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
Institute of Medical and Clinical Biochemistry, Faculty of Medicine, University of Belgrade, Belgrade, Serbia; Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
Institute of Occupational Health, Belgrade, Serbia; Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
PLoS One. 2014 Jun 10;9(6):e99448. doi: 10.1371/journal.pone.0099448. eCollection 2014.
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.
我们研究了谷胱甘肽S - 转移酶A1、M1、P1和T1基因多态性的作用，以及塞尔维亚男性膀胱癌患者职业接触不同化学物质对其潜在的效应修饰作用。
一项基于医院的男性膀胱癌病例对照研究，包括143例经组织学确诊的病例和114例年龄匹配的男性对照。采用聚合酶链反应法鉴定谷胱甘肽S - 转移酶M1和T1的缺失多态性。采用限制性片段长度多态性方法鉴定谷胱甘肽S - 转移酶A1和P1的单核苷酸多态性。作为效应大小的度量指标，计算比值比（OR）及相应的95%置信区间（95%CI）。
谷胱甘肽S - 转移酶A1、T1和P1基因型对膀胱癌风险无独立影响，而谷胱甘肽S - 转移酶M1缺失基因型在病例组中比例过高（OR = 2.1，95%CI = 1.1 - 4.2，p = 0.032）。对于低活性谷胱甘肽S - 转移酶A1基因型，观察到职业接触溶剂与谷胱甘肽S - 转移酶基因型对膀胱癌风险的影响最为显著（OR = 9.2，95%CI = 2.4 - 34.7，p = 0.001）。谷胱甘肽S - 转移酶M1缺失基因型也增加了接触溶剂者患膀胱癌的风险（OR = 6.5，95%CI = 2.1 - 19.7，p = 0.
