When stratifying by smoking status, no statistically significant differences in BCa risk were found for NAT1*10 versus non-NAT1*10 acetylators among the different subgroups.
There was no association between NAT1*10 allele and bladder cancer risk in a random-effects model (OR = 0.96, 95% CI, 0.84-1.10) or in a fixed-effects model (OR = 0.95, 95% CI, 0.87-1.03).
In contrast to the Berlin study from 2001, data in present study demonstrated that NAT1*10 haplotype was not associated with a significantly decreased bladder cancer risk.
The incidence of bladder cancer is closely associated with exposure to aromatic amines, that can cause cancer only after metabolic activation regulated by N-acetyl transferase 1 and 2 (NAT1 and NAT2).
We evaluated the association between hair dye use and bladder cancer risk and effect modification by N-acetyltransferase-1 (NAT1), NAT2, glutathione S-transferase Mu-1 (GSTM1) and glutathione S-transferase theta-1 (GSTT1) genotypes in a population-based case-control study of 1193 incident cases and 1418 controls from Maine, Vermont and New Hampshire enrolled between 2001 and 2004.
An increased risk of bladder cancer was found in NAT2 slow acetylators (odds ratio = 1.46, 95% credible interval (CI): 1.26, 1.68) but not in NAT1 fast acetylators (odds ratio = 1.01, 95% CI: 0.86, 1.22).
Individuals carrying NAT1wt/*10 and NAT1*10/*10 showed higher relative risks of bladder cancer (OR = 2.8, 95% CI = 0.8-10.1 and OR = 2.2, 95% CI = 0.6-8.3, respectively).
We assessed the association between common polymorphisms identified in the GSTM1, GSTT1, NAT1, and NAT2 genes and the risk of bladder cancer in two nested case-control studies within the Nurses' Health Study (n = 78 female cases, 234 female controls) and the Health Professionals' Follow-up Study (n = 139 male cases, 293 male controls).
Individuals carrying NAT1wt/*10 and NAT1*10/*10 showed higher relative risks of bladder cancer (OR = 2.8, 95% CI = 0.8-10.1 and OR = 2.2, 95% CI = 0.6-8.3, respectively).
The methodology is implemented in an original meta-analysis of studies relating the risk of bladder cancer to two N-acetyltransferase genes, NAT1 and NAT2, and smoking status.
The present data show that NAT1*10 neither displayed an association with an elevated grading of urothelial cells nor a clear impact on the risk for bladder cancer in benzidine-exposed Chinese workers.
We also hypothesized that allelic variants of the NAT1 and NAT2 genes might modify the effect of the XPD codon 751 polymorphism on smoking-associated bladder-cancer risk.
Thus, NAT1 polymorphisms may affect the individual bladder cancer risk by interacting with environmental factors (smoking and occupational risks) and by interacting with the NAT2 gene.
We have also shown that NAT1 genotype (NAT1*10 allele) is associated with increased DNA adduct levels in urothelial tissue and higher risk of bladder cancer among smokers.
The results are consistent with the hypothesis that NAT1 and NAT2 might modulate the susceptibility to bladder cancer associated with cigarette smoking.
In this study, fluorescence in situ hybridization (FISH) was used for study of the relationship between chromosome 8 deletions in the region of NAT1 and NAT2 and grade and stage of tumor in bladder cancer.
To explore the combined role of these genes and exposure on bladder cancer risk, we examined the NAT1 and NAT2 genotype in a case-control study of bladder cancer in which detailed exposure histories were available on all 230 cases and 203 frequency-matched controls.
It was published that the NAT1 allele 10 was associated with high enzyme activity and that there was an overrepresentation of carriers of NAT1*10 in bladder and colon cancer, but we could only detect a moderately elevated activity of NAT1*10 and an underrepresentation of fast NAT1 alleles in bladder cancer.
Of these alleles, NAT1*10 is responsible for increased NAT1 enzyme levels and is reported to be associated with increased risk for colorectal and bladder cancers.
Likewise, analyses of the NAT1 and glutathione S-transferase mu 1 (GSTM1) genotypes showed no associations between the NAT1 or GSTM1 genotypes and bladder cancer risk.
In collaborative studies, we now have found that NAT1 is also expressed polymorphically in human bladder due to mutations in the NAT1 polyadenylation signal, which has recently been associated with increased bladder cancer risk.