Urate-lowering drugs and colorectal cancer risk: an observational study and Mendelian randomization analysis

CAO Hongfei; ZHANG Jie; ZHANG Zixing; WEI Sitong; YE Dongqing; FANG Xinyu

doi:10.16462/j.cnki.zhjbkz.2025.06.001

Volume 29 Issue 6

Jun. 2025

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CAO Hongfei, ZHANG Jie, ZHANG Zixing, WEI Sitong, YE Dongqing, FANG Xinyu. Urate-lowering drugs and colorectal cancer risk: an observational study and Mendelian randomization analysis[J]. CHINESE JOURNAL OF DISEASE CONTROL & PREVENTION, 2025, 29(6): 621-627. doi: 10.16462/j.cnki.zhjbkz.2025.06.001

Citation:

CAO Hongfei, ZHANG Jie, ZHANG Zixing, WEI Sitong, YE Dongqing, FANG Xinyu. Urate-lowering drugs and colorectal cancer risk: an observational study and Mendelian randomization analysis[J]. CHINESE JOURNAL OF DISEASE CONTROL & PREVENTION, 2025, 29(6): 621-627. doi: 10.16462/j.cnki.zhjbkz.2025.06.001

Citation:

CAO Hongfei, ZHANG Jie, ZHANG Zixing, WEI Sitong, YE Dongqing, FANG Xinyu. Urate-lowering drugs and colorectal cancer risk: an observational study and Mendelian randomization analysis[J]. CHINESE JOURNAL OF DISEASE CONTROL & PREVENTION, 2025, 29(6): 621-627. doi: 10.16462/j.cnki.zhjbkz.2025.06.001

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Urate-lowering drugs and colorectal cancer risk: an observational study and Mendelian randomization analysis

doi: 10.16462/j.cnki.zhjbkz.2025.06.001

CAO Hongfei^{1, 2},
ZHANG Jie³,
ZHANG Zixing^{1, 2},
WEI Sitong^{1, 2},
YE Dongqing^{1, 2, 3
,
,},
FANG Xinyu^{1, 2
,
,}

1.
Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, Hefei 230032, China
2.
Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Hefei 230032, China
3.
School of Public Health, Anhui University of Science and Technology, Hefei 231131, China

Funds:

National Natural Science Foundation Youth Project 82304217

Anhui Province Clinical Medicine Research Translation Special Project 202304295107020041

Anhui Province Clinical Medicine Research Translation Special Project 202304295107020048

More Information

Corresponding author: YE Dongqing, E-mail: ahmuydq@126.com; FANG Xinyu, E-mail: xinyufang@ahmu.edu.cn
Received Date: 2025-03-15
Rev Recd Date: 2025-05-28

Available Online: 2025-07-07

Publish Date: 2025-06-10

Abstract

Abstract

Objective Assessing the association between uric acid-lowering drugs and their targets with the incidence of colorectal cancer (CRC). Methods Based on data from the UK Biobank from 2006 to 2010 (application No: 62663), a prospective cohort study was conducted to explore the impact of uric acid-lowering drug use on the risk of CRC using propensity score matching and Cox proportional hazards model. Additionally, Mendelian randomization (MR) was employed, utilizing expression quantitative trait loci of genes targeted by uric acid-lowering drugs as instrumental variables, to analyze the associations between three types of uric acid-lowering drugs and the occurrence of CRC. Results The study included a total of 5 440 users of uric acid-lowering drugs, with a median age of 52.0 years, of whom 92.1% were male. The median follow-up period was 12.75 years, during which 117 cases of CRC were reported. The Cox proportional hazards model showed that the risk of CRC in users of uric acid-lowering drugs was reduced by 20.2% compared to non-users (HR=0.798, 95% CI: 0.652-0.976, P=0.029). MR analysis suggested that targeting solute carrier family 22 member 12 (SLC22A12) may reduce the risk of CRC (OR=0.834, 95% CI: 0.734-0.949, P=0.006). Conclusions Uric acid-lowering drugs and SLC22A12-targeted uricosuric agents are associated with the occurrence of CRC, providing possible insights into explaining the relationship between uric acid-lowering drugs and CRC.
- Urate-lowering drugs,
- Colorectal cancer,
- Mendelian randomization,
- Prospective cohort

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References(25)

References

[1]	Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2024, 74(3): 229-263. DOI: 10.3322/caac.21834.
[2]	Abedizadeh R, Majidi F, Khorasani HR, et al. Colorectal cancer: a comprehensive review of carcinogenesis, diagnosis, and novel strategies for classified treatments[J]. Cancer Metastasis Rev, 2024, 43(2): 729-753. DOI: 10.1007/s10555-023-10158-3.
[3]	Mi SY, Gong L, Sui ZQ. Friend or foe? an unrecognized role of uric acid in cancer development and the potential anticancer effects of uric acid-lowering drugs[J]. J Cancer, 2020, 11(17): 5236-5244. DOI: 10.7150/jca.46200.
[4]	Mao LN, Guo C, Zheng S. Elevated urinary 8-oxo-7, 8-dihydro-2'-deoxyguanosine and serum uric acid are associated with progression and are prognostic factors of colorectal cancer[J]. Onco Targets Ther, 2018, 11: 5895-5902. DOI: 10.2147/OTT.S175112.
[5]	Li WQ, Liu T, Siyin ST, et al. The relationship between serum uric acid and colorectal cancer: a prospective cohort study[J]. Sci Rep, 2022, 12(1): 16677. DOI: 10.1038/s41598-022-20357-7.
[6]	Wei F, Nian Q, Zhao MY, et al. Natural products and mitochondrial allies in colorectal cancer therapy[J]. Biomed Pharmacother, 2023, 167: 115473. DOI: 10.1016/j.biopha.2023.115473.
[7]	Fu Q, Liao HN, Li ZH, et al. Preventive effects of 13 different drugs on colorectal cancer: a network Meta-analysis[J]. Arch Med Sci, 2023, 19(5): 1428-1445. DOI: 10.5114/aoms/167480.
[8]	Zhang HP. Pros and cons of mendelian randomization[J]. Fertil Steril, 2023, 119(6): 913-916. DOI: 10.1016/j.fertnstert.2023.03.029.
[9]	Sanderson E, Glymour MM, Holmes MV, et al. Mendelian randomization[J]. Nat Rev Meth Primers, 2022, 2: 6. DOI: 10.1038/s43586-021-00092-5.
[10]	Wang LJ, Mesa-Eguiagaray I, Campbell H, et al. A phenome-wide association and factorial Mendelian randomization study on the repurposing of uric acid-lowering drugs for cardiovascular outcomes[J]. Eur J Epidemiol, 2024, 39(8): 869-880. DOI: 10.1007/s10654-024-01138-0.
[11]	Leung N, Yip K, Pillinger MH, et al. Lowering and raising serum urate levels: off-label effects of commonly used medications[J]. Mayo Clin Proc, 2022, 97(7): 1345-1362. DOI: 10.1016/j.mayocp.2022.02.027.
[12]	Cicero AFG, Fogacci F, Cincione RI, et al. Clinical effects of xanthine oxidase inhibitors in hyperuricemic patients[J]. Med Princ Pract, 2021, 30(2): 122-130. DOI: 10.1159/000512178.
[13]	Fujita K, Isozumi N, Zhu QN, et al. Unique binding sites of uricosuric agent dotinurad for selective inhibition of renal uric acid reabsorptive transporter URAT1[J]. J Pharmacol Exp Ther, 2024, 390(1): 99-107. DOI: 10.1124/jpet.124.002096.
[14]	Lin SQ, Wu S, Zhao W, et al. TargetGene: a comprehensive database of cell-type-specific target genes for genetic variants[J]. Nucleic Acids Res, 2024, 52(D1): D1072-D1081. DOI: 10.1093/nar/gkad901.
[15]	Pan HX, Liu ZH, Ma JH, et al. Genome-wide association study using whole-genome sequencing identifies risk loci for Parkinson's disease in Chinese population[J]. NPJ Parkinsons Dis, 2023, 9(1): 22. DOI: 10.1038/s41531-023-00456-6.
[16]	Zhou SR, Butler-Laporte G, Nakanishi T, et al. A Neanderthal OAS1 isoform protects individuals of European ancestry against COVID-19 susceptibility and severity[J]. Nat Med, 2021, 27(4): 659-667. DOI: 10.1038/s41591-021-01281-1.
[17]	Liu YN, Chen W, Yang RQ, et al. Effect of serum uric acid and gout on the incidence of colorectal cancer: a Meta-analysis[J]. Am J Med Sci, 2024, 367(2): 119-127. DOI: 10.1016/j.amjms.2023.11.013.
[18]	Alam S, Doherty E, Ortega-Prieto P, et al. Membrane transporters in cell physiology, cancer metabolism and drug response[J]. Dis Model Mech, 2023, 16(11): dmm050404. DOI: 10.1242/dmm.050404.
[19]	Qu Z, Wu KL, Qiu HT, et al. Genetic association between SLC22A12 variants and susceptibility to hyperuricemia: a Meta-analysis[J]. Genet Test Mol Biomarkers, 2022, 26(2): 81-95. DOI: 10.1089/gtmb.2021.0175.
[20]	Wang L, Ye JP. Commentary: Gut microbiota reduce the risk of hyperuricemia and gout in the human body[J]. Acta Pharm Sin B, 2024, 14(1): 433-435. DOI: 10.1016/j.apsb.2023.11.013.
[21]	Sutkowy P, Czeleń P. Redox balance in cancer in the context of tumor prevention and treatment[J]. Biomedicines, 2025, 13(5): 1149. DOI: 10.3390/biomedicines13051149.
[22]	Li HL, Zhang CJ, Zhang H, et al. Xanthine oxidoreductase promotes the progression of colitis-associated colorectal cancer by causing DNA damage and mediating macrophage M1 polarization[J]. Eur J Pharmacol, 2021, 906: 174270. DOI: 10.1016/j.ejphar.2021.174270.
[23]	Copur S, Demiray A, Kanbay M. Uric acid in metabolic syndrome: does uric acid have a definitive role?[J]. Eur J Intern Med, 2022, 103: 4-12. DOI: 10.1016/j.ejim.2022.04.022.
[24]	Allegrini S, Garcia-Gil M, Pesi R, et al. The good, the bad and the new about uric acid in cancer[J]. Cancers (Basel), 2022, 14(19): 4959. DOI: 10.3390/cancers14194959.
[25]	Cabǎu G, Crisan TO, Klück V, et al. Urate-induced immune programming: consequences for gouty arthritis and hyperuricemia[J]. Immunol Rev, 2020, 294(1): 92-105. DOI: 10.1111/imr.12833.