Association of Molecular Genetic Markers of TP53 , MDM2, and CDKN1A Genes with Progression-Free Survival of Patients wit
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Bulletin of Experimental Biology and Medicine, Vol. 169, No. 4, August, 2020
ONCOLOGY Association of Molecular Genetic Markers of TP53, MDM2, and CDKN1A Genes with Progression-Free Survival of Patients with Ovarian Cancer after Platinum-Based Chemotherapy T. M. Zavarykina1, A. S. Tyulyandina2, S. V. Khokhlova3, G. N. Khabas3, A. V. Asaturova3, Yu. A. Nosova3, P. K. Brenner1, M. A. Kapralova1,4, M. V. Atkarskaya1, D. S. Khodyrev5, A. M. Burdennyi1,7, V. I. Loginov6, M. B. Stenina2, and G. T. Sukhikh3
Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 169, No. 4, pp. 472-476, April, 2020 Original article submitted December 30, 2019 We studied the association of polymorphic markers of cell cycle control genes (Arg72Pro of the TP53 gene, T(-410)G of the MDM2 gene, and Ser31Arg of the CDKN1A gene) in ovarian cancer and progression-free survival following platinum-based chemotherapy. Tumor tissue samples obtained from 49 patients who had undergone chemotherapy were examined. Patients received standard platinum-based chemotherapy and were observed until disease progression. Polymorphic markers of genes were evaluated by PCR-RFLP and real-time PCR. In patients carrying the G allele of the T(-410)G marker of the MDM2 gene, a decreasing trend was observed in median progression-free survival. An increase in the median progression-free survival was observed in carriers of the Pro allele of the TP53 gene (p=0.045). Furthermore, a stronger association was noted with carriers of the minor Pro/Pro homozygous genotype relative to the Arg/Arg genotype (p=0.007). In the subgroup of patients who underwent optimal or complete cytoreductive surgery, carriage of the minor Arg allele of the Ser31Arg marker (CDN1A gene) was associated with a decrease in the median progression-free survival time (p=0.004). Key Words: ovarian cancer; polymorphic marker; cell cycle control; progression-free survival; platinum-based chemotherapy Ovarian cancer (OC) is one of the most prevalent tumors involving the female reproductive system. OC N. M. Emanuel Institute of Biochemical Physics, Russian Academy of Sciences; 2N. N. Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation; 3V. I. Kulakov National Research Medical Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of the Russian Federation; 4K. I. Skryabin Moscow State Academy of Veterinary Medicine and Biotechnology; 5 Federal Research Clinical Center of Specialized Types of Medical Care and Medical Technologies, Federal Medical-Biological Agency of Russia; 6Research Institute of General Pathology and Pathophysiology, Moscow, Russia. Address for correspondence: tpalievskaya@yandex. ru. T. M. Zavarykina 1
is characterized by long asymptomatic course resul ting in late disease detection; this makes radical surgical treatment impossible and determines high relapse rate after primary treatment, as well as high mortality rates [1,3,4,14]. Chemotherapy (CT) is an integral part of OC treatment. In OC, one of the mos
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