ERCC1, XRCC1, and GSTP1 Polymorphisms and Treatment Outcomes of Advanced Epithelial Ovarian Cancer Patients Treated with Platinum-based Chemotherapy

Asian Pac J Cancer Prev. 2020 Jul 1;21(7):1925-1929. doi: 10.31557/APJCP.2020.21.7.1925.

Abstract

Objective: The first line regimen for treating epithelial ovarian cancer (EOC) is platinum-based chemotherapy. Various factors impact its effectiveness including polymorphisms of enzymes in platinum-related metabolism processes. Methods: We conducted the study to investigate the association between polymorphisms of ERCC1, XRCC1 and GSTP1, which responsible for platinum's metabolisms in Thai epithelial ovarian cancer patients.

Results: Fifty-two patients with advanced epithelial ovarian cancer were enrolled into this study. Genotyping analysis of ERCC1 (C->A, rs3212986), XRCC1 (A->G, rs25487) and GSTP (A->G, rs1695) were performed which variant allele frequencies were found at 35.6%, 28.9% and 10.6%, respectively. Patients with homozygous variant type (A/A) of ERCC1 C8092A had higher rate of platinum-resistance (75% vs 16.7%, p =0.046). In addition, the significant association of GSTP1 polymorphism and grade 2 anemia was found. Patients with A/G genotype of GSTP1 had higher rate of grade 2 anemia (81.8% vs 46.3%, p =0.036).

Conclusions: Genetic polymorphisms of ERCC1, and GSTP1 might be useful biomarkers for prediction of clinical benefit and toxicities of platinum-based chemotherapy in Thai epithelial ovarian cancer patients.<br />.

Keywords: Ovarian Cancer; platinum chemotherapy; polymorphisms.

MeSH terms

  • Adenocarcinoma, Clear Cell / drug therapy
  • Adenocarcinoma, Clear Cell / genetics
  • Adenocarcinoma, Clear Cell / pathology
  • Adenocarcinoma, Mucinous / drug therapy
  • Adenocarcinoma, Mucinous / genetics
  • Adenocarcinoma, Mucinous / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor
  • Carboplatin / administration & dosage
  • Cystadenocarcinoma, Serous / drug therapy
  • Cystadenocarcinoma, Serous / genetics
  • Cystadenocarcinoma, Serous / pathology
  • DNA-Binding Proteins / genetics*
  • Drug Resistance, Neoplasm / genetics*
  • Endometrial Neoplasms / drug therapy
  • Endometrial Neoplasms / genetics
  • Endometrial Neoplasms / pathology
  • Endonucleases / genetics*
  • Female
  • Follow-Up Studies
  • Glutathione S-Transferase pi / genetics*
  • Humans
  • Middle Aged
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / pathology*
  • Paclitaxel / administration & dosage
  • Polymorphism, Single Nucleotide*
  • Prognosis
  • X-ray Repair Cross Complementing Protein 1 / genetics*

Substances

  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • X-ray Repair Cross Complementing Protein 1
  • XRCC1 protein, human
  • Carboplatin
  • GSTP1 protein, human
  • Glutathione S-Transferase pi
  • ERCC1 protein, human
  • Endonucleases
  • Paclitaxel