title: Association of genotypes of carcinogen-metabolizing enzymes and smoking status with bladder cancer in a Japanese population.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Public Health, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjou, Chuo-ku, Kumamoto 860-8556, Japan.
authors.forename: Xiaoyi
authors.initials: X
authors.lastname: Cui
authors.forename: Xi
authors.initials: X
authors.lastname: Lu
authors.forename: Mizue
authors.initials: M
authors.lastname: Hiura
authors.forename: Hisamitsu
authors.initials: H
authors.lastname: Omori
authors.forename: Wataru
authors.initials: W
authors.lastname: Miyazaki
authors.forename: Takahiko
authors.initials: T
authors.lastname: Katoh
mesh_terms: D000368:Aged; D001191:Arylamine N-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D015239:Arylsulfotransferase / Q000235:genetics / Q000378:metabolism; D002295:Carcinoma, Transitional Cell / Q000139:chemically induced / Q000453:epidemiology* / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics / Q000378:metabolism; D005260:Female; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012907:Smoking / Q000453:epidemiology; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced / Q000453:epidemiology* / Q000235:genetics*
chemical_list: C504573:CYP1A2 protein, human; D019388:Cytochrome P-450 CYP1A2; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human; C491474:UGT2B7 protein, human; D014453:Glucuronosyltransferase; D015239:Arylsulfotransferase; C117544:SULT1A1 protein, human