ArticleCancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology2022
Circulating Isovalerylcarnitine and Lung Cancer Risk: Evidence from Mendelian Randomization and Prediagnostic Blood Measurements.
Article in Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it, 14 citations in OpenAlex.
- Causal relationships of metabolites with allergic diseases: a trans-ethnic Mendelian randomization study.Respiratory research · 2024Pooled it
- Associations between Metabolomic Signatures of Persistent Smoking Effects and Lung Cancer Risk among Former Smokers.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2026Article
- Public Transcriptomic Data Mining for SCLC: From Candidate Ma rkers to Therapeutic Exploration.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Article
- Linking Processed and Red Meat Consumption to Specific Lung Cancer Subtypes: A Mendelian Randomization Analysis.Current pharmaceutical biotechnology · 2026Article
- Article
- Unveiling the endocrine connections of NAFLD: evidence from a comprehensive mendelian randomization study.Biomedical engineering letters · 2025Article
- Identifying therapeutic targets for cancer among 2074 circulating proteins and risk of nine cancers.Nature communications · 2024Article
- What Can Current Biomarker Data Tell Us About the Risks of Lung Cancer Posed by Heated Tobacco Products?Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2024Article
- Article
- Development and internal validation of nomograms based on plasma metabolites to predict non-small cell lung cancer risk in smoking and nonsmoking populations.Thoracic cancer · 2023Article
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Authors and funding
33 authors at 19 institutions in 9 countries.
Funding
Abstract
backgroundTobacco exposure causes 8 of 10 lung cancers, and identifying additional risk factors is challenging due to confounding introduced by smoking in traditional observational studies. MATERIALS AND
methodsWe used Mendelian randomization (MR) to screen 207 metabolites for their role in lung cancer predisposition using independent genome-wide association studies (GWAS) of blood metabolite levels (n = 7,824) and lung cancer risk (n = 29,266 cases/56,450 controls). A nested case-control study (656 cases and 1,296 matched controls) was subsequently performed using prediagnostic blood samples to validate MR association with lung cancer incidence data from population-based cohorts (EPIC and NSHDS).
resultsAn MR-based scan of 207 circulating metabolites for lung cancer risk identified that blood isovalerylcarnitine (IVC) was associated with a decreased odds of lung cancer after accounting for multiple testing (log10-OR = 0.43; 95% CI, 0.29-0.63). Molar measurement of IVC in prediagnostic blood found similar results (log10-OR = 0.39; 95% CI, 0.21-0.72). Results were consistent across lung cancer subtypes.
conclusionsIndependent lines of evidence support an inverse association of elevated circulating IVC with lung cancer risk through a novel methodologic approach that integrates genetic and traditional epidemiology to efficiently identify novel cancer biomarkers. IMPACT: Our results find compelling evidence in favor of a protective role for a circulating metabolite, IVC, in lung cancer etiology. From the treatment of a Mendelian disease, isovaleric acidemia, we know that circulating IVC is modifiable through a restricted protein diet or glycine and L-carnatine supplementation. IVC may represent a modifiable and inversely associated biomarker for lung cancer.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.