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Published in: Medical Oncology 6/2014

01-06-2014 | Original Paper

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

Authors: Marta Vilčková, Jana Jurečeková, Dušan Dobrota, Viera Habalová, Lucia Klimčáková, Iveta Waczulíková, Peter Slezák, Ján Kliment, Monika Kmeťová Sivoňová

Published in: Medical Oncology | Issue 6/2014

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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.
Literature
1.
go back to reference Jang TL, Yossepowitch O, Bianco FJ Jr, Scardino PT. Low risk prostate cancer in men under age 65: the case for definitive treatment. Urol Oncol. 2007;25:510–4.PubMedCentralPubMedCrossRef Jang TL, Yossepowitch O, Bianco FJ Jr, Scardino PT. Low risk prostate cancer in men under age 65: the case for definitive treatment. Urol Oncol. 2007;25:510–4.PubMedCentralPubMedCrossRef
2.
go back to reference Ondrusova M, Ondrus D, Karabinos J, Muzik J, Kliment J, Gulis G. Trends in prostate cancer incidence and mortality before and after the introduction of PSA testing in the Slovak and Czech Republics. Tumori. 2011;97(2):149–55.PubMed Ondrusova M, Ondrus D, Karabinos J, Muzik J, Kliment J, Gulis G. Trends in prostate cancer incidence and mortality before and after the introduction of PSA testing in the Slovak and Czech Republics. Tumori. 2011;97(2):149–55.PubMed
3.
go back to reference Sivoňová MK, Dobrota D, Dušenka R, Waczulíková I, Slezák P, Matáková T, Mahmoodová S, Mištuna D, Kliment J. Effect of CYP17 and PSA gene polymorphisms on prostate cancer risk and circulating PSA levels in the Slovak population. Mol Biol Rep. 2012;39(8):7871–80.PubMedCrossRef Sivoňová MK, Dobrota D, Dušenka R, Waczulíková I, Slezák P, Matáková T, Mahmoodová S, Mištuna D, Kliment J. Effect of CYP17 and PSA gene polymorphisms on prostate cancer risk and circulating PSA levels in the Slovak population. Mol Biol Rep. 2012;39(8):7871–80.PubMedCrossRef
4.
go back to reference Stamatiou KN. Elderly and prostate cancer screening. Urol J. 2011;8(2):83–7.PubMed Stamatiou KN. Elderly and prostate cancer screening. Urol J. 2011;8(2):83–7.PubMed
5.
go back to reference Sivonova MK, Dobrota D, Matakova T, Dusenka R, Grobarcikova S, Habala V, Salagovic J, Tajtakova M, Pidanicova A, Valansky L, Lachvacs L, Kliment J Jr, Nagy V, Kliment J. Microsomal epoxide hydrolase polymorphisms, cigarette smoking and prostate cancer risk in the Slovak population. Neoplasma. 2012;59(1):79–84.PubMedCrossRef Sivonova MK, Dobrota D, Matakova T, Dusenka R, Grobarcikova S, Habala V, Salagovic J, Tajtakova M, Pidanicova A, Valansky L, Lachvacs L, Kliment J Jr, Nagy V, Kliment J. Microsomal epoxide hydrolase polymorphisms, cigarette smoking and prostate cancer risk in the Slovak population. Neoplasma. 2012;59(1):79–84.PubMedCrossRef
6.
7.
go back to reference Hein DW. N-acetyltransferase SNPs: emerging concepts serve as a paradigm for understanding complexities of personalized medicine. Expert Opin Drug Metab Toxicol. 2009;5(4):353–66.PubMedCentralPubMedCrossRef Hein DW. N-acetyltransferase SNPs: emerging concepts serve as a paradigm for understanding complexities of personalized medicine. Expert Opin Drug Metab Toxicol. 2009;5(4):353–66.PubMedCentralPubMedCrossRef
8.
go back to reference Liu L, Von Vett A, Zhang N, Walters KJ, Wagner CR, Hanna PE. Arylamine N-acetyltransferases: characterization of the substrate specificities and molecular interactions of environmental arylamines with human NAT1 and NAT2. Chem Res Toxicol. 2007;20(9):1300–8.PubMedCrossRef Liu L, Von Vett A, Zhang N, Walters KJ, Wagner CR, Hanna PE. Arylamine N-acetyltransferases: characterization of the substrate specificities and molecular interactions of environmental arylamines with human NAT1 and NAT2. Chem Res Toxicol. 2007;20(9):1300–8.PubMedCrossRef
9.
go back to reference Rajasekaran M, Abirami S, Chen C. Effects of single nucleotide polymorphisms on human N-acetyltransferase 2 structure and dynamics by molecular dynamics simulation. PLoS ONE. 2011;6(9):e25801.PubMedCentralPubMedCrossRef Rajasekaran M, Abirami S, Chen C. Effects of single nucleotide polymorphisms on human N-acetyltransferase 2 structure and dynamics by molecular dynamics simulation. PLoS ONE. 2011;6(9):e25801.PubMedCentralPubMedCrossRef
10.
go back to reference Sim E, Lack N, Wang CJ, Long H, Westwood I, Fullam E, Kawamura A. Arylamine N-acetyltransferases: structural and functional implications of polymorphisms. Toxicology. 2008;254(3):170–83.PubMedCrossRef Sim E, Lack N, Wang CJ, Long H, Westwood I, Fullam E, Kawamura A. Arylamine N-acetyltransferases: structural and functional implications of polymorphisms. Toxicology. 2008;254(3):170–83.PubMedCrossRef
11.
go back to reference Windmill KF, Gaedigk A, Hall PM, Samaratunga H, Grant DM, McManus ME. Localization of N-acetyltransferases NAT1 and NAT2 in human tissues. Toxicol Sci. 2000;54(1):19–29.PubMedCrossRef Windmill KF, Gaedigk A, Hall PM, Samaratunga H, Grant DM, McManus ME. Localization of N-acetyltransferases NAT1 and NAT2 in human tissues. Toxicol Sci. 2000;54(1):19–29.PubMedCrossRef
12.
go back to reference Blum M, Grant DM, McBride W, Heim M, Meyer UA. Human arylamine N-acetyltransferase genes: isolation, chromosomal localization, and functional expression. DNA Cell Biol. 1990;9(3):193–203.PubMedCrossRef Blum M, Grant DM, McBride W, Heim M, Meyer UA. Human arylamine N-acetyltransferase genes: isolation, chromosomal localization, and functional expression. DNA Cell Biol. 1990;9(3):193–203.PubMedCrossRef
13.
go back to reference Gong C, Hu X, Gao Y, Cao Y, Gao F, Mo Z. A meta-analysis of the NAT1 and NAT2 polymorphisms and prostate cancer: a huge review. Med Oncol. 2011;28(1):365–76.PubMedCrossRef Gong C, Hu X, Gao Y, Cao Y, Gao F, Mo Z. A meta-analysis of the NAT1 and NAT2 polymorphisms and prostate cancer: a huge review. Med Oncol. 2011;28(1):365–76.PubMedCrossRef
15.
go back to reference Walraven JM, Zang Y, Trent JO, Hein DW. Structure/function evaluations of single nucleotide polymorphisms in human N-acetyltransferase 2. Curr Drug Metab. 2008;9(6):471–86.PubMedCentralPubMedCrossRef Walraven JM, Zang Y, Trent JO, Hein DW. Structure/function evaluations of single nucleotide polymorphisms in human N-acetyltransferase 2. Curr Drug Metab. 2008;9(6):471–86.PubMedCentralPubMedCrossRef
16.
go back to reference Agundez JA. Polymorphisms of human N-acetyltransferases and cancer risk. Curr Drug Metab. 2008;9(6):520–31.PubMedCrossRef Agundez JA. Polymorphisms of human N-acetyltransferases and cancer risk. Curr Drug Metab. 2008;9(6):520–31.PubMedCrossRef
17.
go back to reference Hein DW, Doll MA, Fretland AJ, Leff MA, Webb SJ, Xiao GH, Devanaboyina US, Nangju NA, Feng Y. Molecular genetics and epidemiology of the NAT1 and NAT2 acetylation polymorphisms. Cancer Epidemiol Biomark Prev. 2000;9(1):29–42. Hein DW, Doll MA, Fretland AJ, Leff MA, Webb SJ, Xiao GH, Devanaboyina US, Nangju NA, Feng Y. Molecular genetics and epidemiology of the NAT1 and NAT2 acetylation polymorphisms. Cancer Epidemiol Biomark Prev. 2000;9(1):29–42.
18.
go back to reference Meyer UA, Zanger UM. Molecular mechanisms of genetic polymorphisms of drug metabolism. Annu Rev Pharmacol Toxicol. 1997;37:269–96.PubMedCrossRef Meyer UA, Zanger UM. Molecular mechanisms of genetic polymorphisms of drug metabolism. Annu Rev Pharmacol Toxicol. 1997;37:269–96.PubMedCrossRef
19.
go back to reference Hamasaki T, Inatomi H, Katoh T, Aono H, Ikuyama T, Muratani T, Matsumoto T. N-acetyltransferase-2 gene polymorphism as a possible biomarker for prostate cancer in Japanese men. Int J Urol. 2003;10(3):167–73.PubMedCrossRef Hamasaki T, Inatomi H, Katoh T, Aono H, Ikuyama T, Muratani T, Matsumoto T. N-acetyltransferase-2 gene polymorphism as a possible biomarker for prostate cancer in Japanese men. Int J Urol. 2003;10(3):167–73.PubMedCrossRef
20.
go back to reference de Lima Junior MM, Reis LO, Guilhen AC, Granja F, de Lima Oliveira MN, Ferreira U, Cunha LL, Ward LS. N-acetyltransferase-2 gene polymorphisms and prostate cancer susceptibility in Latin American patients. Med Oncol. 2012;29(4):2889–94.PubMedCrossRef de Lima Junior MM, Reis LO, Guilhen AC, Granja F, de Lima Oliveira MN, Ferreira U, Cunha LL, Ward LS. N-acetyltransferase-2 gene polymorphisms and prostate cancer susceptibility in Latin American patients. Med Oncol. 2012;29(4):2889–94.PubMedCrossRef
21.
go back to reference Wadelius M, Autrup JL, Stubbins MJ, Andersson SO, Johansson JE, Wadelius C, Wolf CR, Autrup H, Rane A. Polymorphisms in NAT2, CYP2D6, CYP2C19 and GSTP1 and their association with prostate cancer. Pharmacogenetics. 1999;9(3):333–40.PubMedCrossRef Wadelius M, Autrup JL, Stubbins MJ, Andersson SO, Johansson JE, Wadelius C, Wolf CR, Autrup H, Rane A. Polymorphisms in NAT2, CYP2D6, CYP2C19 and GSTP1 and their association with prostate cancer. Pharmacogenetics. 1999;9(3):333–40.PubMedCrossRef
22.
go back to reference Hooker S, Bonilla C, Akereyeni F, Ahaghotu C, Kittles RA. NAT2 and NER genetic variants and sporadic prostate cancer susceptibility in African Americans. Prostate Cancer Prostatic Dis. 2008;11(4):349–56.PubMedCrossRef Hooker S, Bonilla C, Akereyeni F, Ahaghotu C, Kittles RA. NAT2 and NER genetic variants and sporadic prostate cancer susceptibility in African Americans. Prostate Cancer Prostatic Dis. 2008;11(4):349–56.PubMedCrossRef
23.
go back to reference Iguchi T, Sugita S, Wang CY, Newman NB, Nakatani T, Haas GP. MnSOD genotype and prostate cancer risk as a function of NAT genotype and smoking status. In Vivo. 2009;23(1):7–12.PubMedCentralPubMed Iguchi T, Sugita S, Wang CY, Newman NB, Nakatani T, Haas GP. MnSOD genotype and prostate cancer risk as a function of NAT genotype and smoking status. In Vivo. 2009;23(1):7–12.PubMedCentralPubMed
24.
go back to reference Rovito PM Jr, Morse PD, Spinek K, Newman N, Jones RF, Wang CY, Haas GP. Heterocyclic amines and genotype of N-acetyltransferases as risk factors for prostate cancer. Prostate Cancer Prostatic Dis. 2005;8(1):69–74.PubMedCrossRef Rovito PM Jr, Morse PD, Spinek K, Newman N, Jones RF, Wang CY, Haas GP. Heterocyclic amines and genotype of N-acetyltransferases as risk factors for prostate cancer. Prostate Cancer Prostatic Dis. 2005;8(1):69–74.PubMedCrossRef
25.
go back to reference Agúndez JA, Martínez C, Olivera M, Gallardo L, Ladero JM, Rosado C, Prados J, Rodriguez-Molina J, Resel L, Benítez J. Expression in human prostate of drug- and carcinogen-metabolizing enzymes: association with prostate cancer risk. Br J Cancer. 1998;78(10):1361–7.PubMedCentralPubMedCrossRef Agúndez JA, Martínez C, Olivera M, Gallardo L, Ladero JM, Rosado C, Prados J, Rodriguez-Molina J, Resel L, Benítez J. Expression in human prostate of drug- and carcinogen-metabolizing enzymes: association with prostate cancer risk. Br J Cancer. 1998;78(10):1361–7.PubMedCentralPubMedCrossRef
26.
go back to reference Srivastava DS, Mittal RD. Genetic polymorphism of the N-acetyltransferase 2 gene, and susceptibility to prostate cancer: a pilot study in north Indian population. BMC Urol. 2005;6:5–12. Srivastava DS, Mittal RD. Genetic polymorphism of the N-acetyltransferase 2 gene, and susceptibility to prostate cancer: a pilot study in north Indian population. BMC Urol. 2005;6:5–12.
27.
go back to reference Costa S, Pinto D, Morais A, Vasconcelos A, Oliveira J, Lopes C, Medeiros R. Acetylation genotype and the genetic susceptibility to prostate cancer in a southern European population. Prostate. 2005;64(3):246–52.PubMedCrossRef Costa S, Pinto D, Morais A, Vasconcelos A, Oliveira J, Lopes C, Medeiros R. Acetylation genotype and the genetic susceptibility to prostate cancer in a southern European population. Prostate. 2005;64(3):246–52.PubMedCrossRef
28.
go back to reference Xue W, Warshawsky D. Metabolic activation of polycyclic and heterocyclic aromatic hydrocarbons and DNA damage: a review. Toxicol Appl Pharmacol. 2005;206(1):73–93.PubMedCrossRef Xue W, Warshawsky D. Metabolic activation of polycyclic and heterocyclic aromatic hydrocarbons and DNA damage: a review. Toxicol Appl Pharmacol. 2005;206(1):73–93.PubMedCrossRef
29.
go back to reference Cleary SP, Cotterchio M, Shi E, Gallinger S, Harper P. Cigarette smoking, genetic variants in carcinogen-metabolizing enzymes, and colorectal cancer risk. Am J Epidemiol. 2010;172(9):1000–14.PubMedCentralPubMedCrossRef Cleary SP, Cotterchio M, Shi E, Gallinger S, Harper P. Cigarette smoking, genetic variants in carcinogen-metabolizing enzymes, and colorectal cancer risk. Am J Epidemiol. 2010;172(9):1000–14.PubMedCentralPubMedCrossRef
30.
go back to reference Klimčáková L, Habalová V, Sivoňová M, Nagy V, Šalagovič J, Židzik J. Effect of NAT2 gene polymorphism on bladder cancer risk in Slovak population. Mol Biol Rep. 2011;38(2):1287–93.PubMedCrossRef Klimčáková L, Habalová V, Sivoňová M, Nagy V, Šalagovič J, Židzik J. Effect of NAT2 gene polymorphism on bladder cancer risk in Slovak population. Mol Biol Rep. 2011;38(2):1287–93.PubMedCrossRef
31.
go back to reference Garcia-Martin E. Interethnic and intraethnic variability of NAT2 single nucleotide polymorphisms. Curr Drug Metab. 2008;9:487–97.PubMedCrossRef Garcia-Martin E. Interethnic and intraethnic variability of NAT2 single nucleotide polymorphisms. Curr Drug Metab. 2008;9:487–97.PubMedCrossRef
32.
go back to reference Zang Y, Doll MA, Zhao S, States JC, Hein DW. Functional characterization of single-nucleotide polymorphisms and haplotypes of human N-acetyltransferase 2. Carcinogenesis. 2007;28(8):1665–71.PubMedCentralPubMedCrossRef Zang Y, Doll MA, Zhao S, States JC, Hein DW. Functional characterization of single-nucleotide polymorphisms and haplotypes of human N-acetyltransferase 2. Carcinogenesis. 2007;28(8):1665–71.PubMedCentralPubMedCrossRef
33.
go back to reference Touré A, Diop C, Cabral M, Fall M, Lhermitte M, Diouf A, Broly F, Allorge D. Study of NAT2 genetic polymorphism in West African subjects: example of an healthy non-smoker Senegalese population. Mol Biol Rep. 2012;39(12):10489–96.PubMedCrossRef Touré A, Diop C, Cabral M, Fall M, Lhermitte M, Diouf A, Broly F, Allorge D. Study of NAT2 genetic polymorphism in West African subjects: example of an healthy non-smoker Senegalese population. Mol Biol Rep. 2012;39(12):10489–96.PubMedCrossRef
34.
go back to reference Leff MA, Fretland AJ, Doll MA, Hein DW. Novel human N-acetyltransferase 2 alleles that differ in mechanism for slow acetylator phenotype. J Biol Chem. 1999;274(49):34519–22.PubMedCrossRef Leff MA, Fretland AJ, Doll MA, Hein DW. Novel human N-acetyltransferase 2 alleles that differ in mechanism for slow acetylator phenotype. J Biol Chem. 1999;274(49):34519–22.PubMedCrossRef
35.
go back to reference Semiz S, Dujic T, Ostanek B, Velija-Asimi Z, Prnjavorac B, Bego T, Malenica M, Mlinar B, Heljic B, Marc J, Causevic A. Association of NAT2 polymorphisms with type 2 diabetes in a population from Bosnia and Herzegovina. Arch Med Res. 2011;42(4):311–7.PubMedCrossRef Semiz S, Dujic T, Ostanek B, Velija-Asimi Z, Prnjavorac B, Bego T, Malenica M, Mlinar B, Heljic B, Marc J, Causevic A. Association of NAT2 polymorphisms with type 2 diabetes in a population from Bosnia and Herzegovina. Arch Med Res. 2011;42(4):311–7.PubMedCrossRef
36.
go back to reference Wang CY, Debiec-Rychter M, Schut HA, Morse P, Jones RF, Archer C, King CM, Haas GP. N-Acetyltransferase expression and DNA binding of N-hydroxyheterocyclic amines in human prostate epithelium. Carcinogenesis. 1999;20(8):1591–5.PubMedCrossRef Wang CY, Debiec-Rychter M, Schut HA, Morse P, Jones RF, Archer C, King CM, Haas GP. N-Acetyltransferase expression and DNA binding of N-hydroxyheterocyclic amines in human prostate epithelium. Carcinogenesis. 1999;20(8):1591–5.PubMedCrossRef
37.
go back to reference Hein DW, Doll MA, Rustan TD, Gray K, Feng Y, Ferguson RJ, Grant DM. Metabolic activation and deactivation of arylamine carcinogens by recombinant human NAT1 and polymorphic NAT2 acetyltransferases. Carcinogenesis. 1993;14(8):1633–8.PubMedCrossRef Hein DW, Doll MA, Rustan TD, Gray K, Feng Y, Ferguson RJ, Grant DM. Metabolic activation and deactivation of arylamine carcinogens by recombinant human NAT1 and polymorphic NAT2 acetyltransferases. Carcinogenesis. 1993;14(8):1633–8.PubMedCrossRef
38.
go back to reference Reistad R, Nyholm SH, Haug LS, Becher G, Alexander J. 2-Amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) in human hair as biomarker for dietary exposure. Biomarkers. 1999;4(4):263–71.CrossRef Reistad R, Nyholm SH, Haug LS, Becher G, Alexander J. 2-Amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) in human hair as biomarker for dietary exposure. Biomarkers. 1999;4(4):263–71.CrossRef
39.
go back to reference Koutros S, Berndt SI, Sinha R, Ma X, Chatterjee N, Alavanja MC, Zheng T, Huang WY, Hayes RB, Cross AJ. Xenobiotic metabolizing gene variants, dietary heterocyclic amine intake, and risk of prostate cancer. Cancer Res. 2009;69(5):1877–84.PubMedCentralPubMedCrossRef Koutros S, Berndt SI, Sinha R, Ma X, Chatterjee N, Alavanja MC, Zheng T, Huang WY, Hayes RB, Cross AJ. Xenobiotic metabolizing gene variants, dietary heterocyclic amine intake, and risk of prostate cancer. Cancer Res. 2009;69(5):1877–84.PubMedCentralPubMedCrossRef
Metadata
Title
Variation in N-acetyltransferase 2 (NAT2), smoking and risk of prostate cancer in the Slovak population
Authors
Marta Vilčková
Jana Jurečeková
Dušan Dobrota
Viera Habalová
Lucia Klimčáková
Iveta Waczulíková
Peter Slezák
Ján Kliment
Monika Kmeťová Sivoňová
Publication date
01-06-2014
Publisher
Springer US
Published in
Medical Oncology / Issue 6/2014
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-014-0987-3

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