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; I2 = 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 I2 = 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.