Does Occupational Exposure to Solvents and Pesticides in Association with Glutathione S-Transferase A1, M1, P1, and T1 Polymorphisms Increase the Risk of Bladder Cancer? The Belgrade Case-Control Study

• Published in: PloS one Vol. 9; no. 6; p. e99448
• Main Authors: Matic, Marija G., Coric, Vesna M., Savic-Radojevic, Ana R., Bulat, Petar V., Pljesa-Ercegovac, Marija S., Dragicevic, Dejan P., Djukic, Tatjana I., Simic, Tatjana P., Pekmezovic, Tatjana D.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 10.06.2014; Public Library of Science (PLoS)
• Subjects: Agrochemicals; Biochemistry; Bladder; Bladder cancer; Cancer; Cancer research; Case studies; Case-Control Studies; Confidence intervals; Control methods; Enzymes; Epidemiology; Exposure; Gene deletion; Gene polymorphism; Genes; Genetic aspects; Genetic Predisposition to Disease; Genotypes; Glutathione; Glutathione S-Transferase pi - genetics; Glutathione transferase; Glutathione Transferase - genetics; Health risk assessment; Health risks; Humans; Hydrocarbons; Male; Males; Medicine; Medicine and Health Sciences; Metabolism; Metabolites; Middle Aged; Occupational exposure; Occupational Exposure - adverse effects; Occupational health; Patients; Pesticides; Pesticides - adverse effects; Polymerase chain reaction; Polymorphism; Polymorphism, Genetic; Restriction fragment length polymorphism; Risk; Risk Factors; Serbia; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Solvents; Solvents - adverse effects; Studies; Thiols; Urinary bladder; Urinary Bladder Neoplasms - enzymology; Urinary Bladder Neoplasms - genetics; Serbia
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0099448

We investigated the role of the glutathione S-transferase A1, M1, P1 and T1 gene polymorphisms and potential effect modification by occupational exposure to different chemicals in Serbian bladder cancer male patients. A hospital-based case-control study of bladder cancer in men comprised 143 histologically confirmed cases and 114 age-matched male controls. Deletion polymorphism of glutathione S-transferase M1 and T1 was identified by polymerase chain reaction method. Single nucleotide polymorphism of glutathione S-transferase A1 and P1 was identified by restriction fragment length polymorphism method. As a measure of effect size, odds ratio (OR) with corresponding 95% confidence interval (95%CI) was calculated. The glutathione S-transferase A1, T1 and P1 genotypes did not contribute independently toward the risk of bladder cancer, while the glutathione S-transferase M1-null genotype was overrepresented among cases (OR = 2.1, 95% CI = 1.1-4.2, p = 0.032). The most pronounced effect regarding occupational exposure to solvents and glutathione S-transferase genotype on bladder cancer risk was observed for the low activity glutathione S-transferase A1 genotype (OR = 9.2, 95% CI = 2.4-34.7, p = 0.001). The glutathione S-transferase M1-null genotype also enhanced the risk of bladder cancer among subjects exposed to solvents (OR = 6,5, 95% CI = 2.1-19.7, p = 0.001). The risk of bladder cancer development was 5.3-fold elevated among glutathione S-transferase T1-active patients exposed to solvents in comparison with glutathione S-transferase T1-active unexposed patients (95% CI = 1.9-15.1, p = 0.002). Moreover, men with glutathione S-transferase T1-active genotype exposed to pesticides exhibited 4.5 times higher risk in comparison with unexposed glutathione S-transferase T1-active subjects (95% CI = 0.9-22.5, p = 0.067). Null or low-activity genotypes of the glutathione S-transferase A1, T1, and P1 did not contribute independently towards the risk of bladder cancer in males. However, in association with occupational exposure, low activity glutathione S-transferase A1 and glutathione S-transferase M1-null as well as glutathione S-transferase T1-active genotypes increase individual susceptibility to bladder cancer.