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Vilckova M.,Comenius University | Jurecekova J.,Comenius University | Dobrota D.,Comenius University | Habalova V.,Safarikiensis University in Kosice | And 5 more authors.
Medical Oncology | Year: 2014

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 xeno-biotic-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. © Springer Science+Business Media 2014.

Kmetova Sivonova M.,Comenius University | Dobrota D.,Comenius University | Matakova T.,Comenius University | Dusenka R.,Comenius University | And 10 more authors.
Neoplasma | Year: 2012

Polymorphisms in tobacco carcinogen metabolizing enzymes may generate interindividual variations towards the risk of developing prostate cancer. One of these enzymes is microsomal epoxide hydrolase (EPHX1) which metabolizes polycyclic aromatic hydrocarbons, or PAH, carcinogens found in cigarette smoke. The activity of this enzyme is affected by two polymorphisms, a substitution of Tyr113 by His in exon 3 and a substitution of His139 by Arg in exon 4. The aim of this study was to use a population-based case-control study to investigate whether or not such genetic polymorphisms in EPHX1 gene can modify the relationship between smoking status and the risk of developing prostate cancer. We used restriction fragment length polymorphism, or PCR-RFLP to determine EPHX1 genotypes in subjects comprising 194 patients with histologically verified prostate cancer and 305 healthy individuals as control. We found no overall association between prostate cancer risk and functional polymorphisms of EPHX1 gene in exon 3 and exon 4. We further analysed the association between the EPHX1 genotypes and smoking. Smokers carrying the exon 3 Tyr/Tyr and Tyr/His genotypes were at no significant risk compared to non-smokers with the "rapid" Tyr/Tyr genotype. By contrast, a significant interaction of smoking and the exon 4 polymorphism was present (p < 0.05). Excess statistically significant risk was apparent among smokers with imputed normal phenotype in comparison to non-smokers with normal phenotype (p < 0.01). Based on these results we conclude that in the Slovak population studied, EPHX1 gene polymorphism in exon 4 would alter the risk of prostate cancer, particularly among smokers. Further analysis of other polymorphic variants in biotransformation enzymes and evaluation of gene-gene interactions may provide a more complete picture of how EPHX1 might influence the risk of developing prostate cancer.

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