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Genetic variation in targets of roxadustat and risk of common cancers: A Mendelian randomization analysis

Xiaona He, Hongxi Chen, Yue Qi

    Clinical Nephrology
    |November 5, 2025
    PubMed
    Abstract

    Insights

    This study investigated roxadustat targets and cancer risk using Mendelian randomization. Genetic variants in EGLN1 and EGLN2 were linked to increased risk for breast and lung cancers, and decreased risk for skin and kidney cancers.

    Area of Science:

    • Genetics and Oncology
    • Pharmacogenomics
    • Cancer Etiology

    Background:

    • Roxadustat treats chronic kidney disease (CKD), often in cancer patients.
    • Potential links between roxadustat and cancer progression require mechanistic investigation.

    Purpose of the Study:

    • To explore associations between genetic variants in roxadustat targets and 14 cancer types.
    • To investigate potential causal links between roxadustat targets and cancer development.

    Main Methods:

    • Two-sample Mendelian randomization (MR) analysis.
    • Used single-nucleotide polymorphisms (SNPs) in EGLN1 and EGLN2 genes as instrumental variables.
    • Employed IVW-MR, SMR, MR-Egger, MR-PRESSO, and HEIDI tests.

    Main Results:

    • EGLN1 variants associated with increased breast and lung adenocarcinoma risk.
    • Negative associations for EGLN1 with skin and kidney cancers.
    • EGLN2 associated with prostate and lung cancers; negatively with ER- breast and brain cancers.

    Conclusions:

    • Findings suggest a potential causal relationship between EGLN1/EGLN2 inhibition and specific cancer types.
    • Supports further research into roxadustat's role in cancer development.

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