Polymorphisms in the NAT2 and the HLA-DPB1(G)(lu69) genes provide classic examples of how genetic susceptibility markers have a clear role in identifying disease risk in bladder cancer and chronic beryllium disease, respectively.
For the NAT2 slow acetylator genotypes, the NAT2*5/*7 diplotype was found to have a 7-fold increased risk to develop bladder cancer (OR = 7.14; 95% CI: 1.30-51.41).
Two established bladder cancer susceptibility genotypes, NAT2 slow-acetylation and GSTM1-null, exhibited similar associations among the subphenotypes, as did VEGF-rs25648, which was previously identified in our study.
In the pathogenesis of human bladder cancer due to occupational exposure to "classical" aromatic amines (benzidine, 4-aminodiphenyl, 1-naphthylamine) acetylation by NAT2 is regarded as a detoxication step.
In our analysis of smoking and bladder cancer, the tests for multiplicative interaction seemed to more commonly identify susceptibility loci with associations in never smokers, whereas the additive interaction analysis identified more loci with associations among smokers-including the known smoking and NAT2 acetylation interaction.
In this case-control investigation of 113 patients with primary bladder cancer and 221 control subjects, we compared the association of bladder cancer with genetic polymorphisms of NAT2, GSTM1 and GSTT1, demographic characteristics, smoking status, and medical histories in a molecular epidemiological way.
A metaanalysis risk estimate of case-control studies of NAT2 acetylation and bladder cancer in Asian populations without occupational arylamine exposures showed an increased risk for slow acetylators.
The phase II enzymes N-acetyltransferase 2 (NAT2), glutathione S-transferases M1 (GSTM1), and T1 (GSTT1) and the single nucleotide polymorphism (SNP) rs11892031[A/C] reported to be associated with bladder cancer in genome-wide association studies were genotyped.
NAT2 slow acetylator was associated with marginally increased risk of bladder cancer (OR = 1.50, 95% CI = 0.99-2.27), and the OR for the joint effect with occupational exposure of aromatic amines was 3.26 (95% CI = 1.06-9.95).
Polymorphisms in NAT2 have long been recognized to modulate toxicity produced by the anti-tubercular drug isoniazid, with molecular epidemiologic studies suggesting a link between acetylator phenotype and increased risk for bladder cancer.
On the basis of the results of recent genetic studies in relation to bladder carcinogenesis, several genetic polymorphisms of detoxification or DNA repair such as N-acetyltransferase 2, glutathione S-transferases, and human 8-oxoguanine DNA glycosylase 1 give us important information in relation to environmental risk factors and ethnic differences for predicting the prognosis of patients with bladder cancer.
It is suggested that NAT2 slow-acetylator, GSTM1 null, GSTM1/GSTT1-double null, and variant CYP2A6 genotypes may play important roles in the development of bladder cancer in Henan area, China.
Evidence for a putative association of NAT1 polymorphism and myeloma, lung and bladder cancer, as well as association of NAT2 polymorphisms with non-Hodgkin lymphoma, liver, colorectal and bladder cancer have been reported.
For bladder cancer, the significantly excessive risks were observed in regular drinkers (OR = 2.74, 95% CI = 1.28-5.87) and residents of the black-foot disease endemic area (OR = 7.53, 95% CI = 2.16-26.33), and interaction of regular drinking and slow type of NAT2 (OR = 18.04, 95% CI = 2.28-142.80).
In conclusion, molecular genetic analysis of a large sample specified the increased bladder cancer risk of those who are deficient in NAT2 and GSTM1; the other traits proved to be of minor impact.
Numerous studies have shown that slow NAT2 haplotypes are associated with increased urinary bladder cancer risk and increased risk of anti-tuberculosis drug-induced hepatotoxicity.
The nuclear matrix protein 22 (NMP22), bladder cancer-4 (BLCA-4), and total level proteins NMP22 and BLCA-4 (NMBL) in BC patients with genetic predisposition NAT2 (classified as slow acetylators, SA), DNA damage (8-OHdG), and detoxification by isoenzyme GST<i>π</i> activity were measured.