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Environmental Health and Preventive Medicine
Published in: Environmental Health and Preventive Medicine 2/2013

01-03-2013 | Regular Article

Association of genotypes of carcinogen-metabolizing enzymes and smoking status with bladder cancer in a Japanese population

Authors: Xiaoyi Cui, Xi Lu, Mizue Hiura, Hisamitsu Omori, Wataru Miyazaki, Takahiko Katoh

Published in: Environmental Health and Preventive Medicine | Issue 2/2013

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Abstract

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.
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Metadata
Title
Association of genotypes of carcinogen-metabolizing enzymes and smoking status with bladder cancer in a Japanese population
Authors
Xiaoyi Cui
Xi Lu
Mizue Hiura
Hisamitsu Omori
Wataru Miyazaki
Takahiko Katoh
Publication date
01-03-2013
Publisher
Springer Japan
Published in
Environmental Health and Preventive Medicine / Issue 2/2013
Print ISSN: 1342-078X
Electronic ISSN: 1347-4715
DOI
https://doi.org/10.1007/s12199-012-0302-x

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