Abstract
Both chronic obstructive pulmonary disease (COPD) and lung cancer are major causes of death worldwide. In most cases this reflects cigarette smoke exposure which is able to induce an inflammatory response in the airways of smokers. Indeed, COPD is characterized by lower airway inflammation, and importantly, the presence of COPD is by far the greatest risk factor for lung cancer amongst smokers. Cigarette smoke induces the release of many inflammatory mediators and growth factors including TGF-β, EGFR, IL-1, IL-8 and G-CSF through oxidative stress pathways and this inflammation may persist for decades after smoking cessation. Mucus production is also increased by these inflammatory mediators, further linking airway inflammation to an important mechanism of lung cancer. A greater understanding of the molecular and cellular pathobiology that distinguishes smokers with lung cancer from smokers with and without COPD is needed to unravel the complex molecular interactions between COPD and lung cancer. By understanding the common signalling pathways involved in COPD and lung cancer the hope is that treatments will be developed that not only treat the underlying disease process in COPD, but also reduce the currently high risk of developing lung cancer in these patients.
Journal Section:
Editor's choice
References
1.
National Institutes of Health, National Heart, Lung and Blood Institute. Global Initiative for Chronic Obstructive Lung Disease (GOLD): Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease. NHLBI/WHO workshop report. NIH Publication No 2701A, March 2001. www goldcopd com (accessibility verified May 15, 2010).
2.
Salvi SS, Barnes PJ: Chronic obstructive pulmonary disease in non-smokers. Lancet 2009;374:733–743.
[PubMed]
3.
Lopez AD, Mathers CD, Ezzati M, Jamison DT, Murray CJ: Global and regional burden of disease and risk factors, 2001: systematic analysis of population health data. Lancet 2006;367:1747–1757.
[PubMed]
4.
Sin DD, Man SF: Systemic inflammation and mortality in chronic obstructive pulmonary disease. Can J Physiol Pharmacol 2007;85:141–147.
[PubMed]
5.
Ben-Zaken CS, Pare PD, Man SF, Sin DD: The growing burden of chronic obstructive pulmonary disease and lung cancer in women: examining sex differences in cigarette smoke metabolism. Am J Respir Crit Care Med 2007;176:113–120.
[PubMed]
6.
Mannino DM: Epidemiology and global impact of chronic obstructive pulmonary disease. Semin Respir Crit Care Med 2005;26:204–210.
[PubMed]
7.
Punturieri A, Szabo E, Croxton TL, Shapiro SD, Dubinett SM: Lung cancer and chronic obstructive pulmonary disease: needs and opportunities for integrated research. J Natl Cancer Inst 2009;101:554–559.
[PubMed]
8.
Purdue MP, Gold L, Jarvholm B, Alavanja MC, Ward MH, Vermeulen R: Impaired lung function and lung cancer incidence in a cohort of Swedish construction workers. Thorax 2007;62:51–56.
[PubMed]
9.
Tockman MS, Anthonisen NR, Wright EC, Donithan MG: Airways obstruction and the risk for lung cancer. Ann Intern Med 1987;106:512–518.
[PubMed]
10.
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;34:380–386.
[PubMed]
11.
Wasswa-Kintu S, Gan WQ, Man SF, Pare PD, Sin DD: Relationship between reduced forced expiratory volume in one second and the risk of lung cancer: a systematic review and meta-analysis. Thorax 2005;60:570–575.
[PubMed]
12.
Seibold MA, Schwartz DA: The lung: the natural boundary between nature and nurture. Annu Rev Physiol 2010, E-pub ahead of print.
13.
Schwartz DA: Epigenetics and environmental lung disease. Proc Am Thorac Soc 2010;7:123–125.
[PubMed]
14.
Abidoye O, Ferguson MK, Salgia R: Lung carcinoma in African Americans. Nat Clin Pract Oncol 2007;4:118–129.
[PubMed]
15.
Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ: Cancer statistics, 2009. CA Cancer J Clin 2009;59:225–249.
[PubMed]
16.
Youlden DR, Cramb SM, Baade PD: The international epidemiology of lung cancer: geographical distribution and secular trends. J Thorac Oncol 2008;3:819–831.
[PubMed]
17.
Egleston BL, Meireles SI, Flieder DB, Clapper ML: Population-based trends in lung cancer incidence in women. Semin Oncol 2009;36:506–515.
[PubMed]
18.
Scagliotti GV, Longo M, Novello S: Nonsmall cell lung cancer in never smokers. Curr Opin Oncol 2009;21:99–104.
[PubMed]
19.
Anthonisen NR, Skeans MA, Wise RA, Manfreda J, Kanner RE, Connett JE: The effects of a smoking cessation intervention on 14.5-year mortality: a randomized clinical trial. Ann Intern Med 2005;142:233–239.
[PubMed]
20.
Yao H, Rahman I: Current concepts on the role of inflammation in COPD and lung cancer. Curr Opin Pharmacol 2009;9:375–383.
[PubMed]
21.
Molina JR, Yang P, Cassivi SD, Schild SE, Adjei AA: Non-small cell lung cancer: epidemiology, risk factors, treatment, and survivorship. Mayo Clin Proc 2008;83:584–594.
[PubMed]
22.
Papi A, Casoni G, Caramori G, Guzzinati I, Boschetto P, Ravenna F, Calia N, Petruzzelli S, Corbetta L, Cavallesco G, Forini E, Saetta M, Ciaccia A, Fabbri LM: COPD increases the risk of squamous histological subtype in smokers who develop non-small cell lung carcinoma. Thorax 2004;59:679–681.
[PubMed]
23.
Janssen-Heijnen ML, Coebergh JW: Trends in incidence and prognosis of the histological subtypes of lung cancer in North America, Australia, New Zealand and Europe. Lung Cancer 2001;31:123–137.
[PubMed]
24.
Carney DN: Lung cancer – time to move on from chemotherapy. N Engl J Med 2002;346:126–128.
[PubMed]
25.
Parkin DM, Bray F, Ferlay J, Pisani P: Global cancer statistics, 2002. CA Cancer J Clin 2005;55:74–108.
[PubMed]
26.
Hogg JC, Chu F, Utokaparch S, Woods R, Elliott WM, Buzatu L, Cherniack RM, Rogers RM, Sciurba FC, Coxson HO, Pare PD: The nature of small-airway obstruction in chronic obstructive pulmonary disease. N Engl J Med 2004;350:2645–2653.
[PubMed]
27.
Chung KF, Adcock IM: Multifaceted mechanisms in COPD: inflammation, immunity, and tissue repair and destruction. Eur Respir J 2008;31:1334–1356.
[PubMed]
28.
Hogg JC: Pathophysiology of airflow limitation in chronic obstructive pulmonary disease. Lancet 2004;364:709–721.
[PubMed]
29.
Barnes PJ: Alveolar macrophages in chronic obstructive pulmonary disease (COPD). Cell Mol Biol (Noisy-le-grand) 2004;50 Online Pub: OL627–OL637.
30.
Barnes PJ: Medicine. Neutrophils find smoke attractive. Science 2010;330:40–41.
[PubMed]
31.
Lacoste JY, Bousquet J, Chanez P, Van Vyve T, Simony-Lafontaine J, Lequeu N, Vic P, Enander I, Godard P, Michel FB: Eosinophilic and neutrophilic inflammation in asthma, chronic bronchitis, and chronic obstructive pulmonary disease. J Allergy Clin Immunol 1993;92:537–548.
[PubMed]
32.
Linden M, Rasmussen JB, Piitulainen E, Tunek A, Larson M, Tegner H, Venge P, Laitinen LA, Brattsand R: Airway inflammation in smokers with nonobstructive and obstructive chronic bronchitis. Am Rev Respir Dis 1993;148:1226–1232.
[PubMed]
33.
Fujimoto K, Kubo K, Yamamoto H, Yamaguchi S, Matsuzawa Y: Eosinophilic inflammation in the airway is related to glucocorticoid reversibility in patients with pulmonary emphysema. Chest 1999;115:697–702.
[PubMed]
34.
Panzner P, Lafitte JJ, Tsicopoulos A, Hamid Q, Tulic MK: Marked up-regulation of T lymphocytes and expression of interleukin-9 in bronchial biopsies from patients with chronic bronchitis with obstruction. Chest 2003;124:1909–1915.
[PubMed]
35.
Lams BE, Sousa AR, Rees PJ, Lee TH: Immunopathology of the small-airway submucosa in smokers with and without chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1998;158:1518–1523.
[PubMed]
36.
Chanez P, Vignola AM, O’Shaugnessy T, Enander I, Li D, Jeffery PK, Bousquet J: Corticosteroid reversibility in COPD is related to features of asthma. Am J Respir Crit Care Med 1997;155:1529–1534.
[PubMed]
37.
Pizzichini E, Pizzichini MM, Gibson P, Parameswaran K, Gleich GJ, Berman L, Dolovich J, Hargreave FE: Sputum eosinophilia predicts benefit from prednisone in smokers with chronic obstructive bronchitis. Am J Respir Crit Care Med 1998;158:1511–1517.
[PubMed]
38.
Fujimoto K, Kubo K, Yamamoto H, Yamaguchi S, Matsuzawa Y: Eosinophilic inflammation in the airway is related to glucocorticoid reversibility in patients with pulmonary emphysema. Chest 1999;115:697–702.
[PubMed]
39.
O’Shaughnessy TC, Ansari TW, Barnes NC, Jeffery PK: Inflammation in bronchial biopsies of subjects with chronic bronchitis: inverse relationship of CD8+ T lymphocytes with FEV1. Am J Respir Crit Care Med 1997;155:852–857.
[PubMed]
40.
van der Strate BW, Postma DS, Brandsma CA, Melgert BN, Luinge MA, Geerlings M, Hylkema MN, van den BA, Timens W, Kerstjens HA: Cigarette smoke-induced emphysema: a role for the B cell? Am J Respir Crit Care Med 2006;173:751–758.
[PubMed]
41.
Lee SH, Goswami S, Grudo A, Song LZ, Bandi V, Goodnight-White S, Green L, Hacken-Bitar J, Huh J, Bakaeen F, Coxson HO, Cogswell S, Storness-Bliss C, Corry DB, Kheradmand F: Antielastin autoimmunity in tobacco smoking-induced emphysema. Nat Med 2007;13:567–569.
[PubMed]
42.
Demedts IK, Bracke KR, Van Pottelberge G, Testelmans D, Verleden GM, Vermassen FE, Joos GF, Brusselle GG: Accumulation of dendritic cells and increased CCL20 levels in the airways of patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2007;175:998–1005.
[PubMed]
43.
Innes AL, Woodruff PG, Ferrando RE, Donnelly S, Dolganov GM, Lazarus SC, Fahy JV: Epithelial mucin stores are increased in the large airways of smokers with airflow obstruction. Chest 2006;130:1102–1108.
[PubMed]
44.
de Marco R, Accordini S, Cerveri I, Corsico A, Anto JM, Kunzli N, Janson C, Sunyer J, Jarvis D, Chinn S, Vermeire P, Svanes C, Ackermann-Liebrich U, Gislason T, Heinrich J, Leynaert B, Neukirch F, Schouten JP, Wjst M, Burney P: Incidence of chronic obstructive pulmonary disease in a cohort of young adults according to the presence of chronic cough and phlegm. Am J Respir Crit Care Med 2007;175:32–39.
[PubMed]
45.
Puchelle E, Zahm JM, Tournier JM, Coraux C: Airway epithelial repair, regeneration, and remodeling after injury in chronic obstructive pulmonary disease. Proc Am Thorac Soc 2006;3:726–733.
[PubMed]
46.
Cosio M, Ghezzo H, Hogg JC, Corbin R, Loveland M, Dosman J, Macklem PT: The relations between structural changes in small airways and pulmonary-function tests. N Engl J Med 1978;298:1277–1281.
[PubMed]
47.
Kelsen SG, Duan X, Ji R, Perez O, Liu C, Merali S: Cigarette smoke induces an unfolded protein response in the human lung: a proteomic approach. Am J Respir Cell Mol Biol 2008;38:541–550.
[PubMed]
48.
O’Donnell RA, Richter A, Ward J, Angco G, Mehta A, Rousseau K, Swallow DM, Holgate ST, Djukanovic R, Davies DE, Wilson SJ: Expression of ErbB receptors and mucins in the airways of long-term current smokers. Thorax 2004;59:1032–1040.
[PubMed]
49.
Kurie JM, Shin HJ, Lee JS, Morice RC, Ro JY, Lippman SM, Hittelman WN, Yu R, Lee JJ, Hong WK: Increased epidermal growth factor receptor expression in metaplastic bronchial epithelium. Clin Cancer Res 1996;2:1787–1793.
[PubMed]
50.
Lapperre TS, Sont JK, van Schadewijk A, Gosman MM, Postma DS, Bajema IM, Timens W, Mauad T, Hiemstra PS, GLUCOLD Study Group: Smoking cessation and bronchial epithelial remodelling in COPD: a cross-sectional study. Respir Res 2007;8:85.
[PubMed]
51.
Franklin WA, Veve R, Hirsch FR, Helfrich BA, Bunn PA Jr: Epidermal growth factor receptor family in lung cancer and premalignancy. Semin Oncol 2002;29:3–14.
[PubMed]
52.
Wistuba II, Lam S, Behrens C, Virmani AK, Fong KM, LeRiche J, Samet JM, Srivastava S, Minna JD, Gazdar AF: Molecular damage in the bronchial epithelium of current and former smokers. J Natl Cancer Inst 1997;89:1366–1373.
[PubMed]
53.
Franklin WA, Gazdar AF, Haney J, Wistuba II, La Rosa FG, Kennedy T, Ritchey DM, Miller YE: Widely dispersed p53 mutation in respiratory epithelium. A novel mechanism for field carcinogenesis. J Clin Invest 1997;100:2133–2137.
[PubMed]
54.
Burgel PR, Nadel JA: Roles of epidermal growth factor receptor activation in epithelial cell repair and mucin production in airway epithelium. Thorax 2004;59:992–996.
[PubMed]
55.
Auerbach O, Hammond EC, Garfinkel L: Changes in bronchial epithelium in relation to cigarette smoking, 1955–1960 vs. 1970–1977. N Engl J Med 1979;300:381–385.
[PubMed]
56.
Steiling K, Ryan J, Brody JS, Spira A: The field of tissue injury in the lung and airway. Cancer Prev Res (Phila) 2008;1:396–403.
[PubMed]
57.
Wistuba II: Genetics of preneoplasia: lessons from lung cancer. Curr Mol Med 2007;7:3–14.
[PubMed]
58.
Segal RA, Martonen TB, Kim CS, Shearer M: Computer simulations of particle deposition in the lungs of chronic obstructive pulmonary disease patients. Inhal Toxicol 2002;14:705–720.
[PubMed]
59.
Giangreco A, Groot KR, Janes SM: Lung cancer and lung stem cells: strange bedfellows? Am J Respir Crit Care Med 2007;175:547–553.
[PubMed]
60.
Dovey JS, Zacharek SJ, Kim CF, Lees JA: Bmi1 is critical for lung tumorigenesis and bronchioalveolar stem cell expansion. Proc Natl Acad Sci USA 2008;105:11857–11862.
[PubMed]
61.
Kim CF, Jackson EL, Woolfenden AE, Lawrence S, Babar I, Vogel S, Crowley D, Bronson RT, Jacks T: Identification of bronchioalveolar stem cells in normal lung and lung cancer. Cell 2005;121:823–835.
[PubMed]
62.
Kim CF: Paving the road for lung stem cell biology: bronchioalveolar stem cells and other putative distal lung stem cells. Am J Physiol Lung Cell Mol Physiol 2007;293:L1092–L1098.
[PubMed]
63.
Regala RP, Davis RK, Kunz A, Khoor A, Leitges M, Fields AP: Atypical protein kinase C{iota} is required for bronchioalveolar stem cell expansion and lung tumorigenesis. Cancer Res 2009;69:7603–7611.
[PubMed]
64.
Pierrou S, Broberg P, O’Donnell RA, Pawlowski K, Virtala R, Lindqvist E, Richter A, Wilson SJ, Angco G, Moller S, Bergstrand H, Koopmann W, Wieslander E, Stromstedt PE, Holgate ST, Davies DE, Lund J, Djukanovic R: Expression of genes involved in oxidative stress responses in airway epithelial cells of smokers with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2007;175:577–586.
[PubMed]
65.
Spira A, Beane J, Pinto-Plata V, Kadar A, Liu G, Shah V, Celli B, Brody JS: Gene expression profiling of human lung tissue from smokers with severe emphysema. Am J Respir Cell Mol Biol 2004;31:601–610.
[PubMed]
66.
Spira A, Beane JE, Shah V, Steiling K, Liu G, Schembri F, Gilman S, Dumas YM, Calner P, Sebastiani P, Sridhar S, Beamis J, Lamb C, Anderson T, Gerry N, Keane J, Lenburg ME, Brody JS: Airway epithelial gene expression in the diagnostic evaluation of smokers with suspect lung cancer. Nat Med 2007;13:361–366.
[PubMed]
67.
Steiling K, Kadar AY, Bergerat A, Flanigon J, Sridhar S, Shah V, Ahmad QR, Brody JS, Lenburg ME, Steffen M, Spira A: Comparison of proteomic and transcriptomic profiles in the bronchial airway epithelium of current and never smokers. PLoS One 2009;4:e5043.
[PubMed]
68.
Beane J, Sebastiani P, Liu G, Brody JS, Lenburg ME, Spira A: Reversible and permanent effects of tobacco smoke exposure on airway epithelial gene expression. Genome Biol 2007;8:R201.
[PubMed]
69.
Spira A, Beane J, Shah V, Liu G, Schembri F, Yang X, Palma J, Brody JS: Effects of cigarette smoke on the human airway epithelial cell transcriptome. Proc Natl Acad Sci USA 2004;101:10143–10148.
[PubMed]
70.
Fukumoto S, Yamauchi N, Moriguchi H, Hippo Y, Watanabe A, Shibahara J, Taniguchi H, Ishikawa S, Ito H, Yamamoto S, Iwanari H, Hironaka M, Ishikawa Y, Niki T, Sohara Y, Kodama T, Nishimura M, Fukayama M, Dosaka-Akita H, Aburatani H: Overexpression of the aldo-keto reductase family protein AKR1B10 is highly correlated with smokers’ non-small cell lung carcinomas. Clin Cancer Res 2005;11:1776–1785.
[PubMed]
71.
Beane J, Sebastiani P, Whitfield TH, Steiling K, Dumas YM, Lenburg ME, Spira A: A prediction model for lung cancer diagnosis that integrates genomic and clinical features. Cancer Prev Res (Phila) 2008;1:56–64.
[PubMed]
72.
Lacroix L, Commo F, Soria JC: Gene expression profiling of non-small-cell lung cancer. Expert Rev Mol Diagn 2008;8:167–178.
[PubMed]
73.
Pleasance ED, Stephens PJ, O’Meara S, McBride DJ, Meynert A, Jones D, Lin ML, Beare D, Lau KW, Greenman C, Varela I, Nik-Zainal S, Davies HR, Ordonez GR, Mudie LJ, Latimer C, Edkins S, Stebbings L, Chen L, Jia M, Leroy C, Marshall J, Menzies A, Butler A, Teague JW, Mangion J, Sun YA, McLaughlin SF, Peckham HE, Tsung EF, Costa GL, Lee CC, Minna JD, Gazdar A, Birney E, Rhodes MD, McKernan KJ, Stratton MR, Futreal PA, Campbell PJ: A small-cell lung cancer genome with complex signatures of tobacco exposure. Nature 2010;463:184–190.
[PubMed]
74.
Pleasance ED, Cheetham RK, Stephens PJ, McBride DJ, Humphray SJ, Greenman CD, Varela I, Lin ML, Ordonez GR, Bignell GR, Ye K, Alipaz J, Bauer MJ, Beare D, Butler A, Carter RJ, Chen L, Cox AJ, Edkins S, Kokko-Gonzales PI, Gormley NA, Grocock RJ, Haudenschild CD, Hims MM, James T, Jia M, Kingsbury Z, Leroy C, Marshall J, Menzies A, Mudie LJ, Ning Z, Royce T, Schulz-Trieglaff OB, Spiridou A, Stebbings LA, Szajkowski L, Teague J, Williamson D, Chin L, Ross MT, Campbell PJ, Bentley DR, Futreal PA, Stratton MR: A comprehensive catalogue of somatic mutations from a human cancer genome. Nature 2010;463:191–196.
[PubMed]
75.
Goto Y, Shinjo K, Kondo Y, Shen L, Toyota M, Suzuki H, Gao W, An B, Fujii M, Murakami H, Osada H, Taniguchi T, Usami N, Kondo M, Hasegawa Y, Shimokata K, Matsuo K, Hida T, Fujimoto N, Kishimoto T, Issa JP, Sekido Y: Epigenetic profiles distinguish malignant pleural mesothelioma from lung adenocarcinoma. Cancer Res 2009;69:9073–9082.
[PubMed]
76.
Landi MT, Zhao Y, Rotunno M, Koshiol J, Liu H, Bergen AW, Rubagotti M, Goldstein AM, Linnoila I, Marincola FM, Tucker MA, Bertazzi PA, Pesatori AC, Caporaso NE, McShane LM, Wang E: MicroRNA expression differentiates histology and predicts survival of lung cancer. Clin Cancer Res 2010;16:430–441.
[PubMed]
77.
Sato M, Shames DS, Gazdar AF, Minna JD: A translational view of the molecular pathogenesis of lung cancer. J Thorac Oncol 2007;2:327–343.
[PubMed]
78.
Molfino NA, Coyle AJ: Gene-environment interactions in chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis 2008;3:491–497.
[PubMed]
79.
Patel BD, Coxson HO, Pillai SG, Agusti AG, Calverley PM, Donner CF, Make BJ, Muller NL, Rennard SI, Vestbo J, Wouters EF, Hiorns MP, Nakano Y, Camp PG, Nasute Fauerbach PV, Screaton NJ, Campbell EJ, Anderson WH, Pare PD, Levy RD, Lake SL, Silverman EK, Lomas DA: Airway wall thickening and emphysema show independent familial aggregation in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2008;178:500–505.
[PubMed]
80.
Etzel CJ, Amos CI, Spitz MR: Risk for smoking-related cancer among relatives of lung cancer patients. Cancer Res 2003;63:8531–8535.
[PubMed]
81.
Cote 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;293:3036–3042.
[PubMed]
82.
Bailey-Wilson JE, Amos CI, Pinney SM, Petersen GM, de AM, Wiest JS, Fain P, Schwartz AG, You M, Franklin W, Klein C, Gazdar A, Rothschild H, Mandal D, Coons T, Slusser J, Lee J, Gaba C, Kupert E, Perez A, Zhou X, Zeng D, Liu Q, Zhang Q, Seminara D, Minna J, Anderson MW: A major lung cancer susceptibility locus maps to chromosome 6q23–25. Am J Hum Genet 2004;75:460–474.
[PubMed]
83.
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.
[PubMed]
84.
Spitz MR, Wei Q, Dong Q, Amos CI, Wu X: Genetic susceptibility to lung cancer: the role of DNA damage and repair. Cancer Epidemiol Biomarkers Prev 2003;12:689–698.
[PubMed]
85.
Gresner P, Gromadzinska J, Wasowicz W: Polymorphism of selected enzymes involved in detoxification and biotransformation in relation to lung cancer. Lung Cancer 2007;57:1–25.
[PubMed]
86.
Rotunno M, Yu K, Lubin JH, Consonni D, Pesatori AC, Goldstein AM, Goldin LR, Wacholder S, Welch R, Burdette L, Chanock SJ, Bertazzi PA, Tucker MA, Caporaso NE, Chatterjee N, Bergen AW, Landi MT: Phase I metabolic genes and risk of lung cancer: multiple polymorphisms and mRNA expression. PLoS One 2009;4:e5652.
[PubMed]
87.
Zhang JY, Wang Y, Prakash C: Xenobiotic-metabolizing enzymes in human lung. Curr Drug Metab 2006;7:939–948.
[PubMed]
88.
Caramori G, Adcock I: Gene-environment interactions in the development of chronic obstructive pulmonary disease. Curr Opin Allergy Clin Immunol 2006;6:323–328.
[PubMed]
89.
Cheng SL, Yu CJ, Yang PC: Genetic polymorphisms of cytochrome p450 and matrix metalloproteinase in chronic obstructive pulmonary disease. Biochem Genet 2009;47:591–601.
[PubMed]
90.
Dialyna IA, Miyakis S, Georgatou N, Spandidos DA: Genetic polymorphisms of CYP1A1, GSTM1 and GSTT1 genes and lung cancer risk. Oncol Rep 2003;10:1829–1835.
[PubMed]
91.
Hu G, Shi Z, Hu J, Zou G, Peng G, Ran P: Association between polymorphisms of microsomal epoxide hydrolase and COPD: results from meta-analyses. Respirology 2008;13:837–850.
[PubMed]
92.
Lee J, Nordestgaard BG, Dahl M: EPHX1 polymorphisms, COPD and asthma in 47,000 individuals and in meta-analysis. Eur Respir J 2011;37:18–25.
[PubMed]
93.
Kikuchi A, Yamaya M, Suzuki S, Yasuda H, Kubo H, Nakayama K, Handa M, Sasaki T, Shibahara S, Sekizawa K, Sasaki H: Association of susceptibility to the development of lung adenocarcinoma with the heme oxygenase-1 gene promoter polymorphism. Hum Genet 2005;116:354–360.
[PubMed]
94.
Fu WP, Sun C, Dai LM, Yang LF, Zhang YP: Relationship between COPD and polymorphisms of HOX-1 and mEPH in a Chinese population. Oncol Rep 2007;17:483–488.
[PubMed]
95.
Calikoglu M, Tamer L, Ates AN, Karakas S, Ercan B: The association between polymorphic genotypes of glutathione S-transferases and COPD in the Turkish population. Biochem Genet 2006;44:307–319.
[PubMed]
96.
Kim WJ, Hoffman E, Reilly J, Hersh C, Demeo D, Washko G, Silverman EK: Association of COPD candidate genes with computed tomography emphysema and airway phenotypes in severe COPD. Eur Respir J 2011;37:39–43.
[PubMed]
97.
Young RP, Whittington CF, Hopkins RJ, Hay BA, Epton MJ, Black PN, Gamble GD: Chromosome 4q31 locus in COPD is also associated with lung cancer. Eur Respir J 2010;36:1375–1382.
[PubMed]
98.
Shibata T, Ohta T, Tong KI, Kokubu A, Odogawa R, Tsuta K, Asamura H, Yamamoto M, Hirohashi S: Cancer related mutations in NRF2 impair its recognition by Keap1-Cul3 E3 ligase and promote malignancy. Proc Natl Acad Sci USA 2008;105:13568–13573.
[PubMed]
99.
Singh A, Misra V, Thimmulappa RK, Lee H, Ames S, Hoque MO, Herman JG, Baylin SB, Sidransky D, Gabrielson E, Brock MV, Biswal S: Dysfunctional KEAP1-NRF2 interaction in non-small-cell lung cancer. PLoS Med 2006;3:e420.
[PubMed]
100.
Ohta T, Iijima K, Miyamoto M, Nakahara I, Tanaka H, Ohtsuji M, Suzuki T, Kobayashi A, Yokota J, Sakiyama T, Shibata T, Yamamoto M, Hirohashi S: Loss of Keap1 function activates Nrf2 and provides advantages for lung cancer cell growth. Cancer Res 2008;68:1303–1309.
[PubMed]
101.
Padmanabhan B, Tong KI, Ohta T, Nakamura Y, Scharlock M, Ohtsuji M, Kang MI, Kobayashi A, Yokoyama S, Yamamoto M: Structural basis for defects of Keap1 activity provoked by its point mutations in lung cancer. Mol Cell 2006;21:689–700.
[PubMed]
102.
Rangasamy T, Cho CY, Thimmulappa RK, Zhen L, Srisuma SS, Kensler TW, Yamamoto M, Petrache I, Tuder RM, Biswal S: Genetic ablation of Nrf2 enhances susceptibility to cigarette smoke-induced emphysema in mice. J Clin Invest 2004;114:1248–1259.
[PubMed]
103.
Goven D, Boutten A, Lecon-Malas V, Marchal-Somme J, Amara N, Crestani B, Fournier M, Leseche G, Soler P, Boczkowski J, Bonay M: Altered Nrf2/Keap1-Bach1 equilibrium in pulmonary emphysema. Thorax 2008;63:916–924.
[PubMed]
104.
Malhotra D, Thimmulappa R, Navas-Acien A, Sandford A, Elliott M, Singh A, Chen L, Zhuang X, Hogg J, Pare P, Tuder RM, Biswal S: Decline in NRF2-regulated antioxidants in chronic obstructive pulmonary disease lungs due to loss of its positive regulator, DJ-1. Am J Respir Crit Care Med 2008;178:592–604.
[PubMed]
105.
Suzuki M, Betsuyaku T, Ito Y, Nagai K, Nasuhara Y, Kaga K, Kondo S, Nishimura M: Down-regulated NF-E2-related factor 2 in pulmonary macrophages of aged smokers and patients with chronic obstructive pulmonary disease. Am J Respir Cell Mol Biol 2008;39:673–682.
[PubMed]
106.
Amos CI, Wu X, Broderick P, Gorlov IP, Gu J, Eisen T, Dong Q, Zhang Q, Gu X, Vijayakrishnan J, Sullivan K, Matakidou A, Wang Y, Mills G, Doheny K, Tsai YY, Chen WV, Shete S, Spitz MR, Houlston RS: Genome-wide association scan of tag SNPs identifies a susceptibility locus for lung cancer at 15q25.1. Nat Genet 2008;40:616–622.
[PubMed]
107.
Falvella FS, Galvan A, Colombo F, Frullanti E, Pastorino U, Dragani TA: Promoter polymorphisms and transcript levels of nicotinic receptor CHRNA5. J Natl Cancer Inst 2010;102:1366–1370.
[PubMed]
108.
Thorgeirsson TE, Geller F, Sulem P, Rafnar T, Wiste A, Magnusson KP, Manolescu A, Thorleifsson G, Stefansson H, Ingason A, Stacey SN, Bergthorsson JT, Thorlacius S, Gudmundsson J, Jonsson T, Jakobsdottir M, Saemundsdottir J, Olafsdottir O, Gudmundsson LJ, Bjornsdottir G, Kristjansson K, Skuladottir H, Isaksson HJ, Gudbjartsson T, Jones GT, Mueller T, Gottsater A, Flex A, Aben KK, de Vegt F, Mulders PF, Isla D, Vidal MJ, Asin L, Saez B, Murillo L, Blondal T, Kolbeinsson H, Stefansson JG, Hansdottir I, Runarsdottir V, Pola R, Lindblad B, van Rij AM, Dieplinger B, Haltmayer M, Mayordomo JI, Kiemeney LA, Matthiasson SE, Oskarsson H, Tyrfingsson T, Gudbjartsson DF, Gulcher JR, Jonsson S, Thorsteinsdottir U, Kong A, Stefansson K: A variant associated with nicotine dependence, lung cancer and peripheral arterial disease. Nature 2008;452:638–642.
[PubMed]
109.
Hung RJ, McKay JD, Gaborieau V, Boffetta P, Hashibe M, Zaridze D, Mukeria A, Szeszenia-Dabrowska N, Lissowska J, Rudnai P, Fabianova E, Mates D, Bencko V, Foretova L, Janout V, Chen C, Goodman G, Field JK, Liloglou T, Xinarianos G, Cassidy A, McLaughlin J, Liu G, Narod S, Krokan HE, Skorpen F, Elvestad MB, Hveem K, Vatten L, Linseisen J, Clavel-Chapelon F, Vineis P, Bueno-de-Mesquita HB, Lund E, Martinez C, Bingham S, Rasmuson T, Hainaut P, Riboli E, Ahrens W, Benhamou S, Lagiou P, Trichopoulos D, Holcatova I, Merletti F, Kjaerheim K, Agudo A, Macfarlane G, Talamini R, Simonato L, Lowry R, Conway DI, Znaor A, Healy C, Zelenika D, Boland A, Delepine M, Foglio M, Lechner D, Matsuda F, Blanche H, Gut I, Heath S, Lathrop M, Brennan P: A susceptibility locus for lung cancer maps to nicotinic acetylcholine receptor subunit genes on 15q25. Nature 2008;452:633–637.
[PubMed]
110.
Liu P, Vikis HG, Wang D, Lu Y, Wang Y, Schwartz AG, Pinney SM, Yang P, de Andrade M, Petersen GM, Wiest JS, Fain PR, Gazdar A, Gaba C, Rothschild H, Mandal D, Coons T, Lee J, Kupert E, Seminara D, Minna J, Bailey-Wilson JE, Wu X, Spitz MR, Eisen T, Houlston RS, Amos CI, Anderson MW, You M: Familial aggregation of common sequence variants on 15q24–25.1 in lung cancer. J Natl Cancer Inst 2008;100:1326–1330.
[PubMed]
111.
Wu C, Hu Z, Yu D, Huang L, Jin G, Liang J, Guo H, Tan W, Zhang M, Qian J, Lu D, Wu T, Lin D, Shen H: Genetic variants on chromosome 15q25 associated with lung cancer risk in Chinese populations. Cancer Res 2009;69:5065–5072.
[PubMed]
112.
Song JY, Lim JW, Kim H, Kim KH: Role of NF-kappaB and DNA repair protein Ku on apoptosis in pancreatic acinar cells. Ann NY Acad Sci 2003;1010:259–263.
[PubMed]
113.
Song JY, Lim JW, Kim H, Morio T, Kim KH: Oxidative stress induces nuclear loss of DNA repair proteins Ku70 and Ku80 and apoptosis in pancreatic acinar AR42J cells. J Biol Chem 2003;278:36676–36687.
[PubMed]
114.
Pieper MP, Chaudhary NI, Park JE: Acetylcholine-induced proliferation of fibroblasts and myofibroblasts in vitro is inhibited by tiotropium bromide. Life Sci 2007;80:2270–2273.
[PubMed]
115.
Carlisle DL, Liu X, Hopkins TM, Swick MC, Dhir R, Siegfried JM: Nicotine activates cell-signaling pathways through muscle-type and neuronal nicotinic acetylcholine receptors in non-small cell lung cancer cells. Pulm Pharmacol Ther 2007;20:629–641.
[PubMed]
116.
Saccone NL, Wang JC, Breslau N, Johnson EO, Hatsukami D, Saccone SF, Grucza RA, Sun L, Duan W, Budde J, Culverhouse RC, Fox L, Hinrichs AL, Steinbach JH, Wu M, Rice JP, Goate AM, Bierut LJ: The CHRNA5-CHRNA3-CHRNB4 nicotinic receptor subunit gene cluster affects risk for nicotine dependence in African-Americans and in European-Americans. Cancer Res 2009;69:6848–6856.
[PubMed]
117.
Lips EH, Gaborieau V, McKay JD, Chabrier A, Hung RJ, Boffetta P, Hashibe M, Zaridze D, Szeszenia-Dabrowska N, Lissowska J, Rudnai P, Fabianova E, Mates D, Bencko V, Foretova L, Janout V, Field JK, Liloglou T, Xinarianos G, McLaughlin J, Liu G, Skorpen F, Elvestad MB, Hveem K, Vatten L, Study E, Benhamou S, Lagiou P, Holcatova I, Merletti F, Kjaerheim K, Agudo A, Castellsague X, Macfarlane TV, Barzan L, Canova C, Lowry R, Conway DI, Znaor A, Healy C, Curado MP, Koifman S, Eluf-Neto J, Matos E, Menezes A, Fernandez L, Metspalu A, Heath S, Lathrop M, Brennan P: Association between a 15q25 gene variant, smoking quantity and tobacco-related cancers among 17 000 individuals. Int J Epidemiol 2010;39:563–577.
[PubMed]
118.
Anderson GP, Bozinovski S: Acquired somatic mutations in the molecular pathogenesis of COPD. Trends Pharmacol Sci 2003;24:71–76.
[PubMed]
119.
Sancar A, Lindsey-Boltz LA, Unsal-Kacmaz K, Linn S: Molecular mechanisms of mammalian DNA repair and the DNA damage checkpoints. Annu Rev Biochem 2004;73:39–85.
[PubMed]
120.
Meek K, Gupta S, Ramsden DA, Lees-Miller SP: The DNA-dependent protein kinase: the director at the end. Immunol Rev 2004;200:132–141.
[PubMed]
121.
Meek K, Dang V, Lees-Miller SP: DNA-PK: the means to justify the ends? Adv Immunol 2008;99:33–58.
[PubMed]
122.
Downs JA, Jackson SP: A means to a DNA end: the many roles of Ku. Nat Rev Mol Cell Biol 2004;5:367–378.
[PubMed]
123.
Caramori G, Papi A: Pathogenic link between chronic obstructive pulmonary disease and squamous cell lung cancer. Expert Rev Respir Med 2007;1:171–175.
[PubMed]
124.
Brody JS, Spira A: State of the art. Chronic obstructive pulmonary disease, inflammation, and lung cancer. Proc Am Thorac Soc 2006;3:535–537.
[PubMed]
125.
Popanda O, Schattenberg T, Phong CT, Butkiewicz D, Risch A, Edler L, Kayser K, Dienemann H, Schulz V, Drings P, Bartsch H, Schmezer P: Specific combinations of DNA repair gene variants and increased risk for non-small cell lung cancer. Carcinogenesis 2004;25:2433–2441.
[PubMed]
126.
Wei Q, Cheng L, Amos CI, Wang LE, Guo Z, Hong WK, Spitz MR: Repair of tobacco carcinogen-induced DNA adducts and lung cancer risk: a molecular epidemiologic study. J Natl Cancer Inst 2000;92:1764–1772.
[PubMed]
127.
Gehring M, Reik W, Henikoff S: DNA demethylation by DNA repair. Trends Genet 2009;25:82–90.
[PubMed]
128.
Miller KM, Tjeertes JV, Coates J, Legube G, Polo SE, Britton S, Jackson SP: Human HDAC1 and HDAC2 function in the DNA-damage response to promote DNA nonhomologous end-joining. Nat Struct Mol Biol 2010;17:1144–1151.
[PubMed]
129.
Vempati RK, Jayani RS, Notani D, Sengupta A, Galande S, Haldar D: p300-mediated acetylation of histone H3 lysine 56 functions in DNA damage response in mammals. J Biol Chem 2010;285:28553–28564.
[PubMed]
130.
Yuan Z, Zhang X, Sengupta N, Lane WS, Seto E: SIRT1 regulates the function of the Nijmegen breakage syndrome protein. Mol Cell 2007;27:149–162.
[PubMed]
131.
Ito K, Ito M, Elliott WM, Cosio B, Caramori G, Kon OM, Barczyk A, Hayashi S, Adcock IM, Hogg JC, Barnes PJ: Decreased histone deacetylase activity in chronic obstructive pulmonary disease. N Engl J Med 2005;352:1967–1976.
[PubMed]
132.
Nakamaru Y, Vuppusetty C, Wada H, Milne JC, Ito M, Rossios C, Elliot M, Hogg J, Kharitonov S, Goto H, Bemis JE, Elliott P, Barnes PJ, Ito K: A protein deacetylase SIRT1 is a negative regulator of metalloproteinase-9. FASEB J 2009;23:2810–2819.
[PubMed]
133.
Rajendrasozhan S, Yang SR, Kinnula VL, Rahman I: SIRT1, an antiinflammatory and antiaging protein, is decreased in lungs of patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2008;177:861–870.
[PubMed]
134.
Tuder RM, Yun JH, Graham BB: Cigarette smoke triggers code red: p21CIP1/WAF1/SDI1 switches on danger responses in the lung. Am J Respir Cell Mol Biol 2008;39:1–6.
[PubMed]
135.
Hwang SJ, Cheng LS, Lozano G, Amos CI, Gu X, Strong LC: Lung cancer risk in germline p53 mutation carriers: association between an inherited cancer predisposition, cigarette smoking, and cancer risk. Hum Genet 2003;113:238–243.
[PubMed]
136.
Arif E, Vibhuti A, Deepak D, Singh B, Siddiqui MS, Pasha MA: COX2 and p53 risk-alleles coexist in COPD. Clin Chim Acta 2008;397:48–50.
[PubMed]
137.
Lee YL, Chen W, Tsai WK, Lee JC, Chiou HL, Shih CM, Wang YC: Polymorphisms of p53 and p21 genes in chronic obstructive pulmonary disease. J Lab Clin Med 2006;147:228–233.
[PubMed]
138.
Tomita K, Caramori G, Lim S, Ito K, Hanazawa T, Oates T, Chiselita I, Jazrawi E, Chung KF, Barnes PJ, Adcock IM: Increased p21(CIP1/WAF1) and B cell lymphoma leukemia-x(L) expression and reduced apoptosis in alveolar macrophages from smokers. Am J Respir Crit Care Med 2002;166:724–731.
[PubMed]
139.
Tsuji T, Aoshiba K, Nagai A: Alveolar cell senescence in patients with pulmonary emphysema. Am J Respir Crit Care Med 2006;174:886–893.
[PubMed]
140.
Tsuji T, Aoshiba K, Nagai A: Alveolar cell senescence exacerbates pulmonary inflammation in patients with chronic obstructive pulmonary disease. Respiration 2010;80:59–70.
[PubMed]
141.
Belinsky SA, Palmisano WA, Gilliland FD, Crooks LA, Divine KK, Winters SA, Grimes MJ, Harms HJ, Tellez CS, Smith TM, Moots PP, Lechner JF, Stidley CA, Crowell RE: Aberrant promoter methylation in bronchial epithelium and sputum from current and former smokers. Cancer Res 2002;62:2370–2377.
[PubMed]
142.
Russo AL, Thiagalingam A, Pan H, Califano J, Cheng KH, Ponte JF, Chinnappan D, Nemani P, Sidransky D, Thiagalingam S: Differential DNA hypermethylation of critical genes mediates the stage-specific tobacco smoke-induced neoplastic progression of lung cancer. Clin Cancer Res 2005;11:2466–2470.
[PubMed]
143.
Soria JC, Rodriguez M, Liu DD, Lee JJ, Hong WK, Mao L: Aberrant promoter methylation of multiple genes in bronchial brush samples from former cigarette smokers. Cancer Res 2002;62:351–355.
[PubMed]
144.
Ocak S, Sos ML, Thomas RK, Massion PP: High-throughput molecular analysis in lung cancer: insights into biology and potential clinical applications. Eur Respir J 2009;34:489–506.
[PubMed]
145.
Guil S, Esteller M: DNA methylomes, histone codes and miRNAs: tying it all together. Int J Biochem Cell Biol 2009;41:87–95.
[PubMed]
146.
Dubey S, Powell CA: Update in lung cancer 2008. Am J Respir Crit Care Med 2009;179:860–868.
[PubMed]
147.
Esteller M: Epigenetics in cancer. N Engl J Med 2008;358:1148–1159.
[PubMed]
148.
Irizarry RA, Ladd-Acosta C, Wen B, Wu Z, Montano C, Onyango P, Cui H, Gabo K, Rongione M, Webster M, Ji H, Potash JB, Sabunciyan S, Feinberg AP: The human colon cancer methylome shows similar hypo- and hypermethylation at conserved tissue-specific CpG island shores. Nat Genet 2009;41:178–186.
[PubMed]
149.
Adcock IM, Ford P, Barnes PJ, Ito K: Epigenetics and airways disease. Respir Res 2006;7:21.
[PubMed]
150.
Rauch TA, Zhong X, Wu X, Wang M, Kernstine KH, Wang Z, Riggs AD, Pfeifer GP: High-resolution mapping of DNA hypermethylation and hypomethylation in lung cancer. Proc Natl Acad Sci USA 2008;105:252–257.
[PubMed]
151.
Palmisano WA, Divine KK, Saccomanno G, Gilliland FD, Baylin SB, Herman JG, Belinsky SA: Predicting lung cancer by detecting aberrant promoter methylation in sputum. Cancer Res 2000;60:5954–5958.
[PubMed]
152.
Belinsky SA, Nikula KJ, Palmisano WA, Michels R, Saccomanno G, Gabrielson E, Baylin SB, Herman JG: Aberrant methylation of p16(INK4a) is an early event in lung cancer and a potential biomarker for early diagnosis. Proc Natl Acad Sci USA 1998;95:11891–11896.
[PubMed]
153.
Brock MV, Hooker CM, Ota-Machida E, Han Y, Guo M, Ames S, Glockner S, Piantadosi S, Gabrielson E, Pridham G, Pelosky K, Belinsky SA, Yang SC, Baylin SB, Herman JG: DNA methylation markers and early recurrence in stage I lung cancer. N Engl J Med 2008;358:1118–1128.
[PubMed]
154.
Lai JC, Wu JY, Cheng YW, Yeh KT, Wu TC, Chen CY, Lee H: O6-Methylguanine-DNA methyltransferase hypermethylation modulated by 17beta-estradiol in lung cancer cells. Anticancer Res 2009;29:2535–2540.
[PubMed]
155.
Liu F, Killian JK, Yang M, Walker RL, Hong JA, Zhang M, Davis S, Zhang Y, Hussain M, Xi S, Rao M, Meltzer PA, Schrump DS: Epigenomic alterations and gene expression profiles in respiratory epithelia exposed to cigarette smoke condensate. Oncogene 2010;29:3650–3664.
[PubMed]
156.
Hu Z, Chen J, Tian T, Zhou X, Gu H, Xu L, Zeng Y, Miao R, Jin G, Ma H, Chen Y, Shen H: Genetic variants of miRNA sequences and non-small cell lung cancer survival. J Clin Invest 2008;118:2600–2608.
[PubMed]
157.
Tian T, Shu Y, Chen J, Hu Z, Xu L, Jin G, Liang J, Liu P, Zhou X, Miao R, Ma H, Chen Y, Shen H: A functional genetic variant in microRNA-196a2 is associated with increased susceptibility of lung cancer in Chinese. Cancer Epidemiol Biomarkers Prev 2009;18:1183–1187.
[PubMed]
158.
Schembri F, Sridhar S, Perdomo C, Gustafson AM, Zhang X, Ergun A, Lu J, Liu G, Zhang X, Bowers J, Vaziri C, Ott K, Sensinger K, Collins JJ, Brody JS, Getts R, Lenburg ME, Spira A: MicroRNAs as modulators of smoking-induced gene expression changes in human airway epithelium. Proc Natl Acad Sci USA 2009;106:2319–2324.
[PubMed]
159.
Van Pottelberge GR, Mestdagh P, Bracke KR, Thas O, van Durme YM, Joos GF, Vandesompele J, Brusselle GG: MicroRNA Expression in induced sputum of smokers and patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2010, E-pub ahead of print.
160.
Sato T, Liu X, Nelson A, Nakanishi M, Kanaji N, Wang X, Kim M, Li Y, Sun J, Michalski J, Patil A, Basma H, Holz O, Magnussen H, Rennard SI: Reduced miR-146a increases prostaglandin Ein chronic obstructive pulmonary disease fibroblasts. Am J Respir Crit Care Med 2010;182:1020–1029.
[PubMed]
161.
Balkwill F, Mantovani A: Inflammation and cancer: back to Virchow? Lancet 2001;357:539–545.
[PubMed]
162.
Balkwill F, Mantovani A: Cancer and inflammation: implications for pharmacology and therapeutics. Clin Pharmacol Ther 2010;87:401–406.
[PubMed]
163.
Reiman JM, Kmieciak M, Manjili MH, Knutson KL: Tumor immunoediting and immunosculpting pathways to cancer progression. Semin Cancer Biol 2007;17:275–287.
[PubMed]
164.
Otsuka S, Bebb G: The CXCR4/SDF-1 chemokine receptor axis: a new target therapeutic for non-small cell lung cancer. J Thorac Oncol 2008;3:1379–1383.
[PubMed]
165.
Tauler J, Mulshine JL: Lung cancer and inflammation: interaction of chemokines and hnRNPs. Curr Opin Pharmacol 2009;9:384–388.
[PubMed]
166.
Pan H, Luo C, Li R, Qiao A, Zhang L, Mines M, Nyanda AM, Zhang J, Fan GH: Cyclophilin A is required for CXCR4-mediated nuclear export of heterogeneous nuclear ribonucleoprotein A2, activation and nuclear translocation of ERK1/2, and chemotactic cell migration. J Biol Chem 2008;283:623–637.
[PubMed]
167.
Katsimpoula S, Patrinou-Georgoula M, Makrilia N, Dimakou K, Guialis A, Orfanidou D, Syrigos KN: Overexpression of hnRNPA2/B1 in bronchoscopic specimens: a potential early detection marker in lung cancer. Anticancer Res 2009;29:1373–1382.
[PubMed]
168.
Sueoka E, Sueoka N, Iwanaga K, Sato A, Suga K, Hayashi S, Nagasawa K, Nakachi K: Detection of plasma hnRNP B1 mRNA, a new cancer biomarker, in lung cancer patients by quantitative real-time polymerase chain reaction. Lung Cancer 2005;48:77–83.
[PubMed]
169.
Chen Y, Chen P, Hanaoka M, Droma Y, Kubo K: Enhanced levels of prostaglandin E2 and matrix metalloproteinase-2 correlate with the severity of airflow limitation in stable COPD. Respirology 2008;13:1014–1021.
[PubMed]
170.
Xaubet A, Roca-Ferrer J, Pujols L, Ramirez J, Mullol J, Marin-Arguedas A, Torrego A, Gimferrer JM, Picado C: Cyclooxygenase-2 is up-regulated in lung parenchyma of chronic obstructive pulmonary disease and down-regulated in idiopathic pulmonary fibrosis. Sarcoidosis Vasc Diffuse Lung Dis 2004;21:35–42.
[PubMed]
171.
Slatore CG, Au DH, Littman AJ, Satia JA, White E: Association of nonsteroidal anti-inflammatory drugs with lung cancer: results from a large cohort study. Cancer Epidemiol Biomarkers Prev 2009;18:1203–1207.
[PubMed]
172.
Van Dyke AL, Cote ML, Prysak G, Claeys GB, Wenzlaff AS, Schwartz AG: Regular adult aspirin use decreases the risk of non-small cell lung cancer among women. Cancer Epidemiol Biomarkers Prev 2008;17:148–157.
[PubMed]
173.
Harris RE: Cyclooxygenase-2 (cox-2) blockade in the chemoprevention of cancers of the colon, breast, prostate, and lung. Inflammopharmacology 2009;17:55–67.
[PubMed]
174.
Campa D, Zienolddiny S, Maggini V, Skaug V, Haugen A, Canzian F: Association of a common polymorphism in the cyclooxygenase 2 gene with risk of non-small cell lung cancer. Carcinogenesis 2004;25:229–235.
[PubMed]
175.
Karin M: NF-kappaB as a critical link between inflammation and cancer. Cold Spring Harb Perspect Biol 2009;1:a000141.
176.
Caramori G, Adcock IM, Ito K: Anti-inflammatory inhibitors of IkappaB kinase in asthma and COPD. Curr Opin Investig Drugs 2004;5:1141–1147.
[PubMed]
177.
Di Stefano A, Caramori G, Oates T, Capelli A, Lusuardi M, Gnemmi I, Ioli F, Chung KF, Donner CF, Barnes PJ, Adcock IM: Increased expression of nuclear factor-kappaB in bronchial biopsies from smokers and patients with COPD. Eur Respir J 2002;20:556–563.
[PubMed]
178.
Tang X, Liu D, Shishodia S, Ozburn N, Behrens C, Lee JJ, Hong WK, Aggarwal BB, Wistuba II: Nuclear factor-kappaB (NF-kappaB) is frequently expressed in lung cancer and preneoplastic lesions. Cancer 2006;107:2637–2646.
[PubMed]
179.
Tichelaar JW, Zhang Y, leRiche JC, Biddinger PW, Lam S, Anderson MW: Increased staining for phospho-Akt, p65/RELA and cIAP-2 in pre-neoplastic human bronchial biopsies. BMC Cancer 2005;5:155.
[PubMed]
180.
Greten FR, Karin M: The IKK/NF-kappaB activation pathway – a target for prevention and treatment of cancer. Cancer Lett 2004;206:193–199.
[PubMed]
181.
Takahashi H, Ogata H, Nishigaki R, Broide DH, Karin M: Tobacco smoke promotes lung tumorigenesis by triggering IKKbeta- and JNK1-dependent inflammation. Cancer Cell 2010;17:89–97.
[PubMed]
182.
Levy D, Kuo AJ, Chang Y, Schaefer U, Kitson C, Cheung P, Espejo A, Zee BM, Liu CL, Tangsombatvisit S, Tennen RI, Kuo AY, Tanjing S, Cheung R, Chua KF, Utz PJ, Shi X, Prinjha RK, Lee K, Garcia BA, Bedford MT, Tarakhovsky A, Cheng X, Gozani O: Lysine methylation of the NF-kappaB subunit RelA by SETD6 couples activity of the histone methyltransferase GLP at chromatin to tonic repression of NF-kappaB signaling. Nat Immunol 2011;12:29–36.
[PubMed]
183.
Adcock IM, Chung KF, Caramori G, Ito K: Kinase inhibitors and airway inflammation. Eur J Pharmacol 2006;533:118–132.
[PubMed]
184.
Marwick JA, Caramori G, Casolari P, Mazzoni F, Kirkham PA, Adcock IM, Chung KF, Papi A: A role for phosphoinositol 3-kinase delta in the impairment of glucocorticoid responsiveness in patients with chronic obstructive pulmonary disease. J Allergy Clin Immunol 2010;125:1146–1153.
[PubMed]
185.
Marwick JA, Chung KF, Adcock IM: Phosphatidylinositol 3-kinase isoforms as targets in respiratory disease. Ther Adv Respir Dis 2010;4:19–34.
[PubMed]
186.
Popkie AP, Zeidner LC, Albrecht AM, D’Ippolito A, Eckardt S, Newsom DE, Groden J, Doble BW, Aronow B, McLaughlin KJ, White P, Phiel CJ: Phosphatidylinositol 3-kinase (PI3K) signaling via glycogen synthase kinase-3 (Gsk-3) regulates DNA methylation of imprinted loci. J Biol Chem 2010;285:41337–41347.
[PubMed]
187.
Gustafson AM, Soldi R, Anderlind C, Scholand MB, Qian J, Zhang X, Cooper K, Walker D, McWilliams A, Liu G, Szabo E, Brody J, Massion PP, Lenburg ME, Lam S, Bild AH, Spira A: Airway PI3K pathway activation is an early and reversible event in lung cancer development. Sci Transl Med 2010;2:26ra25.
188.
Nanjundan M, Byers LA, Carey MS, Siwak DR, Raso MG, Diao L, Wang J, Coombes KR, Roth JA, Mills GB, Wistuba II, Minna JD, Heymach JV: Proteomic profiling identifies pathways dysregulated in non-small cell lung cancer and an inverse association of AMPK and adhesion pathways with recurrence. J Thorac Oncol 2010;5:1894–1904.
[PubMed]
189.
Mountzios G, Planchard D, Besse B, Validire P, Girard P, Devisme C, Dimopoulos MA, Soria JC, Fouret P: Mitogen-activated protein kinase activation in lung adenocarcinoma: a comparative study between ever smokers and never smokers. Clin Cancer Res 2008;14:4096–4102.
[PubMed]
190.
Matsuo Y, Amano S, Furuya M, Namiki K, Sakurai K, Nishiyama M, Sudo T, Tatsumi K, Kuriyama T, Kimura S, Kasuya Y: Involvement of p38alpha mitogen-activated protein kinase in lung metastasis of tumor cells. J Biol Chem 2006;281:36767–36775.
[PubMed]
191.
St Germain C, Niknejad N, Ma L, Garbuio K, Hai T, Dimitroulakos J: Cisplatin induces cytotoxicity through the mitogen-activated protein kinase pathways and activating transcription factor 3. Neoplasia 2010;12:527–538.
[PubMed]
192.
Hui L, Bakiri L, Stepniak E, Wagner EF: p38alpha: a suppressor of cell proliferation and tumorigenesis. Cell Cycle 2007;6:2429–2433.
[PubMed]
193.
Lai SY, Johnson FM: Defining the role of the JAK-STAT pathway in head and neck and thoracic malignancies: implications for future therapeutic approaches. Drug Resist Updat 2010;13:67–78.
[PubMed]
194.
He B, You L, Xu Z, Mazieres J, Lee AY, Jablons DM: Activity of the suppressor of cytokine signaling-3 promoter in human non-small-cell lung cancer. Clin Lung Cancer 2004;5:366–370.
[PubMed]
195.
Huang WL, Yeh HH, Lin CC, Lai WW, Chang JY, Chang WT, Su WC: Signal transducer and activator of transcription 3 activation up-regulates interleukin-6 autocrine production: a biochemical and genetic study of established cancer cell lines and clinical isolated human cancer cells. Mol Cancer 2010;9:309.
[PubMed]
196.
Belvisi MG, Mitchell JA: Targeting PPAR receptors in the airway for the treatment of inflammatory lung disease. Br J Pharmacol 2009;158:994–1003.
[PubMed]
197.
Li MY, Yuan H, Ma LT, Kong AW, Hsin MK, Yip JH, Underwood MJ, Chen GG: Roles of peroxisome proliferator-activated receptor-alpha and -gamma in the development of non-small cell lung cancer. Am J Respir Cell Mol Biol 2010;43:674–683.
[PubMed]
198.
Ford PA, Durham AL, Russell RE, Gordon F, Adcock IM, Barnes PJ: Treatment effects of low-dose theophylline combined with an inhaled corticosteroid in COPD. Chest 2010;137:1338–1344.
[PubMed]
199.
Spange S, Wagner T, Heinzel T, Kramer OH: Acetylation of non-histone proteins modulates cellular signalling at multiple levels. Int J Biochem Cell Biol 2009;41:185–198.
[PubMed]
200.
Cho HY, Reddy SP, Kleeberger SR: Nrf2 defends the lung from oxidative stress. Antioxid Redox Signal 2006;8:76–87.
[PubMed]
201.
Valinluck V, Tsai HH, Rogstad DK, Burdzy A, Bird A, Sowers LC: Oxidative damage to methyl-CpG sequences inhibits the binding of the methyl-CpG binding domain (MBD) of methyl-CpG binding protein 2 (MeCP2). Nucleic Acids Res 2004;32:4100–4108.
[PubMed]
202.
Cappuzzo F, Ciuleanu T, Stelmakh L, Cicenas S, Szczesna A, Juhasz E, Esteban E, Molinier O, Brugger W, Melezinek I, Klingelschmitt G, Klughammer B, Giaccone G: Erlotinib as maintenance treatment in advanced non-small-cell lung cancer: a multicentre, randomised, placebo-controlled phase 3 study. Lancet Oncol 2010;11:521–529.
[PubMed]
203.
Woodruff PG, Wolff M, Hohlfeld JM, Krug N, Dransfield MT, Sutherland ER, Criner GJ, Kim V, Prasse A, Nivens MC, Tetzlaff K, Heilker R, Fahy JV: Safety and efficacy of an inhaled epidermal growth factor receptor inhibitor (BIBW 2948 BS) in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2010;181:438–445.
[PubMed]
204.
Balansky R, Ganchev G, Iltcheva M, Steele VE, De Flora S: Prevention of cigarette smoke-induced lung tumors in mice by budesonide, phenethyl isothiocyanate, and N-acetylcysteine. Int J Cancer 2010;126:1047–1054.
[PubMed]
205.
Kiri VA, Fabbri LM, Davis KJ, Soriano JB: Inhaled corticosteroids and risk of lung cancer among COPD patients who quit smoking. Respir Med 2009;103:85–90.
[PubMed]
206.
van den Berg RM, Teertstra HJ, van Zandwijk N, van Tinteren H, Visser C, Pasic A, Sutedja TG, Baas P, Golding RP, Postmus PE, Smit EF: CT detected indeterminate pulmonary nodules in a chemoprevention trial of fluticasone. Lung Cancer 2008;60:57–61.
[PubMed]
207.
van den Berg RM, van Tinteren H, van Zandwijk N, Visser C, Pasic A, Kooi C, Sutedja TG, Baas P, Grunberg K, Mooi WJ, Snijders PJ, Postmus PE, Smit EF: The influence of fluticasone inhalation on markers of carcinogenesis in bronchial epithelium. Am J Respir Crit Care Med 2007;175:1061–1065.
[PubMed]
208.
Lam S, leRiche JC, McWilliams A, MacAulay C, Dyachkova Y, Szabo E, Mayo J, Schellenberg R, Coldman A, Hawk E, Gazdar A: A randomized phase IIb trial of pulmicort turbuhaler (budesonide) in people with dysplasia of the bronchial epithelium. Clin Cancer Res 2004;10:6502–6511.
[PubMed]
209.
Calverley PM, Anderson JA, Celli B, Ferguson GT, Jenkins C, Jones PW, Yates JC, Vestbo J: Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. N Engl J Med 2007;356:775–789.
[PubMed]
210.
Song P, Spindel ER: Basic and clinical aspects of non-neuronal acetylcholine: expression of non-neuronal acetylcholine in lung cancer provides a new target for cancer therapy. J Pharmacol Sci 2008;106:180–185.
[PubMed]
211.
Song P, Sekhon HS, Fu XW, Maier M, Jia Y, Duan J, Proskosil BJ, Gravett C, Lindstrom J, Mark GP, Saha S, Spindel ER: Activated cholinergic signaling provides a target in squamous cell lung carcinoma. Cancer Res 2008;68:4693–4700.
[PubMed]
212.
Tashkin DP, Celli B, Senn S, Burkhart D, Kesten S, Menjoge S, Decramer M: A 4-year trial of tiotropium in chronic obstructive pulmonary disease. N Engl J Med 2008;359:1543–1554.
[PubMed]
213.
Lin Y, Bai L, Chen W, Xu S: The NF-kappaB activation pathways, emerging molecular targets for cancer prevention and therapy. Expert Opin Ther Targets 2010;14:45–55.
[PubMed]
214.
Denlinger CE, Rundall BK, Jones DR: Proteasome inhibition sensitizes non-small cell lung cancer to histone deacetylase inhibitor-induced apoptosis through the generation of reactive oxygen species. J Thorac Cardiovasc Surg 2004;128:740–748.
[PubMed]
215.
Rundall BK, Denlinger CE, Jones DR: Combined histone deacetylase and NF-kappaB inhibition sensitizes non-small cell lung cancer to cell death. Surgery 2004;136:416–425.
[PubMed]
216.
Stathopoulos GT, Sherrill TP, Cheng DS, Scoggins RM, Han W, Polosukhin VV, Connelly L, Yull FE, Fingleton B, Blackwell TS: Epithelial NF-kappaB activation promotes urethane-induced lung carcinogenesis. Proc Natl Acad Sci USA 2007;104:18514–18519.
[PubMed]
217.
Komarova EA, Krivokrysenko V, Wang K, Neznanov N, Chernov MV, Komarov PG, Brennan ML, Golovkina TV, Rokhlin OW, Kuprash DV, Nedospasov SA, Hazen SL, Feinstein E, Gudkov AV: p53 is a suppressor of inflammatory response in mice. FASEB J 2005;19:1030–1032.
[PubMed]
218.
Lawless MW, O’Byrne KJ, Gray SG: Oxidative stress induced lung cancer and COPD: opportunities for epigenetic therapy. J Cell Mol Med 2009;13:2800–2821.
[PubMed]
219.
Decramer M, Rutten-van Mölken M, Dekhuijzen PN, Troosters T, van Herwaarden C, Pellegrino R, van Schayck CP, Olivieri D, Del Donna M, De Backer W, Lankhorst I, Ardia A: Effects of N-acetylcysteine on outcomes in chronic obstructive pulmonary disease (Bronchitis Randomized on NAC Cost-Utility Study, BRONCUS): a randomised placebo-controlled trial. Lancet 2005;365:1552–1560.
[PubMed]
220.
van Zandwijk N, Dalesio O, Pastorino U, de Vries N, van Tinteren H: EUROSCAN, a randomized trial of vitamin A and N-acetylcysteine in patients with head and neck cancer or lung cancer. For the EUropean Organization for Research and Treatment of Cancer Head and Neck and Lung Cancer Cooperative Groups. J Natl Cancer Inst 2000;92:977–986.
[PubMed]
221.
Smith RA, Murphy MP: Animal and human studies with the mitochondria-targeted antioxidant MitoQ. Ann NY Acad Sci 2010;1201:96–103.
[PubMed]
222.
Rahman I, Adcock IM: Oxidative stress and redox regulation of lung inflammation in COPD. Eur Respir J 2006;28:219–242.
[PubMed]
© 2011 S. Karger AG, Basel
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
2011
You do not currently have access to this content.
