Skip to main content
SpringerLink
Log in

Inflammation and Lung Cancer: Molecular Pathology

  • Chapter
  • First Online:
Inflammation and Lung Cancer

  • 1279 Accesses

Abstract

Many cancers arise from sites of infection or chronic inflammation. The lung is a site for various repetitive or chronic inflammatory injuries. Accumulative evidence points to a causal rather than a coincidental relationship between inflammation and lung cancer development. For example, inflammatory cells, both innate and adaptive, foster lung tumor development and progression through various cytokine, chemokine and transcription factor networks, and reactive oxygen species (ROS) production. Epidemiological studies demonstrate that persons with lung infections (e.g., tuberculosis), chronic inflammatory pulmonary conditions (e.g., COPD), or genetic polymorphisms in the inflammatory pathway exhibit increased lung cancer risk. However, the role of inflammation in lung cancer is not fully understood. Studies suggest both similarities and differences in the inflammatory processes between chronic inflammatory lung diseases and lung cancer. Understanding the molecular pathology of inflammation in the context of the stage of lung tumor development is crucial for developing new anti-inflammatory or immunomodulatory preventive and therapeutic approaches.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Balkwill F, Mantovani A (2001) Inflammation and cancer: back to Virchow? Lancet 357(9255):539–545

    Google Scholar 

  2. de Visser KE, Eichten A, Coussens LM (2006) Paradoxical roles of the immune system during cancer development. Nat Rev Cancer 6(1):24–37

    Google Scholar 

  3. Ran M, Witz IP (1972) Tumor-associated immunoglobulins. Enhancement of syngeneic tumors by IgG2-containing tumor eluates. Int J Cancer 9(1):242–247 (Journal international du cancer)

    Google Scholar 

  4. Coussens LM, Werb Z (2002) Inflammation and cancer. Nature 420(6917):860–867

    Google Scholar 

  5. Ekbom A, Helmick C, Zack M, Adami HO (1990) Ulcerative colitis and colorectal cancer. A population-based study. N Engl J Med 323(18):1228–1233

    Google Scholar 

  6. Tan EM, Shi FD (2003) Relative paradigms between autoantibodies in lupus and autoantibodies in cancer. Clin Exp Immunol 134(2):169–177

    Google Scholar 

  7. Dannenberg AJ, Subbaramaiah K (2003) Targeting cyclooxygenase-2 in human neoplasia: rationale and promise. Cancer Cell 4(6):431–436

    Google Scholar 

  8. Imada A, Shijubo N, Kojima H, Abe S (2000) Mast cells correlate with angiogenesis and poor outcome in stage I lung adenocarcinoma. Eur Respir J 15(6):1087–1093

    Google Scholar 

  9. Finke J, Ferrone S, Frey A, Mufson A, Ochoa A (1999) Where have all the T cells gone? Mechanisms of immune evasion by tumors. Immunol Today 20(4):158–160

    Google Scholar 

  10. Miotto D, Cascio N L, Stendardo M, Querzoli P, Pedriali M, De Rosa E, Fabbri LM, Mapp CE, Boschetto P (2010) CD8 + T cells expressing IL-10 are associated with a favourable prognosis in lung cancer. Lung Cancer 69(3):355–360

    Google Scholar 

  11. Smyth MJ, Thia KY, Street SE, Cretney E, Trapani JA, Taniguchi M, Kawano T, Pelikan SB, Crowe NY, Godfrey DI (2000) Differential tumor surveillance by natural killer (NK) and NKT cells. J Exp Med 191(4):661–668

    Google Scholar 

  12. Cho WC, Kwan CK, Yau S, So PP, Poon PC, Au JS (2011) The role of inflammation in the pathogenesis of lung cancer. Expert Opin Ther Targets 15(9):1127–1137

    Google Scholar 

  13. Engels EA (2008) Inflammation in the development of lung cancer: epidemiological evidence. Expert Rev Anticancer Ther 8(4):605–615

    CAS  PubMed  Google Scholar 

  14. Houghton AM (2013) Mechanistic links between COPD and lung cancer. Nat Rev Cancer 13(4):233–245

    CAS  PubMed  Google Scholar 

  15. Wistuba II (2007) Genetics of preneoplasia: lessons from lung cancer. Curr Mol Med 7(1):3–14

    CAS  PubMed  Google Scholar 

  16. Alavanja MC, Brownson RC, Boice JD Jr, Hock E (1992) Preexisting lung disease and lung cancer among nonsmoking women. Am J Epidemiol 136(6):623–632

    CAS  PubMed  Google Scholar 

  17. Ernst PB, Gold BD (2000) The disease spectrum of Helicobacter pylori: the immunopathogenesis of gastroduodenal ulcer and gastric cancer. Annu Rev Microbiol 54:615–640

    CAS  PubMed  Google Scholar 

  18. Truong T, Sauter W, McKay JD, Hosgood HD 3rd, Gallagher C, Amos CI, Spitz M, Muscat J, Lazarus P, Illig T, Wichmann HE, Bickeboller H, Risch A, Dienemann H, Zhang ZF, Naeim BP, Yang P, Zienolddiny S, Haugen A, Marchand L L, Hong YC, Kim JH, Duell EJ, Andrew AS, Kiyohara C, Shen H, Matsuo K, Suzuki T, Seow A, Ng DP, Lan Q, Zaridze D, Szeszenia-Dabrowska N, Lissowska J, Rudnai P, Fabianova E, Constantinescu V, Bencko V, Foretova L, Janout V, Caporaso NE, Albanes D, Thun M, Landi MT, Trubicka J, Lener M, Lubinski J, lung E, Wang Y, Chabrier A, Boffetta P, Brennan P, Hung RJ (2010) International lung cancer consortium: coordinated association study of 10 potential lung cancer susceptibility variants. Carcinogenesis 31(4):625–633

    CAS  PubMed Central  PubMed  Google Scholar 

  19. Wong KK, Jacks T, Dranoff G (2010) NF-kappaB fans the flames of lung carcinogenesis. Cancer Prev Res 3(4):403–405

    CAS  Google Scholar 

  20. Kim ES, Hong WK, Lee JJ, Mao L, Morice RC, Liu DD, Jimenez CA, Eapen GA, Lotan R, Tang X, Newman RA, Wistuba II, Kurie JM (2010) Biological activity of celecoxib in the bronchial epithelium of current and former smokers. Cancer Prev Res 3(2):148–159

    CAS  Google Scholar 

  21. Stearman RS, Dwyer-Nield L, Grady MC, Malkinson AM, Geraci MW (2008) A macrophage gene expression signature defines a field effect in the lung tumor microenvironment. Cancer Res 68(1):34–43

    CAS  PubMed  Google Scholar 

  22. Punturieri A, Szabo E, Croxton TL, Shapiro SD, Dubinett SM (2009) Lung cancer and chronic obstructive pulmonary disease: needs and opportunities for integrated research. J Natl Cancer Inst 101(8):554–559

    PubMed Central  PubMed  Google Scholar 

  23. Moghaddam SJ, Li H, Cho SN, Dishop MK, Wistuba II, Ji L, Kurie JM, Dickey BF, Demayo FJ (2009) Promotion of lung carcinogenesis by chronic obstructive pulmonary disease-like airway inflammation in a K-ras-induced mouse model. Am J Respir Cell Mol Biol 40(4):443–453

    CAS  PubMed Central  PubMed  Google Scholar 

  24. Herbst RS, Heymach JV, Lippman SM (2008) Lung cancer. N Engl J Med 359(13):1367–1380

    CAS  PubMed  Google Scholar 

  25. Steiling K, Ryan J, Brody JS, Spira A (2008) The field of tissue injury in the lung and airway. Cancer Prev Res 1(6):396–403

    CAS  Google Scholar 

  26. Muller T, Hengstermann A (2012) Nrf2: friend and foe in preventing cigarette smoking-dependent lung disease. Chem Res Toxicol 25(9):1805–1824

    PubMed  Google Scholar 

  27. Spira A, Beane J, Shah V, Liu G, Schembri F, Yang X, Palma J, Brody JS (2004) Effects of cigarette smoke on the human airway epithelial cell transcriptome. Proc Natl Acad Sci U S A 101(27):10143–10148

    CAS  PubMed Central  PubMed  Google Scholar 

  28. Goldkorn T, Filosto S (2010) Lung injury and cancer: mechanistic insights into ceramide and EGFR signaling under cigarette smoke. Am J Respir Cell Mol Biol 43(3):259–268

    CAS  PubMed Central  PubMed  Google Scholar 

  29. Schwartz L, Guais A, Chaumet-Riffaud P, Grevillot G, Sasco AJ, Molina TJ, Mohammad A (2010) Carbon dioxide is largely responsible for the acute inflammatory effects of tobacco smoke. Inhal Toxicol 22(7):543–551

    CAS  PubMed  Google Scholar 

  30. Ji H, Houghton AM, Mariani TJ, Perera S, Kim CB, Padera R, Tonon G, McNamara K, Marconcini LA, Hezel A, El-Bardeesy N, Bronson RT, Sugarbaker D, Maser RS, Shapiro SD, Wong KK (2006) K-ras activation generates an inflammatory response in lung tumors. Oncogene 25(14):2105–2112

    CAS  PubMed  Google Scholar 

  31. Tao Q, Fujimoto J, Men T, Ye X, Deng J, Lacroix L, Clifford JL, Mao L, Van Pelt CS, Lee JJ, Lotan D, Lotan R (2007) Identification of the retinoic acid-inducible Gprc5a as a new lung tumor suppressor gene. J Natl Cancer Inst 99(22):1668–1682

    CAS  PubMed  Google Scholar 

  32. Deng J, Fujimoto J, Ye XF, Men TY, Van Pelt CS, Chen YL, Lin XF, Kadara H, Tao Q, Lotan D, Lotan R (2010) Knockout of the tumor suppressor gene Gprc5a in mice leads to NF-kappaB activation in airway epithelium and promotes lung inflammation and tumorigenesis. Cancer Prev Res 3(4):424–437

    CAS  Google Scholar 

  33. Sparmann A, Bar-Sagi D (2004) Ras-induced interleukin-8 expression plays a critical role in tumor growth and angiogenesis. Cancer Cell 6(5):447–458

    CAS  PubMed  Google Scholar 

  34. Eikawa S, Ohue Y, Kitaoka K, Aji T, Uenaka A, Oka M, Nakayama E (2010) Enrichment of Foxp3 + CD4 regulatory T cells in migrated T cells to IL-6- and IL-8-expressing tumors through predominant induction of CXCR1 by IL-6. J Immunol 185(11):6734–6740

    CAS  PubMed  Google Scholar 

  35. 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 (2007) Airway epithelial gene expression in the diagnostic evaluation of smokers with suspect lung cancer. Nat Med 13(3):361–366

    CAS  PubMed  Google Scholar 

  36. Song L, Rawal B, Nemeth JA, Haura EB (2011) JAK1 activates STAT3 activity in non-small-cell lung cancer cells and IL-6 neutralizing antibodies can suppress JAK1-STAT3 signaling. Mol Cancer Ther 10(3):481–494

    CAS  PubMed Central  PubMed  Google Scholar 

  37. Yao Z, Fenoglio S, Gao DC, Camiolo M, Stiles B, Lindsted T, Schlederer M, Johns C, Altorki N, Mittal V, Kenner L, Sordella R (2010) TGF-beta IL-6 axis mediates selective and adaptive mechanisms of resistance to molecular targeted therapy in lung cancer. Proc Natl Acad Sci U S A 107(35):15535–15540

    CAS  PubMed Central  PubMed  Google Scholar 

  38. Ochoa CE, Mirabolfathinejad SG, Ruiz VA, Evans SE, Gagea M, Evans CM, Dickey BF, Moghaddam SJ (2011) Interleukin 6, but not T helper 2 cytokines, promotes lung carcinogenesis. Cancer Prev Res 4(1):51–64

    CAS  Google Scholar 

  39. Cheng CY, Kuo CT, Lin CC, Hsieh HL, Yang CM (2010) IL-1beta induces expression of matrix metalloproteinase-9 and cell migration via a c-Src-dependent, growth factor receptor transactivation in A549 cells. Br J Pharmacol 160(7):1595–1610

    CAS  PubMed Central  PubMed  Google Scholar 

  40. Cheng CY, Hsieh HL, Sun CC, Lin CC, Luo SF, Yang CM (2009) IL-1 beta induces urokinase-plasminogen activator expression and cell migration through PKC alpha, JNK1/2, and NF-kappaB in A549 cells. J Cell Physiol 219(1):183–193

    CAS  PubMed  Google Scholar 

  41. Herfs M, Hubert P, Poirrier AL, Vandevenne P, Renoux V, Habraken Y, Cataldo D, Boniver J, Delvenne P (2012) Proinflammatory cytokines induce bronchial hyperplasia and squamous metaplasia in smokers: implications for chronic obstructive pulmonary disease therapy. Am J Respir Cell Mol Biol 47(1):67–79

    CAS  PubMed  Google Scholar 

  42. Schmid MC, Avraamides CJ, Foubert P, Shaked Y, Kang SW, Kerbel RS, Varner JA (2011) Combined blockade of integrin-alpha4beta1 plus cytokines SDF-1alpha or IL-1beta potently inhibits tumor inflammation and growth. Cancer Res 71(22):6965–6975

    CAS  PubMed Central  PubMed  Google Scholar 

  43. Gocheva V, Wang HW, Gadea BB, Shree T, Hunter KE, Garfall AL, Berman T, Joyce JA (2010) IL-4 induces cathepsin protease activity in tumor-associated macrophages to promote cancer growth and invasion. Genes Dev 24(3):241–255

    CAS  PubMed Central  PubMed  Google Scholar 

  44. Todaro M, Lombardo Y, Francipane MG, Alea MP, Cammareri P, Iovino F, Stefano AB D, Bernardo C D, Agrusa A, Condorelli G, Walczak H, Stassi G (2008) Apoptosis resistance in epithelial tumors is mediated by tumor-cell-derived interleukin-4. Cell Death Differ 15(4):762–772

    CAS  PubMed  Google Scholar 

  45. Neurath MF, Finotto S (2012) The emerging role of T cell cytokines in non-small cell lung cancer. Cytokine Growth Factor Rev 23(6):315–322

    CAS  PubMed  Google Scholar 

  46. Wang L, Yi T, Kortylewski M, Pardoll DM, Zeng D, Yu H (2009) IL-17 can promote tumor growth through an IL-6-Stat3 signaling pathway. J Exp Med 206(7):1457–1464

    CAS  PubMed Central  PubMed  Google Scholar 

  47. Liu L, Ge D, Ma L, Mei J, Liu S, Zhang Q, Ren F, Liao H, Pu Q, Wang T, You Z (2012) Interleukin-17 and prostaglandin E2 are involved in formation of an M2 macrophage-dominant microenvironment in lung cancer. J Thorac Oncol 7(7):1091–1100. (Official publication of the International Association for the Study of Lung Cancer)

    CAS  PubMed Central  PubMed  Google Scholar 

  48. Shembade N, Harhaj EW (2011) IKKi: a novel regulator of Act1, IL-17 signaling and pulmonary inflammation. Cell Mol Immunol 8(6):447–449

    CAS  PubMed Central  PubMed  Google Scholar 

  49. Ye ZJ, Zhou Q, Gu YY, Qin SM, Ma WL, Xin JB, Tao XN, Shi HZ (2010) Generation and differentiation of IL-17-producing CD4+ T cells in malignant pleural effusion. J Immunol 185(10):6348–6354

    CAS  PubMed  Google Scholar 

  50. Alcorn JF, Crowe CR, Kolls JK (2010) TH17 cells in asthma and COPD. Annu Rev Physiol 72:495–516

    CAS  PubMed  Google Scholar 

  51. Krieg C, Letourneau S, Pantaleo G, Boyman O (2010) Improved IL-2 immunotherapy by selective stimulation of IL-2 receptors on lymphocytes and endothelial cells. Proc Natl Acad Sci U S A 107(26):11906–11911

    CAS  PubMed Central  PubMed  Google Scholar 

  52. Maeno T, Houghton AM, Quintero PA, Grumelli S, Owen CA, Shapiro SD (2007) CD8 + T Cells are required for inflammation and destruction in cigarette smoke-induced emphysema in mice. J Immunol 178(12):8090–8096

    CAS  PubMed  Google Scholar 

  53. Suzuki K, Kadota K, Sima CS, Nitadori J, Rusch VW, Travis WD, Sadelain M, Adusumilli PS (2013) Clinical impact of immune microenvironment in stage I lung adenocarcinoma: tumor interleukin-12 receptor beta2 (IL-12Rbeta2), IL-7R, and stromal FoxP3/CD3 ratio are independent predictors of recurrence. J Clin Oncol 31(4):490–498

    CAS  PubMed Central  PubMed  Google Scholar 

  54. Cero FT, Hillestad V, Loberg EM, Christensen G, Larsen KO, Skjonsberg OH (2012) IL-18 and IL-12 synergy induces matrix degrading enzymes in the lung. Exp Lung Res 38(8):406–419

    CAS  PubMed  Google Scholar 

  55. Keane MP, Belperio JA, Xue YY, Burdick MD, Strieter RM (2004) Depletion of CXCR2 inhibits tumor growth and angiogenesis in a murine model of lung cancer. J Immunol 172(5):2853–2860

    CAS  PubMed  Google Scholar 

  56. Wislez M, Fujimoto N, Izzo JG, Hanna AE, Cody DD, Langley RR, Tang H, Burdick MD, Sato M, Minna JD, Mao L, Wistuba I, Strieter RM, Kurie JM (2006) High expression of ligands for chemokine receptor CXCR2 in alveolar epithelial neoplasia induced by oncogenic kras. Cancer Res 66(8):4198–4207

    CAS  PubMed  Google Scholar 

  57. Yanagawa J, Walser TC, Zhu LX, Hong L, Fishbein MC, Mah V, Chia D, Goodglick L, Elashoff DA, Luo J, Magyar CE, Dohadwala M, Lee JM, John MA St, Strieter RM, Sharma S, Dubinett SM (2009) Snail promotes CXCR2 ligand-dependent tumor progression in non-small cell lung carcinoma. Clin Cancer Res 15(22):6820–6829

    CAS  PubMed Central  PubMed  Google Scholar 

  58. Saintigny P, Massarelli E, Lin S, Ahn YH, Chen Y, Goswami S, Erez B, O’Reilly MS, Liu D, Lee JJ, Zhang L, Ping Y, Behrens C, Solis Soto LM, Heymach JV, Kim ES, Herbst RS, Lippman SM, Wistuba II, Hong WK, Kurie JM, Koo JS (2013) CXCR2 expression in tumor cells is a poor prognostic factor and promotes invasion and metastasis in lung adenocarcinoma. Cancer Res 73(2):571–582

    CAS  PubMed Central  PubMed  Google Scholar 

  59. Pinto A, Morello S, Sorrentino R (2011) Lung cancer and Toll-like receptors. Cancer Immunol Immunother 60(9):1211–1220 (CII)

    CAS  PubMed  Google Scholar 

  60. Shapiro SD, Goldstein NM, Houghton AM, Kobayashi DK, Kelley D, Belaaouaj A (2003) Neutrophil elastase contributes to cigarette smoke-induced emphysema in mice. Am J Pathol 163(6):2329–2335

    CAS  PubMed Central  PubMed  Google Scholar 

  61. Houghton AM, Rzymkiewicz DM, Ji H, Gregory AD, Egea EE, Metz HE, Stolz DB, Land SR, Marconcini LA, Kliment CR, Jenkins KM, Beaulieu KA, Mouded M, Frank SJ, Wong KK, Shapiro SD (2010) Neutrophil elastase-mediated degradation of IRS-1 accelerates lung tumor growth. Nat Med 16(2):219–223

    CAS  PubMed Central  PubMed  Google Scholar 

  62. Foley CJ, Luo C, O’Callaghan K, Hinds PW, Covic L, Kuliopulos A (2012) Matrix metalloprotease-1a promotes tumorigenesis and metastasis. J Biol Chem 287(29):24330–24338

    CAS  PubMed Central  PubMed  Google Scholar 

  63. Lu X, Wang Q, Hu G, Van Poznak C, Fleisher M, Reiss M, Massague J, Kang Y (2009) ADAMTS1 and MMP1 proteolytically engage EGF-like ligands in an osteolytic signaling cascade for bone metastasis. Genes Dev 23(16):1882–1894

    CAS  PubMed Central  PubMed  Google Scholar 

  64. D'Armiento J, Dalal SS, Okada Y, Berg RA, Chada K (1992) Collagenase expression in the lungs of transgenic mice causes pulmonary emphysema. Cell 71(6):955–961

    PubMed  Google Scholar 

  65. Vignola AM, Riccobono L, Mirabella A, Profita M, Chanez P, Bellia V, Mautino G, D’Accardi P, Bousquet J, Bonsignore G (1998) Sputum metalloproteinase-9/tissue inhibitor of metalloproteinase-1 ratio correlates with airflow obstruction in asthma and chronic bronchitis. Am J Respir Crit Care Med 158(6):1945–1950

    CAS  PubMed  Google Scholar 

  66. Creighton C, Hanash S (2003) Expression of matrix metalloproteinase 9 (MMP-9/gelatinase B) in adenocarcinomas strongly correlated with expression of immune response genes. In Silico Biol 3(3):301–311

    CAS  PubMed  Google Scholar 

  67. Hautamaki RD, Kobayashi DK, Senior RM, Shapiro SD (1997) Requirement for macrophage elastase for cigarette smoke-induced emphysema in mice. Science 277(5334):2002–2004

    CAS  PubMed  Google Scholar 

  68. Acuff HB, Sinnamon M, Fingleton B, Boone B, Levy SE, Chen X, Pozzi A, Carbone DP, Schwartz DR, Moin K, Sloane BF, Matrisian LM (2006) Analysis of host- and tumor-derived proteinases using a custom dual species microarray reveals a protective role for stromal matrix metalloproteinase-12 in non-small cell lung cancer. Cancer Res 66(16):7968–7975

    CAS  PubMed  Google Scholar 

  69. Houghton AM, Grisolano JL, Baumann ML, Kobayashi DK, Hautamaki RD, Nehring LC, Cornelius LA, Shapiro SD (2006) Macrophage elastase (matrix metalloproteinase-12) suppresses growth of lung metastases. Cancer Res 66(12):6149–6155

    CAS  PubMed  Google Scholar 

  70. Qu P, Du H, Wang X, Yan C (2009) Matrix metalloproteinase 12 overexpression in lung epithelial cells plays a key role in emphysema to lung bronchioalveolar adenocarcinoma transition. Cancer Res 69(18):7252–7261

    CAS  PubMed Central  PubMed  Google Scholar 

  71. Li Q, Withoff S, Verma IM (2005) Inflammation-associated cancer: NF-kappaB is the lynchpin. Trends Immunol 26(6):318–325

    PubMed  Google Scholar 

  72. Tsurutani J, Castillo SS, Brognard J, Granville CA, Zhang C, Gills JJ, Sayyah J, Dennis PA (2005) Tobacco components stimulate Akt-dependent proliferation and NFkappaB-dependent survival in lung cancer cells. Carcinogenesis 26(7):1182–1195

    CAS  PubMed  Google Scholar 

  73. Shishodia S, Koul D, Aggarwal BB (2004) Cyclooxygenase (COX)-2 inhibitor celecoxib abrogates TNF-induced NF-kappa B activation through inhibition of activation of I kappa B alpha kinase and Akt in human non-small cell lung carcinoma: correlation with suppression of COX-2 synthesis. J Immunol 173(3):2011–2022

    CAS  PubMed  Google Scholar 

  74. Tichelaar JW, Zhang Y, leRiche JC, Biddinger PW, Lam S, Anderson MW (2005) Increased staining for phospho-Akt, p65/RELA and cIAP-2 in pre-neoplastic human bronchial biopsies. BMC Cancer 5:155

    PubMed Central  PubMed  Google Scholar 

  75. Tang X, Liu D, Shishodia S, Ozburn N, Behrens C, Lee JJ, Hong WK, Aggarwal BB, Wistuba II (2006) Nuclear factor-kappaB (NF-kappaB) is frequently expressed in lung cancer and preneoplastic lesions. Cancer 107(11):2637–2646

    CAS  PubMed  Google Scholar 

  76. Behrens C, Feng L, Kadara H, Kim HJ, Lee JJ, Mehran R, Hong WK, Lotan R, Wistuba II (2010) Expression of interleukin-1 receptor-associated kinase-1 in non-small cell lung carcinoma and preneoplastic lesions. Clin Cancer Res 16(1):34–44

    CAS  PubMed Central  PubMed  Google Scholar 

  77. Pikarsky E, Porat RM, Stein I, Abramovitch R, Amit S, Kasem S, Gutkovich-Pyest E, Urieli-Shoval S, Galun E, Ben-Neriah Y (2004) NF-kappaB functions as a tumour promoter in inflammation-associated cancer. Nature 431(7007):461–466

    CAS  PubMed  Google Scholar 

  78. DiDonato JA, Mercurio F, Karin M (2012) NF-kappaB and the link between inflammation and cancer. Immunol Rev 246(1):379–400

    PubMed  Google Scholar 

  79. Meylan E, Dooley AL, Feldser DM, Shen L, Turk E, Ouyang C, Jacks T (2009) Requirement for NF-kappaB signalling in a mouse model of lung adenocarcinoma. Nature 462(7269):104–107

    CAS  PubMed Central  PubMed  Google Scholar 

  80. Lee NJ, Choi DY, Song JK, Jung YY, Kim DH, Kim TM, Kim DJ, Kwon SM, Kim KB, Choi KE, Moon DC, Kim Y, Han SB, Hong JT (2012) Deficiency of C-C chemokine receptor 5 suppresses tumor development via inactivation of NF-kappaB and inhibition of monocyte chemoattractant protein-1 in urethane-induced lung tumor model. Carcinogenesis 33(12):2520–2528

    CAS  PubMed  Google Scholar 

  81. Sfikas A, Batsi C, Tselikou E, Vartholomatos G, Monokrousos N, Pappas P, Christoforidis S, Tzavaras T, Kanavaros P, Gorgoulis VG, Marcu KB, Kolettas E (2012) The canonical NF-kappaB pathway differentially protects normal and human tumor cells from ROS-induced DNA damage. Cell Signal 24(11):2007–2023

    CAS  PubMed Central  PubMed  Google Scholar 

  82. Houghton AM, Mouded M, Shapiro SD (2008) Common origins of lung cancer and COPD. Nat Med 14(10):1023–1024

    CAS  PubMed  Google Scholar 

  83. Fujimoto J, Kadara H, Men T, van Pelt C, Lotan D, Lotan R (2010) Comparative functional genomics analysis of NNK tobacco-carcinogen induced lung adenocarcinoma development in Gprc5a-knockout mice. PloS One 5(7):e11847

    PubMed Central  PubMed  Google Scholar 

  84. Fujimoto J, Kadara H, Garcia MM, Kabbout M, Behrens C, Liu DD, Lee JJ, Solis LM, Kim ES, Kalhor N, Moran C, Sharafkhaneh A, Lotan R, Wistuba II (2012) G-protein coupled receptor family C, group 5, member A (GPRC5A) expression is decreased in the adjacent field and normal bronchial epithelia of patients with chronic obstructive pulmonary disease and non-small-cell lung cancer. J Thorac Oncol 7(12):1747–1754 (Official publication of the International Association for the Study of Lung Cancer)

    CAS  PubMed Central  PubMed  Google Scholar 

  85. Xue W, Meylan E, Oliver TG, Feldser DM, Winslow MM, Bronson R, Jacks T (2011) Response and resistance to NF-kappaB inhibitors in mouse models of lung adenocarcinoma. Cancer Discov 1(3):236–247

    CAS  PubMed Central  PubMed  Google Scholar 

  86. Suzuki J, Ogawa M, Muto S, Itai A, Isobe M, Hirata Y, Nagai R (2011) Novel IkB kinase inhibitors for treatment of nuclear factor-kB-related diseases. Expert Opin Investig Drugs 20(3):395–405

    CAS  PubMed  Google Scholar 

  87. Dannenberg AJ, Altorki NK, Boyle JO, Dang C, Howe LR, Weksler BB, Subbaramaiah K (2001) Cyclo-oxygenase 2: a pharmacological target for the prevention of cancer. Lancet Oncol 2(9):544–551

    CAS  PubMed  Google Scholar 

  88. Huang RY, Chen GG (2011) Cigarette smoking, cyclooxygenase-2 pathway and cancer. Biochim Biophys Acta 1815(2):158–169

    CAS  PubMed  Google Scholar 

  89. Hasturk S, Kemp B, Kalapurakal SK, Kurie JM, Hong WK, Lee JS (2002) Expression of cyclooxygenase-1 and cyclooxygenase-2 in bronchial epithelium and nonsmall cell lung carcinoma. Cancer 94(4):1023–1031

    CAS  PubMed  Google Scholar 

  90. Mascaux C, Martin B, Verdebout JM, Ninane V, Sculier JP (2005) COX-2 expression during early lung squamous cell carcinoma oncogenesis. Eur Respir J 26(2):198–203

    CAS  PubMed  Google Scholar 

  91. Khuri FR, Wu H, Lee JJ, Kemp BL, Lotan R, Lippman SM, Feng L, Hong WK, Xu XC (2001) Cyclooxygenase-2 overexpression is a marker of poor prognosis in stage I non-small cell lung cancer. Clin Cancer Res 7(4):861–867

    CAS  PubMed  Google Scholar 

  92. Schroeder CP, Kadara H, Lotan D, Woo JK, Lee HY, Hong WK, Lotan R (2006) Involvement of mitochondrial and Akt signaling pathways in augmented apoptosis induced by a combination of low doses of celecoxib and N-(4-hydroxyphenyl) retinamide in premalignant human bronchial epithelial cells. Cancer Res 66(19):9762–9770

    CAS  PubMed  Google Scholar 

  93. Sporn MB, Liby KT (2012) NRF2 and cancer: the good, the bad and the importance of context. Nat Rev Cancer 12(8):564–571

    CAS  PubMed  Google Scholar 

  94. Nguyen T, Nioi P, Pickett CB (2009) The Nrf2-antioxidant response element signaling pathway and its activation by oxidative stress. J Biol Chem 284(20):13291–13295

    CAS  PubMed Central  PubMed  Google Scholar 

  95. Rangasamy T, Cho CY, Thimmulappa RK, Zhen L, Srisuma SS, Kensler TW, Yamamoto M, Petrache I, Tuder RM, Biswal S (2004) Genetic ablation of Nrf2 enhances susceptibility to cigarette smoke-induced emphysema in mice. J Clin Invest 114(9):1248–1259

    CAS  PubMed Central  PubMed  Google Scholar 

  96. Satoh H, Moriguchi T, Taguchi K, Takai J, Maher JM, Suzuki T, Winnard PT Jr, Raman V, Ebina M, Nukiwa T, Yamamoto M (2010) Nrf2-deficiency creates a responsive microenvironment for metastasis to the lung. Carcinogenesis 31(10):1833–1843

    CAS  PubMed  Google Scholar 

  97. Eba S, Hoshikawa Y, Moriguchi T, Mitsuishi Y, Satoh H, Ishida K, Watanabe T, Shimizu T, Shimokawa H, Okada Y, Yamamoto M, Kondo T (2013) The Nrf2 activator oltipraz attenuates chronic hypoxia-induced cardiopulmonary alterations in mice. Am J Respir Cell Mol Biol 49(2):324–333

    CAS  PubMed  Google Scholar 

  98. DeNicola GM, Karreth FA, Humpton TJ, Gopinathan A, Wei C, Frese K, Mangal D, Yu KH, Yeo CJ, Calhoun ES, Scrimieri F, Winter JM, Hruban RH, Iacobuzio-Donahue C, Kern SE, Blair IA, Tuveson DA (2011) Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis. Nature 475(7354):106–109

    CAS  PubMed Central  PubMed  Google Scholar 

  99. Homma S, Ishii Y, Morishima Y, Yamadori T, Matsuno Y, Haraguchi N, Kikuchi N, Satoh H, Sakamoto T, Hizawa N, Itoh K, Yamamoto M (2009) Nrf2 enhances cell proliferation and resistance to anticancer drugs in human lung cancer. Clin Cancer Res 15(10):3423–3432

    CAS  PubMed  Google Scholar 

  100. Solis LM, Behrens C, Dong W, Suraokar M, Ozburn NC, Moran CA, Corvalan AH, Biswal S, Swisher SG, Bekele BN, Minna JD, Stewart DJ, Wistuba II (2010) Nrf2 and Keap1 abnormalities in non-small cell lung carcinoma and association with clinicopathologic features. Clin Cancer Res 16(14):3743–3753

    CAS  PubMed Central  PubMed  Google Scholar 

  101. Cancer Genome Atlas Research Network (2012) Comprehensive genomic characterization of squamous cell lung cancers. Nature 489(7417):519–525

    Google Scholar 

  102. Imielinski M, Berger AH, Hammerman PS, Hernandez B, Pugh TJ, Hodis E, Cho J, Suh J, Capelletti M, Sivachenko A, Sougnez C, Auclair D, Lawrence MS, Stojanov P, Cibulskis K, Choi K, de Waal L, Sharifnia T, Brooks A, Greulich H, Banerji S, Zander T, Seidel D, Leenders F, Ansen S, Ludwig C, Engel-Riedel W, Stoelben E, Wolf J, Goparju C, Thompson K, Winckler W, Kwiatkowski D, Johnson BE, Janne PA, Miller VA, Pao W, Travis WD, Pass HI, Gabriel SB, Lander ES, Thomas RK, Garraway LA, Getz G, Meyerson M (2012) Mapping the hallmarks of lung adenocarcinoma with massively parallel sequencing. Cell 150(6):1107–1120

    CAS  PubMed Central  PubMed  Google Scholar 

  103. Satoh H, Moriguchi T, Takai J, Ebina M, Yamamoto M (2013) Nrf2 prevents initiation but accelerates progression through the Kras signaling pathway during lung carcinogenesis. Cancer Res 76(13):4158–4168

    Google Scholar 

  104. Topalian SL, Drake CG, Pardoll DM (2012) Targeting the PD-1/B7-H1(PD-L1) pathway to activate anti-tumor immunity. Curr Opin Immunol 24(2):207–212

    CAS  PubMed Central  PubMed  Google Scholar 

  105. Grosso JF, Jure-Kunkel MN (2013) CTLA-4 blockade in tumor models: an overview of preclinical and translational research. Cancer Immu 13:5

    Google Scholar 

  106. Lynch TJ, Bondarenko I, Luft A, Serwatowski P, Barlesi F, Chacko R, Sebastian M, Neal J, Lu H, Cuillerot JM, Reck M (2012) Ipilimumab in combination with paclitaxel and carboplatin as first-line treatment in stage IIIB/IV non-small-cell lung cancer: results from a randomized, double-blind, multicenter phase II study. J Clin Oncol 30(17):2046–2054

    CAS  PubMed  Google Scholar 

  107. Zielinski C, Knapp S, Mascaux C, Hirsch F (2013) Rationale for targeting the immune system through checkpoint molecule blockade in the treatment of non-small-cell lung cancer. Ann Oncol 24(5):1170–1179 (Official journal of the European Society for Medical Oncology/ ESMO)

    CAS  PubMed Central  PubMed  Google Scholar 

  108. Dong H, Strome SE, Salomao DR, Tamura H, Hirano F, Flies DB, Roche PC, Lu J, Zhu G, Tamada K, Lennon VA, Celis E, Chen L (2002) Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med 8(8):793–800

    CAS  PubMed  Google Scholar 

  109. Freeman GJ, Long AJ, Iwai Y, Bourque K, Chernova T, Nishimura H, Fitz LJ, Malenkovich N, Okazaki T, Byrne MC, Horton HF, Fouser L, Carter L, Ling V, Bowman MR, Carreno BM, Collins M, Wood CR, Honjo T (2000) Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med 192(7):1027–1034

    CAS  PubMed Central  PubMed  Google Scholar 

  110. Zhang Y, Huang S, Gong D, Qin Y, Shen Q (2010) Programmed death-1 upregulation is correlated with dysfunction of tumor-infiltrating CD8+ T lymphocytes in human non-small cell lung cancer. Cell Mol Immunol 7(5):389–395

    PubMed Central  PubMed  Google Scholar 

  111. Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Carvajal RD, Sosman JA, Atkins MB, Leming PD, Spigel DR, Antonia SJ, Horn L, Drake CG, Pardoll DM, Chen L, Sharfman WH, Anders RA, Taube JM, McMiller TL, Xu H, Korman AJ, Jure-Kunkel M, Agrawal S, McDonald D, Kollia GD, Gupta A, Wigginton JM, Sznol M (2012) Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 366(26):2443–2454

    CAS  PubMed Central  PubMed  Google Scholar 

  112. Brahmer JR, Tykodi SS, Chow LQ, Hwu WJ, Topalian SL, Hwu P, Drake CG, Camacho LH, Kauh J, Odunsi K, Pitot HC, Hamid O, Bhatia S, Martins R, Eaton K, Chen S, Salay TM, Alaparthy S, Grosso JF, Korman AJ, Parker SM, Agrawal S, Goldberg SM, Pardoll DM, Gupta A, Wigginton JM (2012) Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med 366(26):2455–2465

    CAS  PubMed Central  PubMed  Google Scholar 

  113. Engels EA, Wu X, Gu J, Dong Q, Liu J, Spitz MR (2007) Systematic evaluation of genetic variants in the inflammation pathway and risk of lung cancer. Cancer Res 67(13):6520–6527

    CAS  PubMed  Google Scholar 

  114. Kiyohara C, Horiuchi T, Takayama K, Nakanishi Y (2010) IL1B rs1143634 polymorphism, cigarette smoking, alcohol use, and lung cancer risk in a Japanese population. J Thorac Oncol 5(3):299–304 (Official publication of the International Association for the Study of Lung Cancer)

    PubMed  Google Scholar 

  115. Song B, Liu Y, Liu J, Song X, Wang Z, Wang M, Zhu Y, Han J (2011) CTLA-4+ 49A > G polymorphism is associated with advanced non-small cell lung cancer prognosis. Respiration 82(5):439–444 (International review of thoracic diseases)

    CAS  PubMed  Google Scholar 

  116. Karabon L, Pawlak E, Tomkiewicz A, Jedynak A, Passowicz-Muszynska E, Zajda K, Jonkisz A, Jankowska R, Krzakowski M, Frydecka I (2011) CTLA-4, CD28, and ICOS gene polymorphism associations with non-small-cell lung cancer. Hum Immunol 72(10):947–954

    CAS  PubMed  Google Scholar 

  117. 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 (2008) Genome-wide association scan of tag SNPs identifies a susceptibility locus for lung cancer at 15q25.1. Nat Genet 40(5):616–622

    CAS  PubMed Central  PubMed  Google Scholar 

  118. Thorgeirsson TE, Gudbjartsson DF, Surakka I, Vink JM, Amin N, Geller F, Sulem P, Rafnar T, Esko T, Walter S, Gieger C, Rawal R, Mangino M, Prokopenko I, Magi R, Keskitalo K, Gudjonsdottir IH, Gretarsdottir S, Stefansson H, Thompson JR, Aulchenko YS, Nelis M, Aben KK, den Heijer M, Dirksen A, Ashraf H, Soranzo N, Valdes AM, Steves C, Uitterlinden AG, Hofman A, Tonjes A, Kovacs P, Hottenga JJ, Willemsen G, Vogelzangs N, Doring A, Dahmen N, Nitz B, Pergadia ML, Saez B, De Diego V, Lezcano V, Garcia-Prats MD, Ripatti S, Perola M, Kettunen J, Hartikainen AL, Pouta A, Laitinen J, Isohanni M, Huei-Yi S, Allen M, Krestyaninova M, Hall AS, Jones GT, van Rij AM, Mueller T, Dieplinger B, Haltmayer M, Jonsson S, Matthiasson SE, Oskarsson H, Tyrfingsson T, Kiemeney LA, Mayordomo JI, Lindholt JS, Pedersen JH, Franklin WA, Wolf H, Montgomery GW, Heath AC, Martin NG, Madden PA, Giegling I, Rujescu D, Jarvelin MR, Salomaa V, Stumvoll M, Spector TD, Wichmann HE, Metspalu A, Samani NJ, Penninx BW, Oostra BA, Boomsma DI, Tiemeier H, van Duijn CM, Kaprio J, Gulcher JR, Consortium E, McCarthy MI, Peltonen L, Thorsteinsdottir U, Stefansson K (2010) Sequence variants at CHRNB3-CHRNA6 and CYP2A6 affect smoking behavior. Nat Genet 42(5):448–453

    CAS  PubMed Central  PubMed  Google Scholar 

  119. Truong T, Hung RJ, Amos CI, Wu X, Bickeboller H, Rosenberger A, Sauter W, Illig T, Wichmann HE, Risch A, Dienemann H, Kaaks R, Yang P, Jiang R, Wiencke JK, Wrensch M, Hansen H, Kelsey KT, Matsuo K, Tajima K, Schwartz AG, Wenzlaff A, Seow A, Ying C, Staratschek-Jox A, Nurnberg P, Stoelben E, Wolf J, Lazarus P, Muscat JE, Gallagher CJ, Zienolddiny S, Haugen A, van der Heijden HF, Kiemeney LA, Isla D, Mayordomo JI, Rafnar T, Stefansson K, Zhang ZF, Chang SC, Kim JH, Hong YC, Duell EJ, Andrew AS, Lejbkowicz F, Rennert G, Muller H, Brenner H, Marchand L L, Benhamou S, Bouchardy C, Teare MD, Xue X, McLaughlin J, Liu G, McKay JD, Brennan P, Spitz MR (2010) Replication of lung cancer susceptibility loci at chromosomes 15q25, 5p15, and 6p21: a pooled analysis from the international lung cancer consortium. J Natl Cancer Inst 102(13):959–971

    CAS  PubMed Central  PubMed  Google Scholar 

  120. Pillai SG, Kong X, Edwards LD, Cho MH, Anderson WH, Coxson HO, Lomas DA, Silverman EK, Eclipse, Investigators I (2010) Loci identified by genome-wide association studies influence different disease-related phenotypes in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 182(12):1498–1505

    PubMed Central  PubMed  Google Scholar 

  121. Hu C, Wang J, Xu Y, Li X, Chen H, Bunjhoo H, Xiong W, Xu Y, Zhao J (2013) Current evidence on the relationship between five polymorphisms in the matrix metalloproteinases (MMP) gene and lung cancer risk: a meta-analysis. Gene 517(1):65–71

    CAS  PubMed  Google Scholar 

  122. Huang D, Yang L, Liu Y, Zhou Y, Guo Y, Pan M, Wang Y, Tan Y, Zhong H, Hu M, Lu W, Ji W, Wang J, Ran P, Zhong N, Zhou Y, Lu J (2013) Functional polymorphisms in NFkappaB1/IkappaBalpha predict risks of chronic obstructive pulmonary disease and lung cancer in Chinese. Hum Genet 132(4):451–460

    CAS  PubMed  Google Scholar 

  123. Takizawa H, Tanaka M, Takami K, Ohtoshi T, Ito K, Satoh M, Okada Y, Yamasawa F, Umeda A (2000) Increased expression of inflammatory mediators in small-airway epithelium from tobacco smokers. Am J Physiol Lung Cell Mol Physiol 278(5):L906–L913

    CAS  PubMed  Google Scholar 

  124. Pine SR, Mechanic LE, Enewold L, Chaturvedi AK, Katki HA, Zheng YL, Bowman ED, Engels EA, Caporaso NE, Harris CC (2011) Increased levels of circulating interleukin 6, interleukin 8, C-reactive protein, and risk of lung cancer. J Natl Cancer Inst 103(14):1112–1122

    CAS  PubMed Central  PubMed  Google Scholar 

  125. Jungraithmayr W, Frings C, Zissel G, Prasse A, Passlick B, Stoelben E (2008) Inflammatory markers in exhaled breath condensate following lung resection for bronchial carcinoma. Respirology 13(7):1022–1027

    PubMed  Google Scholar 

  126. Seike M, Yanaihara N, Bowman ED, Zanetti KA, Budhu A, Kumamoto K, Mechanic LE, Matsumoto S, Yokota J, Shibata T, Sugimura H, Gemma A, Kudoh S, Wang XW, Harris CC (2007) Use of a cytokine gene expression signature in lung adenocarcinoma and the surrounding tissue as a prognostic classifier. J Natl Cancer Inst 99(16):1257–1269

    CAS  PubMed  Google Scholar 

  127. Brichory FM, Misek DE, Yim AM, Krause MC, Giordano TJ, Beer DG, Hanash SM (2001) An immune response manifested by the common occurrence of annexins I and II autoantibodies and high circulating levels of IL-6 in lung cancer. Proc Natl Acad Sci U S A 98(17):9824–9829

    CAS  PubMed Central  PubMed  Google Scholar 

  128. Kaminska J, Kowalska M, Kotowicz B, Fuksiewicz M, Glogowski M, Wojcik E, Chechlinska M, Steffen J (2006) Pretreatment serum levels of cytokines and cytokine receptors in patients with non-small cell lung cancer, and correlations with clinicopathological features and prognosis. M-CSF—an independent prognostic factor. Oncology 70(2):115–125 (The International Society for Cellular)

    CAS  PubMed  Google Scholar 

  129. Wojciechowska-Lacka A, Matecka-Nowak M, Adamiak E, Lacki JK, Cerkaska-Gluszak B (1996) Serum levels of interleukin-10 and interleukin-6 in patients with lung cancer. Neoplasma 43(3):155–158

    CAS  PubMed  Google Scholar 

  130. Yanagawa H, Sone S, Takahashi Y, Haku T, Yano S, Shinohara T, Ogura T (1995) Serum levels of interleukin 6 in patients with lung cancer. Br J Cancer 71(5):1095–1098

    CAS  PubMed Central  PubMed  Google Scholar 

  131. Cremona M, Calabro E, Randi G, De Bortoli M, Mondellini P, Verri C, Sozzi G, Pierotti MA, Vecchia C L, Pastorino U, Bongarzone I (2010) Elevated levels of the acute-phase serum amyloid are associated with heightened lung cancer risk. Cancer 116(5):1326–1335

    CAS  PubMed  Google Scholar 

  132. Sung HJ, Ahn JM, Yoon YH, Rhim TY, Park CS, Park JY, Lee SY, Kim JW, Cho JY (2011) Identification and validation of SAA as a potential lung cancer biomarker and its involvement in metastatic pathogenesis of lung cancer. J Proteome Res 10(3):1383–1395

    CAS  PubMed  Google Scholar 

  133. Cho WC, Yip TT, Cheng WW, Au JS (2010) Serum amyloid A is elevated in the serum of lung cancer patients with poor prognosis. Br J Cancer 102(12):1731–1735

    CAS  PubMed Central  PubMed  Google Scholar 

  134. O’Dowd C, McRae LA, McMillan DC, Kirk A, Milroy R (2010) Elevated preoperative C-reactive protein predicts poor cancer specific survival in patients undergoing resection for non-small cell lung cancer. J Thorac Oncol 5(7):988–992 (Official publication of the International Association for the Study of Lung Cancer)

    PubMed  Google Scholar 

  135. Koch A, Fohlin H, Sorenson S (2009) Prognostic significance of C-reactive protein and smoking in patients with advanced non-small cell lung cancer treated with first-line palliative chemotherapy. J Thorac Oncol 4(3):326–332 (Official publication of the International Association for the Study of Lung Cancer)

    PubMed  Google Scholar 

  136. Allin KH, Bojesen SE, Nordestgaard BG (2009) Baseline C-reactive protein is associated with incident cancer and survival in patients with cancer. J Clin Oncol 27(13):2217–2224

    CAS  PubMed  Google Scholar 

  137. Il’yasova D, Colbert LH, Harris TB, Newman AB, Bauer DC, Satterfield S, Kritchevsky SB (2005) Circulating levels of inflammatory markers and cancer risk in the health aging and body composition cohort. Cancer Epidemiol Biomarkers Prev 14(10):2413–2418 (a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology)

    PubMed  Google Scholar 

  138. Siemes C, Visser LE, Coebergh JW, Splinter TA, Witteman JC, Uitterlinden AG, Hofman A, Pols HA, Stricker BH (2006) C-reactive protein levels, variation in the C-reactive protein gene, and cancer risk: the Rotterdam Study. J Clin Oncol 24(33):5216–5222

    CAS  PubMed  Google Scholar 

  139. Slaughter DP, Southwick HW, Smejkal W (1953) Field cancerization in oral stratified squamous epithelium; clinical implications of multicentric origin. Cancer 6(5):963–968

    CAS  PubMed  Google Scholar 

  140. Auerbach O, Stout AP, Hammond EC, Garfinkel L (1961) Changes in bronchial epithelium in relation to cigarette smoking and in relation to lung cancer. N Engl J Med 265:253–267

    CAS  PubMed  Google Scholar 

  141. Wistuba II, Behrens C, Milchgrub S, Bryant D, Hung J, Minna JD, Gazdar AF (1999) Sequential molecular abnormalities are involved in the multistage development of squamous cell lung carcinoma. Oncogene 18(3):643–650

    CAS  PubMed  Google Scholar 

  142. Wistuba II, Behrens C, Virmani AK, Mele G, Milchgrub S, Girard L, Fondon JW 3rd, Garner HR, McKay B, Latif F, Lerman MI, Lam S, Gazdar AF, Minna JD (2000) High resolution chromosome 3p allelotyping of human lung cancer and preneoplastic/preinvasive bronchial epithelium reveals multiple, discontinuous sites of 3p allele loss and three regions of frequent breakpoints. Cancer Res 60(7):1949–1960

    CAS  PubMed  Google Scholar 

  143. Wistuba II, Berry J, Behrens C, Maitra A, Shivapurkar N, Milchgrub S, Mackay B, Minna JD, Gazdar AF (2000) Molecular changes in the bronchial epithelium of patients with small cell lung cancer. Clin Cancer Res 6(7):2604–2610

    CAS  PubMed  Google Scholar 

  144. Mao L, Lee JS, Kurie JM, Fan YH, Lippman SM, Lee JJ, Ro JY, Broxson A, Yu R, Morice RC, Kemp BL, Khuri FR, Walsh GL, Hittelman WN, Hong WK (1997) Clonal genetic alterations in the lungs of current and former smokers. J Natl Cancer Inst 89(12):857–862

    CAS  PubMed  Google Scholar 

  145. Wistuba II, Lam S, Behrens C, Virmani AK, Fong KM, LeRiche J, Samet JM, Srivastava S, Minna JD, Gazdar AF (1997) Molecular damage in the bronchial epithelium of current and former smokers. J Natl Cancer Inst 89(18):1366–1373

    CAS  PubMed  Google Scholar 

  146. Hackett NR, Heguy A, Harvey BG, O'Connor TP, Luettich K, Flieder DB, Kaplan R, Crystal RG (2003) Variability of antioxidant-related gene expression in the airway epithelium of cigarette smokers. Am J Respir Cell Mol Biol 29(3 Pt 1):331–343

    CAS  PubMed  Google Scholar 

  147. 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 2(26):26ra25

    Google Scholar 

  148. Kadara H, Shen L, Fujimoto J, Saintigny P, Chow CW, Lang W, Chu Z, Garcia M, Kabbout M, Fan YH, Behrens C, Liu DA, Mao L, Lee JJ, Gold KA, Wang J, Coombes KR, Kim ES, Hong WK, Wistuba II (2013) Characterizing the molecular spatial and temporal field of injury in early-stage smoker non-small cell lung cancer patients after definitive surgery by expression profiling. Cancer Prev Res 6(1):8–17

    CAS  Google Scholar 

  149. Kadara H, Wistuba II (2012) Field cancerization in non-small cell lung cancer: implications in disease pathogenesis. Proc Am Thorac Soc 9(2):38–42

    CAS  PubMed  Google Scholar 

  150. Tang X, Shigematsu H, Bekele BN, Roth JA, Minna JD, Hong WK, Gazdar AF, Wistuba II (2005) EGFR tyrosine kinase domain mutations are detected in histologically normal respiratory epithelium in lung cancer patients. Cancer Res 65(17):7568–7572

    CAS  PubMed  Google Scholar 

  151. Franklin WA, Gazdar AF, Haney J, Wistuba, II, Rosa FG L, Kennedy T, Ritchey DM, Miller YE (1997) Widely dispersed p53 mutation in respiratory epithelium. A novel mechanism for field carcinogenesis. J Clin Invest 100(8):2133–2137

    CAS  PubMed Central  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Ignacio I. Wistuba

  2. Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Humam Kadara

  3. Department of Pathology, University of Colorado Anschutz Medical Campus, 80045, Aurora, CO, USA

    Wilbur A. Franklin

Authors
  1. Humam Kadara
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wilbur A. Franklin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ignacio I. Wistuba
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Wilbur A. Franklin or Ignacio I. Wistuba .

Editor information

Editors and Affiliations

  1. David Geffen School of Medicine at UCLA, Los Angeles, California, USA

    Steven M. Dubinett

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer Science+Business Media New York

About this chapter

Cite this chapter

Kadara, H., Franklin, W., Wistuba, I. (2015). Inflammation and Lung Cancer: Molecular Pathology. In: Dubinett, S. (eds) Inflammation and Lung Cancer. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-2724-1_3

Download citation

Publish with us

Policies and ethics

Search

Navigation