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

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
• treatment response
• toxicity
• single nucleotide polymorphism

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

YZ and ZD designed this study, collected data, interpreted the results and drafted the paper. MT assisted with the design and data collection. PC assisted with interpretation of the results and revised the paper.

Additional information

Funding

This work was funded by 2020 Research Project of Health Commission of Hunan Province [20200136, 20200121], National Natural Science Foundation of China [81903111], as well as Natural Science Foundation of Hunan Province [2020JJ8077].