Dataset Information

Association between serum uric acid and colorectal cancer risk in European population: a two-sample Mendelian randomization study.

ABSTRACT:

Objectives

This study aimed to explore the potential causal associations between serum uric acid (SUA) and the risk of colorectal cancer, colon cancer and rectal cancer.

Methods

Twenty-six SUA-related single nucleotide polymorphisms which were identified by a large meta-analysis of genome-wide association studies (GWASs) were used as instrumental variables in the two-sample Mendelian randomization (MR) study. Meta-analyses were used to synthesize the results of multiple GWASs which were extracted from the MRC Integrative Epidemiology Unit GWAS database for each type of cancer. The inverse variance weighted (IVW) method was used as the primary MR method to analyze the association between SUA and colorectal cancer risk. Several sensitivity analyses were performed to test the robustness of results.

Results

The IVW method showed that there were no causal relationships between SUA and the risk of colorectal cancer [odds ratio (OR): 1.0015; 95% confidence interval (CI): 0.9975-1.0056] and colon cancer (OR: 1.0015; 95% CI: 0.9974-1.0055). The SUA levels were negative correlated with rectal cancer risk (OR: 0.9984; 95% CI: 0.9971-0.9998). The similar results were observed in both males (OR: 0.9987; 95% CI: 0.9975-0.9998) and females (OR: 0.9985; 95% CI: 0.9971-0.9999). The sensitivity analyses suggested no evidence of heterogeneity or horizontal pleiotropy. The leave-one-out analyses showed that one SNP (rs1471633) significantly drove the causal effect of SUA on rectal cancer risk. The MR-Egger regression and weighted median both showed that there were no causal relationships between SUA and the risk of colorectal cancer and its subtypes.

Conclusion

Overall, there was no linear causal association between SUA and the risk of colorectal cancer. However, further research is needed to investigate the role of higher SUA levels such as hyperuricemia or gout in the occurrence of colorectal cancer.

SUBMITTER: Zhou J

PROVIDER: S-EPMC11246881 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature

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Publications

Association between serum uric acid and colorectal cancer risk in European population: a two-sample Mendelian randomization study.

Zhou Jinsong J Fu Rong R Zhang Juwei J Zhang Suhong S Lin Zhifeng Z Lin Zheng Z Liu Xin X Xu Xiaolu X Chen Yulun Y Hu Zhijian Z

Frontiers in oncology 20240701

<h4>Objectives</h4>This study aimed to explore the potential causal associations between serum uric acid (SUA) and the risk of colorectal cancer, colon cancer and rectal cancer.<h4>Methods</h4>Twenty-six SUA-related single nucleotide polymorphisms which were identified by a large meta-analysis of genome-wide association studies (GWASs) were used as instrumental variables in the two-sample Mendelian randomization (MR) study. Meta-analyses were used to synthesize the results of multiple GWASs whic ...[more]

PMID: 39011473

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Project description:BackgroundObservational studies indicated that serum uric acid (SUA) was associated with male sexual hormones and erectile dysfunction (ED). However, their relationship was still heterogeneous.AimThis study conducted 2-sample univariate mendelian randomization (UVMR) and multivariate mendelian randomization (MVMR) to explore the causal relationship between SUA and sexual hormones as well as ED.MethodsGenetic variants associated with SUA were derived from the UK Biobank database (N = 437 354). Outcomes from the IEU Open GWAS and summary data sets were sexual hormones (sex hormone-binding globulin [SHBG], testosterone, estradiol [E2], follicle-stimulating hormone, luteinizing hormone) and ED, with 3301 to 625 650 participants. UVMR analysis primarily utilized the inverse variance weighted method, complemented by MVMR analysis. Thorough sensitivity analyses were carried out to ensure the reliability of results. Moreover, mediation analysis was conducted to estimate the mediated effect between SUA and outcomes.OutcomesThe primary outcomes included results of UVMR and MVMR analysis and mediation analysis, along with sensitivity analyses involving the Cochran Q test, the MR Egger intercept test, leave-1-out analysis, and the MR-PRESSO method (mendelian randomization pleiotropy residual sum and outlier).ResultsUVMR analysis revealed that an elevated SUA level could decrease levels of SHBG (β = -0.10, P = 1.70 × 10-7) and testosterone (β = -0.10, P = 5.94 × 10-3) and had a positive causal effect on ED (odds ratio, 1.10; P = .018). According to reverse mendelian randomization results, increased levels of SHBG (β = -0.06, P = 4.82 × 10-4) and E2 (β = -0.04, P = .037) could also reduce SUA levels. As shown by MVMR analysis, SUA had a negative effect on SHBG and testosterone levels (P < .05), while the significant causal relationship between SUA and ED disappeared. Furthermore, SHBG mediated 98.1% of the effect of SUA on testosterone levels. Results of other mendelian randomization analyses were not statistically significant. No pleiotropy was found by sensitivity analysis in this study.Clinical implicationsGiven the causal relationship between SUA and sexual hormones, we must focus on SUA and E2 levels in men, especially patients with hypogonadism and ED.Strengths and limitationsThis study evaluated the causal effect of SUA on male sexual hormones and ED genetically for the first time, clarifying the common biases in observational studies and confirming the negative relationship between SUA and testosterone level. Limitations include a population based on European ancestry, some crossover of the samples, and unobserved confounding factors.ConclusionGenetic studies provide evidence for the causal relationship between SUA and male sexual hormones (SHBG, testosterone, E2), while the relationship between SUA and ED should be further evaluated.

Project description:BackgroundObservational studies have found an increased risk of stroke in patients with spondyloarthritis, but the results are susceptible to reverse causality and confounders. Therefore, the study aimed to further explore the association between spondyloarthritis and different subtypes of stroke by using a two sample Mendelian randomization (MR) analysis.MethodsGenetic instrumental variables for spondyloarthritis were identified using summary level data from a genome-wide association study involving 201,581 people. Summary statistics from the Multiancestry Genome-wide Association Study of Stroke Consortium were used to obtain genetic data on stroke. There was no sample overlap between the exposure and outcome datasets. Inverse-variance weighted was considered the primary MR method for causal analysis. Heterogeneity, pleiotropy and sensitivity analyses were performed to ensure robustness, and single nucleotide polymorphism (SNP) with potential confounders was further screened in the PhenoScanner database to better evaluate the stability of our study.ResultsOne SNP (rs1065045) was excluded due to schizophrenia. After excluding SNP (rs1065045), results of the second MR analysis were slightly different from the first, which were considered as the final result: a significant positive causality between spondyloarthritis and cardioembolic stroke (OR=1.296, 95% CI:1.094-1.534, p=0.003); a possible positive causality between spondyloarthritis and any stroke (OR=1.082, 95% CI:1.016-1.152, p=0.013)/any ischemic stroke (OR=1.086, 95% CI:1.013-1.163, p=0.020); no significant/possible causality between spondyloarthritis and small vessel stroke (OR=1.168, 95% CI:0.993-1.375, p=0.061). Insufficient power may be one possible reason why a causality was not observed between spondyloarthritis in our study.ConclusionsThis study suggests that the possible causative effects of spondyloarthritis predicted by genetics on stroke may be limited to any stroke, any ischemic stroke, and cardioembolic stroke, especially the last.

Dataset Information

Association between serum uric acid and colorectal cancer risk in European population: a two-sample Mendelian randomization study.

Objectives

Methods

Results

Conclusion

Publications

Association between serum uric acid and colorectal cancer risk in European population: a two-sample Mendelian randomization study.

Similar Datasets

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