59% in bladder carcinoma patients vs 45% in controls, Fisher P=0.03, chi2 P=0.02, OR=1.76, CI=1.08-2.88). In contrast to a previous report, no significant increase in the frequency of the GSTP1b allele was found in the tumor patients. Except for the combined GSTM1-/ T1-null genotype in prostatic carcinoma, none of the combined genotypes showed a significant association with either of the cancers. These findings suggest that specific single polymorphic GST genes, that is GSTM1 in the case of bladder cancer and GSTT1 in the case of prostatic carcinoma, are most relevant for the development of these urological malignancies among the general population in Central Europe.