Association between serum uric acid and prostate cancer risk in East Asian populations: a Mendelian randomization study

Abstract

Purpose: Previous observational studies showed that serum uric acid (SUA) was associated with prostate cancer, but the causal relationship is unclear. This study aimed to explore the potential causal association between SUA and prostate cancer risk using Mendelian randomization (MR) analyses in the East Asian populations.

Methods: Publicly available summary-level genome-wide association studies (GWAS) data on SUA were obtained from a genome-wide meta-analysis of three Japanese cohorts (121,745 subjects). The GWAS data on prostate cancer were derived from Biobank Japan (109,347 subjects with 5,408 cases and 103,939 controls). A total of 34 SUA-related single-nucleotide polymorphisms (SNPs) (P value < 5 × 10^-8) were identified as instrumental variables. The inverse variance weighted method was used as the primary method to compute the odds ratios (ORs) and 95% confidence intervals (95% CIs) for per standard deviation increase in SUA. MR Egger, weighted median, and weighted mode were also applied to test the robustness of the results.

Results: Genetically predicted SUA was positively associated with prostate cancer risk using inverse variance weighted (OR = 1.12; 95% CI 1.00-1.26; P = 0.043). The positive association was robust when MR Egger (OR = 1.16; 95% CI 1.01-1.34; P = 0.048), weighted median (OR = 1.18; 95% CI 1.03-1.36; P = 0.018), and weighted mode (OR = 1.14; 95% CI 1.01-1.29; P = 0.041) were used.

Conclusion: There were potential causal associations between higher genetically predicted SUA levels and increased prostate cancer risk. Further, MR studies with more valid SNPs and more cancer cases are needed. Validation of the findings is also recommended.

Keywords: East Asian population; Mendelian randomization; Prostate cancer; Serum uric acid.