Smoking and some genes (e.g., TP53) can alter the microbiome composition of LC patients, and the lung microbiome in turn can alter the expression of signaling pathways (e.g., IL-17, PI3K, MAPK, and ERK pathways) and alter the local immune microenvironment of LC tissues. The gene discussed is TP53; the disease is laryngotracheoesophageal cleft.