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20DOI: 10.24411/2181-0443/2021-10001 ЛОКУС ARG72PRO ГЕНА TP53 В РАЗВИТИИ ЦЕРВИКАЛЬНОЙ ИНТРАЭПИТЕЛИАЛЬНОЙ НЕОПЛАЗИИ У ЖЕНЩИН УЗБЕКСКОЙ НАЦИОНАЛЬНОСТИ г.ТАШКЕНТА
Няджмутдиновя Дильбяр Кямяритдиновня Кямиловя Ирода Абдурасуловна Пахомова Жанна Евгеньевна Сидикходжяевя Мохиря Адилходжяевня
Ташкентской медицинской академии Бобоев Кодиржон Тухтябяевич
НИИ гематологии и переливания крови Ташкент, Узбекистан
При анализе распределения генотипов полиморфизма Arg72Pro гена TP53 среди 226 пациентов с цервикальной интраэпителиальной неоплазией (ЦИН) было расшифровано 165 условно здоровых женщин и выявлено преобладание аллеля Pro и редкого мутантного гомозиготного генотипа Pro / Pro над генотипом Arg. / Обнаружен гомозиготный генотип Arg.
Увеличение тяжести CIN связано с увеличением частоты редкого мутантного гомозиготного генотипа Pro / Pro: в случае легких интраэпителиальных поражений (Плоскоклеточные интраэпителиальные поражения низкой степени злокачественности (LSIL)) частота генотипа Pro / Pro составляет 18,28% (OR = 1,422); с высокой степенью плоскоклеточного интраэпителиального поражения (Highgrade Squamous Intraepitelial Lesions (HSIL) CIN 56,25% (OR = 7 938); с HSIL CIN 75,00% (OR = 18 522).
Поскольку наличие аллеля Pro также связано с прогрессированием тяжести CIN, очевидно, что генотипы с присутствием этого аллеля являются факторами риска для тяжести CIN.
Ключевые слова: интраэпителиальная неоплазия шейки матки, рак шейки матки, локус Arg72Pro, ген TP53,
аллель.
ТОШКЕНТ ШАХ,РИДАГИ УЗБЕК МИЛЛАТИГА МАНСУБ АЁЛЛАРДА ЦЕРВИКАЛ ИНТРАЭПИТЕЛИАЛ НЕОПЛАЗИЯ РИВОЖЛАНИШИДА TP53 ГЕНИНИНГ ARG72PRO ЛОКУСИ
Цервикал интраэпителиал неоплазия (cervical intraepithelial neoplasia (CIN)) булган 226 та бемор аёллар ва 165 та шартли соРлом аёллар орасида TP53 гени Arg72Pro полиморфизми генотиплари таДлили утказилганида, Arg/ Arg гомозиготли генотипи устидан Pro аллель ва кам учрайдиган Pro/Pro мутант гомозиготли генотип юк;орилиги ани^ланган. CIN оРирлиги ортиши куйидаги Долларда кам учрайдиган Pro/Pro мутант гомозиготли генотип учраши ортиши билан боРлик;: енгил интраэпителиал шикастланишларда (Lowgrade Squamous Intraepitelial Lesions (LSIL)) - Pro/Pro генотипи учраши 18,28% (OR = 1,422); ясси Дужайрали интраэпителиал зарарланишининг ю;ори даражасида (Highgrade Squamous Intraepitelial Lesions (HSIL) CIN II 56,25% (OR = 7,938); HSIL CIN Ill да 75,00% (OR = 18,522). Pro аллель мавжудлиги CIN оРирлиги ортиши билан боРлиКлиги ушбу аллелга эга булган генотиплар CIN оРирлиги ортиши хавф омили эканлигидан далолат беради.
Калит сузляр: интраэпителиал цервикал неоплазия, бачадон буйни раки, локус Arg72Pro, ген ТР53, аллель.
STUDY OF THE ROLE OF THE POLYMORPHIC VARIANTS OF THE ARG72PRO LOCUS OF THE TP53 GENE IN THE DEVELOPMENT OF CERVICAL INTRAEPITELIAL NEOPLASIA FOR WOMEN OF THE UZBEK NATIONALITY OF TASHKENT
When analyzing the distribution of genotypes of the Arg72Pro polymorphism of the TP53 gene among 226 patients with cervical intraepithelial neoplasia (CIN), 165 conditionally healthy women were deciphered and the prevalence of the Pro allele and the rare mutant homozygous Pro / Pro genotype over the Arg / Arg homozygous genotype was found.
An increase in the severity of CIN is associated with an increase in the frequency of the rare mutant homozygous Pro / Pro genotype: in case of mild intraepithelial lesions (Lowgrade Squamous Intraepitelial Lesions (LSIL)), the frequency of the Pro / Pro genotype is 18.28% (OR = 1.422); with a high degree of squamous intraepithelial lesion (Highgrade Squamous Intraepitelial Lesions (HSIL) CIN II 56,25% (OR = 7,938); with HSIL CIN III 75,00% (OR = 18,522).
Since the presence of the Pro allele is also associated with the progression of CIN severity, it is obvious that genotypes with the presence of this allele are risk factors for the severity of CIN.
Key words: cervical intraepithelial neoplasia, cervical cancer, locus Arg72Pro, gene TP53, allele.
Cervical intraepithelial neoplasia is one of the most important problems in modern gynecology. From a clinical and morphological point of view, dysplasia is a violation of differentiation, maturation, aging and apoptosis of epithelial cells lining the cervix. Depending on the severity of dysplastic changes, morphologically, mild (CIN I), moderate (CIN II) and severe (CIN III) dysplasia are distinguished. CIN I is characterized by polymorphism of cellular elements with pronounced hyperchromicity of the nuclei and a high nuclear-cytoplasmic ratio, with the involvement of a third of the stratified squamous epithelium. In the case of CIN II, cellular atypism and numerous mitoses are determined. CIN III is characterized by cellular atypism. According to the WHO classification (1982) and Bethesda (2001, 2004, 2014), the concepts of severe dysplasia and cancer in situ are combined into one pathological process (CIN III and HSIL) [1,2,3].
Despite significant achievments in the treatment of oncological pathology of the cervix, its prevalence is not only not decreasing, but also steadily increasing [4, 5]. At the stage of CIN and microinvasive cervical cancer (MRCM), the disease is diagnosed extremely rarely, and the majority of patients present with a detailed clinical picture of the invasive process [6,7]. What determines the importance of identifying risk factors for carcinogenic remodeling of the cervical epithelium, leading to an unfavorable course of the disease. These include molecular testing of genes called "susceptibility" genes or candidate genes [8].
Human protein-coding genes have molecular differences (polymorphisms) in their structure, leading to the synthesis of proteins with slightly altered structural and functional characteristics. Their features determine not only a person's predisposition to certain diseases, but also the nature of their course in the case of the development of pathology [8,9,10]. The study of the genetic specifics of the development of CIN is necessary for the development of preventive measures and treatment. Obviously, to assess the prognosis of the course and determine the risk of neoplastic transformation of neoplasias,
knowledge of the molecular genetic characteristics of its development is necessary.
The TP53 gene encodes the p53 protein, which, responding to a variety of stress effects on cells, regulates target genes that cause cell cycle inhibition, apoptosis, aging, DNA repair or changes in metabolism, acts as a tumor suppressor in many types of tumors, stimulates apoptosis or growth retardation depending on physiological conditions and cell type. The level of expression of the p53 protein in normal cells is reduced, an increased level of expression is observed in various transformed cell lines, where the p53 protein contributes to the transformation and formation of malignant neoplasms. Mutant p53 proteins have a reduced oncosuppressive activity; somatic mutations of this gene are associated with human malignant neoplasms [5,8,11,12, 13,14].
The molecular genetic mechanisms of persistence, regression, or progression of cervical intraepithelial neoplasia up to invasive cancer are not fully studied and understood.
The aim of the study - was to study the associations of allelic variants of the Arg72Pro polymorphic locus of the TP53 gene in patients with varying severity of cervical intraepithelial neoplasia.
Materials and methods. The study included 391 women of fertile age from 18 to 45 years, where 226 patients with cervical intraepithelial neoplasia and 165 patients without pathology of the reproductive system formed the control group. The studies were carried out during the period 2015-2020 on the basis of the Center for Reproductive Health of Women of the Multidisciplinary Clinic of the Tashkent Medical Academy. Genetic studies were carried out at the Scientific Research Institute of Hematology and Blood Transfusion of the Ministry of Health of Uzbekistan.
In working with patients, the ethical principles of the Declaration of Helsinki of the World Medical Association "Ethical principles of scientific and medical research with human participation" were followed.
The criteria for inclusion of women in the clinical study group were: the presence of cervical intraepithelial neoplasia, the absence of therapy with immunomodulatory drugs in the
last 6 months, and exacerbation of chronic inflammatory processes in the small pelvis. The study also did not include women under 18 years old and over 45 years old, with a positive pregnancy test, with severe somatic pathology, as well as patients taking medications that could affect the studied parameters.
Based on clinical and cytological studies out of 226 patients of the main group, 186 were diagnosed with mild CIN I, moderate CIN II was found with 32 patients, and severe (CIN I), moderate (CIN II) and severe (CIN III) III were diagnosed with 8 patients. The control group consisted of 165 patients of comparable age, social and marital status, who applied to antenatal clinics for a preventive examination.
When conducting a comprehensive examination, a colposcopic examination was performed, smears were taken for the degree of vaginal purity, bacterial culture from the vagina, examination for sexually transmitted infections by means of polymerase chain reaction (PCR), oncocytology from the cervix, ultrasound examination of the pelvic organs.
Isolation of genomic DNA from whole blood was performed using a kit of reagents "Ampli Prime Ribot-prep" (LLC "Next Bio", Russia). Detection of DNA samples from the Arg72Pro locus of the TP53 gene was carried out by allele-specific PCR on an Applied Biosystems 2720 thermocycler, using sets of NPF Litekh, according to the manufacturer's instructions.
The estimation of the deviation of the frequencies of the observed and expected genotypes from the canonical Hardy-Weinberg distribution was carried out using the GenePop package of the genetic-population program [15].
In the sample of patients with cervical intraepithelial neoplasia and in the control group (without pathology of the reproductive organs), the distribution of alleles and genotypes was tested for the observance of the Hardy-Weinberg equilibrium (p2AA + 2pqAa + q2aa = 1).
To assess the association between the studied parameters and the risk of developing the analyzed event, the odds ratio (OR) with a
95% confidence interval (CI) was calculated. When comparing the frequencies of features, the standard Pearson x2 test and Fisher's exact test were used.
Research results and discussion
The main task that solves the problem of preventing oncological pathology is the implementation of studies that determine the diagnostic value of the studied gene polymorphisms.
For this purpose, studies were carried out on a cohort of patients with clinically and cytologically verified CIN of varying severity, which will make it possible to assess both the diagnostic and prognostic value of the studied genetic markers.
At the first stage of this work, the distribution of allele and genotype frequencies of TP53 gene polymorphisms was calculated in the group of patients with cervical intraepithelial neoplasia and in the control sample.
Statistical analysis of the differences in the distribution of the Arg72Pro alleles of the TP53 gene and the genotypes of the TP53 gene polymorphism between the group of patients with cervical intraepithelial neoplasia and the control group of women without pathology of the reproductive system made it possible to establish that the "cases" and "control" are in Hardy - Weinberg equilibrium, which makes it possible to analyze the data and compare the results of the study (table 1).
The analysis of combinations of allelic variants of the polymorphism of the Arg72Pro locus of the TP53 gene, shown in Table 1, showed that in patients with cervical intraepithelial neoplasia, a statistically significant increase in the frequency of the Pro allele was observed, amounting to 47.35%, versus 37.58% in apparently healthy women (group control) (x2 = 7.418; P< 0.007; OR = 1.495; DI 95% 1.118 -1.995). A decrease in the frequency of carriage of the Arg allele was found to be 52.65% versus 62.42%, respectively ^ = 7.418; P< 0.007; OR = 0.669; DI 95% 0.51 - 0.894). It is obvious that a decrease in the carriage of the Arg allele has a protective effect on the risks of CIN.
Expected and observed frequencies of genotypes of Arg72Pro polymorphism of TP53 _gene according to Hardy-Weinberg distribution_
The main group of the patient with CIN n=226
Allele Allele frequency
Arg 0,53 df
Pro 0,47 1
Genotypes Genotypes frequency x2 p df
Observed Expected
Arg/Arg 0,31 0,28 0,216 0,642 P>0,05
Arg/Pro 0,44 0,50 0,723 0,396 P>0,05
Pro/Pro 0,25 0,22 0,250 0,617 P>0,05
Total 1,0 1,0 0,727 0,696 P>0,05 2
Control group n=165
Allele Allele frequency
Arg 0,62 df
Pro 0,38 1
Genotypes Genotypes frequency X2 P df
Observed Expected
Arg/Arg 0,39 0,39 0,00 1,0 P>0,05
Arg/Pro 0,47 0,47 0,00 1,0 P>0,05
Pro/Pro 0,14 0,14 0,00 1,0 P>0,05
Total 1,0 1,0 0,00 1,0 P>0,05 2
Analysis of the distribution of often genotypes showed a statistically significant difference between the groups in the frequency of registration of the homozygous Pro / Pro genotype: in patients with cervical intraepithelial neoplasia, the frequency of carriage was 25.66% versus 13.94% in the control group (x2 = 7.982; P<0.005; OR = 2.131; DI 95% 1.252 - 3.629).
A statistically insignificant decrease was observed in the frequency of carriage of the heterozygous genotype Arg/Pro was found, which amounted to 43.36% in patients with CIN versus 47.27% in the control group (x2 = 0.589; P > 0.05; OR = 0.854; DI 95% - 0.571 - 1.278 )
and an insignificant decrease in the frequency of carriage of the homozygous genotype Arg/Arg, respectively, 30.97% versus 48.79% ^ = 2.585; P> 0.05; OR = 0.708; DI 95% 0.465 - 1.079) (table 2).
Thus, the homozygous Arg/Arg state of the analyzed polymorphic variant is more favorable for carriers than the rare homozygous Pro/Pro variant. The revealed protective character of Arg/Arg can be explained by its association with a low level of TP53 gene transcription. Since the carriage of the Pro allele is also associated with CIN, genotypes with this allele are also risk factors for the severity of CIN.
Comparative analysis of the frequency distribution of alleles and genotypes of the Arg 72 Pro polymorphism of the TP53 gene in patients with cervical intraepithelial neoplasia
Genotypes and alleles of Arg72Pro polymorphism of TP53 gene Characteristics of the examined x2; p OR; 95% CI
Main group with CIN n = 226 Control group n = 165
Genotypes
Arg/Arg 70/30,97 64/38,79 2,585; P>0,108 0,708 0,465-1,079
Arg/Pro 98/43,36 78/47,27 0,589; P>0,443 0,854 0,571-1,278
Pro/Pro 58/25,66 23/13,94 7,982; P<0,005 2,131 1,252-3,629
E 226/100,0 165/100,0
Allele
Arg 238/52,65 206/62,42 7,418 P<0,007 0,669 0,501-0,894
Pro 214/47,35 124/37,58 1,494 1,118-1,995
E 452/100,0 330/100,0
Our results on the nature of the distribution of allelic and genotypic variants of the Arg72Pro polymorphism of the TP53 gene in patients with cervical intraepithelial neoplasia are similar to the patterns obtained in other population studies, as a rule, in European populations. According to Siegel R.L., Miller K.D., Jemal A. (2016) and Fu W., Zhuo Z.J., Chen Y.C. et al. (2017), the presence of the Pro/Pro mutant genotype leads to more pronounced inflammatory clinical symptoms, and the homozygous Arg / Arg genotype has a more favorable variant. The Pro/Pro genotype has been shown to be associated with breast cancer [16,17]. Despite the intensive study of the influence of the Arg72Pro gene TP53 polymorphism on the progression of pathology of the cervix and reproductive system organs, the data on the formation of the severity of pathology and its oncological transformation are contradictory.
It is currently considered an indisputable fact that the combinations of genetic characteristics (intergenic interactions) differ significantly in different populations [8,9]. Obviously, the effect of PT53 polymorphism is determined by many factors, the leading of
which is the degree of differentiation, maturation, aging and apoptosis of epithelial cells lining the cervix, which determines the relevance of further studies to expand the understanding of the role of TP53 genetic polymorphism in the progression and oncological transformation of cervical intraepithelial neoplasia.
In this connection, we analyzed the distribution of alleles and genotypes of the Arg72Pro polymorphism of the TP53 gene in patients with cervical intraepithelital neoplasia in the dynamics of increasing the severity of the pathology (tables 3 - 4).
A statistically significant increase in the increase in the frequency of occurrence of the Pro allele, synchronized with the severity of the disease, was established.
So, with a relatively favorable course in patients with clinically and colposcopically verified LSIL, the frequency of carriage of the Pro allele was 45.16% and was lower than the prevalence in the control group - 54.84% (x2 = 4.142; P<0.042; OR = 0.725; CI 95 % 0.536 -0.981); then with an increase in the severity of the clinical course of HSIL CIN II, the
frequency of the Pro allele increased to 56.25% versus 43.75% (x2 = 7.751; P<0.006; OR = 2.153; CI 95% 1.252 - 3.703); and in patients with a high risk of malignant transformation with HSIL CIN Ill, the frequency of the Pro allele increased to 62.50% versus 37.50% (x2 = 3.995; P<0.046; OR = 2.791; CI 95% 0.990 -
Table 3
Distribution of allele frequencies of Arg 72 Pro polymorphism of TP53 gene in patients with different severity of cervical intraepithelial neoplasia
7.870). Thus, the carriage of the Pro allele increased the risk of CIN II by 2.153 times, and the risk of CIN III by 2.791 times; whereas the carriage of the Arg allele, on the contrary, reduced these risks by 0.464 and 0.535 times (table 3).
Allele Allele Arg Allele Pro
Diagnosis CIN Frequency x2 P OR 95% CI Frequency X2 P OR 95% CI
LSIL 4,142 0,725 168/45,16 4,142 1,379
n=186 372/100,0 204/54,84 P<0,042 0,5360,981 P<0,042 1,0191,867
HSIL CIN 64/100,0 28/43,75 7,751 0,464 36/56,25 7,751 2,153
II 0,270- 1,252-
n=32 P<0,006 0,799 P<0,006 3,703
HSIL CIN 16/100,0 6/37,50 3,995 0,535 10/62,5 3,995 2,791
III 0,127- 0,990-
n=8 P<0,046 0,010 P<0,046 7,870
E 452/100,0 238/52,65 7,418 P<0,007 0,689 0,5010,894 214/47,35 7,418 P<0,007 1,494 1,1181,995
Control 06/62,40 124/37,5
group n=165 330/100,0
Analysis of the distribution of the genotype frequencies of the Arg72Pro polymorphism of the TP53 gene revealed a statistically significant increase in the frequency of the Pro/Pro genotype, adapted to the severity of CIN (table 4).
Thus, the frequency of carriage of the homozygous Pro / Pro genotype progressively increased in the series CIN I ^ CIN II ^ CIN III from 22.50%; up to 37.50% and 50.00% versus 13.94% in the control group, significantly exceeding the indicators of the control group in patients with CIN I ^ = 4.327; P<0.038; OR = 1.801; CI 95% 1.030 - 3.194); CIN II ^ = 10.183; P<0.002; OR = 3.368; CI 95% 1.468 -7.723) and CIN III ^ = 7.533; P<0.002; OR = 6.174; CI 95% - 1.442 - 26.433). Thus, carriage of the homozygous Pro/Pro genotype increases the risk of disease in patients with CIN I 1.801
times; with CIN II - 3.368 times and with CIN III - 6.174 times.
A statistically insignificant decrease in the frequency of carriage of the heterozygous genotype Arg/Pro, equal to 45.70% at CIN, was established; with CIN II - 31.25% and with CIN III 37.50% versus 47.27% in the control group. The frequency of the homozygous Arg/Arg genotype in patients with CIN was lower than the frequency of carriage in the control group, although this difference did not have statistically significant differences. So, with patients with CIN I, the frequency of carriage of the homozygous genotype Arg/Arg is 31.72% (x2 = 1.919; P>0.167; OR = 0733; CI 95% 0.472 -1.138); with CIN II - 31.25% ^ = 0.649; P>0.421; OR = 0717; CI 95% 0.319 - 1.613) and CIN III 12.50% (x2 = 2.248; P>0.134; OR = 0225; CI 95 % 0.027 - 1.876) versus carriage frequency 38.90% in the control group. Thus,
the carriage of the homozygous genotype Arg/Arg has a protective effect on the risk of developing cervical neoplasia, reducing the squeak of the development of the disease, respectively, by 0.733; 0.717 and 0.225 times (table 4).
A significant association of the homozygous Pro/Pro genotype of the Arg72Pro locus polymorphism of the TP53 gene with CIN and a statistically significant increase in the frequency of carriage of this genotype with an increase in the severity of pathology may be evidence of the pathogenetic significance in complex molecular genetic changes that determine the severity of the clinical course of CIN.
Conclusion
It is difficult to predict the biological behavior of cervical cells in the precancerous stage and in the early stages of oncological transformation. In this regard, the identification of new markers that make it possible to accurately predict the evolution of the disease is of great importance. In addition, difficult tasks are to determine the stage of the disease, differential diagnosis of benign and malignant disorders [3,7,18]. It is noted that 94 cases of cervical cancer identified types of human papillomavirus [1,2,19].
In the pathogenesis of the progression of the atypical process in the cervix, the leading role is assigned to the human papillomavirus (HPV). When the virus replicates, its DNA enters the genome of the infected cell, stimulating proliferative processes in it and suppressing apoptosis of the cells of the cervical epithelium [2, 4, 14, 20,21].
Analysis of modern literature shows that a large amount of research is currently being carried out on the development of objective molecular genetic criteria for predicting the course of cervical diseases [7,9,13,19,20]. That dictates the need to analyze changes in genes of proliferation, apoptosis and differentiation in cervical intraepithelial neoplasia in cervical cancer [8,12].
Of particular interest is the involvement of TP53 gene abnormalities in the development of different types of tumors, which is explained by the performance of a wide range of functions
that prevent and / or inhibit tumor growth [2,7,11,12].
Analysis of the distribution of genotypes of the Arg72Pro polymorphism of the TP53 gene among 226 patients with cervical intraepithelial neoplasia and 165 conditionally healthy women revealed the prevalence of the rare mutant homozygous Pro/Pro genotype over the homozygous Arg/Arg genotype.
Polymorphic locus of the TP53 gene are actively studied by many researchers in cancer pathologies of various localization. In oncological pathology, the high diagnostic and prognostic significance of polymorphic loci of the TP53 gene is shown. The single nucleotide polymorphism of Arg72Pro 4 exon of the TP53 gene is characterized by a substitution of a base G by a C base in codon 72 and leads to an amino acid substitution in the primary structure of the corresponding protein arginine for proline. This polymorphism is associated with the risk of developing oncological and somatic pathologies of various origins [5,11]. The unfavorable Pro/Pro genotype enhances the expression of the mutant p53 protein, which has pro-oncogenic properties [4, 12].
In our studies, the progression of the severity of CIN is associated with an increase in the frequency of the rare mutant homozygous Pro/Pro genotype: in LSIL, the frequency of the Pro/Pro genotype is 18.28% (OR = 1.422); at HSIL CIN II 56.25% (OR = 7.938); at HSIL CIN III 75.00% (OR = 18.522).
Since the presence of the Pro allele is also associated with the progression of CIN severity, it is obvious that genotypes with the presence of this allele are risk factors for the severity of CIN.
Thus, our study showed that the development of CIN is associated with the carriage of the Pro allele and the rare mutant homozygous Pro/Pro genotype. The presence of TP53 gene Pro/Pro polymorphism in the Pro/Pro genotype of the Arg72Pro locus in women can be considered as a high risk of developing cervical intraepithelial neoplasia.
Comparative analysis of the frequency distribution of the genotypes of the Arg 72 Pro polymorphism of the TP53 gene with patients with
varying severity of cervical intraepithelial neoplasia
Diagnosis CIN Genotype Arg/Arg Genotype Arg/Pro Genotype Pro/Pro
Frequency x2 P OR 95% CI Frequency X2 P OR 95% CI Frequency X2 P OR 95% CI
LSIL n=186/100,0 59/31,72 1,919 P>0,167 0,733 0,472-1,138 85/45,70 0,087 P>0,768 0,939 0,617-1,429 42/22,58 4,327 P<0,038 1,801 0,030-3,149
HSIL CIN II n=32/100,0 10/31,25 0,649 P>0,421 0,717 0,319-1,613 10/31,25 2,784 P>0,096 0,507 0,226-1,137 12/37,50 10,183 P<0,002 3,368 1,468-7,723
HSIL CIN III n=8/100,0 1/12,5 2,248 P>0,134 0,225 0,027-1,876 3/37,5 0,293 P>0,589 0,669 0,155-2,892 4/50,0 7,533 P<0,007 6,174 1,44226,433
E-226/100,0 70/30,97 2,585 P>0,108 0,708 0,465-1,079 98/43,36 0,589 P>0,443 0,854 0,571-1,278 58/25,66 7,982 P<0,005 2,131 1,252-3,629
Control group n=165 64/38,79 78/47,27 23/13,94
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Thus, our study showed that the development of CIN is associated with the carriage of the Pro allele and the rare mutant homozygous Pro/Pro genotype. The presence of TP53 gene Pro/Pro polymorphism in the Pro/Pro genotype of the Arg72Pro locus in women can be considered as a high risk of developing cervical intraepithelial neoplasia.
As a result of the analysis, it was found that the formation of CIN reveals significant changes in polymorphic variants of the Pro/Pro genotype of the Arg72Pro TP53 locus gene. Disruption of programmed cell death processes as a result of TP53 dysfunction may be a trigger factor for the development of neoplastic changes in the cervical epithelium and progression to cervical cancer.
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