Impact of Gout on Colorectal Cancer and Its Survival: a Two-sample Mendelian Randomization Study

Overview

Journal Discov Oncol

Publisher Springer

Specialty Oncology

Date 2024 Dec 21

PMID 39708204

Authors

Li-Qiang Wei

Yi-Bei Song

Dong Lan

Xue-Jing Miao

Chun-Yu Lin

Shu-Ting Yang

Deng-He Liu

Xiao-Jv Chi

Affiliations

Soon will be listed here.

Abstract

Background: The relationship between gout and colorectal cancer (CRC) remains unclear, emphasizing the need for additional research to clarify the potential cumulative effect of gout on CRC development.

Methods: Leveraging a single nucleotide polymorphism-based genome-wide association study, the potential causal correlation between gout and CRC was initially analyzed using Mendelian randomization (MR). Subsequently, our analysis was expanded to include an assessment of patient survival, with the aim of evaluating the potential causal correlation between gout and CRC and the impact of gout on CRC survival outcomes.

Results: According to MR findings, a substantial relationship was observed between gout and the incidence of CRC when CRC was used as the outcome (OR = 0.954, 95% CI = 0.915-0.995). These results indicate a negative relationship between gout and the likelihood of developing CRC. In addition, when evaluating the overall survival (OS) or cancer-specific survival (CSS) of patients with CRC as outcomes, gout exhibited a significant relationship with survival. The inverse variance weighting approach demonstrated a progressive enhancement in CRC survival with the cumulative impact of gout (OS: OR = 2.000 × 10, 95% CI = 1.560 × 10-0.292; CSS: OR = 2.200 × 10, 95% CI = 4.660 × 10-0.104).

Conclusion: As gout accumulates, it exerts an inhibitory influence on CRC, indicating a potential protective effect. This study provides robust evidence that can guide the development of future clinical treatment approaches and research priorities.

References

Spoljaric K, Selo G, Pesut E, Martinovic J, Planinic M, Tisma M . Antioxidant and antiproliferative potentials of phenolic-rich extracts from biotransformed grape pomace in colorectal Cancer. BMC Complement Med Ther. 2023; 23(1):29. PMC: 9890866. DOI: 10.1186/s12906-023-03852-w. View

Zha X, Yang B, Xia G, Wang S . Combination of Uric Acid and Pro-Inflammatory Cytokines in Discriminating Patients with Gout from Healthy Controls. J Inflamm Res. 2022; 15:1413-1420. PMC: 8896041. DOI: 10.2147/JIR.S357159. View

Lee M, Nam S . The causal relationship of serum uric acid on colorectal cancer: A Mendelian randomization study. Medicine (Baltimore). 2024; 103(26):e38722. PMC: 11466122. DOI: 10.1097/MD.0000000000038722. View

Fu Q, Liao H, Li Z, Chen X, Zhang X, Di J . Preventive effects of 13 different drugs on colorectal cancer: a network meta-analysis. Arch Med Sci. 2023; 19(5):1428-1445. PMC: 10507769. DOI: 10.5114/aoms/167480. View

Chang H, Lin Y, Lin M, Lan Y, Wang R . Associations between urate-lowering therapy and the risk of type 2 diabetes mellitus. PLoS One. 2019; 14(1):e0210085. PMC: 6322774. DOI: 10.1371/journal.pone.0210085. View

Bockenhauer D, Jaureguiberry G . HNF1B-associated clinical phenotypes: the kidney and beyond. Pediatr Nephrol. 2015; 31(5):707-14. DOI: 10.1007/s00467-015-3142-2. View

Slobodnick A, Krasnokutsky S, Lehmann R, Keenan R, Quach J, Francois F . Colorectal Cancer Among Gout Patients Undergoing Colonoscopy. J Clin Rheumatol. 2019; 25(8):335-340. DOI: 10.1097/RHU.0000000000000893. View

Ahmad O, Forsti A . The complementary roles of genome-wide approaches in identifying genes linked to an inherited risk of colorectal cancer. Hered Cancer Clin Pract. 2023; 21(1):1. PMC: 9883872. DOI: 10.1186/s13053-023-00245-5. View

Weisshaar S, Litschauer B, Reichardt B, Gruber F, Leitner S, Sibinovic S . Cardiovascular risk and mortality in patients with hyperuricemia treated with febuxostat or allopurinol: a retrospective nation-wide cohort study in Austria 2014-2017. Rheumatol Int. 2022; 42(9):1597-1603. PMC: 9349126. DOI: 10.1007/s00296-022-05139-8. View

10.

Yu H, Xue W, Yu H, Song Y, Liu X, Qin L . Single-cell transcriptomics reveals variations in monocytes and Tregs between gout flare and remission. JCI Insight. 2023; 8(23). PMC: 10795830. DOI: 10.1172/jci.insight.171417. View

11.

Ozmen N, Kaya-Sezginer E, Bakar-Ates F . The Cellular Uptake and Apoptotic Efficiency of Colchicine is Correlated with Downregulation of MMP-9 mRNA Expression in SW480 Colon Cancer Cells. Anticancer Agents Med Chem. 2018; 18(13):1927-1933. DOI: 10.2174/1871520618666180821102047. View

12.

Chi X, Zhang H, Zhang S, Ma K . Chinese herbal medicine for gout: a review of the clinical evidence and pharmacological mechanisms. Chin Med. 2020; 15:17. PMC: 7017512. DOI: 10.1186/s13020-020-0297-y. View

13.

Boustany A, Rahhal R, Mitri J, Onwuzo S, Zeid H, Asaad I . INCREASED RISK OF COLORECTAL CANCER IN PATIENTS WITH CHRONIC TOPHACEOUS GOUT: A POPULATION-BASED STUDY. Arq Gastroenterol. 2023; 60(3):339-344. DOI: 10.1590/S0004-2803.230302023-43. View

14.

Kwon M, Han K, Kim J, Kim J, Kim M, Kim N . Gout and Colorectal Cancer Likelihood: Insights from a Nested Case-Control Study of the Korean Population Utilizing the Korean National Health Insurance Service-National Sample Cohort. Cancers (Basel). 2023; 15(23). PMC: 10705350. DOI: 10.3390/cancers15235602. View

15.

Zhang L, Zhuang Z, Zhang G, Huang T, Fan D . Assessment of bidirectional relationships between 98 genera of the human gut microbiota and amyotrophic lateral sclerosis: a 2-sample Mendelian randomization study. BMC Neurol. 2022; 22(1):8. PMC: 8721912. DOI: 10.1186/s12883-021-02522-z. View

16.

Lin T, Yen K, Chen C, Yan S, Su K, Chiang Y . Label-Free Uric Acid Estimation of Spot Urine Using Portable Device Based on UV Spectrophotometry. Sensors (Basel). 2022; 22(8). PMC: 9025019. DOI: 10.3390/s22083009. View

17.

Huang Y, Chen Z, Chen B, Li J, Yuan X, Li J . Dietary sugar consumption and health: umbrella review. BMJ. 2023; 381:e071609. PMC: 10074550. DOI: 10.1136/bmj-2022-071609. View

18.

Boffetta P, Nordenvall C, Nyren O, Ye W . A prospective study of gout and cancer. Eur J Cancer Prev. 2009; 18(2):127-32. DOI: 10.1097/CEJ.0b013e328313631a. View

19.

Yang Y, Liu Q, Wu Z, Li X, Deng C, Zhou S . Is hyperuricemia a recognizable biomarker for low risk of stroke in patients with atrial fibrillation?. Int J Cardiol. 2015; 203:624-5. DOI: 10.1016/j.ijcard.2015.11.019. View

20.

Liu Y, Chen W, Yang R, Zeng X, Zhang J . Effect of serum uric acid and gout on the incidence of colorectal cancer: A meta-analysis. Am J Med Sci. 2023; 367(2):119-127. DOI: 10.1016/j.amjms.2023.11.013. View