Gene Environmental Interactions for Bladder Cancer

BrooklynDodger(s) comment: First, urothelial carcinoma is the most common type of bladder cancer - the Dodger(s) had to google it. Learn something every day. The trouble with most genetic studies of cancer is they end with blaming the victim - or the victims' ancestors - and yield no new ideas for intervention. Controlling for less resistant genetic types would enable better human studies of associations with exposures. Glutathione continues to get more play, compared to cytochrome. CYP can be thought of as activating and dotoxicating, while GST is mostly detox unless there's an ad hoc Houdini hypothesis, as for methylene chloride.


Toxicology and Applied Pharmacology
Volume 241, Issue 1, 15 November 2009, Pages 111-118

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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Yuan-Hung Wang^{a, b}, Shauh-Der Yeh^b, Kun-Hung Shen^c, Cheng-Huang Shen^d, Guang-Dar Juang^e, Ling-I Hsu^f, Hung-Yi Chiou^{a, ,} and Chien-Jen Chen^{f, g}

^aSchool of Public Health, Taipei Medical University, Taipei 110, Taiwan

^bDepartment of Urology, Taipei Medical University Hospital, Taipei 110, Taiwan

^cDepartment of Urology, Chi-Mei Medical Center, Tainan 710, Taiwan

^dDepartment of Urology, Chiayi Christian Hospital, Chia-Yi 600, Taiwan

^eDivision of Urology, Department of Surgery, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei 111, Taiwan

^fThe Genomics Research Center, Academia Sinica, Taipei 115, Taiwan

^gGraduate Institute of Epidemiology, College of Public Health, National Taiwan University, Taipei 100, Taiwan

Received 17 April 2009;

revised 3 August 2009;

accepted 7 August 2009.

Available online 15 August 2009.

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.