Sun TF, Fan KX, Luo YX, Song J, Han ZX, Zhang XL. Relationship between uric acid and colon cancer risk: Dose-response analysis and mechanisms. World J Gastrointest Oncol 2025; 17(9): 107651 [DOI: 10.4251/wjgo.v17.i9.107651]
Corresponding Author of This Article
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
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
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.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
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 1 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.
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.
