Search for associations of polymorphic variants of the <i>MTHFR, MET, CHEK2</i> genes, identified through next-generation sequencing, with cervical cancer
Introduction. Worldwide, cervical cancer is the 4th most common cancer in women, and morbidity continues to grow. Supposedly, development of human papilloma virus-associated cervical cancer depends on genetic and epigenetic factors, but molecular pathogenesis of this pathology has not yet been estab...
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ABV-press
2025-04-01
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| Series: | Успехи молекулярной онкологии |
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| Online Access: | https://umo.abvpress.ru/jour/article/view/761 |
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| author | K. V. Lenkova R. M. Minyazeva V. L. Akhmetova I. R. Gilyazova R. I. Khusainova I. R. Minniakhmetov |
| author_facet | K. V. Lenkova R. M. Minyazeva V. L. Akhmetova I. R. Gilyazova R. I. Khusainova I. R. Minniakhmetov |
| author_sort | K. V. Lenkova |
| collection | DOAJ |
| description | Introduction. Worldwide, cervical cancer is the 4th most common cancer in women, and morbidity continues to grow. Supposedly, development of human papilloma virus-associated cervical cancer depends on genetic and epigenetic factors, but molecular pathogenesis of this pathology has not yet been established. Recently obtained data show that germline substitutions not only increase the risk of cancer but also affect tumor progression and form the picture of somatic changes in this malignant neoplasm.Aim. To investigate germline variants of the MTHFR, MET and CHEK2 genes and evaluate their significance in development of genetic predisposition towards cervical cancer.Materials and methods. DNA of 108 women with cervical cancer was analyzed. The comparison group included 51 patients with human papilloma virus elimination and 333 relatively healthy women. In the patient cohort, an analysis was performed using next-generation sequencing (NGS) and a custom panel aimed at genes participating in tumor designed by us. Additionally, clinical significance of the identified substitutions was evaluated using literature data, databases and bioinformatics methods. Additional association studies were performed for с.677С>Т and с.1298A>C variants of the MTHFR gene, c.2962C>T variant of the MET gene, с.972G>C variant of the CHEK2 gene.Results. It was observed that polymorphic variants с.972G>C and c.1312С>A of the CHEK2 gene have pathogenic potential. Among 11 substitutions in the MET gene identified during the study, variants c.2962C>T, c.2975C>T and c.3895G>C are liable to be pathogenic. Correlations between T locus allele c.2962C>T of the MET gene (p = 0.002; χ2 = 9.8) and C locus allele с.972G>C of the CHEK2 gene (p = 0.05; χ2 = 3.8) with the risk of cervical cancer development were found.Conclusion. During the study, a group of germline substitutions in the MTHFR, MET and CHEK2 genes with unclear clinical significance was identified. It was shown that substitutions с.972G>C and c.1312С>A in the CHEK2 gene and c.2962C>T, c.2975C>T, c.3895G>C in the MET gene have pathogenic potential in the context of cervical cancer. Additionally, previously unknown associations between loci c.2962C>T of the MET gene and с.972G>C of the CHEK2 gene with this pathology were described. |
| format | Article |
| id | doaj-art-82a638d2d4d74e9a8d97441fcf66db78 |
| institution | Kabale University |
| issn | 2313-805X 2413-3787 |
| language | Russian |
| publishDate | 2025-04-01 |
| publisher | ABV-press |
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| series | Успехи молекулярной онкологии |
| spelling | doaj-art-82a638d2d4d74e9a8d97441fcf66db782025-08-20T03:38:02ZrusABV-pressУспехи молекулярной онкологии2313-805X2413-37872025-04-01121849510.17650/2313-805X-2025-12-1-84-95363Search for associations of polymorphic variants of the <i>MTHFR, MET, CHEK2</i> genes, identified through next-generation sequencing, with cervical cancerK. V. Lenkova0R. M. Minyazeva1V. L. Akhmetova2I. R. Gilyazova3R. I. Khusainova4I. R. Minniakhmetov5Institute of Biochemistry and Genetics of the Ufa Federal Research Centre of the Russian Academy of SciencesBashkir State Medical University, Ministry of Health of RussiaInstitute of Biochemistry and Genetics of the Ufa Federal Research Centre of the Russian Academy of Sciences; Ufa University of Science and TechnologyInstitute of Biochemistry and Genetics of the Ufa Federal Research Centre of the Russian Academy of Sciences; Bashkir State Medical University, Ministry of Health of RussiaInstitute of Biochemistry and Genetics of the Ufa Federal Research Centre of the Russian Academy of Sciences; National Medical Research Center of Endocrinology, Ministry of Health of RussiaNational Medical Research Center of Endocrinology, Ministry of Health of RussiaIntroduction. Worldwide, cervical cancer is the 4th most common cancer in women, and morbidity continues to grow. Supposedly, development of human papilloma virus-associated cervical cancer depends on genetic and epigenetic factors, but molecular pathogenesis of this pathology has not yet been established. Recently obtained data show that germline substitutions not only increase the risk of cancer but also affect tumor progression and form the picture of somatic changes in this malignant neoplasm.Aim. To investigate germline variants of the MTHFR, MET and CHEK2 genes and evaluate their significance in development of genetic predisposition towards cervical cancer.Materials and methods. DNA of 108 women with cervical cancer was analyzed. The comparison group included 51 patients with human papilloma virus elimination and 333 relatively healthy women. In the patient cohort, an analysis was performed using next-generation sequencing (NGS) and a custom panel aimed at genes participating in tumor designed by us. Additionally, clinical significance of the identified substitutions was evaluated using literature data, databases and bioinformatics methods. Additional association studies were performed for с.677С>Т and с.1298A>C variants of the MTHFR gene, c.2962C>T variant of the MET gene, с.972G>C variant of the CHEK2 gene.Results. It was observed that polymorphic variants с.972G>C and c.1312С>A of the CHEK2 gene have pathogenic potential. Among 11 substitutions in the MET gene identified during the study, variants c.2962C>T, c.2975C>T and c.3895G>C are liable to be pathogenic. Correlations between T locus allele c.2962C>T of the MET gene (p = 0.002; χ2 = 9.8) and C locus allele с.972G>C of the CHEK2 gene (p = 0.05; χ2 = 3.8) with the risk of cervical cancer development were found.Conclusion. During the study, a group of germline substitutions in the MTHFR, MET and CHEK2 genes with unclear clinical significance was identified. It was shown that substitutions с.972G>C and c.1312С>A in the CHEK2 gene and c.2962C>T, c.2975C>T, c.3895G>C in the MET gene have pathogenic potential in the context of cervical cancer. Additionally, previously unknown associations between loci c.2962C>T of the MET gene and с.972G>C of the CHEK2 gene with this pathology were described.https://umo.abvpress.ru/jour/article/view/761cervical cancergenetic predispositiononcogeneticsnext-generation sequencinghuman papilloma virusmthfrmetchek2 |
| spellingShingle | K. V. Lenkova R. M. Minyazeva V. L. Akhmetova I. R. Gilyazova R. I. Khusainova I. R. Minniakhmetov Search for associations of polymorphic variants of the <i>MTHFR, MET, CHEK2</i> genes, identified through next-generation sequencing, with cervical cancer Успехи молекулярной онкологии cervical cancer genetic predisposition oncogenetics next-generation sequencing human papilloma virus mthfr met chek2 |
| title | Search for associations of polymorphic variants of the <i>MTHFR, MET, CHEK2</i> genes, identified through next-generation sequencing, with cervical cancer |
| title_full | Search for associations of polymorphic variants of the <i>MTHFR, MET, CHEK2</i> genes, identified through next-generation sequencing, with cervical cancer |
| title_fullStr | Search for associations of polymorphic variants of the <i>MTHFR, MET, CHEK2</i> genes, identified through next-generation sequencing, with cervical cancer |
| title_full_unstemmed | Search for associations of polymorphic variants of the <i>MTHFR, MET, CHEK2</i> genes, identified through next-generation sequencing, with cervical cancer |
| title_short | Search for associations of polymorphic variants of the <i>MTHFR, MET, CHEK2</i> genes, identified through next-generation sequencing, with cervical cancer |
| title_sort | search for associations of polymorphic variants of the i mthfr met chek2 i genes identified through next generation sequencing with cervical cancer |
| topic | cervical cancer genetic predisposition oncogenetics next-generation sequencing human papilloma virus mthfr met chek2 |
| url | https://umo.abvpress.ru/jour/article/view/761 |
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