A Significantly Joint Effect between Arsenic and Occupational Exposures and Risk Genotypes/Diplotypes of Cyp2e1, Gsto1 and Gsto2 on Risk of Urothelial Carcinoma
Resource
TOXICOLOGY AND APPLIED PHARMACOLOGY v.241 n.1 pp.111-118
Journal
Toxicology and Applied Pharmacology
Pages
111-118
Date Issued
2009
Date
2009
Author(s)
WANG, YUAN-HUNG
SHEN, CHENG-HUANG
HSU, LING-I
CHIOU, HUNG-YI
CHEN, CHIEN-JEN
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 or 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.
Subjects
CYP2E1
GSTO1
GSTO2
Diplotype
Urothelial carcinoma
SDGs
Other Subjects
arsenic; cytochrome P450 2E1; glutathione transferase; glutathione transferase omega 1; glutathione transferase omega 2; protein GSTO1; protein GSTO2; unclassified drug; adult; aged; alcohol consumption; article; cancer risk; case control study; cigarette smoking; controlled study; environmental factor; female; genetic polymorphism; genotype; human; human tissue; major clinical study; male; occupational exposure; polymerase chain reaction; restriction fragment length polymorphism; single nucleotide polymorphism; urinary tract carcinoma; urothelium carcinoma; Aged; Alcohol Drinking; Arsenic; Case-Control Studies; Cytochrome P-450 CYP2E1; Female; Genotype; Glutathione Transferase; Humans; Kidney Neoplasms; Male; Middle Aged; Occupational Exposure; Polymorphism, Restriction Fragment Length; Polymorphism, Single Nucleotide; Risk Factors; Smoking; Ureteral Neoplasms; Urinary Bladder Neoplasms; Urothelium
Type
journal article