Serum urate and lung cancer: a cohort study and Mendelian randomization using UK Biobank
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.
We investigated the observational and potentially causal associations between serum urate and lung cancer incidence using one-sample Mendelian randomization (MR) and the UK Biobank resource. We instrumented serum urate level using genetic variants that explain ~ 5% of population-level variability. Incident lung cancer events 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.
The analysis included 359,192 participants and 1,924 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 predicted 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 to support a causal association between genetically predicted serum urate and lung cancer or FEV1. Although low serum urate levels might be useful for identifying male smokers at highest risk, we found no evidence that urate is a modifiable risk factor for lung cancer.
Figure 1
Figure 2
Figure 3
This is a list of supplementary files associated with this preprint. Click to download.
Posted 18 Jan, 2021
On 21 Feb, 2021
Invitations sent on 09 Jan, 2021
On 03 Jan, 2021
On 03 Jan, 2021
On 03 Jan, 2021
On 03 Jan, 2021
Serum urate and lung cancer: a cohort study and Mendelian randomization using UK Biobank
Posted 18 Jan, 2021
On 21 Feb, 2021
Invitations sent on 09 Jan, 2021
On 03 Jan, 2021
On 03 Jan, 2021
On 03 Jan, 2021
On 03 Jan, 2021
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.
We investigated the observational and potentially causal associations between serum urate and lung cancer incidence using one-sample Mendelian randomization (MR) and the UK Biobank resource. We instrumented serum urate level using genetic variants that explain ~ 5% of population-level variability. Incident lung cancer events 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.
The analysis included 359,192 participants and 1,924 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 predicted 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 to support a causal association between genetically predicted serum urate and lung cancer or FEV1. Although low serum urate levels might be useful for identifying male smokers at highest risk, we found no evidence that urate is a modifiable risk factor for lung cancer.
Figure 1
Figure 2
Figure 3