Variation in N-acetyltransferase 2 (NAT2), smoking and risk of prostate cancer in the Slovak population

Abstract

N-acetyltransferase 2 (NAT2) is an enzyme involved in the biotransformation of xenobiotics, mainly aromatic and heterocyclic amines and hydrazines, all of which represent an important class of carcinogens found in tobacco smoke. Polymorphism in NAT2 gene is reported to be associated with susceptibility to various types of cancer. This study investigated the relationship between the NAT2 polymorphism and the risk of prostate cancer with reference to the link between cigarette smoking and the xenobiotic-metabolizing enzyme NAT2. Overall, 281 cases and 395 controls from Slovakia were studied using polymerase chain reaction-restriction fragment length polymorphism assay. We found no statistically significant association between NAT2 genotypes and prostate cancer risk (slow acetylation vs. rapid acetylation: OR 1.13; 95 % CI 0.83-1.55). We report here a statistically significant correlation between the NAT2*5C/NAT2*6A slow acetylator genotype and the risk for developing prostate cancer (OR 2.91; 95 % CI 1.43-5.94; p = 0.003) when compared with the rapid phenotype. Smokers with NAT2 rapid phenotype had a five percent (5 %) reduced risk of prostate cancer compared with non-smokers carrying the rapid acetylator genotype. The association was reversed among smokers and non-smokers with NAT2 slow phenotype. On the basis of the foregoing, we conclude that the NAT2 phenotypes whether alone or in association with smoking do not correlate with susceptibility to prostate cancer within the Slovak population.

Assessment of N-acetyltransferase 2 (NAT2) gene polymorphisms in bladder cancer patients

“…On the other hand, there were no significant differences neither in M2 nor M3 among bladder cancer patients and control groups. These data are in accordance to Vilčková et al (6) who reported that M2 was detected in 8.89% of bladder cancer patients and 8.38% of controls, while M3 was detected in 2% in both patients and controls. In this study, it was found that 32 out of 35 bladder cancer individuals and 14 out of 15 subjects of each control group were identified as fast acetylators.…”

“…The activity of NAT2 is predicted from the combination of the NAT2 alleles. The presence of at least one wild type allele is considered a fast acetylator where the absence of any wild type allele is considered as slow acetylator (6). The two NAT2 phenotypes have been described; fast and slow.…”

Isoniazid acetylation phenotypes in the Sudanese population; findings and implications

“…These findings are also important as certain diseases including prostate cancer appear correlated with slow acetylators. The rate of prostrate cancer was approximately three times higher compared with fast acetylators phenotype (OR, 2.91; 95% CI 1.43 – 5.94) in a Slovak population [57]. Consequently, it would appear worthwhile monitoring the risk factors associated with cancer.…”

“…Being slow acetylators negatively impacted on liver toxicity (OR, 2.615; 95%CI 1.264–5.411), another reason for determining the extent of slow acetylation among populations [55]. In addition, slow acetylators genotypes among Indonesian Malay ethnic group were found to increase the risk of cancer and liver injury [56], with, as mentioned, slow acetylation known to increase the risk of prostate cancer in Slovak populations [57].…”

Associations of polymorphisms in NAT2 gene with risk and metastasis of osteosarcoma in young Chinese population

“… 4 A meta-analysis on rs1799930 and rs1799931 polymorphisms with the risk of multiple types of cancer demonstrated that NAT2 rs1799930 was associated with an elevated risk of cancer in Asian, whereas NAT2 rs1799931 polymorphism was a protective factor against cancer development. 13 There were also negative results in studies on prostate cancer in Slovak population, 14 esophageal cancer in Chinese population, 15 and breast cancer in Lebanese women. 16 Varied results in different ethnic populations call for further studies to investigate NAT2 polymorphisms in different malignancies.…”