Journal Article

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

Djukic, Tatjana I., Coric, Vesna M., Pekmezovic, Tatjana D., Simic, Tatjana P., Pljesa-Ercegovac, Marija S., Matic, Marija G., Bulat, Petar V., Savic-Radojevic, Ana R., Dragicevic, Dejan P.

2014

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: 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 / Men / Metabolism / Metabolites / Middle Aged / Nucleotides / 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