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. 2025 May 5:17:1237-1245.
doi: 10.2147/IJWH.S493564. eCollection 2025.

The Relationship Between Serum Uric Acid and Gynecologic Cancer Risk: A Mendelian Randomization Study

Lei Cai  1 , Chenmin Yang  1
Affiliations

The Relationship Between Serum Uric Acid and Gynecologic Cancer Risk: A Mendelian Randomization Study

Lei Cai et al. Int J Womens Health. .

Abstract

Aim: High serum uric acid (UA) levels have been linked to cancer development through chronic inflammation and oxidative damage. Traditional epidemiological studies have shown inconsistent results regarding the relationship between uric acid and gynecological cancers. This study uses Mendelian randomization (MR) to explore the potential association between serum UA levels and various gynecological cancers.

Methods: In this two-sample MR study, summary statistical data of the genome-wide association studies (GWASs) on serum UA levels were extracted from the UK Biobank (UKB), and those on gynecological cancers were obtained from the FinnGen consortium, the Epidemiology of Endometrial Cancer Consortium (E2C2), and the Ovarian Cancer Association Consortium (OCAC). Inverse variance weighted (IVW), weighted median, MR-Egger, weighted mode, MR-Pleiotropy RESidual Sum and Outlier (MR-PRESSO), and MR-Radial methods were utilized to investigate the bidirectional causal associations of serum UA levels with gynecological cancers. The evaluation indexes were odds ratios (ORs) and confidence intervals (CIs). Tests for horizontal pleiotropism and heterogeneity of instrumental variables (IVs) were performed, respectively using MR-Egger test and Cochran's Q statistics. In addition, leave-one-out and MR scatter plots were employed for sensitivity analyses.

Results: IVW estimates suggested that serum UA levels elevated 1 unit had a potential causal association with higher odds of both cervical cancer (CC) (OR=1.147, 95% CI: 1.020-1.290) and invasive mucinous ovarian cancer (IMOC) (OR=1.199, 95% CI: 1.033-1.393). Also, endometrial carcinoma (EC) had a potential causal association with it (OR=1.012, 95% CI: 1.000-1.024). Additionally, sensitivity analyses showed the potential causal associations between UA and CC/IMOC were relatively robust.

Conclusion: An elevated serum UA level had potential associations with CC and IMOC, whereas patients with EC should pay attention to it in clinical practice, which may reduce the potential risk of gynecological cancers. However, further evidence is needed to clarify the true relationships between UA and gynecological cancers.

Keywords: Mendelian randomization study; causal association; gynecological cancers; serum UA level.

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Conflict of interest statement

The authors declare no competing interests in this work.

Figures

None
Graphical abstract
Figure 1
Figure 1
Flowchart of the research process.
Figure 2
Figure 2
Potential causal associations of serum UA levels with different gynecological cancers. The P value of association between UA and CCOC is 0.050392.
Figure 3
Figure 3
Reversed potential causal association of serum UA levels with different gynecological cancers.
See this image and copyright information in PMC

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