The relationship between COPD and lung cancer

A L Durham, I M Adcock, A L Durham, I M Adcock

Abstract

Both COPD and lung cancer are major worldwide health concerns owing to cigarette smoking, and represent a huge, worldwide, preventable disease burden. Whilst the majority of smokers will not develop either COPD or lung cancer, they are closely related diseases, occurring as co-morbidities at a higher rate than if they were independently triggered by smoking. Lung cancer and COPD may be different aspects of the same disease, with the same underlying predispositions, whether this is an underlying genetic predisposition, telomere shortening, mitochondrial dysfunction or premature aging. In the majority of smokers, the burden of smoking may be dealt with by the body's defense mechanisms: anti-oxidants such as superoxide dismutases, anti-proteases and DNA repair mechanisms. However, in the case of both diseases these fail, leading to cancer if mutations occur or COPD if damage to the cell and proteins becomes too great. Alternatively COPD could be a driving factor in lung cancer, by increasing oxidative stress and the resulting DNA damage, chronic exposure to pro-inflammatory cytokines, repression of the DNA repair mechanisms and increased cellular proliferation. Understanding the mechanisms that drive these processes in primary cells from patients with these diseases along with better disease models is essential for the development of new treatments.

Keywords: COPD; Cancer; ROS.

Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Figures

Fig. 1
Fig. 1
Reactive oxygen and nitrogen species (RNOS) derived from both exogenous and endogenous sources drive many of the pathways in both COPD and lung cancer. RNOS can react with DNA, leading to DNA damage, which if not correctly repaired leads to mutations. Mechanisms that prevent mutation, including DNA repair and apoptosis can be inhibited by RNOS activity. Additionally RNOS can contribute to susceptibility to infection and drive inflammation in the lungs. Inflammation can lead to further cellular and DNA damage, both through the generation of further RNOS and also through the action of cytokines and proteases. RNOS are capable of inhibiting the protective mechanisms, such as anti-proteases. Damage to the lungs is repaired by processes including cellular proliferation, which can in turn promote tumourgenesis.

References

    1. Zagorevski D.V., Loughmiller-Newman J.A. The detection of nicotine in a Late Mayan period flask by gas chromatography and liquid chromatography mass spectrometry methods. Rapid Commun. Mass Spectrom. 2012;26(4):403–411.
    1. Trends in Tobacco Use. American Lung Association, Research and Program Services, Epidemiology and Statistics Unit, 2011.
    1. Tolley H.D., Crane L., Shipley N. Chapter 3: smoking prevalence and lung cancer death rates. In: Shopland D.R., editor. Tobacco Control Monograph 1: Strategies to Control Tobacco Use in the Unites States. National Cancer Institute; 1991. pp. 73–144.
    1. Villeneuve P., Mao Y. Lifetime probability of developing lung cancer, by smoking status Canada. Can. J. Public Health. 1994;85(6):4.
    1. Jemal A. Global cancer statistics. CA. Cancer J. Clin. 2011;61(2):69–90.
    1. McErlean A., Ginsberg M.S. Epidemiology of lung cancer. Semin. Roentgenol. 2011;46(3):173–177.
    1. Jemal A. Cancer statistics, 2010. CA. Cancer J. Clin. 2010;60(5):277–300.
    1. UK C.R. Types of lung cancer. 2013 cited June 2013; Available from: .
    1. Reck M. Management of non-small-cell lung cancer: recent developments. Lancet. 2015;382(9893):709–719.
    1. Vestbo J. Global Strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease, GOLD executive summary. Am. J. Respir. Crit. Care Med. 2012
    1. Lundbäck B. Not 15 but 50% of smokers develop COPD?—report from the obstructive lung disease in northern sweden studies. Respir. Med. 2003;97(2):8.
    1. Burney P.G.J. Global and regional trends in COPD mortality, 1990–2010. Eur. Respir. J. 2015;45(5):1239–1247.
    1. Brusselle G.G., Joos G.F., Bracke K.R. New insights into the immunology of chronic obstructive pulmonary disease. Lancet. 2015;378(9795):1015–1026.
    1. Papi A. COPD increases the risk of squamous histological subtype in smokers who develop non-small cell lung carcinoma. Thorax. 2004;59(8):679–681.
    1. Young R.P., Hopkins R.J. Link between COPD and lung cancer. Respir. Med. 2010;104(5):758–759.
    1. Young R.P. Airflow limitation and histology-shift in the national lung screening trial: the NLST–ACRIN Cohort Substudy (N = 18,714) Am. J. Respir. Crit. Care Med. 2015
    1. Barnes P.J., Adcock I.M. Chronic obstructive pulmonary disease and lung cancer: a lethal association. Am. J. Respir. Crit. Care Med. 2011;184(8):866–867.
    1. Kamo K.-I. Lifetime and age-conditional probabilities of developing or dying of cancer in Japan. Jpn. J. Clin. Oncol. 2008;38(8):571–576.
    1. Rosenberger A. Do genetic factors protect for early onset lung cancer? A case control study before the age of 50 years. BMC Cancer. 2008;8(1):60.
    1. Fletcher C., Peto R. The natural history of chronic airflow obstruction. BMJ. 1977;1(6077):1645–1648.
    1. Ito K., Barnes P.J. COPD as a disease of accelerated lung aging. CHEST J. 2009;135(1):173–180.
    1. Caramori G. Unbalanced oxidant-induced DNA damage and repair in COPD: a link towards lung cancer. Thorax. 2011;66(6):521–527.
    1. Church D.F., Pryor W.A. Free-radical chemistry of cigarette smoke and its toxicological implications. Environ. Health Perspect. 1985;64:111–126.
    1. Pryor W.A., Stone K. Oxidants in cigarette smoke radicals, hydrogen peroxide, peroxynitrate, and peroxynitrite. Ann. N. Y. Acad. Sci. 1993;686(1):12–27.
    1. Schetter A.J., Heegaard N.H.H., Harris C.C. Inflammation and cancer: interweaving microRNA, free radical, cytokine and p53 pathways. Carcinogenesis. 2010;31(1):37–49.
    1. Lennon F.E., Salgia R. Mitochondrial dynamics: biology and therapy in lung cancer. Expert Opin. Investig. Drugs. 2014;23(5):675–692.
    1. Harman D. Free radical theory of aging: an update. Ann. N. Y. Acad. Sci. 2006;1067(1):10–21.
    1. Kryston T.B. Role of oxidative stress and DNA damage in human carcinogenesis. Mutat. Res./Fundam. Mol. Mech. Mutagen. 2011;711(1–2):193–201.
    1. Mambo E. Oxidized guanine lesions and hOgg1 activity in lung cancer. Oncogene. 2005;24(28):4496–4508.
    1. Vulimiri S.V. Analysis of aromatic DNA adducts and 7,8-dihydro-8-oxo- 2′-deoxyguanosine in lymphocyte DNA from a case-control study of lung cancer involving minority populations. Mol. Carcinog. 2000;27(1):34–46.
    1. Erhola M. Biomarker evidence of DNA oxidation in lung cancer patients: association of urinary 8-hydroxy-2′-deoxyguanosine excretion with radiotherapy, chemotherapy, and response to treatment. FEBS Lett. 1997;409(2):287–291.
    1. Jaruga P. Oxidative DAN base damage and antioxidant enzyme activities in human lung cancer. FEBS Lett. 1994;341(1):59–64.
    1. Hussain S.P., Hofseth L.J., Harris C.C. Radical causes of cancer. Nat. Rev. Cancer. 2003;3(4):276–285.
    1. Winn L.M., Kim P.M., Nickoloff J.A. Oxidative stress-induced homologous recombination as a novel mechanism for phenytoin-initiated toxicity. J. Pharmacol. Exp. Ther. 2003;306(2):523–527.
    1. Pryor W.A. Cigarette smoke radicals and the role of free radicals in chemical carcinogenicity. Environ. Health Perspect. 1997;105(4):8.
    1. Kobliakov V.A. Mechanisms of tumor promotion by reactive oxygen species. Biochem. (Moscow) 2010;75(6):675–685.
    1. Adcock I., Caramori G., Barnes P. Chronic obstructive pulmonary disease and lung cancer: new molecular insights. Respiration. 2011;81(4):19.
    1. Ngkelo A. LPS induced inflammatory responses in human peripheral blood mononuclear cells is mediated through NOX4 and Gialpha dependent PI-3kinase signalling. J. Inflammation. 2012;9(1):1.
    1. Cattaruzza M., Hecker M. Protein carbonylation and decarboylation: a new twist to the complex response of vascular cells to oxidative stress. Circ. Res. 2008;102(3):273–274.
    1. Lee H. ROS1 receptor tyrosine kinase, a druggable target, is frequently overexpressed in non-small cell lung carcinomas via genetic and epigenetic mechanisms. Ann. Surg. Oncol. 2013;20(1):200–208.
    1. Charest A. ROS fusion tyrosine kinase activates a sh2 domain—containing phosphatase-2/Phosphatidylinositol 3-Kinase/Mammalian target of rapamycin signaling axis to form glioblastoma in mice. Cancer Res. 2006;66(15):7473–7481.
    1. Schreck R., Albermann K., Baeuerle P. Nuclear factor kappa B: an oxidative stress-responsive transcription factor of eukaryotic cells (a review) Free Radic. Res. Commun. 1992;17(4):221–237.
    1. Osoata G. Oxidative stress causes HDAC2 reduction by nitration, ubiquitinylation and proteasomal degradation. Proc. Am. Thorac. Soc. 2005;2:pA755.
    1. Osoata G.O. Nitration of distinct tyrosine residues causes inactivation of histone deacetylase 2. Biochem. Biophys. Res. Commun. 2009;384(3):366–371.
    1. Kirkham P.A. Oxidative Stress—induced antibodies to carbonyl-modified protein correlate with severity of chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 2011;184(7):796–802.
    1. Stewart S.A., Weinberg R.A. Telomeres: cancer to human aging. Annu. Rev. Cell Dev. Biol. 2006;22(1):531–557.
    1. Morlá M. Telomere shortening in smokers with and without COPD. Eur. Respir. J. 2006;27(3):525–528.
    1. Jang J.S. Telomere length and the risk of lung cancer. Cancer Sci. 2008;99(7):1385–1389.
    1. Hosgood Iii H.D. Genetic variation in telomere maintenance genes, telomere length, and lung cancer susceptibility. Lung Cancer. 2009;66(2):157–161.
    1. Wu X. Telomere dysfunction: a potential cancer predisposition factor. J. Natl. Cancer Inst. 2003;95(16):1211–1218.
    1. Frías C. Telomere shortening is associated with poor prognosis and telomerase activity correlates with DNA repair impairment in non-small cell lung cancer. Lung Cancer. 2008;60(3):416–425.
    1. Savale L. Shortened telomeres in circulating leukocytes of patients with chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 2009;179(7):566–571.
    1. Amsellem V. Telomere dysfunction causes sustained inflammation in chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 2011;184(12):1358–1366.
    1. Alder J.K. Telomere length is a determinant of emphysema susceptibility. Am. J. Respir. Crit. Care Med. 2011;184(8):904–912.
    1. Schwartz A.G., Ruckdeschel J.C. Familial lung cancer: genetic susceptibility and relationship to chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 2006;173(1):16–22.
    1. Joost O. Genetic loci influencing lung function: a genomewide scan in the framingham study. Am. J. Respir. Crit. Care Med. 2002;165(6):795–799.
    1. Silverman E.K. Genome-wide linkage analysis of severe, early-onset chronic obstructive pulmonary disease: airflow obstruction and chronic bronchitis phenotypes. Hum. Mol. Genet. 2002;11(6):623–632.
    1. Yang I.A., Holloway J.W., Fong K.M. Genetic susceptibility to lung cancer and co-morbidities. J. Thorac. Dis. 2013:S454–S462.
    1. Wang H. Genetic variant in the 3'-untranslated region of VEGFR1 gene influences chronic obstructive pulmonary disease and lung cancer development in Chinese population. Mutagenesis. 2014;29(5):311–317.
    1. Van Dyke A.L. Cytokine and cytokine receptor single-nucleotide polymorphisms predict risk for non–small cell lung cancer among women. Cancer Epidemiol. Biomarkers Prev. 2009;18(6):1829–1840.
    1. Franco R. Oxidative stress, DNA methylation and carcinogenesis. Cancer Lett. 2008;266(1):6–11.
    1. Kabesch M., Adcock I.M. Epigenetics in asthma and COPD. Biochimie. 2012;94(11):2231–2241.
    1. Guilleret I. Hypermethylation of the human telomerase catalytic subunit (hTERT) gene correlates with telomerase activity. Int. J. Cancer. 2002;101(4):335–341.
    1. Liloglou T. Epigenetic biomarkers in lung cancer. Cancer Lett. 2014;342(2):200–212.
    1. Das P.M., Singal R. DNA methylation and cancer. J. Clin. Oncol. 2004;22(22):4632–4642.
    1. Sato M. A translational view of the molecular pathogenesis of lung cancer. J. Thorac. Oncol. 2007;2(4):327–343.
    1. Sato T. Epigenetic clustering of lung adenocarcinomas based on DNA methylation profiles in adjacent lung tissue: its correlation with smoking history and chronic obstructive pulmonary disease. Int. J. Cancer. 2014;135(2):319–334.
    1. Tessema M. Epigenetic repression of CCDC37 and MAP1B links chronic obstructive pulmonary disease to lung cancer. J. Thorac. Oncol. 2015;10(8)
    1. Qiu W., et al. Variable D.N.A. Methylation is associated with chronic obstructive pulmonary disease and lung function. Am. J. Respir. Crit. Care Med. 2012;185(4):373–381.
    1. Islam K.N., Mendelson C.R. Glucocorticoid/glucocorticoid receptor inhibition of surfactant Protein-A (SP-A) gene expression in lung type ii cells is mediated by repressive changes in histone modification at the SP-A promoter. Mol. Endocrinol. 2008;22(3):585–596.
    1. Ito K. Decreased histone deacetylase activity in chronic obstructive pulmonary disease. N. Engl. J. Med. 2005;352:1967.
    1. Ford P.A. Treatment effects of low-dose theophylline combined with an inhaled corticosteroid in COPD. Chest. 2010;137(6):1338–1344.
    1. Neal J.W., Sequist L.V. Complex role of histone deacetylase inhibitors in the treatment of non—small-cell lung cancer. J. Clin. Oncol. 2012;30(18):2280–2282.
    1. Bhadury J. BET and HDAC inhibitors induce similar genes and biological effects and synergize to kill in Myc-induced murine lymphoma. Proc. Natl. Acad. Sci. 2014;111(26):E2721–E2730.
    1. Esteller M. Non-coding RNAs in human disease. Nat. Rev. Genet. 2011;12(12):861–874.
    1. Lu L.-F., Liston A. MicroRNA in the immune system, microRNA as an immune system. Immunology. 2009;127(3):291–298.
    1. Leidinger P. Specific peripheral miRNA profiles for distinguishing lung cancer from COPD. Lung Cancer. 2011;74(1):41–47.
    1. Lewis A. Downregulation of the serum response factor/miR-1 axis in the quadriceps of patients with COPD. Thorax. 2012;67(1):26–34.
    1. Williams A.E. Role of miRNA-146a in the regulation of the innate immune response and cancer. Biochem. Soc. Trans. 2008;36:p5.
    1. Ding S.-Z., Zheng P.-Y. Helicobacter pylori infection induced gastric cancer; advance in gastric stem cell research and the remaining challenges. Gut Pathog. 2012;4(1):18.
    1. Hoffmann R. Prolonged cigarette smoke exposure alters mitochondrial structure and function in airway epithelial cells. Respir. Res. 2013;14(1):97.
    1. Peng H. Expression and methylation of mitochondrial transcription factor a in chronic obstructive pulmonary disease patients with lung cancer. PLoS One. 2013;8(12):e82739.
    1. Dranoff G. Cytokines in cancer pathogenesis and cancer therapy. Nat. Rev. Cancer. 2004;4(1):11–22.
    1. Lin E.Y. Colony-stimulating factor 1 promotes progression of mammary tumors to malignancy. J. Exp. Med. 2001;193(6):727–740.
    1. Di Stefano A. Association of increased CCL5 and CXCL7 chemokine expression with neutrophil activation in severe stable COPD. Thorax. 2009;64(11):968–975.
    1. Chang S.H. T helper 17 cells play a critical pathogenic role in lung cancer. Proc. Natl. Acad. Sci. 2014;111(15):5664–5669.
    1. Shen H.-M., Tergaonkar V. NFκB signaling in carcinogenesis and as a potential molecular target for cancer therapy. Apoptosis. 2009;14(4):348–363.
    1. Ito K., Caramori G., Adcock I.M. Therapeutic potential of phosphatidylinositol 3-kinase inhibitors in inflammatory respiratory disease. J. Pharmacol. Exp. Ther. 2007;321(1):1–8.
    1. de Boer W.I. Expression of epidermal growth factors and their receptors in the bronchial epithelium of subjects with chronic obstructive pulmonary disease. Am. J. Clin. Pathol. 2006;125(2):184–192.
    1. Bartolotti M., Franceschi E., Brandes A.A., EGF receptor tyrosine kinase inhibitors in the treatment of brain metastases from non-small-cell lung cancer. Expert Rev. Anticancer Ther. 2012;12(11):1429–1435.
    1. Baarsma H.A. Activation of WNT/β-Catenin signaling in pulmonary fibroblasts by TGF-β1 is increased in chronic obstructive pulmonary disease. PLoS One. 2011;6(9):e25450.
    1. Zhang D.-Y. Wnt/β-catenin signaling induces the aging of mesenchymal stem cells through promoting the ROS production. Mol. Cell. Biochem. 2013;374(1–2):13–20.
    1. Pacheco-Pinedo E.C. Wnt/β-catenin signaling accelerates mouse lung tumorigenesis by imposing an embryonic distal progenitor phenotype on lung epithelium. J. Clin. Invest. 2011;121(5):1935–1945.
    1. Markowitz S.D., Bertagnolli M.M. Molecular basis of colorectal cancer. N. Engl. J. Med. 2009;361(25):2449–2460.
    1. Sohal S. Evaluation of epithelial mesenchymal transition in patients with chronic obstructive pulmonary disease. Respir. Res. 2011;12(1):130.
    1. Wang H. Resveratrol inhibits TGF-β1-induced epithelial-to-mesenchymal transition and suppresses lung cancer invasion and metastasis. Toxicology. 2013;303:139–146.
    1. Azimzadeh Jamalkandi S. Signaling network of lipids as a comprehensive scaffold for omics data integration in sputum of COPD patients. Biochim. Biophys. Acta (BBA)—Mol. Cell Biol. Lipids. 2015;1851(10):1383–1393.
    1. Ellis P.M. Use of the epidermal growth factor receptor inhibitors gefitinib, erlotinib, afatinib, dacomitinib, and icotinib in the treatment of non-small-cell lung cancer: a systematic review. Curr. Oncol. 2015;(3):e183–e215.
    1. Villaruz L., Socinski M. The role of anti-angiogenesis in non-small-cell lung cancer: an update. Curr. Oncol. Rep. 2015;17(6):1–13.
    1. Tse H., Tseng C. Update on the pathological processes, molecular biology, and clinical utility of N-acetylcysteine in chronic obstructive pulmonary disease. Int. J. Chron. Obstruct. Pulmon. Dis. 2014;9(1):825–836.
    1. Aitio M.-L. N-acetylcysteine—passe-partout or much ado about nothing? Br. J. Clin. Pharmacol. 2006;61(1):5–15.
    1. Sayin V.I. Antioxidants accelerate lung cancer progression in mice. Sci. Transl. Med. 2014;6(221):221ra15.

Source: PubMed

Sponsorzy i współpracownicy

Warunki medyczne

Interwencje lekowe

3
Subskrybuj