Exploring the link between serum uric acid and colorectal cancer: Insights from genetic evidence and observational data.

Colorectal cancer (CRC) is a major cause of cancer-related mortality worldwide. Urate, known for its antioxidant properties, may influence CRC risk and prognosis, but research on this is limited. We used Mendelian randomization (MR) analysis to explore the causal relationship between serum urate levels and CRC risk. Additionally, we analyzed National Health and Nutrition Examination Survey data to assess the impact of serum urate on CRC prognosis. MR analysis in the European population indicated that higher serum urate levels are associated with a reduced CRC risk (odds ratios [OR] inverse-variance weighted: 0.90, 95% CI: 0.81-0.99, P = .04; OR MR-Egger: 0.86, 95% CI: 0.75-0.98, P = .03; OR Weighted-Median: 0.85, 95% CI: 0.74-0.96, P = .01; OR Weighted-Mode: 0.83, 95% CI: 0.74-0.94, P = .002). Validation datasets supported this (OR inverse-variance weighted: 0.83, 95% CI: 0.72-0.96, P = .011). However, National Health and Nutrition Examination Survey data showed that higher serum urate levels are linked to poorer CRC outcomes (HR 1.50, 95% CI: 1.08-2.10, P = .02). This study suggests that elevated serum urate levels may reduce CRC risk but are associated with worse prognosis in CRC patients, highlighting its potential as a biomarker for CRC risk and prognosis.