Serum urate and lung cancer: a cohort study and Mendelian randomization using UK Biobank

BACKGROUND: Serum urate is the most abundant small molecule with antioxidant properties found in blood and the epithelial lining fluid of the respiratory system. Moderately raised serum urate is associated with lower rates of lung cancer and COPD in smokers but whether these relationships reflect antioxidant properties or residual confounding is unknown. METHODS: We investigated the observational and potentially causal associations of serum urate with lung cancer incidence and FEV(1) using one-sample Mendelian randomization (MR) and the UK Biobank resource. Incident lung cancer events were identified from national cancer registries as FEV(1) was measured at baseline. Observational and genetically instrumented incidence rate ratios (IRRs) and risk differences per 10,000 person-years (PYs) by smoking status were estimated. RESULTS: The analysis included 359,192 participants and 1,924 lung cancer events. The associations between measured urate levels and lung cancer were broadly U-shaped but varied by sex at birth with the strongest associations in current smoking men. After adjustment for confounding variables, current smoking men with low serum urate (100 µmol/L) had the highest predicted lung cancer incidence at 125/10,000 PY (95%CI 56–170/10,000 PY) compared with 45/10,000 PY (95%CI 38–47/10,000 PY) for those with the median level (300 µmol/L). Raised measured urate was associated with a lower baseline FEV(1). The MR results did not support a causal relationship between serum urate and lung cancer or FEV(1). CONCLUSIONS: We found no evidence that serum urate is a modifiable risk factor for respiratory health or lung cancer. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12931-021-01768-y.