廣島 健三

It is well known that chronic obstructive pulmonary disease (COPD) is a significant risk factor for lung cancer. Approximately 1% of COPD patients develop lung cancer every year, which may be associated with genetic susceptibility to cigarette smoke. Chronic inflammation caused by toxic gases can induce COPD and lung cancer. Inflammatory mediators may promote the growth of bronchioalveolar stem cells, and activation of nuclear factor-κB and signal transducer and activator of transcription 3 play crucial roles in the development of lung cancer from COPD. Low-dose computed tomography (LDCT) is an effective procedure for the early detection of lung cancer in high-risk patients. However, determining which patients should be screened for lung cancer in a primary care setting is difficult. In this article, we review the epidemiology and aetiology of lung cancer associated with COPD, verify the efficacy of lung cancer screening by LDCT, and discuss the importance of early detection of COPD for lung cancer surveillance. We propose that, for the prevention of both diseases, COPD screening in smokers should be initiated as early as possible, so they can stop smoking and so that candidates for an efficient lung cancer screening programme can be identified. Copyright©ERS 2012.

Objective. The Wnt and EGFR signaling pathways play crucial roles in the pathogenesis of a variety of malignant tumors. While the details of each cascade are understood, very little is known about their collective effects in non-small cell lung cancer (NSCLC). Methods. A total of 238 NSCLC samples were examined for methylation of Wnt antagonists (sFRP-1, sFRP-2, sFRP-5, Wif-1, Dkk-3) and for EGFR and KRAS mutations. Protein expression levels of β-catenin were assayed in 91 of the 238 NSCLCs. Results. We found that (a) aberrant methylation of Wnt antagonists is common in NSCLCs (b) methylation of sFRP-2 is more prevalent in females, non-smokers, and adenocarcinoma cases (c) there is a positive correlation between activated EGFR mutation and nuclear accumulation of β-catenin (d) KRAS mutation and aberrant methylation of Wnt antagonists are positively correlated and (e) EGFR mutation is significantly associated with a good prognosis in tumors lacking methylated Wnt antagonist genes. Conclusion. These results contribute to a better understanding of the cross-talk between the Wnt and EGFR signaling pathways, and help foster development of chemotherapeutic treatments in NSCLCs. © 2009 The Japan Lung Cancer Society.