title: Differential association for N-acetyltransferase 2 genotype and phenotype with bladder cancer risk in Chinese population.
abstract: BACKGROUND
  N-acetyltransferase 2 (NAT2) is involved in both carcinogen detoxification through hepatic N-acetylation and carcinogen activation through local O-acetylation. NAT2 slow acetylation status is significantly associated with increased bladder cancer risk among European populations, but its association in Asian populations is inconclusive.
  
  
  METHODS
  NAT2 acetylation status was determined by both single nucleotide polymorphisms (SNPs) and caffeine metabolic ratio (CMR), in a population-based study of 494 bladder cancer patients and 507 control subjects in Shanghai, China.
  
  
  RESULTS
  The CMR, a functional measure of hepatic N-acetylation, was significantly reduced in a dose-dependent manner among both cases and controls possessing the SNP-inferred NAT2 slow acetylation status (all P-values<5.0×10-10). The CMR-determined slow N-acetylation status (CMR<0.34) was significantly associated with a 50% increased risk of bladder cancer (odds ratio = 1.50, 95% confidence interval = 1.10-2.06) whereas the SNP-inferred slow acetylation statuses were significantly associated with an approximately 50% decreased risk of bladder cancer. The genotype-disease association was strengthened after the adjustment for CMR and was primarily observed among never smokers.
  
  
  CONCLUSIONS
  The apparent differential associations for phenotypic and genetic measures of acetylation statuses with bladder cancer risk may reflect dual functions of NAT2 in bladder carcinogenesis because the former only measures the capacity of carcinogen detoxification pathway while the latter represents both carcinogen activation and detoxification pathways. Future studies are warranted to ascertain the specific role of N- and O-acetylation in bladder carcinogenesis, particularly in populations exposed to different types of bladder carcinogens.
authors.affiliation: University of Pittsburgh Cancer Institute, and Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.|Current affiliation: School of Bioscience and Bioengineering, Guangdong Provincial Key Laboratory of Fermentation and Enzyme Engineering, South China University of Technology, Guangzhou China.
authors.forename: Lei
authors.initials: L
authors.lastname: Quan
authors.affiliation: University of Pittsburgh Cancer Institute, and Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Koushik
authors.initials: K
authors.lastname: Chattopadhyay
authors.affiliation: Masonic Cancer Center, and Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA.
authors.forename: Heather H
authors.initials: HH
authors.lastname: Nelson
authors.affiliation: Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA.
authors.forename: Kenneth K
authors.initials: KK
authors.lastname: Chan
authors.affiliation: Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Yong-Bing
authors.initials: YB
authors.lastname: Xiang
authors.affiliation: Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: University of Pittsburgh Cancer Institute, and Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Renwei
authors.initials: R
authors.lastname: Wang
authors.affiliation: Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Yu-Tang
authors.initials: YT
authors.lastname: Gao
authors.affiliation: University of Pittsburgh Cancer Institute, and Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Jian-Min
authors.initials: JM
authors.lastname: Yuan
mesh_terms: D000368:Aged; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D044466:Asian People; D002110:Caffeine / Q000378:metabolism; D002273:Carcinogens / Q000378:metabolism; D016022:Case-Control Studies; D002681:China; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D001749:Urinary Bladder Neoplasms / Q000208:ethnology / Q000235:genetics* / Q000473:pathology*
chemical_list: D002273:Carcinogens; D002110:Caffeine; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human
keywords: N-acetylation; NAT2; O-acetylation; bladder cancer; case-control