Association of Molecular Genetic Markers of TP53, MDM2, and CDKN1A Genes with Progression-Free Survival of Patients with Ovarian Cancer after Platinum-Based Chemotherapy

Bull Exp Biol Med. 2020 Aug;169(4):486-490. doi: 10.1007/s10517-020-04915-5. Epub 2020 Sep 10.

Abstract

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).

Keywords: cell cycle control; ovarian cancer; platinum-based chemotherapy; polymorphic marker; progression-free survival.

MeSH terms

  • Adult
  • Aged
  • Alleles
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carboplatin / therapeutic use*
  • Carcinoma, Ovarian Epithelial / drug therapy
  • Carcinoma, Ovarian Epithelial / genetics*
  • Carcinoma, Ovarian Epithelial / mortality
  • Carcinoma, Ovarian Epithelial / pathology
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics*
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Frequency
  • Genotype
  • Humans
  • Middle Aged
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / mortality
  • Ovarian Neoplasms / pathology
  • Paclitaxel / therapeutic use
  • Polymorphism, Restriction Fragment Length
  • Polymorphism, Single Nucleotide
  • Progression-Free Survival
  • Proto-Oncogene Proteins c-mdm2 / genetics*
  • Proto-Oncogene Proteins c-mdm2 / metabolism
  • Treatment Outcome
  • Tumor Suppressor Protein p53 / genetics*
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Carboplatin
  • MDM2 protein, human
  • Proto-Oncogene Proteins c-mdm2
  • Paclitaxel