S83 Genetically raised serum urate and lung cancer: a cohort study and mendelian randomisation 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 amongst smokers but is not known whether these relationships reflect antioxidant properties or residual confounding. Objective Investigate the observational and causal relationships between serum urate and lung cancer incidence using one-sample Mendelian randomisation (MR) and UK Biobank. Methods We instrumented serum urate level using variants that explain ~5% of population-level variability. Lung cancer events occurring after recruitment were identified from national cancer registries. Observational and genetically instrumented incidence rate ratios (IRRs) and risk differences per 10,000 person-years (PYs) by smoking status were estimated. Results We included 376,771 participants and 2002 lung cancer events. The relationships between observed urate levels and lung cancer were generally 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 lung cancer incidence at 125/10,000PY (95%CI: 56–170/10,000PY) compared with 45/10,000PY (95%CI: 38–47/10,000PY) for those with the median level (300 µmol/L). The associations were weaker for women. We found no strong evidence of a causal relationship between genetically predicted serum urate and lung cancer using MR. Conclusion Although low serum urate levels might be useful for identifying male smokers at highest risk, we found no evidence that the purported antioxidant properties of urate can protect against lung cancer.