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Testing for Causal Association between Serum Urate, Gout, and Prostatic Cancer in European Males
Sumanth R Chandrupatla1,2, Nicholas Sumpter3, Riku Takei2
1Heersink School of Medicine, University of Alabama at Birmingham, AL, United States.
Medrxiv : the Preprint Server for Health Sciences
|May 19, 2025
Summary
Gout, specifically its inflammatory component, causally increases prostate cancer risk in men. Serum urate levels, however, do not appear to influence prostate cancer risk. This suggests inflammation, not hyperuricemia, is key.
Area of Science:
- Genetics and Epidemiology
- Urology and Rheumatology
Background:
- Serum urate (SU) is linked to gout, a condition characterized by inflammation.
- The relationship between SU, gout, and prostate cancer is not fully understood.
- Previous studies have yielded conflicting results regarding these associations.
Purpose of the Study:
- To investigate the potential causal relationship between serum urate (SU) and prostate cancer.
- To examine the causal effect of gout, distinct from hyperuricemia, on prostate cancer risk.
- To conduct a two-sample Mendelian randomization (MR) study exclusively in men.
Main Methods:
- Utilized genome-wide association studies (GWAS) for SU, gout, and prostate cancer.
- Employed instrumental variables (IVs): 20 SNPs for gout's non-hyperuricemia component and 4 SNPs for SU levels.
- Applied MR methods including inverse-variance-weighted (IVW) and weighted median, with MR-Egger regression for pleiotropy assessment.
Main Results:
- Gout's non-hyperuricemia component showed a causal effect on prostate cancer (Weighted median P=0.01).
- Serum urate levels did not demonstrate a causal effect on prostate cancer (IVW P=0.83).
- No evidence of horizontal pleiotropy was found for either SU or gout IVs.
- Key genes implicated in the gout-to-prostate cancer link include IL1R1, IL1RN, and SLC30A5.
Conclusions:
- Evidence supports a causal effect of gout's inflammatory component on prostate cancer in European men.
- The findings implicate gout-associated inflammation, mediated by genes like IL1R1 and IL1RN, in prostate cancer development.
- Serum urate levels were not found to causally influence prostate cancer risk.
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