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Objectives: Arylamines are considered to be the primary causative agent of bladder cancer in tobacco smokers. To test the hypothesis that variation in the genes that metabolize tobacco carcinogens contribute to bladder cancer, we examined the effects of single nucleotide polymorphisms in the genes of four key enzymes: cytochrome P450 1A2, N- acetyltransferase ( NAT) 2, sulfotransferase 1A1, and UDP- glucuronosyltransferase ( UGT) 2B7. Methods: In this study, 282 Japanese patients with transitional cell carcinoma, the most common bladder cancer, and 257 healthy controls were surveyed and compared for frequencies of the genotypes of the four enzymes. Genotypes were determined using PCR-restriction fragment length polymorphism and TaqMan assays. Smoking information was collected by personal interview. Logistic regression analysis and the chi-square test were employed as statistical methods. Results: The NAT2 slow genotype was significantly associated with the risk of bladder cancer [odds ratio (OR) 3.41, 95 % confidence interval (95 % CI) 1.68-6.87; p < 0.05). The NAT2 slow genotype also significantly increased the risk of bladder cancer in heavy smokers (OR 8.57, 95 % CI 1.82-40.25; p < 0.05). Among the different combinations of the four enzyme genotypes, the highest OR (4.20; 95 % CI 1.34-13.14; p < 0.05) was obtained with the NAT2 slow genotype when present in combination with the UGT2B7 *2/ *2 or *1/ *2 genotype. Conclusions: Our results suggest that individuals with different genotypes for the enzymes involved in metabolizing carcinogenic arylamines have a different risk of developing bladder cancer. In particularly, the combination of the NAT2 slow genotype with UGT2B7 *1/ *2 or *2/ *2 genotype is a high risk factor for bladder cancer. [ABSTRACT FROM AUTHOR]

Objectives: Inherited impairment of xenobiotic metabolism is a postulated mechanism underlying environmentally associated pathogeneses such as multiple chemical sensitivity (MCS). Using the Quick Environmental Exposure and Sensitivity Inventory (QEESI), we defined people who have a strong response to chemical substances as 'chemical sensitive populations (CSP).' The aim of this study is to evaluate the condition of subjects sensitive to chemicals and to analyze their genotypes in order to identify susceptibility factors in CSPs in Japanese populations. Methods: A total of 1,084 employees of Japanese companies were surveyed using the QEESI, history of MCS, and sick house syndrome. The common genotypes of the participants were analyzed for glutathione S-transferase ( GST) M1, GSTT1, aldehyde dehydrogenase2 ( ALDH2), and paraoxonase1 ( PON1) in order to identify factors in the susceptibility to sensitivity to chemicals. Results: Four subjects had history of diagnosis of MCS; no subjects had diagnosis of sick house syndrome. The subjects were divided into four levels according to scores of 0, 1-19, 20-39, and 40 or more on three of the QEESI subscales. In addition, we used the MCS criteria by Hojo to differentiate between cases (CSP) and controls. No significant differences in the allelic distribution of genetic polymorphisms in the GSTM1, GSTT1, ALDH2 or PON1 genes were found among the four levels of each subscale, or between cases and controls. Conclusions: Our findings suggest that the common genotypes of GSTM1, GSTT1, ALDH2, and PON1 are of little importance to CSP in a Japanese population. [ABSTRACT FROM AUTHOR]