U-shaped relationship between serum uric acid and gastric cancer risk: a large prospective cohort study

Junjun Huang; Ningning Mi; Jingli Yang; Ya Zheng; Jinqiu Yuan; Wenbo Meng

doi:10.3389/fonc.2024.1482814

U-shaped relationship between serum uric acid and gastric cancer risk: a large prospective cohort study

Front Oncol. 2024 Dec 23:14:1482814. doi: 10.3389/fonc.2024.1482814. eCollection 2024.

Authors

Junjun Huang^#¹, Ningning Mi^#², Jingli Yang³, Ya Zheng⁴, Jinqiu Yuan^{5

6}, Wenbo Meng^{2

7

8

9

10}

Affiliations

¹ Scientific research & Planning Department, The First Hospital of Lanzhou University, Lanzhou, China.
² The First Clinical Medical School, Lanzhou University, Lanzhou, China.
³ College of Earth and Environmental Sciences, Lanzhou University, Lanzhou, China.
⁴ Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, China.
⁵ Clinical Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China.
⁶ Scientific Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China.
⁷ Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, China.
⁸ Institute of Genetics, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China.
⁹ Gansu Province Institute of Hepatopancreatobiliary, Lanzhou, China.
¹⁰ Gansu Province Key Laboratory Biotherapy and Regenerative Medicine, Lanzhou, China.

^# Contributed equally.

Abstract

Objective: We conducted this study to investigate the relationship between serum uric acid (SUA) levels and the risk of upper gastrointestinal cancer.

Methods: We conducted a prospective cohort study with 475659 cancer-free participants from the UK Biobank. All subjects were grouped into quartiles, and we used a Cox proportional hazards model to analyze the association between SUA levels and the risk of upper gastrointestinal cancer and explore the potential sex-specific relationship.

Results: Of the 475659 participants, 883 eventually developed upper gastrointestinal cancers over a median follow-up period of 6.7 years. We observed that SUA level was positively correlated with the risk of female oral cancer (hazard ratio _{Quartile 4 vs Quartile 1} (95% CI): 2.05(1.03,4.06)) and negatively associated with the risk of esophageal cancer in the general population (hazard ratio _{Quartile 3 vs Quartile 1} (95% CI): 0.65(0.45,0.93)). The risk of gastric cancer in males showed a U-shaped trend, decreasing and then increasing as SUA levels increased (hazard ratio _{Quartile 3 vs Quartile 1} (95% CI): 0.51(0.32,0.81)). The risk of small intestine cancer in females showed a trend of increasing and then decreasing with increasing SUA levels (hazard ratio _{Quartile 3 vs Quartile 1} (95% CI): 3.34(1.10,10.13)). Interaction analysis indicated that various factors, such as age, sex, smoking and drinking status, family history of cancer and BMI might play an important role in the relationship between SUA and cancer.

Conclusion: SUA levels are positively associated with the risk of oral cancer risk in females and negatively associated with the risk of esophageal cancer in the general population. Both low and high SUA levels were associated with increased risk of gastric cancer, supporting a U-shaped association.

Keywords: U-shaped relationship; UK biobank; cohort study; upper gastrointestinal cancer; uric acid.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the Foundation of the First Hospital of Lanzhou University (Grant No. ldyyyn2021-125), the Foundation of Gansu Provincial Education Technology Innovation (Grant No. 2022B-010) and the Natural Science Foundation of Gansu Province (Grant No. 23JRRA0939).