SynthesisMedicine2025
Causal validation of the relationship between air pollution and lung cancer: A bidirectional Mendelian randomization study and meta-analysis.
Synthesis in Medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Authors and funding
4 authors.
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Abstract
Recent studies suggest a link between air pollution and lung cancer, but causality remains uncertain due to confounding and reverse causation. Mendelian randomization (MR) reduces such bias and offers a new way to explore this relationship. MR is a method that uses genetic variants as instrumental variables to assess the causal relationship between an exposure and an outcome, effectively controlling for confounding and reverse causation. The inverse-variance weighted method is a commonly used approach in MR analysis, which estimates the overall causal effect by weighting the effect ratios of multiple single nucleotide polymorphisms, assuming all instruments are valid. Based on 2-sample MR, this study incorporated 5 air pollution indices and conducted MR analyses with lung cancer outcome data from 2 different sources. Subsequently, a meta-analysis was performed on the primary inverse-variance weighted results, followed by multiple corrections of the thresholds after the meta-analysis to ensure accuracy. Finally, reverse causality was tested through MR analysis for air pollution indices significantly associated with lung cancer. And the selection criteria for instrumental variables were: P < 5 × 10⁻⁶, F > 10, minor allele frequency > 0.01, clump_kb = 10,000, and clump_r2 = 0.001. Five air pollution indices were analyzed using MR analysis and meta-analysis with lung cancer data from the FinnGen R12 and OpenGWAS databases. Multiple corrections were applied to the significance threshold results after the meta-analysis. The final results showed that only nitrogen dioxide (NO₂) exhibited a significant association, with an OR of 3.426 (95% CI: 1.897-6.186, P = 2.21 × 10⁻⁴). Additionally, the positive air pollution index NO₂ showed no evidence of reverse causality with lung cancer from either data source. This study demonstrates a significant causal association between NO₂ and lung cancer, indicating that NO₂ may be a potential risk factor for lung cancer.
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