The causal relationship of serum uric acid on colorectal cancer: A Mendelian randomization study

Abstract

Colorectal cancer (CRC) is a significant public health issue owing to its widespread occurrence and substantial morbidity and mortality rates. Recent studies have highlighted serum uric acid (SUA) level as a probable risk factor for CRC; however, the inconsistency in these findings has created doubt. We performed a Mendelian randomization (MR) study utilizing extensive cohort data from the UK BioBank and the NHGRI-EBI Genome-Wide Association Study (GWAS) Catalog to investigate the causal connection between SUA levels and CRC incidence. Our MR study addresses the constraints of earlier studies, including limited sample sizes and inconsistent results. Considering SUA levels as the exposure and CRC as the outcome, the inverse variance-weighted (IVW) approach in MR showed that the odds ratios (ORs) for CRC for each unit increase in SUA were 0.232 (95% confidence interval [CI] of OR 0.094–0.570; P = .001) and 0.551 (95% CI of OR 0.325–0.934; P = .027). Pleiotropic tests and sensitivity analysis confirmed minimal horizontal pleiotropy and the robustness of causality. Our research deepens the understanding of the association between SUA levels and CRC, offering insights into prevention strategies and patient outcomes prediction.