Exploring the causal relationship between serum uric acid and gastrointestinal cancer based on Mendelian randomization studies and bioinformatics approaches

Recent observational studies show a correlation between serum uric acid (SUA) levels and colorectal and gastric cancers (CRC and GC). It is unclear, nevertheless, what the biological mechanisms and causation of these connections are. Using summary data from the genome-wide association study, we analyzed 2-sample Mendelian randomization (MR). Inverse-variance weighted (IVW) was the main technique for determining causality. The weighted median, weighted mode, MR-Egger, Wald ratio, and IVW were employed to investigate the causal link between SUA and GC/CRC. To evaluate weak instrumental variable (IV) bias, F-statistics were computed. Using MR-PRESSO, outliers were found and removed. Cochran Q test, MR-Egger test, and leave-one-out approach were employed to find heterogeneity and stability in MR results. Ultimately, bioinformatics investigations were carried out to investigate plausible biological pathways linking GC/CRC and SUA. According to IVW data, SUA dramatically lowered the chance of GC (OR = 0.804, 95% Cl: 0.700-0.922, P = .002). There was no discernible cause-and-effect connection between SUA and CRC (OR = 0.999, 95% Cl: 0.997-1.000, P = .080). Furthermore, the reliability of the multiple validity and heterogeneity tests demonstrated the validity of the MR data. A total of 10 hub genes were found, with the majority of them being enriched in the AMPK signaling pathway, lipid metabolism, glucose metabolism, and cholesterol metabolism. This study indicates that SUA lowers the chance of developing GC, regardless of the risk of acquiring CRC. The link between SUA and GC could be due to several metabolic processes.