Abstract
Chronic obstructive pulmonary disease (COPD) and lung cancer are closely related. The annual incidence of lung cancer arising from COPD has been reported to be 0.8–1.7 %. Treatment of lung cancer from COPD is very difficult due to low cardiopulmonary function, rapid tumor growth, and resistance to molecularly targeted therapies. Chronic inflammation caused by toxic gases can induce COPD and lung cancer. Carcinogenesis in the inflammatory microenvironment occurs during cycles of tissue injury and repair. Cellular damage can induce induction of necrotic cell death and loss of tissue integrity. Quiescent normal stem cells or differentiated progenitor cells are introduced to repair injured tissues. However, inflammatory mediators may promote the growth of bronchioalveolar stem cells, and activation of NF-κB and signal transducer and activator of transcription 3 (STAT3) play crucial roles in the development of lung cancer from COPD. Many of the protumorgenic effects of NF-κB and STAT3 activation in immune cells are mediated through paracrine signaling. NF-κB and STAT3 also contribute to epithelial–mesenchymal transition. To improve lung cancer treatment outcomes, lung cancer from COPD must be overcome. In this article, we review the characteristics of lung cancer from COPD and the mechanisms of carcinogenesis in the inflammatory microenvironment. We also propose the necessity of identifying the mechanisms underlying progression of COPD to lung cancer, and comment on the clinical implications with respect to lung cancer prevention, screening, and therapy.
Similar content being viewed by others
References
The top 10 causes of death, programmes and projects in World Health Organization (WHO). http://www.who.int/mediacentre/factsheets/fs310/en/index.html updated: 5 Jan 2014.
Koshiol J, Rotunno M, Consonni D, Pesatori AC, De Matteis S, Goldstein AM, et al. Chronic obstructive pulmonary disease and altered risk of lung cancer in a population-based case-control study. PLoS One. 2009; 4: e7380. http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0007380 updated: 5 Jan 2014.
Turner MC, Chen Y, Krewski D, Calle EE, Thun MJ. Chronic obstructive pulmonary disease is associated with lung cancer mortality in a prospective study of never smokers. Am J Respir Crit Care Med. 2007;176:285–90.
Sekine Y, Katsura H, Koh E, Hiroshima K, Fujisawa T. Early detection of COPD is important for lung cancer surveillance. Eur Respir J. 2012;39(5):1230–40.
Young RP, Hopkins RJ, Christmas T, Black PN, Metcalf P, Gamble GD. COPD prevalence is increased in lung cancer, independent of age, sex and smoking history. Eur Respir J. 2009;34:380–6.
Wilson DO, Weissfeld JL, Balkan A, Schragin JG, Fuhrman CR, Fisher SN, et al. Association of radiographic emphysema and airflow obstruction with lung cancer. Am J Respir Crit Care Med. 2008;178:738–44.
Congleton J, Muers MF. The incidence of airflow obstruction in bronchial carcinoma, its relation to breathlessness, and response to bronchodilator therapy. Respir Med. 1995;89:291–6.
Kurishima K, Satoh H, Ishikawa H, Yamashita YT, Homma T, Ohtsuka M, et al. Lung cancer patients with chronic obstructive pulmonary disease. Oncol Rep. 2001;8:63–5.
Tockman MS, Anthonisen NR, Wright EC, Donithan MG. Airways obstruction and the risk for lung cancer. Ann Intern Med. 1987;106:512–8.
Vineis P, Airoldi L, Veglia F, Olgiati L, Pastorelli R, Autrup H, et al. Environmental tobacco smoke and risk of respiratory cancer and chronic obstructive pulmonary disease in former smokers and never smokers in the EPIC prospective study. BMJ. 2005;330:277.
de Torres JP, Marín JM, Casanova C, Cote C, Carrizo S, Cordoba-Lanus E, et al. Lung cancer in patients with chronic obstructive pulmonary disease–incidence and predicting factors. Am J Respir Crit Care Med. 2011;184(8):913–9.
Sin DD, Anthonisen NR, Soriano JB, Agusti AG. Mortality in COPD: role of comorbidities. Eur Respir J. 2006;28:1245–57.
Sekine Y, Fujisawa T, Suzuki K, Tsutatani S, Kubota K, Ikegami H, et al. Detection of chronic obstructive pulmonary disease in community-based annual lung cancer screening: Chiba COPD lung cancer screening study group. Respirology. 2014;19(1):98–104.
Mannino DM, Aguayo SM, Petty TL, Redd SC. Low lung function and incident lung cancer in the United States: data from the first National Health and Nutrition Examination Survey follow-up. Arch Intern Med. 2003;163:1475–80.
Calabrò E, Randi G, La Vecchia C, Sverzellati N, Marchianò A, Villani M, et al. Lung function predicts lung cancer risk in smokers: a tool for targeting screening programmes. Eur Respir J. 2010;35:146–51.
Spitz MR, Wei Q, Dong Q, Amos CI, Wu X. Genetic susceptibility to lung cancer: the role of DNA damage and repair. Cancer Epidemiol Biomark Prev. 2003;12:689–98.
Cohen BH. Chronic obstructive pulmonary disease: a challenge in genetic epidemiology. Am J Epidemiol. 1980;112:274–88.
Coté ML, Kardia SL, Wenzlaff AS, Ruckdeschel JC, Schwartz AG. Risk of lung cancer among white and black relatives of individuals with early-onset lung cancer. JAMA. 2005;293:3036–42.
Schwartz AG, Ruckdeschel JC. Familial lung cancer: genetic susceptibility and relationship to chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2006;173:16–22.
Sekine Y, Suzuki H, Yamada Y, Koh E, Yoshino I. Severity of chronic obstructive pulmonary disease and its relationship to lung cancer prognosis after surgical resection. Thorac Cardiovasc Surg. 2013;61(2):124–30.
Kondo R, Yoshida K, Eguchi T, Kobayashi N, Saito G, Hamanaka K, et al. Clinical features of lung cancer in smokers with light and mild chronic obstructive pulmonary disease: a retrospective analysis of Japanese surgical cases. Eur J Cardiothorac Surg. 2011;40(6):1439–43.
Sekine Y, Kesler KA, Behnia M, Brooks-Brunn JA, Sekine E, Brown JW. COPD may increases the incidence of refractory supraventricular arrhythmias following pulmonary resection for non-small cell lung cancer. Chest. 2001;120:1783–90.
Sekine Y, Behnia M, Fujisawa T. Impact of COPD on pulmonary complications and long term survival in patients with surgical treatment for NSCLC. Lung Cancer. 2002;37:95–101.
Sekine Y, Yamada Y, Chiyo M, Iwata T, Nakajima T, Yasufuku K, et al. Association of chronic obstructive pulmonary disease and tumor recurrence in patients with stage IA lung cancer after complete resection. Ann Thorac Surg. 2007;84:946–50.
Nakajima T, Sekine Y, Yamada Y, Suzuki H, Yasufuku K, Yoshida S, et al. Long-term surgical outcome in patients with lung cancer and coexisting severe COPD. Thorac Cardiovasc Surg. 2009;57:339–42.
Sekine Y, Sakairi Y, Yoshino M, Koh E, Hata A, Suzuki H, et al. The impact of combined pulmonary fibrosis and chronic obstructive pulmonary disease on long-term survival after lung cancer surgery. Thorac Cardiovasc Surg. 2014 (in press). doi: 10.1055/s-0033-1363478.
Sekine Y, Chiyo M, Iwata T, Yasufuku K, Furukawa S, Iizasa T, et al. Perioperative rehabilitation and physiotherapy for lung cancer patients with chronic obstructive pulmonary disease. Jpn J Thorac Cardiovasc Surg. 2005;53:237–43.
Suzuki H, Sekine Y, Nakajima T, Yasufuku K, Yoshida S, Suzuki M, et al. Efficacy of peri-operative administration of long-acting bronchodilator on post-operative pulmonary function and quality of life in lung cancer patients with chronic obstructive pulmonary disease—preliminary results of a randomized control study. Surgery Today. 2010;40:923–30.
Sekine Y, Iwata T, Chiyo M, Yasufuku K, Motohashi S, Yoshida S, et al. Minimal alteration of pulmonary function after lobectomy in lung cancer patients with COPD. Ann Thorac Surg. 2003;76:356–61.
Yamada Y, Sekine Y, Suzuki H, Iwata T, Chiyo M, Nakajima T, et al. Trends of bacterial colonisation and the risk of postoperative pneumonia in lung cancer patients with chronic obstructive pulmonary disease. Eur J Cardiothorac Surg. 2010;37:752–7.
Sekine Y, Koh E, Oishi H, Miwa M. A simple and effective technique for identification of intersegmental planes by infrared thoracoscopy after transbronchial injection of indocianine green. J Thorac Cardiovasc Surg. 2012;143(6):1330–5.
Nakao M, Yoshida J, Goto K, Ishii G, Kawase A, Aokage K, et al. Long-term outcomes of 50 cases of limited-resection trial for pulmonary ground-glass opacity nodules. J Thorac Oncol. 2012;7(10):1563–6.
Brody JS, Spira A. State of the art. Chronic obstructive pulmonary disease, inflammation, and lung cancer. Proc Am Thorac Soc. 2006;3(6):535–7.
Adcock IM, Caramori G, Barnes PJ. Chronic obstructive pulmonary disease and lung cancer: new molecular insights. Respiration. 2011;81(4):265–84.
Weiss J, Sos ML, Seidel D, Peifer M, Zander T, Heuckmann JM, et al. Frequent and focal FGFR1 amplification associates with therapeutically tractable FGFR1 dependency in squamous cell lung cancer. Sci Transl Med. 2010;2(62):62ra93.
Vermaelen K, Brusselle G. Exposing a deadly alliance: novel insights into the biological links between COPD and lung cancer. Pulm Pharmacol Ther. 2013;26(5):544–54.
Houghton AM, Mouded M, Shapiro SD. Common origins of lung cancer and COPD. Nat Med. 2008;14:1023–4.
Kim CF, Jackson EL, Woolfenden AE, Lawrence S, Babar I, Vogel S, et al. Identification of bronchioalveolar stem cells in normal lung and lung cancer. Cell. 2005;121:823–35.
Kratz JR, Yagui-Beltrán A, Jablons DM. Cancer stem cells in lung tumorigenesis. Ann Thorac Surg. 2010;89(6):S2090–5.
Alamgeer M, Peacock CD, Matsui W, Ganju V, Watkins DN. Cancer stem cells in lung cancer: evidence and controversies. Respirology. 2013;18(5):757–64.
Grivennikov SI, Karin M. Dangerous liaisons: STAT3 and NF-kappaB collaboration and crosstalk in cancer. Cytokine Growth Factor Rev. 2010;21(1):11–9.
Castaño Z, Fillmore CM, Kim CF, McAllister SS. The bed and the bugs: interactions between the tumor microenvironment and cancer stem cells. Semin Cancer Biol. 2012;22(5–6):462–70.
Young RP, Hopkins RJ. How the genetics of lung cancer may overlap with COPD. Respirology. 2011;16(7):1047–55.
Acknowledgments
This work was supported by a grant-in-aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan to Y. Sekine (No. 23592075).
Conflict of interest
All authors have declared no conflicts of interest.
Author information
Authors and Affiliations
Corresponding author
Additional information
This review was submitted at the invitation of the editorial committee.
Rights and permissions
About this article
Cite this article
Sekine, Y., Hata, A., Koh, E. et al. Lung carcinogenesis from chronic obstructive pulmonary disease: characteristics of lung cancer from COPD and contribution of signal transducers and lung stem cells in the inflammatory microenvironment. Gen Thorac Cardiovasc Surg 62, 415–421 (2014). https://doi.org/10.1007/s11748-014-0386-x
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11748-014-0386-x