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

doi:10.4251/wjgo.v17.i9.107651

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World Journal of Gastrointestinal Oncology

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World J Gastrointest Oncol. Sep 15, 2025; 17(9): 107651
Published online Sep 15, 2025. doi: 10.4251/wjgo.v17.i9.107651

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

Teng-Fei Sun, Ke-Xin Fan, Yu-Xin Luo, Jia Song, Zhuo-Xiao Han, Xiao-Lan Zhang

Teng-Fei Sun, Yu-Xin Luo, Jia Song, Xiao-Lan Zhang, Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Hebei Clinical Research Center for Digestive Diseases, Shijiazhuang 050000, Hebei Province, China

Teng-Fei Sun, Department of Gastroenterology, First Hospital of Qinhuangdao, Qinhuangdao 066000, Hebei Province, China

Ke-Xin Fan, Zhuo-Xiao Han, Department of Pulmonary and Critical Care Medicine, First Hospital of Qinhuangdao, Qinhuangdao 066000, Hebei Province, China

Author contributions: Sun TF was responsible for drafting the manuscript and analyzing the data; Sun TF and Fan KX conducted the majority of the experiments; Fan KX was responsible collecting the data; Fan KX and Han ZX contributed in statistical analysis; Luo YX provided a review and criticism of the statistical analysis; Song J provided interpretation of the data; Han ZX contributed in criticism of the design; Zhang XL was responsible for interpreting the results of the analysis, criticizing the statistical analysis, and revising the manuscript. All authors read and approved the final manuscript.

Institutional review board statement: This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of the First Hospital of Qinhuangdao, No. 2024W006-02.

Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.

Data sharing statement: The datasets generated analyzed during the current study are available from the corresponding author on reasonable request.

Corresponding author: Xiao-Lan Zhang, Professor, Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Hebei Clinical Research Center for Digestive Diseases, No. 80 Huanghe Road, Yuhua District, Shijiazhuang 050000, Hebei Province, China. xiaolanzh@hebmu.edu.cn

Received: March 28, 2025
Revised: May 3, 2025
Accepted: June 30, 2025
Published online: September 15, 2025
Processing time: 172 Days and 7.7 Hours

Abstract

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.

Keywords: Uric acid; Colon cancer; Reactive oxygen species; Phosphoinositide 3-kinases; Mammalian target of rapamycin

Core Tip: This study, encompassing 2020 colon cancer cases and 6060 controls, revealed an inverse association between uric acid levels and the risk of colon cancer. To delve deeper into the underlying mechanisms, we conducted in vitro experiments using colon cancer cells. Our findings demonstrated that uric acid potently inhibits cell proliferation and migration. Mechanistically, these effects were mediated by the induction of reactive oxygen species and the suppression of the phosphoinositide 3-kinases/protein kinase B/mammalian target of rapamycin signaling pathway.