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

Background: 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.

Aim: To elucidate the association between UA and colon cancer risk and its mechanisms.

Methods: 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.

Results: 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.

Conclusion: 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.