OBJECTIVES To investigate effects of genetic polymorphism of glutathione S-transferase M1 (GSTM1), glutathione S-transferase T1 (GSTT1), glutathione S-transferase P1 (GSTP1), N-acetyltransferase (NAT2), cytochrome P450 2E1 (CYP2E1) and cytochrome P450 1A1 (CYP1A1) on pneumoconiosis. METHODS Eighty-five pneumoconiosis patients and 122 age and sex matched healthy controls were enrolled. Direct interview and standard questionnaire were conducted and the genotypes of GSTM1, GSTT1, GSTP1, NAT2, CYP2E1 and CYP1A1 were investigated using multiplex PCR or PCR-RFLP methods with DNA extracted from venous blood. The relationship was investigated between the severity of pneumoconiosis and the polymorphism of GSTM1, GSTT1, GSTP1, NAT2, CYP2E1 and CYP1A1, and also with various environmental factors including smoking. RESULTS We observed a significantly higher rate of genetic polymorphism in pneumoconiosis patients than in normal subjects. The odds ratio (95% CI) of NAT2 was 2.09 (1.19-3.68). In addition, smoking was related significantly with pneumoconiosis (OR 2.89, 95% CI 1.40-5.95). In multiple logistic regression analyses, NAT2 and smoking were significant risk factors for the development of pneumoconiosis (OR 1.84, 95% CI 1.00-3.37; OR 2.98, 95% CI 1.40-6.35, respectively). The age of onset of the disease and smoking were significantly related with moderate or severe pneumoconiosis (OR 0.91, 95% CI 0.83-0.99; OR 6.94, 95% CI 1.54-31.30, respectively). However there was no significant difference between the rate of genetic polymorphism of GSTM1, GSTT1, GSTP1, CYP2E1 and CYP1A1 in the two groups. CONCLUSION NAT2 genetic polymorphism was higher in pneumoconiosis patients than in normal subjects. The age of onset of the disease and smoking were significantly related with pneumoconiosis. However, the genetic polymorphism of GSTM1, GSTT1, GSTP1, CYP2E1 and CYP1A1 was not related with development or severity of pneumoconiosis.
OBJECTIVES This study was performed to describe the distribution patterns of urinary 1-hydroxypyrene (1-OHP) and 2naphthol concentration in coke oven workers and workers not occupationally exposed to polycyclic aromatic hydrocarbons (PAH), and to determine the effects of occupation life style, and genetic polymorphism of cytochrome P450 1A1 (CYP1A1), glutathione Stransferase mu 1 (GSTM1) and theta 1 (GSTT1) on urinary 1- OHP and 2-naphthol concentration. METHODS The study subjects were 19 coke oven workers and 156 shipyard workers. A questionnaire was used to obtain data about detailed smoking and food intake history. Urinary 1OHP and 2naphthol concentration and genetic polymorphism of CYPIA1, GSTM1, and GSTT1 were analyzed. RESULTS The urinary 1-OHP and 2-naphthol concentration was higher in the coke oven workers and in smokers. Urinary 1-OHP concentration was significantly correlated with time after last intake of roasted meat in non-smoking coke oven workers, whereas urinary 2-naphthol concentration was with amount of cigarette smoking at the sampling day in smoking shipyard workers. Urinary 1-OHP, but not 2-naphthol, concentration of the shipyard workers with Ile/Ile type of CYP1A1 vas significantly lower than that of the shipyard workers with other CYP1A1 genotype. CONCLUSIONS Urinary 1-OHP would be a better marker for occupational exposure to PAH in coke oven workers, and urinary 2naphthol might be better for non-occupational inhalation exposure to PAH. CYP1A1 would not play an important role in the metabolism of naphthalene but in the metabolism of pyrene.
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This study was conducted to integrate the results of studies which assess the relationship between bladder cancer and Glutathione S transferase mu genetic polymorphism. We retrieved the literatures using MEDLINE search, with bladder cancer and Glutathione S transferase as key words, which were reported from 1980 to October 1998. The criteria for quality evaluation were as follows; 1) The paper should have histologically confirmed bladder cancer as case definition. 2) The paper should use the GSTM1 gene typing as method for analysis. Among 59 retrieved articles, fourteen studies were selected for quantitative meta-analysis. The overall effect size of the risk of bladder cancer due to GSTM1 was calculated by common odds ratio. Before the integration of each effect sizes into common effect sizes, the homogeneity test were conducted. All studies were case control design and cases were transitional cell carcinoma or squamous cell carcinoma of bladder. And only four papers used matching technique. Homogeneity of studies were rejected by Breslow-Day test(P<0.01), so random effect model was used for evaluation of odds ratio. The overall odds ratio of GSTM1 associated with bladder cancer was 1.55 (95% confidence interval 1.27 to 1.90) and cumulative odds ratio became more stable when the study subjects were over 1,500. Our result suggested that positive association be found between GSTM1 genetic polymorphism and bladder cancer.