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Causal associations between liver function biomarkers and prostate cancer risk in European and East Asian

Xinyu Xu1, Wenjing Zhu1, Yu Peng2

  • 1Department of Urology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, No. 110 Ganhe Road, Hongkou District, Shanghai, 200437, China.

Discover Oncology
|March 27, 2025
PubMed
Summary

Total bilirubin is protective against prostate cancer (PCa) in East Asians, while liver function markers show no causal link to PCa in Europeans. Further research is needed.

Keywords:
GWASLiver function markersMendelian randomizationProstate cancerTotal bilirubin

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Area of Science:

  • Genetics
  • Epidemiology
  • Oncology

Background:

  • Observational studies suggest a link between liver function and prostate cancer (PCa), but causality is unclear.
  • Genetic variations may influence this association across different populations.
  • Mendelian Randomization (MR) is used to investigate genetic causal relationships.

Purpose of the Study:

  • To investigate the genetic causal relationship between liver function markers and PCa in European and East Asian populations.
  • To identify potential gene-disease associations across ancestries.
  • To provide insights for PCa prevention and treatment.

Main Methods:

  • Selected single nucleotide polymorphisms (SNPs) from genome-wide association studies (GWAS) as instrumental variables (IVs).
  • Conducted univariate, multivariable, and bidirectional Mendelian Randomization (MR) analyses.
  • Utilized inverse variance weighting (IVW) and sensitivity analyses for robustness.

Main Results:

  • In Europeans, ALT and AST showed a potential association with reduced PCa risk, but this was not significant after multivariable adjustment. No reverse causality was found.
  • In East Asians, total and direct bilirubin were causally associated with reduced PCa risk.
  • Multivariable MR confirmed total bilirubin's protective effect in East Asians. Reverse MR indicated PCa may cause reduced ALT levels.

Conclusions:

  • The liver function marker-PCa relationship is influenced by genetic background.
  • Total bilirubin acts as an independent protective factor against PCa in East Asian populations.
  • Insufficient evidence for a causal link between liver function markers and PCa risk in Europeans; further research is warranted.