The present NAT2 genotyping study based on molecular methods in discriminating the acetylator genotypes both in controls and prostate cancer patients is the first of its kind in north Indian population. Rapid acetylator genotypes were comparatively predominant (55.7% and 64.6%) as compared to the slow acetylator genotypes (44.3% and 35.4%).
The results observed in the present study suggest, that NAT2 genotype has a trend of association for prostate cancer risk when considered alone (OR = 1.452, 95% CI: 0.54–1.87, P = 0.136) but is statistically non-significant (Table 2). However, no association could be established between NAT2 genotype and PSA and/or Gleason score (Fig 1 and Fig 2). Our findings agree with previous studies that showed significant association of prostate cancer for NAT2 rapid acetylator genotype in American study (23) whereas non significant association was observed in Swedish, Danish ) and Spanish population . On the contrary, there was significant association reported with slow acetylator genotypes of NAT2 in Japanese population . The discrimination in association study from our observation could be related to ethnic variation.
However, in the present study we observed significant association between the NAT2 genotypes in tobacco users as compared to the controls (Table 3). The synergistic interaction between the rapid acetylators genotype with tobacco users obtained in our study implies that exposure to tobacco, activates heterocyclic amines that are substrates for NAT2 which may increase the risk for prostate cancer. These observations are in agreement with the reports published by the investigators in liver and colon. In the liver heterocyclic amines may be N-hydroxylated by the hepatic CYP1A2, and in turn O-acetylated by NAT enzymes to an active form that can develop DNA adducts [5, 9]. NAT2 genotypes studied in hepatocellular carcinoma  and colorectal cancer  have indicated the prevalence of rapid acetylator among patient population. Thus, the present study suggests that rapid acetylator genotype could be associated with the susceptibility to prostate cancer especially in tobacco users. The mechanisms behind this association indicate that the slow acetylator genotypes should decrease the generation of critical intracellular concentration of such ultimate carcinogens, and thus reduce tumorogenesis upon environmental exposure (tobacco users). However, rapid acetylator genotypes should increase the generation of such ultimate carcinogens and enhance tumorogenesis by the pathway of O-acetylation. The results found in the present study reveal a markedly increased frequency of allele encoding the active genotype, among the patients cohort that entirely fit the above model, and are consistent with genotype / phenotype based studied that demonstrate an excess of rapid acetylator among the prostate cancer patients.
In the controls, slow allele of NAT2 is present up to 90% in Arab population , 40–60% in Caucasians including Indian  and 5–25% East Asian . We observed 44% of slow acetylator genotypes; however, another study from South Indian population indicated 74% of slow acetylator genotype . Thus it indicates that frequency of slow allele observed in our population matched with studies in Caucasians population . Differences of distribution of slow allele of NAT2 between our and south Indian population is due to the different ethnic /or geographical environment.