Association between serum uric acid and the risk of breast cancer: A meta-analysis of observational studies

Background: The relationship between serum uric acid and breast cancer remains uncertain. This meta-analysis aimed to elucidate the dose-response association between elevated serum uric acid levels and breast cancer risk. Methods: We systematically searched PubMed, Embase, and Web of Science for observational studies evaluating serum uric acid and breast cancer risk in adult women. Risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Results: Ten studies were included. High serum uric acid was associated with an increased breast cancer risk (RR: 1.34; 95% CI: 1.03-1.73; P = 0.03; I-2 = 78%). Meta-regression analysis revealed that the cutoff for high serum uric acid positively correlated with breast cancer risk (coefficient = 0.24; P < 0.001), explaining heterogeneity (residual I-2 = 0%). Subgroup analysis demonstrated a high serum uric acid was significantly related to an increased breast cancer risk in studies with a cutoff value >= 5.4 mg/dL (RR: 1.95; P < 0.001), but not in those with a cutoff value < 5.4 mg/dL (RR: 0.97; P = 0.44). The dose-response meta-analysis revealed a U-shaped association between serum uric acid levels and the risk of breast cancer (P for nonlinearity = 0.013). The risk of breast cancer fell until around 4.5 mg/dL of serum uric acid, and increased afterward. Conclusion: Serum uric acid may be nonlinearly associated with the risk of breast cancer (U-shaped). The risk of breast cancer increases with serum uric acid above 4.5 mg/dL, and a higher association between serum uric acid and the increased risk of breast cancer could be observed in studies with cutoff of serum uric acid > 5.4 mg/dL.