Pathogenesis of Lung Cancer with Chronic Obstructive Pulmonary Disease

━━ The greatest risk factor for chronic obstructive pulmonary disease (COPD) is a smoking habit, and the prevalence of COPD has been reported to be 8.6% among adults (cid:2) 40 years old in Japan. In addition, the annual incidence rate of lung cancer in patients with COPD was reported to be 1%. The degree of cellular dyspla-sia observed by bronchial endoscopy in patients with COPD increases as the respiratory function decreases. In addition, microsatellite instability was reported to be frequently observed in the sputum of COPD patients. Therefore, it is assumed that gene mutations are likely to occur in the airways of COPD patients. Although the loss of the DNA repair capacity is assumed to be the mechanism underlying the increased incidence of lung cancer in COPD patients, the genes associated with the DNA repair process have not been reported as involved in the risk of COPD in genome-wide association analyses. Chronic inflammation causes carcinogenesis in many dis-eases. COPD is a chronic inflammatory disease of the airways. In an epigenome-wide association analysis, methylation of SOCS3, which is a factor related to the JAK-STAT pathway, was reportedly associated with COPD, and this methylation may be linked to the sustained inflammation observed in patients with COPD. Canakinumab is an antibody against interleukin-1 β . Surprisingly, canakinumab significantly suppressed the incidence of lung cancer in a clinical trial (CANTOS). In addition, some cohort studies have shown that inhaled corticosteroids suppressed the lung cancer incidence in COPD patients. Such clinical evidence strongly suggests that chronic airway inflammation is associated with lung cancer development in COPD patients. 2019;59:447-452)