Erythropoietin promoter polymorphism is associated with treatment efficacy and severe hematologic toxicity for platinum-based chemotherapy

Expert Opin Drug Metab Toxicol. 2021 Apr;17(4):495-502. doi: 10.1080/17425255.2021.1879048. Epub 2021 Feb 7.

Abstract

Background: Erythropoietin (EPO) plays a substantial role in cancer development and probably affects clinical outcomes. A functional polymorphism (rs1617640, G > T) in the promoter region of the EPO increases protein expression. This study investigated the association of EPO rs1617640 with treatment efficacy and severe toxicity in non-small cell lung cancer (NSCLC) patients undergoing platinum-based regimens.Methods: 437 Chinese NSCLC patients treated with platinum-based chemotherapy were recruited. Association between EPO rs1617640 and clinical outcomes was calculated by multivariable logistic regression.Results: The TT genotype of EPO rs1617640 was significantly correlated with a higher response rate to platinum-based treatment than the other genotypes (OR, 0.507; 95% CI: 0.305-0.842; P = 0.009), particularly in elderly patients (>55 years), male gender, smokers, IV stage, cisplatin-based chemotherapies, and platinum-gemcitabine regimen subgroups. As for toxicity, EPO rs1617640 TT genotype demonstrated poorer tolerance to grade 3-4 hematologic toxicity (OR, 1.783; 95% CI: 1.098-2.898; P = 0.019), particularly in subgroups of elderly patients (>55 years), male gender, smokers, IIIA+IIIB stage, and cisplatin-based chemotherapies.Conclusion: Our results demonstrated the role of EPO rs1617640 as a possible predictive marker of treatment efficacy and severe toxicity for platinum-based chemotherapy.

Keywords: Erythropoietin; platinum; single nucleotide polymorphism; toxicity; treatment response.

MeSH terms

  • Age Factors
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Asian People
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Cisplatin / administration & dosage
  • Erythropoietin / genetics*
  • Female
  • Genotype
  • Hematologic Diseases / chemically induced
  • Humans
  • Lung Neoplasms / drug therapy*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Promoter Regions, Genetic
  • Severity of Illness Index
  • Sex Factors
  • Treatment Outcome

Substances

  • EPO protein, human
  • Erythropoietin
  • Cisplatin