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Association of Molecular Genetic Markers of TP53, MDM2, and CDKN1A Genes with Progression-Free Survival of Patients with Ovarian Cancer after Platinum-Based Chemotherapy
Bulletin of Experimental Biology and Medicine ( IF 0.7 ) Pub Date : 2020-08-01 , DOI: 10.1007/s10517-020-04915-5
T M Zavarykina 1 , A S Tyulyandina 2 , S V Khokhlova 3 , G N Khabas 3 , A V Asaturova 3 , Yu A Nosova 3 , P K Brenner 1 , M A Kapralova 1, 4 , M V Atkarskaya 1 , D S Khodyrev 5 , A M Burdennyi 1 , V I Loginov 6 , M B Stenina 2 , G T Sukhikh 3
Affiliation  

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).

中文翻译:

TP53、MDM2和CDKN1A基因的分子遗传标志物与卵巢癌患者铂类化疗后无进展生存的关联

我们研究了细胞周期控制基因的多态性标志物(TP53 基因的 Arg72Pro、MDM2 基因的 T(-410)G 和 CDKN1A 基因的 Ser31Arg)与铂类化疗后无进展生存期的关联. 检查了从接受化疗的 49 名患者获得的肿瘤组织样本。患者接受标准的铂类化疗并观察直至疾病进展。通过PCR-RFLP和实时PCR评估基因的多态性标记。在携带 MDM2 基因 T(-410)G 标记的 G 等位基因的患者中,观察到中位无进展生存期呈下降趋势。在 TP53 基因的 Pro 等位基因携带者中观察到中位无进展生存期增加 (p=0.045)。此外,注意到与相对于 Arg/Arg 基因型的次要 Pro/Pro 纯合基因型的携带者有更强的关联 (p=0.007)。在接受最佳或完全减瘤手术的患者亚组中,携带 Ser31Arg 标志物(CDN1A 基因)的次要 Arg 等位基因与中位无进展生存时间的减少相关(p = 0.004)。
更新日期:2020-08-01
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