Detection of CYP gene CYP2A6 * 1 and CYP2A6 * 4 alleles in patients with lung cancer of Georgian population and evaluation of lymphocyte metabolic activity

Author: shorena gogoladze
Keywords: CYP2A6 * 1 and CYP2A6 * 4 genotyping, smart amplification, lung cancer, personalized medicine, ribosomal cystones.
Annotation:

Lung cancer (LC) is a topical social and biological problem in the modern world. It is a highly common mailignant tumor and a leading cause of death from cancer. In the vast majority of cases, the main etiological factor of LC is tobacco consumption - smoking.The main ingredient in tobacco - nicotine is metabolized for the first time as metabolite - cotinine, which is catalyzed by one of the enzymes in the cytochrome P-450 family CYP2A6. This enzyme is responsible for the metabolic activation of tobacco-specific nitrosamine (lung-specific potential carcinogen). Genetic variations in the activity of CYP2A6 due to gene mutations - CYP2A6*1 (active metabolite) and CYP2A6*4 (complete inactivation of the enzyme) determine the difference in the metabolism and activation of nicotine and nitrosoamine in the body.The frequencies of these alleles vary across racial/ethnic groups and populations. The importance of their detection in populations for preventive medicine is indicated. In the case of lung cancer, as in any other oncological disease, the study of such an important component of the immune system as the functional state of lymphocytes has a particular importance. Based on the above, the objectives of our study were: at first - to detect the frequency of CYP2A6 * 1 and CYP2A6 * 4 alleles in healthy individuals of Georgian population and LC (which was conducted for the first time in Georgia); on the other hand –to determine the level of metabolic activity in patients with LC.Research material was peripheral bloodcells andcells of lymphocyte culture of clinically healthy smokers, non-smokers and patients with LC from Georgian population.For genotyping -the method of isothermal smart amplification (SmartAmp-2) was used to detect CYP2A6 * 1 and CYP2A6 * 4 alleles; Metabolic activity of lymphocytes in patients with LC was assesed by recording Ag+acrocentric chromosomes containing active ribosomal genes. Based on the conducted tudies, it was determined that: The Georgian population is generally characterized by an active nicotine metabolizer CYP2A6 * 1 with a sharply higher frequency of the allele compared to the CYP2A6 * 4 allele and is closer to the Asian population in terms of this indicator. Georgian population with lung cancer is characterized by a sharp increase in the frequency of CYP2A6 * 1 allele compared to healthy individuals, which once again confirms the special role of this allele in cancer development and brings Georgian population closer to populations at high risk of cancer. Lymphocytes of individuals with lung cancer of the Georgian population maintain metabolic activity against the background of increased genomic instability, which is confirmed by the high associative activity of acrocentrics containing ribosomal genes.Lymphocytes of individuals with LC are characterized by specificty according to the distribution of active nucleolus organizers, which is manifested in the increased associative activity of chromosome 15.

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