TY - JOUR
T1 - Effects of N-acetyl transferase 1 and 2 polymorphisms on bladder cancer risk in Caucasians
AU - Gu, Jian
AU - Liang, Dong
AU - Wang, Yunfei
AU - Lu, Charles
AU - Wu, Xifeng
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2005/3/7
Y1 - 2005/3/7
N2 - Cigarette smoking is the predominant risk factor for bladder cancer (BC). Major carcinogens present in tobacco smoke include a number of aromatic and heterocyclic amines. Two distinct N-acetyl transferase (NAT) enzymes, NAT1 and NAT2, play important roles in the bio-activation and detoxification of these carcinogens. Genes encoding NAT1 and NAT2 are highly polymorphic among human populations, and these polymorphisms result in rapid or slow acetylator phenotypes. Recent studies have suggested that variant alleles leading to slow acetylation by the NAT2 enzyme or rapid acetylation by the NAT1 enzyme constitute possible risk factors for bladder cancer. In this case-control study, we sought to determine whether NAT1 and NAT2 polymorphisms are associated with bladder cancer risk in the largest sample size to date. PCR-RFLP assay was used to determine the presence of NAT1 and NAT2 polymorphisms in 507 Caucasian BC patients and 513 age-, gender-, and ethnicity-matched healthy controls. Overall, we found no significant association between BC risk and NAT1 NAT1 * 10 allele (OR = 0.95; 95% CI 0.73-1.25). However, our data suggested that NAT2 slow acetylator genotypes were associated with a significant increased risk of BC (OR = 1.31; 95% CI, 1.01-1.70). This elevated risk appeared more evident in older individuals (OR = 1.41; 95% CI, 1.01-1.98) than in younger individuals (OR = 1.15; 95% CI, 0.76-1.74). Moreover, the risk was greater for heavy smokers (OR = 2.11; 95% CI, 1.33-3.35) than light smokers (OR = 0.96; 95% CI, 0.61-1.53) and never smokers (OR = 1.23; 95% CI, 0.79-1.90). Finally, a joint effect between NAT2 slow acetylators and heavy smokers was observed. Using never smokers with NAT2 rapid acetylator genotypes as a reference group, heavy smokers with NAT2 slow acetylator genotypes showed an over six-fold increase in BC risk. In a multiplicative interaction model, the interaction term was statistically significant (P = 0.02). Our data suggest that having a NAT2 slow acetylator genotype is a significant risk factor for BC, particularly in smokers and older individuals.
AB - Cigarette smoking is the predominant risk factor for bladder cancer (BC). Major carcinogens present in tobacco smoke include a number of aromatic and heterocyclic amines. Two distinct N-acetyl transferase (NAT) enzymes, NAT1 and NAT2, play important roles in the bio-activation and detoxification of these carcinogens. Genes encoding NAT1 and NAT2 are highly polymorphic among human populations, and these polymorphisms result in rapid or slow acetylator phenotypes. Recent studies have suggested that variant alleles leading to slow acetylation by the NAT2 enzyme or rapid acetylation by the NAT1 enzyme constitute possible risk factors for bladder cancer. In this case-control study, we sought to determine whether NAT1 and NAT2 polymorphisms are associated with bladder cancer risk in the largest sample size to date. PCR-RFLP assay was used to determine the presence of NAT1 and NAT2 polymorphisms in 507 Caucasian BC patients and 513 age-, gender-, and ethnicity-matched healthy controls. Overall, we found no significant association between BC risk and NAT1 NAT1 * 10 allele (OR = 0.95; 95% CI 0.73-1.25). However, our data suggested that NAT2 slow acetylator genotypes were associated with a significant increased risk of BC (OR = 1.31; 95% CI, 1.01-1.70). This elevated risk appeared more evident in older individuals (OR = 1.41; 95% CI, 1.01-1.98) than in younger individuals (OR = 1.15; 95% CI, 0.76-1.74). Moreover, the risk was greater for heavy smokers (OR = 2.11; 95% CI, 1.33-3.35) than light smokers (OR = 0.96; 95% CI, 0.61-1.53) and never smokers (OR = 1.23; 95% CI, 0.79-1.90). Finally, a joint effect between NAT2 slow acetylators and heavy smokers was observed. Using never smokers with NAT2 rapid acetylator genotypes as a reference group, heavy smokers with NAT2 slow acetylator genotypes showed an over six-fold increase in BC risk. In a multiplicative interaction model, the interaction term was statistically significant (P = 0.02). Our data suggest that having a NAT2 slow acetylator genotype is a significant risk factor for BC, particularly in smokers and older individuals.
KW - Bladder cancer
KW - N-Acetyl transferase gene
KW - Polymorphism
KW - Tobacco smoke
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U2 - 10.1016/j.mrgentox.2004.11.012
DO - 10.1016/j.mrgentox.2004.11.012
M3 - Article
C2 - 15725609
AN - SCOPUS:13844266270
SN - 1383-5718
VL - 581
SP - 97
EP - 104
JO - Mutation Research - Genetic Toxicology and Environmental Mutagenesis
JF - Mutation Research - Genetic Toxicology and Environmental Mutagenesis
IS - 1-2
ER -