Differential association for N-acetyltransferase 2 genotype and phenotype with bladder cancer risk in Chinese population
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Lei Quan1,2, Koushik Chattopadhyay1, Heather H. Nelson3, Kenneth K. Chan4, Yong-Bing Xiang5, Wei Zhang5, Renwei Wang1, Yu-Tang Gao5, Jian-Min Yuan1
1University of Pittsburgh Cancer Institute, and Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
2Current affiliation: School of Bioscience and Bioengineering, Guangdong Provincial Key Laboratory of Fermentation and Enzyme Engineering, South China University of Technology, Guangzhou China
3Masonic Cancer Center, and Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA
4Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA
5Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
Jian-Min Yuan, email: email@example.com
Keywords: NAT2, N-acetylation, O-acetylation, bladder cancer, case-control
Received: October 01, 2015 Accepted: April 16, 2016 Published: May 19, 2016
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.
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