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

Lei Cai, Chenmin Yang Department of Obstetrics and Gynecology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200023, People’s Republic of ChinaCorrespondence: Chenmin Yang, Department of Obstetrics and Gynecology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, No. 197 Second Ruijin Road, Huangpu District, Shanghai, 200023, People’s Republic of China, Tel +86-13917317396, Email [email protected]: 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: serum UA level, gynecological cancers, Mendelian randomization study, causal association