A significantly joint effect between arsenic and occupational exposures and risk genotypes/diplotypes of CYP2E1, GSTO1 and GSTO2 on risk of urothelial carcinoma.
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.
Wang
Yuan-Hung
YH
School of Public Health, Taipei Medical University, Taipei 110, Taiwan.
Yeh
Shauh-Der
SD
Shen
Kun-Hung
KH
Shen
Cheng-Huang
CH
Juang
Guang-Dar
GD
Hsu
Ling-I
LI
Chiou
Hung-Yi
HY
Chen
Chien-Jen
CJ
D000368:Aged; D000428:Alcohol Drinking / Q000009:adverse effects; D001151:Arsenic / Q000633:toxicity; D016022:Case-Control Studies; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics; D005260:Female; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D007680:Kidney Neoplasms / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure / Q000009:adverse effects; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D014516:Ureteral Neoplasms / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D019459:Urothelium / Q000473:pathology
D019392:Cytochrome P-450 CYP2E1; C490476:GSTO1 protein, human; C492569:GSTO2 protein, human; D005982:Glutathione Transferase; D001151:Arsenic