Serum urate levels and colorectal cancer risk: a prospective cohort study in of the UK biobank and a Mendelian randomization analysis.

ABSTRACT:

Background

Serum urate is the most abundant antioxidant molecule in human blood and may play a role in cancer prevention. However, the association between serum urate levels and colorectal cancer (CRC) risk remains inconclusive, with the underlying causal mechanisms still undefined.

Methods

In the UK Biobank (UKB) cohort, we investigated the prospective association between serum urate levels and the risk of CRC. We used Cox proportional hazards models to estimate the multivariable hazard ratios (HR) for CRC. Subgroup analyses were performed based on anatomical subsite and sex. Additionally, two-sample Mendelian randomization (MR) analysis was conducted to assess the potential causal effect of genetically determined urate levels on CRC risk.

Results

During a median follow-up of 11.58 years, 1960 CRC events were recorded among 180,480 participants without baseline CRC in the UKB. Higher urate levels were associated with a decreased risk of CRC (HR = 0.85, 95% CI: 0.72-0.99, P = 0.038). Moreover, the association between urate levels and CRC risk varied by anatomical subsite and sex. Higher urate levels were associated with a decreased risk of colon cancer in the overall population (HR = 0.79, 95% CI: 0.65-0.96, P = 0.015) and colon cancer in female (HR = 0.66, 95% CI: 0.50-0.87, P = 0.003), but not with rectal cancer or CRC in male. MR results supported a causal relationship between serum urate and CRC risk, with higher serum urate levels corresponding to a lower risk of CRC.

Conclusions

In this study, higher urate levels were associated with a reduced risk of CRC, and MR analysis supported a potential causal relationship between urate levels and CRC risk. However, further studies are needed to confirm causality and to investigate the potential subsite-specific effects of urate on CRC development.

SUBMITTER: Zhou Y 

PROVIDER: S-EPMC12595151 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature