Abstract
The relationship between serum uric acid (UA) levels and cancer risk remains controversial. Here, a two-sample Mendelian randomization analysis was performed to identify a causal effect of serum UA levels on cancer risk. Twenty-six single nucleotide polymorphisms strongly associated with serum UA levels were screened as genetic variants from large-scale meta-analysis data of a genome-wide association study of 110,347 European individuals. Genetic associations with eight common site-specific cancers were subsequently explored. A total of six Mendelian randomization methods were used to estimate the potential effect of serum UA levels on cancer risk, including random effects inverse variance weighting, fix effects inverse variance weighting, MR-Egger, median weighting, mode weighting, and simple mode analysis. Our primary random effects inverse variance weighted analysis revealed that no significant associations with cancers was found (all p > 0.05). Sensitivity analyses and additional analyses also showed similar pooled results. In conclusion, no significant causality between serum UA levels and cancer risk was evidenced.
Highlights
Uric acid (UA) is a byproduct of purine metabolism, with both endogenous and exogenous purines degraded to uric acid (UA) by xanthine oxidase (Benn et al, 2018)
26 Single nucleotide polymorphisms (SNPs) strongly related to serum UA levels were extracted from a genomewide association study (GWAS) meta-analysis based on Global Urate Genetics Consortium (GUGC) data (p < 5 × 10−8; Supplementary Table S1)
All SNPs could be used to identify the potential effect of serum UA levels on cancer risk
Summary
Uric acid (UA) is a byproduct of purine metabolism, with both endogenous and exogenous purines degraded to UA by xanthine oxidase (Benn et al, 2018). Hyperuricemia is a common chronic illness defined by a serum UA level >7.0 mg/dl among men and >5.7 mg/ dl among women. The incidence of hyperuricemia in the United States is 20.2% in men and 20.0% in women (Chen-Xu et al, 2019). Previous studies have reported UA levels to be associated with the incidence of diabetes, cardiovascular disease, kidney disease, and malignancies (Weiner et al, 2008; Battelli et al, 2016; Wang et al, 2018; Borghi et al, 2020). Conventional observational studies have reported that higher serum UA levels are protective against cancer
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