Causal influence of gut microbiota on small cell lung cancer: a Mendelian randomization study
Open Access
- 29 April 2024
- journal article
- research article
- Published by Wiley in The Clinical Respiratory Journal
- Vol. 18 (5) , e13764
Abstract
Background: Previous studies have hinted at a significant link between lung cancer and the gut microbiome, yet their causal relationship remains to be elucidated.Methods: GWAS data for small cell lung cancer (SCLC) was extracted from the FinnGen consortium, comprising 179 cases and 218 613 controls. Genetic variation data for 211 gut microbiota were obtained as instrumental variables from MiBioGen. Mendelian randomization (MR) was employed to determine the causal relationship between the two, with inverse variance weighting (IVW) being the primary method for causal analysis. The MR results were validated through several sensitivity analyses.Results: The study identified a protective effect against SCLC for the genus Eubacterium ruminantium group (OR = 0.413, 95% CI: 0.223–0.767, p = 0.00513), genus Barnesiella (OR = 0.208, 95% CI: 0.0640–0.678, p = 0.00919), family Lachnospiraceae (OR = 0.319, 95% CI: 0.107–0.948, p = 0.03979), and genus Butyricimonas (OR = 0.376, 95% CI: 0.144–0.984, p = 0.04634). Conversely, genus Intestinibacter (OR = 3.214, 95% CI: 1.303–7.926, p = 0.01125), genus Eubacterium oxidoreducens group (OR = 3.391, 95% CI: 1.215–9.467, p = 0.01973), genus Bilophila (OR = 3.547, 95% CI: 1.106–11.371, p = 0.03315), and order Bacillales (OR = 1.860, 95% CI: 1.034–3.347, p = 0.03842) were found to potentially promote the onset of SCLC.Conclusion: We identified potential causal relationships between certain gut microbiota and SCLC, offering new insights into microbiome‐mediated mechanisms of SCLC pathogenesis, resistance, mutations, and more.Keywords
This publication has 49 references indexed in Scilit:
- Emerging pathogenic links between microbiota and the gut–lung axisNature Reviews Microbiology, 2016
- Consistent Estimation in Mendelian Randomization with Some Invalid Instruments Using a Weighted Median EstimatorGenetic Epidemiology, 2016
- Detecting pleiotropy in Mendelian randomisation studies with summary data and a continuous outcomeStatistics in Medicine, 2015
- Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regressionInternational Journal of Epidemiology, 2015
- Microbiota Modulate Tumoral Immune Surveillance in Lung through a γδT17 Immune Cell-Dependent MechanismCancer Research, 2014
- Mendelian Randomization Analysis With Multiple Genetic Variants Using Summarized DataGenetic Epidemiology, 2013
- Use of allele scores as instrumental variables for Mendelian randomizationInternational Journal of Epidemiology, 2013
- Lung Cancer in ChinaChest, 2013
- Genomic analysis identifies association of Fusobacterium with colorectal carcinomaGenome Research, 2011
- Evidence That Hydrogen Sulfide Is a Genotoxic AgentMolecular Cancer Research, 2006