Relationship between uric acid and colon cancer risk: Dose-response analysis and mechanisms

Uric acid (UA), a key antioxidant metabolite, demonstrates dual roles in cancer. Unfortunately, studies on its role in colon cancer risk are uncommon, and the limited results are inconsistent. To elucidate the association between UA and colon cancer risk and its mechanisms. Multivariate logistic regression analysis evaluated the association between UA levels and colon cancer risk. Non-linear relationships were illustrated using restricted cubic splines. The threshold effect was performed to identify cut-off points. Human colon cancer cell lines (HCT-116 and HT29) were exposed to UA for 48 hours. Cell viability was assessed via the cell counting kit-8 assay. The evaluation of cell migration involved wound healing and transwell migration assays. HCT-116 cells were exposed to 4 mg/dL UA for 48 hours. The impact of the subsequent treatment with a phosphoinositide 3-kinases (PI3K) agonist and UA was assessed. After adjusting for potential confounders, an inverse association was observed between UA and colon cancer risk (odds ratio = 0.65, P < 0.05). A non-linear relationship was identified, with a 4.79 mg/dL cut-off point (P < 0.05). UA inhibited colon cancer cell proliferation and migration. These effects were mediated by the induction of reactive oxygen species and the suppression of the PI3K/protein kinase B/mammalian target of rapamycin pathway. UA acts as a protective agent against colon cancer by inhibiting cell proliferation and migration through increased reactive oxygen species production and modulation of the PI3K/protein kinase B/mammalian target of rapamycin pathway.