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Chronic Obstructive Pulmonary Disease Influence on Lung Cancer Risk Through Blood Metabolite Mediation: A Two-Sample
Yan-Nan Cao1,2, Long Wang1,2, Hu-Sen Fan1,2
1School of Clinical Medicine, Shandong Second Medical University, Weifang, Shandong, People's Republic of China.
Summary
Chronic obstructive pulmonary disease (COPD) increases lung cancer (LC) risk. Blood metabolites, not inflammatory factors, partially mediate this link, revealing key mechanisms in COPD-associated LC development.
Area of Science:
- Genetics and Epidemiology
- Pulmonary Medicine
- Metabolomics
Background:
- Chronic obstructive pulmonary disease (COPD) is linked to increased lung cancer (LC) risk.
- Metabolic and inflammatory pathways are implicated in the COPD-LC relationship.
- Understanding causal links and mediating factors is crucial for prevention and treatment.
Purpose of the Study:
- To investigate the causal relationship between COPD and LC.
- To identify potential mediating roles of blood metabolites and inflammatory factors.
- To explore the directionality of the causal link between COPD and LC.
Main Methods:
- Utilized two-sample and two-step Mendelian randomization (MR) analyses.
- Employed summary data from genome-wide association studies (GWAS).
- Conducted reverse MR and sensitivity analyses (e.g., inverse variance weighted) for robustness.
Main Results:
- Confirmed COPD as a significant risk factor for LC (OR=1.114, P=0.002).
- Identified 113 blood metabolites and six inflammatory factors with nominal causal associations with LC risk.
- Found three blood metabolites (specific glycerophosphocholines and epiandrosterone sulfate) mediate the effect of COPD on LC.
Conclusions:
- COPD is a confirmed risk factor for lung cancer development.
- Specific blood metabolites, but not inflammatory factors, partially mediate the association between COPD and LC.
- Findings elucidate mechanisms linking COPD and LC, highlighting metabolite-driven pathways.
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