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Unveiling the association between HMG-CoA reductase inhibitors and bladder cancer: a comprehensive analysis using Mendelian randomization, animal models, and transcriptomics.

Author information

Affiliations

  • 1. Department of Urology, Hubei Key Laboratory of Urological Diseases, Zhongnan Hospital of Wuhan University, Wuhan, China.
      Authors
    • Wei H 1
    • Li Z 1
    • Wang G 1, 2
    • Wang X 1
    (4 authors)
  • 2. Department of Biological Repositories, Human Genetic Resource Preservation Center of Hubei Province, Zhongnan Hospital of Wuhan University, Wuhan, China.
      Authors
    • Qian K 2
    • Ju L 2
    • Shan D 2
    • Yu M 2
    • Fang Y 2
    • Xiao Y 2
    • Wang G 1, 2
    (7 authors)
  • 3. Department of Urology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, China.
      Authors
    • Du W 3
    (1 author)
  • 4. Euler Technology, ZGC Life Sciences Park, Beijing, China.
      Authors
    • Zhang Y 4
    (1 author)

ORCIDs linked to this article

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The Pharmacogenomics Journal, 07 Aug 2024, 24(5):24
https://doi.org/10.1038/s41397-024-00346-x PMID: 39112450 

Abstract 

This study utilized Mendelian randomization (MR) analysis and genome-wide association study (GWAS) data to investigate the association between commonly prescribed drugs and bladder cancer (BLCA) risk. Our results revealed that HMG CoA reductase (HMGCR) inhibitors, specifically simvastatin, are significantly associated with reduced BLCA risk. We further showed that simvastatin could significantly inhibit BLCA proliferation and epithelial-mesenchymal transition in animal models, with transcriptomic data identifying several pathways associated with these processes. Higher expression of HMGCR were linked with BLCA development and progression, and certain blood lipids, such as lipoprotein particles and very low density lipoprotein (VLDL) cholesterol, might influence BLCA risk. These findings suggested that HMGCR inhibitors, particularly simvastatin, could be potential treatment options or adjuvant therapies for BLCA.

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Read article at publisher's site: https://doi.org/10.1038/s41397-024-00346-x

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Funding 

Funders who supported this work.

Fundamental Research Funds for the Central Universities

    National Natural Science Foundation of China (1)

    National Natural Science Foundation of China (National Science Foundation of China) (1)

    Research Fund of Zhongnan Hospital of Wuhan University