Association between Molecular Genetic Markers of DNA Repair and Cell Cycle Control Genes and Response to Platinum-Based Chemotherapy in Ovarian Cancer Patients

• Published in: Bulletin of experimental biology and medicine Vol. 171; no. 6; pp. 755 - 759
• Main Authors: Zavarikina, T. M., Khokhlova, S. V., Tyulyandina, A. S., Khabas, G. N., Asaturova, A. V., Nosova, Yu. V., Brenner, P. K., Kapralova, M. A., Khodirev, D. S., Stenina, M. B.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.10.2021; Springer; Springer Nature B.V
• Subjects: Adenocarcinoma, Clear Cell - diagnosis; Adenocarcinoma, Clear Cell - drug therapy; Adenocarcinoma, Clear Cell - genetics; Adenocarcinoma, Clear Cell - mortality; Adult; Aged; Analysis; Anopheles; Antineoplastic Agents - therapeutic use; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Biomedical and Life Sciences; Biomedicine; BRCA1 protein; BRCA1 Protein - genetics; BRCA1 Protein - metabolism; Cancer; Carcinoma, Endometrioid - diagnosis; Carcinoma, Endometrioid - drug therapy; Carcinoma, Endometrioid - genetics; Carcinoma, Endometrioid - mortality; Care and treatment; Cell Biology; Cell cycle; Cell Cycle - genetics; Chemotherapy; Cyclin-Dependent Kinase Inhibitor p21 - genetics; Cyclin-Dependent Kinase Inhibitor p21 - metabolism; Cystadenocarcinoma, Serous - diagnosis; Cystadenocarcinoma, Serous - drug therapy; Cystadenocarcinoma, Serous - genetics; Cystadenocarcinoma, Serous - mortality; Deoxyribonucleic acid; DNA; DNA methylation; DNA Repair; Female; Gene Expression Regulation, Neoplastic; Genes; Genetic aspects; Genetic markers; Genetics; Genotype & phenotype; Genotypes; Glutamine; Humans; Internal Medicine; Laboratory Medicine; MDM2 protein; Methylation; Middle Aged; Multivariate analysis; Mutation; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Neoplasm Recurrence, Local - diagnosis; Neoplasm Recurrence, Local - drug therapy; Neoplasm Recurrence, Local - genetics; Neoplasm Recurrence, Local - mortality; Ovarian cancer; Ovarian Neoplasms - diagnosis; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - genetics; Ovarian Neoplasms - mortality; p53 Protein; Pathology; Patients; Platinum Compounds - therapeutic use; Progression-Free Survival; Proto-Oncogene Proteins c-mdm2 - genetics; Proto-Oncogene Proteins c-mdm2 - metabolism; Tumor proteins; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism; X-ray Repair Cross Complementing Protein 1 - genetics; X-ray Repair Cross Complementing Protein 1 - metabolism; Xeroderma Pigmentosum Group D Protein - genetics; Xeroderma Pigmentosum Group D Protein - metabolism; XRCC1 protein; platinum-based chemotherapy; cell cycle control; ovarian cancer; DNA repair; BRCA1 gene
• ISSN: 0007-4888; 1573-8221
• DOI: 10.1007/s10517-021-05310-4

We analyzed associations of polymorphic markers of DNA repair genes ( XRCC1 , ERCC2 ), cell cycle control genes ( TP53 , MDM2 , and CDKN1A ), methylation of promoter region, and mutation 5382insC of BRCA1 gene in ovarian cancer with effectiveness of platinumbased chemotherapy assessed by the median of progression-free survival time for markers of DNA repair genes and by relapse risk for all studied markers. An increase in the median of progression-free survival time for carriers of the Gln allele ( р =0.025) and Gln / Gln genotype ( р =0.022) of the Gln399Arg XRCC1 was observed during the 19-months period after chemotherapy. In carriers of C / C genotype of 5382insC mutation of BRCA1 gene ( n =6), no relapses were observed ( р =0.035), while 17 of 49 patients without this mutation developed relapses. Of 14 patients with BRCA1 gene function inactivation due to promoter methylation or the presence of the C / C genotype of 5382insC , one relapse was observed ( p =0.033). Multivariate analysis revealed an association of markers of the XRCC1 , TP53 , MDM2 genes, BRCA1 gene inactivation, and type of surgery with the risk of relapse during the follow-up period up to 19 months after the end of chemotherapy ( р ≤0.0007).