Active cigarette smoking and the risk of development of breast cancer based on of N-acetyltransferase 2 (NAT2) gene polymorphism

Introduction: The nicotine addiction is an important risk factor which is involved in the development of many human diseases. Number of scientific papers have demonstrated a link between smoking and an increased incidence of breast cancer in women. Objective: The aim of our prospective study was to investigate the association between tobacco exposure and NAT2 gene polymorphisms (rs1041983 C/T, rs1801280 T/C, rs1799930 G/A) in connection with the development of breast cancer. We wanted to clarify the clinical prognostic significance of these three gene polymorphisms and their possible association with smoking and breast cancer. Methods: Aiming to detect the association between smoking, NAT2 gene polymorphisms and risk of breast cancer we conducted a case-control study in which a total of 198 women were involved. In our patient group 98 diagnosed breast cancer patients and 100 healthy controls were involved. The detection of above mentioned three polymorphisms of NAT 2 gene was realised using HRM analysis (High Resolution Melting). Results: Analysis of the NAT2 gene polymorphisms in connection with smoking showed significantly higher risk of the disease (p = 0.0286) in women smoking more than 5 cigarettes a day with aberrant TT genotype for rs1041983 compared to the control group. Women with AA genotype for rs1799930 showed significantly (p = 0.0443) higher risk of the disease compared to the control group. Women consuming cigarettes for more than five years with aberrant TT genotype for rs1041983 had higher risk of disease than the control group. Furthermore, we observed that women who smoke more than five years and paralelly carriers aberrant AA genotype in case of rs1799930 G/A had a higher risk of breast cancer than non-smoking women. The difference between groups in the distribution of genotypes was significant (p = 0.0010). Conclusion: Our results support the hypothesis that polymorphisms of NAT2 gene (rs1041983 C/T, rs1801280 T/C and rs1799930 G/A) along with an active and long-term smoking might be a risk factors for the individual susceptibility to breast cancer in a population of Slovak women. Keywords: Harmful effects of cigarettes, Breast cancer, NAT2 gene polymorphisms, The risk of disease Acknowledgement: This study was supported by project VEGA MŠ1/0243/12 and by Grants of Comenius University UK/468/2011; UK/372/2012 and UK/116/2013.