ArticleThorax2020
Genetically raised serum bilirubin levels and lung cancer: a cohort study and Mendelian randomisation using UK Biobank.
Article in Thorax, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 2 of them syntheses that pooled it.
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Who cites it
31 citing papers in PubMed, 2 syntheses or guidelines pooled it, 52 citations in OpenAlex.
- Systematic review of Mendelian randomization studies on risk of cancer.BMC medicine · 2022Pooled it
- Serum bilirubin and chronic obstructive pulmonary disease (COPD): a systematic review.BMC pulmonary medicine · 2021Pooled it
- Serum Bilirubin as a Prognostic Factor in Lung Cancer.Diagnostics (Basel, Switzerland) · 2026Article
- Article
- Sex-Specific Associations of Total Bilirubin, ALBI, and PALBI with Lung Cancer Risk: Interactions with Smoking and Alcohol.Healthcare (Basel, Switzerland) · 2025Article
- Association Between Creatinine and Lung Cancer Risk in Men Smokers: A Comparative Analysis with Antioxidant Biomarkers from the KCPS-II Cohort.Antioxidants (Basel, Switzerland) · 2025Article
- Albumin-bilirubin score: a promising predictor of postoperative distant metastasis in patients with colorectal cancer.Biomarkers in medicine · 2025Article
- Bilirubin metabolism in relation to cancer.Frontiers in oncology · 2025Review
- Article
- Association between depression and liver function biomarkers among US cancer survivors in NHANES 2005-2020.Scientific reports · 2024Article
- Mendelian randomization study of the relationship between blood and urine biomarkers and lung cancer.Frontiers in oncology · 2024Article
- Interplay Of Serum Bilirubin and Tobacco Smoking with Lung and Head and Neck Cancers in a Diverse, EHR-linked Los Angeles Biobank.medRxiv : the preprint server for health sciences · 2023Article
- Heritable Traits and Lung Cancer Risk: A Two-Sample Mendelian Randomization Study.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2023Article
- Genetics of Plasma Bilirubin and Associations between Bilirubin and Cardiometabolic Risk Profiles in Danish Children and Adolescents.Antioxidants (Basel, Switzerland) · 2023Article
- The value of blood-based measures of liver function and urate in lung cancer risk prediction: A cohort study and health economic analysis.Cancer epidemiology · 2023Article
- Article
- Effect of bilirubin and Gilbert syndrome on health: cohort analysis of observational, genetic, and Mendelian randomisation associations.BMJ medicine · 2023Article
- Serum bilirubin and kidney function: a Mendelian randomization study.Clinical kidney journal · 2022Article
- Associations of Pre-Diagnostic Serum Levels of Total Bilirubin and Albumin With Lung Cancer Risk: Results From the Southern Community Cohort Study.Frontiers in oncology · 2022Article
- Association Between Serum Total Bilirubin Level and Lung Function Decline in Patients with COPD: Results from a Pooled Study.International journal of chronic obstructive pulmonary disease · 2022Observational
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4 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundModerately raised serum bilirubin levels are associated with lower rates of lung cancer, particularly among smokers. It is not known whether these relationships reflect antioxidant properties or residual confounding.
objectiveThis study aimed to investigate potential causal relationships between serum total bilirubin and lung cancer incidence using one-sample Mendelian randomisation (MR) and UK Biobank.
methodsWe instrumented serum total bilirubin level using two variants (rs887829 and rs4149056) that together explain ~40% of population-level variability and are linked to mild hereditary hyperbilirubinaemia. Lung cancer events occurring after recruitment were identified from national cancer registries. Observational and genetically instrumented incidence rate ratios (IRRs) and rate differences per 10 000 person-years (PYs) by smoking status were estimated.
resultsWe included 377 294 participants (median bilirubin 8.1 μmol/L (IQR 6.4-10.4)) and 2002 lung cancer events in the MR analysis. Each 5 μmol/L increase in observed bilirubin levels was associated with 1.2/10 000 PY decrease (95% CI 0.7 to 1.8) in lung cancer incidence. The corresponding MR estimate was a decrease of 0.8/10 000 PY (95% CI 0.1 to 1.4). The strongest associations were in current smokers where a 5 μmol/L increase in observed bilirubin levels was associated with a decrease in lung cancer incidence of 10.2/10 000 PY (95% CI 5.5 to 15.0) and an MR estimate of 6.4/10 000 PY (95% CI 1.4 to 11.5). For heavy smokers (≥20/day), the MR estimate was an incidence decrease of 23.1/10 000 PY (95% CI 7.3 to 38.9). There was no association in never smokers and no mediation by respiratory function.
conclusionGenetically raised serum bilirubin, common across human populations, may protect people exposed to high levels of smoke oxidants against lung cancers.
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