Abstract
Background: Serum urate levels have been associated with a lower risk of lung carcinogenesis in observational studies but the causality from serum urate levels on lung cancer has yet to determined. We conducted a bidirectional Mendelian randomization(MR) study to evaluate the causal effect of these associations.
Methods: Summary-level data for serum urate were obtained from 288,649 CKDGen participants of European ancestry. We drew summary statistics of lung cancer from the TRICL (29,266 cases and 56,450 controls), the ILCCO (11,348 cases and 15,861 controls) and the FinnGen study (1,627 cases and 174,006 controls). The inverse-variance-weighted method was applied to estimate the causal effects, whereas weighted median, MR-Egger, and MR pleiotropy residual sum and outlier were performed in the sensitivity analyses. Analyses were conducted per outcome database and were subsequently meta-analyzed using a fixed-effects model.
Results: Genetically determined serum urate levels were associated with lung adenocarcinoma (LUAD) [odds ratio(OR), 0.89; 95% confidence interval (CI), 0.82–0.97; P = 0.007] and overall lung cancer (OR, 0.94; 95% CI, 0.89-0.99; P = 0.014). The main results remained robust in most of the sensitivity analyses. The association pattern remained for the combined results of the three databases[(OR, 0.90; 95% CI, 0.84-0.96; P = 0.002); (OR, 0.94; 95% CI, 0.90-0.98; P = 0.006)]. No consistent evidence was found for the causal effect of lung cancer on serum urate levels.
Conclusions: Our MR estimates provide consistent evidence for the independent effect of serum urate levels on lung cancer, particularly LUAD, which may be mediated by urate metabolic process, but not the reverse effect of lung cancer. Urate-elevating therapy may be of pulmonary benefit in the prevention of lung cancer.