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- A Study on Polymorphism Affecting Excretion of Urinary Methylhippuric Acid due to Xylene Exposure.
- Cheong Sik Kim, Sang Baek Koh, Hyeongsu Kim, Sue Kyung Park, Soung Hoon Chang
- J Prev Med Public Health. 2004;37(4):321-328. Published online November 30, 2004
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Abstract
PDF - OBJECTIVES
The purpose of this study was to investigate the effect of genetic polymorphism of cytochrome P450 2E1 (CYP2E1) and aldehyde dehydrogenase 2 (ALDH2) on the xylene metabolism. METHODS: Among 247 workers, 116 were occupationally exposed to xylene and 131 were not. Workers exposed to xylene had different work such as spray, touch-up, mix & assist, and pre-treat. Questionnaire variables were age, sex, use of personal protective equipment, smoking, previous night's drinking and work duration. The urinary methylhippuric acid was measured in the urine collected in the afternoon and corrected by urinary creatinine concentration. The genotypes of CYP2E1 and ALDH2 were investigated by using PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) methods with DNA extracted from venous blood. RESULTS: 1. The urinary concentrations of o-, m-, and pmethylhippuric acid and total methylhippuric acid in the exposed group were significantly higher than those in the non-exposed group (p< 0.001). 2. In multiple regression analysis, the urinary methylhippuric acid concentration was significantly influenced by exposure grade (Job-exposure matrixes), smoking, drug use and kind of protective equipment (p< 0.1). 3. Genetic polymorphism of CYP2E1 and ALDH2 did not affect urinary methylhippuric acid level in the exposed group (p> 0.05). CONCLUSIONS: Exposure grade, smoking, drug use and kind of protective equipment affected urinary methylhippuric acid level, whereas genetic polymorphism of CYP2E1 and ALDH2 did not. However, further investigation for the effect of genetic polymorphism on the metabolism of xylene with a larger sample size is needed. -
Summary
- A Case-Control Study on Effects of Genetic Polymorphisms of GSTM1, GSTT1, CYP1A1 and CYP2E1 on Risk of Lung Cancer.
- Hong Mei Nan, Heon Kim, Jong Won Kang, Jang Whan Bae, Kang Hyeon Choe, Ki Hyeong Lee, Seung Taik Kim, Choong Hee Won, Yong Min Kim
- Korean J Prev Med. 1999;32(2):123-129.
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Abstract
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- OBJECTIVES
This study was performed to investigate effects of genetic polymorphisms of glutathione S-transferase M1 (GSTM1), glutathione S-transferase M1 (GSTT1), cytochrome P450 1A1 (CYP1A1) and cytochrome P450 2E1 (CYP2E1) on lung cancer development. METHODS: Ninety-eight lung cancer patients and 98 age-sex matched non-cancer patients hospitalized in Chungbuk National University Hospital from March 1997 to August 1998, were the subjects of this case-control study. Direct interview was done and genotypes of GSTM1, GSTT1, CYP1A1 and CYP2E1 were investigated using multiplex PCR or PCR-RFLP methods with DNA extracted from venous blood. Effects of the polymorphisms of GSTM1, GSTT1, CYP1A1 and CYP2E1, lifestyle factors including smoking, and their interactions on lung cancer were statistically analyzed. RESULTS: GSTM1 was deleted in 67.01% of the cases and 58.16% of the controls, and the odds ratio(95% CI) was 1.46(0.82-2.62). GSTT1 deletion was 58.76% for the lung cancer patients and 50.00% for the controls OR:1.43(0.81-2.51). The frequencies of Ile/Ile, Ile/Val and Val/Val of the CYP1A1 polymorphisms were 59.18%, 35.71%, and 5.10% for the cases, and 52.04%, 45.92%, 2.04% for the controls, respectively. Risk of lung cancer was not associated with polymorphism of CYP1A1 (x2trend=0.253, p-value>0.05). The respective frequency of c1/c1, c1/c2, c2/c2 genotypes for CYP2E1 were 50.00%, 42.86%, 7.14% for the lung cancer patients, and 66.33%, 30.61%, 3.06% for the controls (x2trend=5.783, p<0.05). c2 allele was a significant risk factor for lung cancer. We also observed a significant association of cigarette smoking history with lung cancer risk. The odds ratio(95% CI) of cigarette smoking was 3.03(1.58-5.81). In multiple logistic analysis including genotypes of GSTM1, GSTT1, CYP1A1 and CYP2E1, and smoking habit, only smoking habit came out to be a significant risk factor for lung cancer. CONCLUSION: Genetic polymorphisms of GSTM1, GSTT1, CYP1A1 and CYP2E1 are not so strongly associated with lung cancer as lifestyle factors including cigarette smoking. -
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