A significantly joint effect between arsenic and occupational exposures and risk genotypes/diplotypes of CYP2E1, GSTO1 and GSTO2 on risk of urothelial carcinoma |
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Authors: | Yuan-Hung Wang Shauh-Der Yeh Cheng-Huang Shen Ling-I Hsu Chien-Jen Chen |
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Institution: | a School of Public Health, Taipei Medical University, Taipei 110, Taiwan b Department of Urology, Taipei Medical University Hospital, Taipei 110, Taiwan c Department of Urology, Chi-Mei Medical Center, Tainan 710, Taiwan d Department of Urology, Chiayi Christian Hospital, Chia-Yi 600, Taiwan e Division of Urology, Department of Surgery, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei 111, Taiwan f The Genomics Research Center, Academia Sinica, Taipei 115, Taiwan g Graduate Institute of Epidemiology, College of Public Health, National Taiwan University, Taipei 100, Taiwan |
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Abstract: | Cigarette smoking, arsenic and occupational exposures are well-known risk factors for the development of urothelial carcinoma (UC). Therefore, the aim of this study is to investigate whether the effect of cigarette smoking, alcohol consumption, arsenic and occupational exposures on risk of UC could be modified by genetic polymorphisms of cytochrome P450 2E1 and glutathione S-transferase omega. A hospital-based case-control study consisted of 520 histologically confirmed UC cases, and 520 age- and gender-matched cancer-free controls were carried out from September 1998 to December 2007. Genotyping of CYP2E1, GSTO1 and GSTO2 was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Subjects with both of cigarette smoking and alcohol consumption have a significantly increased UC risk (odds ratio OR] = 2.9; 95% confidence interval CI] = 1.9-4.4). Significantly increased UC risks of 1.5 and 1.9 were found for study subjects with high arsenic exposure and those who have been exposed to two or more occupational exposures, respectively. A significantly increased UC risk of 3.9 was observed in study subjects with H2-H2 diplotype of GSTO1 and GSTO2. The significantly highest UC risk of 9.0 was found for those with all environmental risk factors of cigarette smoking, alcohol consumption, arsenic and occupational exposures and two or more risk genotypes/diplotypes of CYP2E1, GSTO1 and GSTO2. Our findings suggest that a significantly joint effect of cigarette smoking, alcohol consumption, arsenic and occupational exposures and risk genotypes/diplotypes of CYP2E1, GSTO1 and GSTO2 on risk of UC was found. |
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Keywords: | CYP cytochrome P450 LD linkage disequilibrium GST glutathione S-transferase HWE Hardy-Weinberg equilibrium OR odds ratio 95% CI 95% confidence interval PAHs polycyclic aromatic hydrocarbons PCR-RFLP polymerase chain reaction-restriction fragment length polymorphism SNP single nucleotide polymorphism UC urothelial carcinoma |
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