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Serum urate and lung cancer: a cohort study and Mendelian randomization using UK Biobank
Laura J Horsfall
University College London
Corresponding Author
ORCiD: https://orcid.org/0000-0002-0868-5660
License:
This work is licensed under a CC BY 4.0 License. Read Full License
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 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.
Results
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.
Conclusions
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.
Keywords
Mendelian randomization, urate, lung function, causal relationship, lung cancer, smoking phenotypes
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CURRENT STATUS: Under Review
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Posted 18 Jan, 2021
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Reviewer #1 agreed
On 21 Feb, 2021
Reviewers invited
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On 03 Jan, 2021
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This preprint is under consideration at Respiratory Research. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
Serum urate and lung cancer: a cohort study and Mendelian randomization using UK Biobank
Laura J Horsfall
University College London
Corresponding Author
ORCiD: https://orcid.org/0000-0002-0868-5660
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 18 Jan, 2021
No community comments so far
Reviewer #1 agreed
On 21 Feb, 2021
Reviewers invited
Invitations sent on 09 Jan, 2021
First submitted
On 03 Jan, 2021
Editor assigned
On 03 Jan, 2021
Submission checks complete
On 03 Jan, 2021
Editor invited
On 03 Jan, 2021
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
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 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.
Results
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.
Conclusions
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