The aim of our study was to assess the correlation between the tobacco exposure and NAT2 gene (rs1041983 C/T, rs1801280 T/C, rs1799930 G/A) polymorphisms in association with breast cancer development. We wanted to determine the prognostic clinical importance of these polymorphisms in association with smoking and breast cancer. For the detection of possible association between smoking, NAT2 gene polymorphisms, and the risk of breast cancer, we designed a case-controlled study with 198 patients enrolled, 98 breast cancer patients and 100 healthy controls. Ten milliliters of peripheral blood from the cubital vein was withdrawn from every patient. The HRM (high resolution melting) analysis was used for the detection of three abovementioned NAT2 gene polymorphisms. When comparing a group of women smoking more than 5 cigarettes a day with the patients smoking fewer than 5 cigarettes a day, we found out that if women were the carriers of aberrant AA genotype for rs1799930, the first group of women had higher risk of breast carcinoma than the second group. If patients were the carriers of aberrant TT genotype for rs1041983, for rs1801280CC genotype, and rs1799930AA genotype and they smoked more than 5 cigarettes a day, they had higher risk of malignant breast disease than never-smoking women. Our results confirm the hypothesis that NAT2 gene polymorphisms (rs1041983 C/T, rs1801280 T/C, and rs1799930 G/A) in association with long-period active smoking could be the possible individual risk-predicting factors for breast cancer development in the population of Slovak women.
Smoking Breast cancer NAT2 gene Polymorphisms
This is a preview of subscription content, log in to check access.
This work was supported by the project “Centre of excellence for perinatology research (CEPV I),” ITMS:26220120016, co-financed by EU grants, by the project “Centre of excellence for perinatology research establishment (CEPV II)”, ITMS: 26220120036, co-financed by EU grants, University grant UK/468/2011, UK/372/2012, UK/116/2013, by project VEGA MŠ1/0243/12 and APVV-14-0815.
Compliance with ethical standards
This study was funded by the project “Centre of excellence for perinatology research (CEPV I)”, ITMS:26220120016, co-financed by EU grants, by the project “Centre of excellence for perinatology research establishment (CEPV II)”, ITMS: 26220120036, co-financed by EU grants, University grant UK/468/2011, UK/372/2012, UK/116/2013, by project VEGA MŠ1/0243/12 and APVV-14-0815.
Conflict of interest
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
Ambrosone CB et al. Cigarette smoking, N-acetyltransferase 2 genotypes, and breast cancer risk: pooled analysis and meta-analysis. Cancer Epidemiol Biomarkers Prev. 2008;17(1):15–26.CrossRefPubMedGoogle Scholar
Anderson LN et al. Passive cigarette smoke exposure during various periods of life, genetic variants, and breast cancer risk among never smokers. Am J Epidemiol. 2012;175(4):289–301.CrossRefPubMedGoogle Scholar
Bradbury BD et al. Departure from multiplicative interaction for catechol-O-methyltransferase genotype and active/passive exposure to tobacco smoke among women with breast cancer. J Carcinog. 2006. Jan 17, 5:3.Google Scholar
Brocton N et al. N-acetyltransferase polymorphisms and colorectal cancer: a HuGE review. Am J Epidemiol. 2000;151:846–61.CrossRefGoogle Scholar
Cox DG et al. Breast and Prostate Cancer Cohort Consortium. N-acetyltransferase 2 polymorphisms, tobacco smoking, and breast cancer risk in the breast and prostate cancer cohort consortium. Am J Epidemiol. 2011;174(11):1316–22.CrossRefPubMedPubMedCentralGoogle Scholar
Cribb AE et al. CYP17, catechol-o-methyltransferase, and glutathione transferase M1 genetic polymorphisms, lifestyle factors, and breast cancer risk in women on Prince Edward Island. Breast J. 2011;17(1):24–31.CrossRefPubMedGoogle Scholar
Egan KM et al. Association of NAT2 and smoking in relation to breast cancer incidence in a population-based case-control study (United States). Cancer Causes Control. 2003;14:43–51.CrossRefPubMedGoogle Scholar
Fernandes MR et al. Association of slow acetylation profile of NAT2 with breast and gastric cancer risk in Brazil. Anticancer Res. 2013;33(9):3683–9.PubMedGoogle Scholar
Firozi PF et al. Aromatic DNA adducts and polymorphisms of CYP1A1, NAT2, and GSTM1 in breast cancer. Carcinogenesis. 2002;23:301–6.CrossRefPubMedGoogle Scholar
Hein DW et al. Molecular genetics and epidemiology of the NAT1 and NAT2 acetylation polymorphisms. Cancer Epidemiol Biomarkers Prev. 2000;9:29–42.PubMedGoogle Scholar
Hunter DJ et al. A prospective study of NAT2 acetylation genotype, cigarette smoking, and risk of breast cancer. Carcinogenesis. 1997;18:2127–32.CrossRefPubMedGoogle Scholar
Johnson KC et al. Active smoking and secondhand smoke increase breast cancer risk: the report of the Canadian Expert Panel on Tobacco Smoke and Breast Cancer Risk (2009). Tob Control. 2011;20(1):e2.CrossRefPubMedGoogle Scholar
Lissowska J et al. Tobacco smoking, NAT2 acetylation genotype and breast cancer risk. Int J Cancer. 2006;119:1961–9.CrossRefPubMedGoogle Scholar
Millikan RC et al. Cigarette smoking, N-acetyltransferases 1 and 2, and breast cancer risk. Cancer Epidemiol Biomarkers Prev. 1998;7:371–8.PubMedGoogle Scholar
Morabia A et al. Breast cancer and active and passive smoking: the role of the N-acetyltransferase 2 genotype. Am J Epidemiol. 2000;152:226–32.CrossRefPubMedGoogle Scholar
Murtaugh MA et al. The CYP1A1 genotype may alter the association of meat consumption patterns and preparation with the risk of colorectal cancer in men and women. J Nutr. 2005;135:179–86.PubMedGoogle Scholar
Ozbek YK et al. Combined effect of CYP1B1 codon 432 polymorphism and N-acetyltransferase 2 slow acetylator phenotypes in relation to breast cancer in the Turkish population. Anticancer Res. 2010;30(7):2885–9.PubMedGoogle Scholar
Rabstein S et al. N-acetyltransferase 2, exposure to aromatic and heterocyclic amines, and receptor-defined breast cancer. Eur J Cancer Prev. 2010;19(2):100–9.CrossRefPubMedGoogle Scholar
Sim E et al. Arylamine N-acetyltransferases—from drug metabolism and pharmacogenetics to identification of novel targets for pharmacological intervention. Adv Pharmacol. 2012;63:169–205.CrossRefPubMedGoogle Scholar
Sim E, Abuhammad A, Ryan A. Arylamine N-acetyltransferases: from Drug Metabolism and Pharmacogenetics to Drug Discovery. Br J Pharmacol. 2014 Jan 28.Google Scholar