Dataset Information

Serum Uric Acid Levels and Risk of Eight Site-Specific Cancers: A Mendelian Randomization Study.

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.

SUBMITTER: Jiang M

PROVIDER: S-EPMC7985250 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Serum Uric Acid Levels and Risk of Eight Site-Specific Cancers: A Mendelian Randomization Study.

Jiang Minxiao M Ren Liangliang L Chen Songzan S Li Gonghui G

Frontiers in genetics 20210309

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 canc ...[more]

PMID: 33767728

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Project description:ObjectiveThe effects of coffee consumption on serum uric acid (SUA) levels and gout risk are controversial. There have hitherto been no reports based on Mendelian randomization (MR) analysis of its effects that consider pleiotropy. Here, we evaluated the effects of coffee consumption across ancestry populations, taking pleiotropy into account.MethodsWe performed the first MR analyses for coffee consumption on SUA levels and gout, considering pleiotropy. We used the following summary statistics of genome-wide association studies from a Japanese population: habitual coffee consumption (152,634 subjects), gout (3053 cases and 4554 controls), and SUA levels (121,745 subjects). In addition to fixed-effect inverse variance weighted (IVW) meta-analysis, we performed a robust evaluation of heterogeneity and removed several instruments for reasons of possible pleiotropy. Previous European datasets were also reevaluated while heterogeneity was considered.ResultsHabitual coffee consumption was significantly and inversely associated with gout (odds ratio [OR] = 0.29, 95% confidence interval [95% CI]: 0.16-0.51, P = 1.9 × 10-5 ) in random-effect IVW (Phet = 5.5 × 10-19 ). Excluding pleiotropic instruments, the protective effect on gout was confirmed in fixed-effect IVW analysis (OR = 0.75, 95% CI: 0.58-0.97, P = 0.026) without heterogeneity (Phet = 0.39). However, we observed no significance in the previous European datasets when heterogeneity was considered. Associations were not observed between coffee consumption and SUA levels in either ancestry in MR analyses that considered pleiotropy. Multivariable MR analysis showed that increased coffee consumption significantly reduced gout risk, even after adjusting for SUA levels (OR = 0.50, 95% CI: 0.31-0.81, P = 0.0046).ConclusionWith pleiotropy taken into account, our MR analyses revealed that coffee consumption can causally reduce gout risk, and that it may reduce gout risk independently of SUA levels.

Dataset Information

Serum Uric Acid Levels and Risk of Eight Site-Specific Cancers: A Mendelian Randomization Study.

Publications

Serum Uric Acid Levels and Risk of Eight Site-Specific Cancers: A Mendelian Randomization Study.

Similar Datasets

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