慢性阻塞性肺疾病（COPD）患者常常表现出胃肠道症状，已经指出了COPD与结直肠癌（CRC）之间的潜在关联，需要进一步研究。本研究从全美国家健康与营养调查(NHANES)、全基因组关联研究和RNA测序数据中收集了COPD和CRC数据，进行了全面分析。我们采用加权逻辑回归模型来探索COPD与CRC发生风险之间的关联关系。Mendelian随机化分析用于评估COPD与CRC之间的因果关系，而交叉表型元分析则用于确定关键位点。多变量Mendelian随机化用于发现连接两种疾病的中介因素。我们的结果在NHANES和GEO数据库上进行了验证。在对NHANES数据集的分析中，我们发现COPD是导致CRC发展的显著因素。MR分析揭示COPD增加了CRC发生和进展的风险（OR：1.16，95% CI 1.01-1.36）。交叉表型元分析确定了与CRC和COPD都有关的四个关键基因。多变量Mendelian随机化表明，在COPD和CRC两种疾病中，体脂肪百分比、ω-3、ω-6和ω-3/ω-6比值可能是潜在的中介因素，这一结果与NHANES数据集一致。此外，使用RNA表达数据，通过加权基因共表达网络分析和Kyoto基因和基因组百科全书富集结果证明了COPD与CRC之间脂肪酸相关模块的相互关系。本研究为COPD和CRC之间的相互作用提供了新的见解，突出了COPD对CRC发展的潜在影响。识别与脂肪酸代谢相关的共享基因和中介因素深化了我们对连接这两种疾病的潜在机制的理解。© 2023. 由Springer Nature的BioMed Central Ltd.发布。

Chronic obstructive pulmonary disease (COPD) patients often exhibit gastrointestinal symptoms, A potential association between COPD and Colorectal Cancer (CRC) has been indicated, warranting further examination.In this study, 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.In our analysis of the NHANES dataset, we identified COPD as a significant contributing factor to CRC development. 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 suggested body fat percentage, omega-3, omega-6, and the omega-3 to omega-6 ratio as potential mediating factors for both diseases, a finding consistent with the NHANES dataset. Further, the interrelation between fatty acid-related modules in COPD and CRC was demonstrated via weighted gene co-expression network analysis and Kyoto Encyclopedia of Genes and Genomes enrichment results using RNA expression data.This study provides novel insights into the interplay between COPD and CRC, highlighting the potential impact of COPD on the development of CRC. The identification of shared genes and mediating factors related to fatty acid metabolism deepens our understanding of the underlying mechanisms connecting these two diseases.© 2023. BioMed Central Ltd., part of Springer Nature.