Effect of erythropoiesis-stimulating agents on malignant neoplasms: FAERS database and mendelian randomization

The relationship between erythropoiesis-stimulating agents (ESAs) and malignant neoplasms (MNs) has been controversial in previous studies. Our study aimed to explore the correlation between ESAs and MNs. Drug-target Mendelian randomization (MR) analyses were conducted to evaluate the causal associations of ESAs for 12 classifications of MNs. Meanwhile, a pharmacovigilance study was performed by extracting adverse events (AEs) in the FDA Adverse Event Reporting System (FAERS) database to validate and complement our findings. MR analysis revealed negative association of ESAs with MN of ovary (p = 0.047), liposarcoma(p = 0.001), small cell lung cancer(p = 0.017), colorectal cancer(p = 0.004), brain meningioma(p = 0.004), and revealed positive association of ESAs with MN of bladder (p = 0.001), eye and adnexa (p = 0.012), heart, mediastinum and pleura (p = 0.032), lip (p = 0.041), larynx (p = 0.015)，non small cell lung cancer (p = 0.009), malignant melanoma (p = 0.001). Positive signals were found in MN of hematological system, digestive organs, central nervous system, eye and adnexa, head and neck cancer, lung cancer, mucinous and mucinous cystic tumor in FAERS database (all reporting odds ratio (ROR) and proportional reporting ratio (PRR) >1). ESAs were causally correlated with many types of MNs. More attention needs to be paid to the use of ESAs in these tumors.