Interplay of Chronic Obstructive Pulmonary Disease and Colorectal Cancer Development: Unravelling the Mediating Role of Fatty Acids through a Comprehensive Multi-Omics Analysis

Abstract

Background: Chronic obstructive pulmonary disease (COPD) patients often exhibit gastrointestinal symptoms, and COPD is potentially associated with colorectal cancer (CRC). Methods: We collected COPD and CRC data from the National Health and Nutrition Examination Survey, genome-wide association studies, and RNA sequence for a comprehensive analysis. We used weighted logistic regression to explore the association between COPD and CRC incidence risk. Mendelian randomization analysis was performed to assess the causal relationship between COPD and CRC, and cross-phenotype meta-analysis was conducted to pinpoint crucial loci. Multivariable mendelian randomization was used to uncover mediating factors connecting the two diseases. Our results were validated using both NHANES and GEO databases. Results: In the NHANES dataset, we found that COPD serves as a contributing factor in the development of CRC. MR analysis revealed that COPD increased the risk of CRC onset and progression (OR: 1.16, 95% CI: 1.01–1.36). Cross-phenotype meta-analysis identified four critical genes associated with both CRC and COPD. Multivariable mendelian randomization results indicated that body fat percentage, omega-3, omega-6, and the omega-3 to omega-6 ratio may be mediating factors impacting both CRC and COPD; these findings were confirmed in the NHANES dataset. In the RNA expression data for COPD and CRC, weighted gene co-expression network analysis and Kyoto Encyclopedia of Genes and Genomes enrichment results demonstrated a strong correlation between fatty acid–related modules in both diseases. Conclusions: Our findings suggest that COPD may contribute to an elevated risk of CRC development through fatty acid–related pathways.