SynthesisInternational journal of epidemiology2019
Appraising the causal relevance of DNA methylation for risk of lung cancer.
Synthesis in International journal of epidemiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 7 of them syntheses that pooled it.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
44 citing papers in PubMed, 7 syntheses or guidelines pooled it, 78 citations in OpenAlex.
- Associations between immune cell phenotypes and lung cancer subtypes: insights from mendelian randomization analysis.BMC pulmonary medicine · 2024Pooled it
- Pooled it
- Dietary and supplemental intake of vitamins C and E is associated with altered DNA methylation in an epigenome-wide association study meta-analysis.Epigenetics · 2023Pooled it
- Epigenome-wide DNA methylation in externalizing behaviours: A review and combined analysis.Neuroscience and biobehavioral reviews · 2023Pooled it
- Methylome-wide association study of antidepressant use in Generation Scotland and the Netherlands Twin Register implicates the innate immune system.Molecular psychiatry · 2022Pooled it
- Systematic review of Mendelian randomization studies on risk of cancer.BMC medicine · 2022Pooled it
- A cell-type deconvolution meta-analysis of whole blood EWAS reveals lineage-specific smoking-associated DNA methylation changes.Nature communications · 2020Pooled it
- Blood-based DNA methylation marker model for short-term and long-term lung cancer risk prediction.BMC medicine · 2026Article
- DNA methylation-based clocks, tobacco smoking, and lung cancer risk.BMC medicine · 2025Article
- Associations between lipids and lung cancer subtypes.Discover oncology · 2025Article
- IARC Workshop on the Key Characteristics of Carcinogens: Assessment of End Points for Evaluating Mechanistic Evidence of Carcinogenic Hazards.Environmental health perspectives · 2025Article
- Integrated genetic and epigenetic analyses uncovered GLP1R association with metabolically healthy obesity.International journal of obesity (2005) · 2024Article
- A novel hypothesis-generating approach for detecting phenotypic associations using epigenetic data.Epigenomics · 2024Article
- Blood-based DNA methylation markers for lung cancer prediction.BMJ oncology · 2024Article
- Exploring the cross-cancer effect of smoking and its fingerprints in blood DNA methylation on multiple cancers: A Mendelian randomization study.International journal of cancer · 2023Article
- Smoking, blood DNA methylation sites and lung cancer risk.Environmental pollution (Barking, Essex : 1987) · 2023Article
- Blood LeukocyteCancer research communications · 2023Article
- Article
- A generalization of moderated statistics to data adaptive semiparametric estimation in high-dimensional biology.Statistical methods in medical research · 2023Article
- The Association of Methylation Level in thePharmacogenomics and personalized medicine · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
27 authors at 13 institutions in 10 countries.
Funding
Abstract
backgroundDNA methylation changes in peripheral blood have recently been identified in relation to lung cancer risk. Some of these changes have been suggested to mediate part of the effect of smoking on lung cancer. However, limitations with conventional mediation analyses mean that the causal nature of these methylation changes has yet to be fully elucidated.
methodsWe first performed a meta-analysis of four epigenome-wide association studies (EWAS) of lung cancer (918 cases, 918 controls). Next, we conducted a two-sample Mendelian randomization analysis, using genetic instruments for methylation at CpG sites identified in the EWAS meta-analysis, and 29 863 cases and 55 586 controls from the TRICL-ILCCO lung cancer consortium, to appraise the possible causal role of methylation at these sites on lung cancer.
resultsSixteen CpG sites were identified from the EWAS meta-analysis [false discovery rate (FDR) < 0.05], for 14 of which we could identify genetic instruments. Mendelian randomization provided little evidence that DNA methylation in peripheral blood at the 14 CpG sites plays a causal role in lung cancer development (FDR > 0.05), including for cg05575921-AHRR where methylation is strongly associated with both smoke exposure and lung cancer risk.
conclusionsThe results contrast with previous observational and mediation analysis, which have made strong claims regarding the causal role of DNA methylation. Thus, previous suggestions of a mediating role of methylation at sites identified in peripheral blood, such as cg05575921-AHRR, could be unfounded. However, this study does not preclude the possibility that differential DNA methylation at other sites is causally involved in lung cancer development, especially within lung tissue.
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Registered trials
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.