A significantly joint effect between arsenic and occupational exposures and risk genotypes/diplotypes of CYP2E1, GSTO1 and GSTO2 on risk of urothelial carcinoma

Journal Article · Sun Nov 15 04:00:00 EST 2009 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2009.08.008· OSTI ID:21344792

Wang, Y -H ^[1]; Yeh, S -D ^[2]; Shen, K -H ^[3]; Shen, Cheng-Huang ^[4]; Juang, G -D ^[5]; Hsu, L -I ^[6]; Chen, C -J ^[7]

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1. School of Public Health, Taipei Medical University, Taipei 110, Taiwan (China)
2. Department of Urology, Taipei Medical University Hospital, Taipei 110, Taiwan (China)
3. Department of Urology, Chi-Mei Medical Center, Tainan 710, Taiwan (China)
4. Department of Urology, Chiayi Christian Hospital, Chia-Yi 600, Taiwan (China)
5. Division of Urology, Department of Surgery, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei 111, Taiwan (China)
6. Genomics Research Center, Academia Sinica, Taipei 115, Taiwan (China)
7. The Genomics Research Center, Academia Sinica, Taipei 115, Taiwan (China)

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.

• OSTI ID: 21344792
• Journal Information: Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Journal Issue: 1 Vol. 241; ISSN TXAPA9; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALCOHOLS
ARSENIC
CARCINOMAS
DISEASES
DRUGS
ELEMENTS
GENE AMPLIFICATION
GENOTYPE
GLUTATHIONE
HYDROXY COMPOUNDS
NEOPLASMS
OCCUPATIONAL EXPOSURE
ORGANIC COMPOUNDS
PEPTIDES
POLYMERASE CHAIN REACTION
POLYPEPTIDES
PROTEINS
RADIOPROTECTIVE SUBSTANCES
RESPONSE MODIFYING FACTORS
SEMIMETALS