Abstract
ObjectiveWe 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.Patients and MethodsA 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.ResultsThe 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).ConclusionNull 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.
Highlights
Bladder cancer is the second most common malignancy of the urinary tract and has the second highest mortality rate among urological neoplasms [1]
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 enhanced the risk of bladder cancer among subjects exposed to solvents (OR = 6,5, 95% CI = 2.1–19.7, p = 0.001)
Summary
Bladder cancer is the second most common malignancy of the urinary tract and has the second highest mortality rate among urological neoplasms [1]. It affected 73,510 patients and lead to 14,880 deaths in 2012 worldwide [2]. Demographic characteristics associated with the greatest risk for bladder cancer include male gender, white race and the increasing age [3]. It has been known that uroepithelial cells are most vulnerable to metabolic end products of different compounds, including carcinogens. This malignancy is characterized by multifactorial etiology, involving both genetic and environmental factors
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