Lung Cancer Prevention

  • Eva SzaboEmail author


Lung cancer is the leading cause of cancer mortality in the United States, representing a greater number of deaths than the sum of the next three causes of cancer mortality combined. Despite a rapidly increasing understanding of the biology of lung cancer and the development of effective new targeted therapies and immunotherapy that improve survival for a significant subgroup of patients, lung cancer continues to represent a major societal burden in both high and low income countries. Although the long-term recognition of cigarette smoking as the major cause of lung cancer, with attendant policy shifts, has helped to curb the lung cancer epidemic in the USA, high use of tobacco products continues in other parts of the world. Early detection and prevention of lung cancer provide opportunities to reduce the global burden of this highly lethal disease.


  1. Alberg AJ, Brock MV, Ford JG, Samet JM, Spivack SD (2013) Epidemiology of lung cancer. Chest 143(Suppl):e1S–e29SPubMedPubMedCentralCrossRefGoogle Scholar
  2. Alexandrov LB, Ju YS, Haase K, Van Loo P, Martincorena I et al (2016) Mutational signatures associated with tobacco smoking in human cancer. Science 354:618–622PubMedPubMedCentralCrossRefGoogle Scholar
  3. Algra AM, Rothwell PM (2012) Effects of regular aspirin on long-term cancer incidence and metastasis: a systematic comparison of evidence from observational studies versus randomised trials. Lancet Oncol 13:518–527PubMedCrossRefPubMedCentralGoogle Scholar
  4. Amos CI, Wu X, Broderick P, Gorlov IP, Gu J et al (2008) Genome-wide association scan of tag SNPs identifies a susceptibility locus for lung cancer at 15q25.1. Nat Gen 40(5):616–622CrossRefGoogle Scholar
  5. 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 265:253–267PubMedCrossRefPubMedCentralGoogle Scholar
  6. Belinsky SA, Palmisano WA, Gilliland FD et al (2002) Aberrant promoter methylation in bronchial epithelium and sputum from current and former smokers. Cancer Res 62:2370–2377Google Scholar
  7. Bell DW, Gore I, Okimoto RA, Godin-Heymann N, Sordella R et al (2005) Inherited susceptibility to lung cancer may be associated with the T790M drug resistance mutation in EGFR. Nat Gen 37(12):1315–1316CrossRefGoogle Scholar
  8. van Boerdonk RAA, Smessein I, Heideman DAM, Coupe VMH, Tio D et al (2015) Close surveillance with long-term follow-up of subjects with preinvasive endobronchial lesions. Am J Respir Crit Care Med 164:1483–1489CrossRefGoogle Scholar
  9. Boffetta P, Nyberg F (2003) Contribution of environmental factors to cancer risk. Br Med Bull 68:71–94PubMedCrossRefPubMedCentralGoogle Scholar
  10. Bota S, Auliac JB, Paris C et al (2001) Follow-up of bronchial precancerous lesions and carcinoma in situ using fluorescence endoscopy. Am J Respir Crit Care Med 164:1688–1693PubMedCrossRefPubMedCentralGoogle Scholar
  11. Bray F, Ferlay J, Soerjomataram I, Siegel RL et al (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68(6):394–424. Scholar
  12. Bresalier RS, Sandler RS, Quan H, Bolognese JA, Oxenius B et al (2005) Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial. N Engl J Med 352(11):1092–2102PubMedPubMedCentralCrossRefGoogle Scholar
  13. Brothers JF, Hijazi K, Mascaux C, El-Zein RA, Spitz MR, Spira A (2013) Bridging the clinical gaps: genetic, epigenetic and transcriptomic bioamarkers for the early detection of lung cancer in the post-National Lung Screening Trial era. BMC Med 11:168PubMedPubMedCentralCrossRefGoogle Scholar
  14. Burotto M, Szabo E (2014) PPARγ in head and neck cancer prevention. Oral Oncol 50(10):924–929PubMedPubMedCentralCrossRefGoogle Scholar
  15. Byun J, Schwartz AG, Lusk C, Wenzlaff AS, de Andrade M et al (2018) Genome-wide association study of familial lung cancer. Carcinogenesis 39(9):1135–1140PubMedPubMedCentralCrossRefGoogle Scholar
  16. Calabrò E, Randi G, La Vecchia C et al (2010) Lung function predicts lung cancer risk in smokers: a tool for targeting screening programmes. Eur Respir J 35(1):146–151PubMedCrossRefPubMedCentralGoogle Scholar
  17. Campbell JD, Mazzilli SA, Reid ME, Dhillon SS, Platero S et al (2016) The case for a pre-cancer genome atlas (PCGA). Cancer Prev Res 9(2):119–124CrossRefGoogle Scholar
  18. Cancer Genome Atlas Research Network (2012) Comprehensive genomic characterization of squamous cell lung cancers. Nature 489:519–525CrossRefGoogle Scholar
  19. Cancer Genome Atlas Research Network (2014) Comprehensive molecular profiling of lung adenocarcinoma. Nature 511:543–550CrossRefGoogle Scholar
  20. Castonguay A, Rioux N, Duperron C, Jalbert G (1998) Inhibition of lung tumorigenesis by NSAIDS: a working hypothesis. Exp Lung Res 24:605–615PubMedCrossRefPubMedCentralGoogle Scholar
  21. Celik I, Gallicchio L, Boyd K et al (2008) Arsenic in drinking water and lung cancer: a systematic review. Environ Res 10(1):48–55CrossRefGoogle Scholar
  22. Chen BH, Hong CJ, Pandey MR, Smith KR (1990) Indoor air pollution in developing countries. World Health Stat Q 43(3):127–138PubMedPubMedCentralGoogle Scholar
  23. Clark LC, Combs GF, Turnbull BW et al (1996) Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. JAMA 276:1957–1963PubMedCrossRefPubMedCentralGoogle Scholar
  24. Cohen JD, Li L, Wang Y, Thoburn C, Afsari B, Danilova L, Douville C, Javed AA, Wong F, Mattox A, Hruban RH (2018) Detection and localization of surgically resectable cancers with a multi-analyte blood test. Science 359(6378):926–930PubMedPubMedCentralCrossRefGoogle Scholar
  25. Cronin KA, Lake AJ, Scott S, Sherman RL, Noone A-M et al (2018) Annual report the nation on the status of cancer, part I: national cancer statistics. Cancer 124:2785–2800PubMedPubMedCentralCrossRefGoogle Scholar
  26. Cykert S, Dilworth-Anderson P, Monroe MH et al (2010) Factors associated with decisions to undergo surgery among patients with newly diagnosed early-stage lung cancer. JAMA 303:2368–2376PubMedPubMedCentralCrossRefGoogle Scholar
  27. Dajani EZ, Islam K (2008) Cardiovascular and gastrointestinal toxicity of selective cyclo-oxygenase-2 inhibitors in man. J Physiol Pharmacol 59(Suppl 2):117–133PubMedPubMedCentralGoogle Scholar
  28. De Flora S, Balansky R, D’Agostini F, Cartiglia C, Longobardi M, Steele VE, Izzotti A (2012) Smoke-induced microRNA and related proteome alterations. Modulation by chemopreventive agents. Int J Cancer 131(12):12763–12773Google Scholar
  29. DeMatteis S, Consonni D, Bertazzi PA (2008) Exposure to occupational carcinogens and lung cancer risk. Evolution of epidemiological estimates of attributable fraction. Acta Biomed 79(suppl):34–42Google Scholar
  30. Dockery DW, Pope CA III, Xu X et al (1993) An association between air pollution and mortality in six U.S. cities. N Engl J Med 329(24):1753–1759PubMedCrossRefPubMedCentralGoogle Scholar
  31. Doll R, Hill AB (1950) Smoking and carcinoma of the lung: preliminary report. Br Med J 2:739–748PubMedPubMedCentralCrossRefGoogle Scholar
  32. Doll R, Vessey MB, Beasley RW, Buckley AR et al (1972) Mortality of gas workers: final report of a prospective study. Br J Ind Med 29:394PubMedPubMedCentralGoogle Scholar
  33. Etzel CJ, Amos CI et al (2003) Risk for smoking-related cancer among relatives of lung cancer patients. Cancer Res 63(23):8531–8535PubMedPubMedCentralGoogle Scholar
  34. Finn OJ, Beatty PL (2016) Cancer immunoprevention. Curr Opin Immunol 39:52–58PubMedPubMedCentralCrossRefGoogle Scholar
  35. Fontana RS, Sanderson DR et al (1984) Early lung cancer detection: results of the initial (prevalence) radiologic and cytologic screening in the Mayo Clinic study. Am Rev Respir Dis 130(4):561–565PubMedPubMedCentralGoogle Scholar
  36. Frost G, Darnton A, Harding AH (2011) The effect of smoking on the risk of lung cancer mortality for asbestos workers in Great Britain (1971-2005). Ann Occup Hyg 55(3):239–247PubMedPubMedCentralGoogle Scholar
  37. Gandini S, Puntoni M, Heckman-Stoddard BM, Dun BK, Ford L et al (2014) Meformin and cancer risk and mortality: a systematic review and meta-analysis taking into account biases and confounders. Cancer Prev Res 7:867–885CrossRefGoogle Scholar
  38. Govindarajan R, Ratnasinghe L, Simmons DL, Siegel ER, Midathada MV et al (2007) Thiazolidinediones and the risk of lung, prostate, and colon cancer in patients with diabetes. J Clin Oncol 25(12):1476–1481PubMedCrossRefPubMedCentralGoogle Scholar
  39. Gunning WT, Kramer PM, Steele VE et al (2002) Chemoprevention by lipoxygenase and leukotriene pathway inhibitors of vinyl carbamate-induced lung tumors in mice. Cancer Res 62:4199–4201PubMedPubMedCentralGoogle Scholar
  40. Gustafson AM, Soldi R, Anderlind C, Scholand MB, Qian J, Zhang X et al (2010) Airway PI3 pathway activation is an early and reversible event in lung cancer development. Sci Transl Med 2:26ra5CrossRefGoogle Scholar
  41. Hammond EC (1966) Smoking in relation to the death rates of one million men and women. Natl Cancer Inst Monogr 19:127–204PubMedPubMedCentralGoogle Scholar
  42. Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674PubMedPubMedCentralCrossRefGoogle Scholar
  43. Hardy D, Xia R, Liu CC, Cormier JN, Nurgalieva Z et al (2009) Racial disparities and survival for nonsmall cell lung cancer in a large cohort of black and white elderly patients. Cancer 115:4807–4818PubMedCrossRefPubMedCentralGoogle Scholar
  44. Hassanein M, Callison JC, Callaway-Lane C, Aldrich MC, Grogan EL, Massion PP (2012) The state of molecular biomarkers for the early detection of lung cancer. Cancer Prev Res 5:992–1006CrossRefGoogle Scholar
  45. Hecht SS (2012) Research opportunities related to establishing standards for tobacco products under the Family Smoking Prevention and Tobacco Control Act. Nicotine Tob Res 14:18–28PubMedCrossRefPubMedCentralGoogle Scholar
  46. Hecht SS, Szabo E (2014) Fifty years of tobacco carcinogenesis research: form mechanisms to early detection and prevention of lung cancer. Cancer Prev Res 7:1–8CrossRefGoogle Scholar
  47. Hecht SS, Kenney PM, Wang M, Upadhyaya P (2001) Dose–response study of myo-inositol as an inhibitor of lung tumorigenesis induced in A/J mice by benzo[a]pyrene and 4-(methylnitrosamino)-1(3pyridyl)-1butanone. Cancer Lett 167:1–6PubMedCrossRefPubMedCentralGoogle Scholar
  48. Heckman-Stoddard BM, Gandini S, Puntoni M, Dunn BK, DeCensi A, Szabo E (2016) Repurposing old drugs to chemoprevention: the case of metformin. Semin Oncol 43:123–133PubMedCrossRefPubMedCentralGoogle Scholar
  49. Hennekens CH, Buring JE, Manson JE et al (1996) Lack of effect of long-term supplementation with beta carotene on the incidence of malignant neoplasms and cardiovascular disease. N Engl J Med 334:1145–1149CrossRefGoogle Scholar
  50. Henschke CI, McCauley DI et al (1999) Early Lung Cancer Action Project: overall design and findings from baseline screening. Lancet 354(9173):99–105PubMedCrossRefPubMedCentralGoogle Scholar
  51. Holford TR, Levy DT, McKay LA et al (2014) Patterns of birth cohort-specific smoking histories, 1965-2009. Am J Prev Med 46:e31–e37PubMedPubMedCentralCrossRefGoogle Scholar
  52. Hong WK, Endicott J, Itri LM et al (1986) 13-cis-retinoic acid in the treatment of oral leukoplakia. N Engl J Med 315:1501–1505PubMedCrossRefPubMedCentralGoogle Scholar
  53. Hong WK, Lippman SM, Itri LM et al (1990) Prevention of second primary tumors with isotretinoin in squamous-cell carcinoma of the head and neck. N Engl J Med 323:795–801PubMedCrossRefPubMedCentralGoogle Scholar
  54. Howard DJ, Ota RB, Briggs LA Hampton M, Pritsos CA (1998) Environmental tobacco smoke in the workplace induces oxidative stress in employees, including increased production of 8-hydroxy-2′-deoxyguanosine. Cancer Epidemiol Biomark Prev 7(2):141–146Google Scholar
  55. Hung RJ, McKay JD, Gaborieau V, Boffetta P, Hashibe M et al (2008) A susceptibility locus for lung cancer maps to nicotinic acetylcholine receptor subunit genes on 15q25. Nature 452(7187):633–637PubMedCrossRefPubMedCentralGoogle Scholar
  56. International Agency for Research on Cancer (2004) Tobacco smoke and involuntary smoking. In: IARC monographs on the evaluation of carcinogenic risks to humans, vol 83. Lyon, FR, IARC, pp 53–1187Google Scholar
  57. Izumchenko E, Chang X, Brait M, Fertig E, Kagohara LT et al (2015) Targeted sequencing reveals clonal genetic changes in the progression of early lung neoplasms and paired circulation DNA. Nat Com 6:8258CrossRefGoogle Scholar
  58. Jamal A, Phillips E, Gentzke AS, Homa DM, Babb SD et al (2018) Current cigarette smoking among adults – United States 2016. Morb Mortal Wkly Rep 67:53–59CrossRefGoogle Scholar
  59. Jarrard JA, Linnoila RI, Lee HR, Steinberg SM, Witschi H, Szabo E (1998) MUC1 is a novel marker for the type II pneumocyte lineage during lung carcinogenesis. Cancer Res 58:5582–5589PubMedPubMedCentralGoogle Scholar
  60. Jemal A, Miller KD, Ma J, Siegel RL, Fedewa SA et al (2018) Higher lung cancer incidence in young women than young men in the United States. N Engl J Med 378:1999–2009PubMedCrossRefPubMedCentralGoogle Scholar
  61. Jha P, Peto R (2014) Global effects of smoking, of quitting, and of taxing tobacco. N Engl J Med 370:60–68PubMedCrossRefPubMedCentralGoogle Scholar
  62. Kakinuma R, Noguchi M, Ashizawa K, Kuriyama K, Maeshima AM et al (2016) Natural history of pulmonary subsolid nodules: a prospective multicenter study. J Thorac Oncol 11(7):1012–1028PubMedCrossRefPubMedCentralGoogle Scholar
  63. Karp DD, Lee SJ, Keller SM et al (2013) Randomized, double-blind, placebo-controlled, phase III chemoprevention trial of selenium supplementation in patients with resected stage I non-small-cell lung cancer: ECOG 5597. J Clin Oncol 31:4179–4187PubMedPubMedCentralCrossRefGoogle Scholar
  64. Keith RL, Miller YE, Hoshikawa Y et al (2002) Manipulation of pulmonary prostacyclin synthase expression prevents murine lung cancer. Cancer Res 62:734–740PubMedPubMedCentralGoogle Scholar
  65. Keith RL, Miller YE, Hudish TM, Girod CE et al (2004) Pulmonary prostacyclin synthase overexpression chemo prevents tobacco smoke lung carcinogenesis in mice. Cancer Res 64:5897–5904PubMedCrossRefPubMedCentralGoogle Scholar
  66. Keith RL, Blatchford PJ, Kittelson J et al (2011) Oral Iloprost improves endobronchial dysplasia in former smokers. Cancer Prev Res 4(6):793–802CrossRefGoogle Scholar
  67. Kennedy TC, Proudfoot SP et al (1996) Cytopathological analysis of sputum in patients with airflow obstruction and significant smoking histories. Cancer Res 56(20):4673–4678PubMedPubMedCentralGoogle Scholar
  68. Kerr K (1997) Adenomatous hyperplasia and the origin of peripheral adenocarcinoma of the lung. In: Corrin B (ed) Pathology of lung tumors. Churchill Livingstone, New York, pp 119–133Google Scholar
  69. Keshamouni VG, Reddy RC, Arenberg DA et al (2004) Peroxisome proliferator-activated receptor-gamma activation inhibits tumor progression in non-small lung cancer. Oncogene 23:100–108PubMedCrossRefPubMedCentralGoogle Scholar
  70. Kim ES, Hong WK, Lee JJ, Mao L, Morice RC et al (2010) Biological activity of celecoxib in the bronchial epithelium of current and former smokers. Cancer Prev Res 3:148–159CrossRefGoogle Scholar
  71. Kovalchik SA, Tammemagi M, Berg CD, Caporaso NE, Riley TL, Korch M et al (2013) Targeting of low-dose CT screening according to the risk of lung -cancer death. N Engl J Med 369:245–254PubMedPubMedCentralCrossRefGoogle Scholar
  72. Krysan K, Reckamp KL, Sharma S, Dubinett SM (2006) The potential and rationale for COX-2 inhibitors in lung cancer. Anti Cancer Agents Med Chem 6:209–220CrossRefGoogle Scholar
  73. Lam S, Szabo E (2015) Preinvasive endobronchial lesions: lung cancer precursors and risk markers? Amer J Respir Crit Care Med 192(12):1411–1412CrossRefGoogle Scholar
  74. Lam S, MacAulay C, leRiche JC, Palcic B (2000) Detection and localization of early lung cancer by fluorescence bronchoscopy. Cancer 89:2468–2473PubMedCrossRefPubMedCentralGoogle Scholar
  75. Lam S, leRiche JC, McWilliams A et al (2004) A randomized phase IIb trial of pulmicort turbuhaler (budesonide) in people with dysplasia of the bronchial epithelium. Clin Cancer Res 10(19):6502–6511PubMedCrossRefPubMedCentralGoogle Scholar
  76. Lam S, McWilliams A, leRiche J, MacAulay C, Wattenberg L et al (2006) A phase I study of myo-inositol for lung cancer chemoprevention. Cancer Epidemiol Biomark Prev 15(8):1526–1531CrossRefGoogle Scholar
  77. Lam S, Mandrekar SJ, Gesthalter Y, Allen Ziegler KL, Seisler DK et al (2016) A randomized phase IIb trial of myo-inositol in smokers with bronchial dysplasia. Cancer Prev Res 9(12):906–914CrossRefGoogle Scholar
  78. Lazzeroni M, Guerrieri-Gonzaga A, Serrano D, Varricchio MC, Veronesi G (2010) Budesonide versus placebo in high-risk population with screen-detected lung nodules: rationale, design and methodology. Contemp Clin Trials 31:612PubMedPubMedCentralCrossRefGoogle Scholar
  79. Le Gal K, Ibrahim MX, Wiel C, Sayin VI, Akula MK et al (2015) Antioxidants can increase melanoma metastasis in mice. Sci Transl Med 7:308re8PubMedCrossRefPubMedCentralGoogle Scholar
  80. Limburg PJ, Mandrekar SJ, Aubry MC, Ziegler KL et al (2013) Randomized phase II trial of sulindac for lung cancer chemoprevention. Lung Cancer 79(3):254–261PubMedCrossRefPubMedCentralGoogle Scholar
  81. Lin HH, Murray M, Cohen T, Colijn C, Ezzati M (2008) Effects of smoking and solid-fuel use on COPD, lung cancer, and tuberculosis in China: a time-based, multiple risk factor modelling study. Lancet 372(9648):1473–1483PubMedPubMedCentralCrossRefGoogle Scholar
  82. Lippman SM, Batsakis JG, Toth BB et al (1993) Comparison of low-dose isotretinoin with beta carotene to prevent oral carcinogenesis. N Engl J Med 328:15–20PubMedCrossRefPubMedCentralGoogle Scholar
  83. Lippman SM, Lee JJ, Karp DD et al (2001) Randomized phase III intergroup trial of isotretinoin to prevent second primary tumors in stage I non-small-cell lung cancer. J Natl Cancer Inst 93:605–6189PubMedCrossRefPubMedCentralGoogle Scholar
  84. Mai PL, Khincha PP, Loud JT, DeCastro RM, Bremer RC et al (2017) Prevalence of cancer at baseline screening in the National Cancer Institute Li-Fraumeni cohort. JAMA Oncol 3(12):1640–1645PubMedPubMedCentralCrossRefGoogle Scholar
  85. Maisonneuve P, Bagnardi V, Bellomi M et al (2011) Lung cancer risk prediction to select smokers for screening CT—a model based on the Italian COSMOS trial. Cancer Prev Res 4(11):1778–1789CrossRefGoogle Scholar
  86. Manser RL, Irving LB, Stone C, Byrnes G, Abramson M, Campbell D (2004) Screening for lung cancer. Cochrane Database Syst Rev 1:CD001991Google Scholar
  87. Mao JT, Roth MD, Fishbein MC, Aberle DR, Zhang ZF et al (2011) Lung cancer chemoprevention with celecoxib in former smokers. Cancer Prev Res 4:984–993CrossRefGoogle Scholar
  88. Marrone KA, Naidoo J, Brahmer JR (2016) Immunotherapy for lung cancer: no longer an abstract concept. Semin Respir Crit Care Med 37(5):771–782PubMedCrossRefPubMedCentralGoogle Scholar
  89. Mayne ST, Buenconsejo J et al (1999) Familial cancer history and lung cancer risk in United States nonsmoking men and women. Cancer Epidemiol Biomark Prev 8(12):1065–1069Google Scholar
  90. McWilliams A, Tammemagi MC, Mayo JR, Roberts H, Liu G et al (2013) Probability of cancer in pulmonary nodules detected on first screening CT. N Engl J Med 369:910–919PubMedPubMedCentralCrossRefGoogle Scholar
  91. Melamed MR, Flehinger BJ et al (1984) Screening for early lung cancer. Results of the Memorial Sloan-Kettering study in New York. Chest 86(1):44–53PubMedCrossRefPubMedCentralGoogle Scholar
  92. Memmot RM, Mercado JR, Maier CR, Kawabata S, Fox SD, Dennis PA (2010) Metformin prevents tobacco carcinogen–induced lung tumorigenesis. Cancer Prev Res 3(9):1066–1076CrossRefGoogle Scholar
  93. Merrick DT, Gao D, Miller YE, Keith RL, Baron AE et al (2016) Persistence of bronchial dysplasia is associated with development of invasive squamous cell carcinoma. Cancer Prev Res 9(1):96–104CrossRefGoogle Scholar
  94. Merrick DT, Edwards MG, Franklin WA, Sugita M, Keith RL et al (2018) Altered cell-cycle control, inflammation, and adhesion in high-risk persistent bronchial dysplasia. Cancer Res 78(17):4971–4983PubMedPubMedCentralCrossRefGoogle Scholar
  95. Mumford JL, He XZ, Chapman RS, Cao SR, Harris DB et al (1987) Lung cancer and indoor air pollution in Xuan Wei, China. Science 235:217–220PubMedCrossRefPubMedCentralGoogle Scholar
  96. National Lung Screening Trial Research Team (2011) Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med 365(5):395–409CrossRefGoogle Scholar
  97. National Lung Screening Trial Research Team (2013) Results of initial low-dose computed tomographic screening for lung cancer. N Engl J Med 368(21):1980–1991CrossRefGoogle Scholar
  98. Nemenoff R, Meyer AM, Hudish TM, Mozer AB et al (2008) Prostacyclin prevents murine lung cancer independent of the membrane receptor by activation of the peroxisomal proliferator—activated receptor gamma. Cancer Prev Res 1(5):349–356CrossRefGoogle Scholar
  99. Neuberger JS, Field RW (2003) Occupation and lung cancer in nonsmokers. Rev Environ Health 18(4):251–267PubMedCrossRefPubMedCentralGoogle Scholar
  100. Odani S, Armour BS, Graffunder CM, Willis G, Hartman AM et al (2018) State-specific prevalence of tobacco product use among adults -United States 2014-2015. Morb Mortal Wkly Rep 67:97–102CrossRefGoogle Scholar
  101. Oken MM, Hocking WG, Kvale PA, Andriole GL, Buys SS et al (2011) Screening by chest radiograph and lung cancer mortality: the Prostate, Lung, Colorectal, and Ovarian (PLCO) randomized trial. JAMA 306(17):1865–1873PubMedCrossRefPubMedCentralGoogle Scholar
  102. Omenn GS (1998) Chemoprevention of lung cancer: The rise and demise of beta-carotene. Annu Rev Public Health 19:73–99PubMedCrossRefPubMedCentralGoogle Scholar
  103. Omenn GS, Goodman GE, Thornquist MD et al (1996) Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease. N Engl J Med 334:1150–1155CrossRefGoogle Scholar
  104. Parimon T, Chien JW, Bryson CL, McDonell MB, Udris EM, Au DH (2007) Inhaled corticosteroid and risk of lung cancer among patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 175:712–719PubMedCrossRefPubMedCentralGoogle Scholar
  105. Pastorino U, Infante M, Maioli M et al (1993) Adjuvant treatment of stage I lung cancer with high-dose vitamin A. J Clin Oncol 11:1216–1222PubMedCrossRefPubMedCentralGoogle Scholar
  106. Pepin P, Bouchard L, Nicole P et al (1992) Effects of sulindac and oltipraz on the tumorigenicity of 4-(methylnitrosamino)1-(3pyridyl)-1-butanone I A/J mouse lung. Carcinogenesis 13:341–348PubMedCrossRefPubMedCentralGoogle Scholar
  107. Pereira MA, Li Y, Al-Yaqoub F et al (2002) Prevention of mouse lung tumors by budesonide and its modulation of biomarkers. Carcinogenesis 23:1185–1192PubMedCrossRefPubMedCentralGoogle Scholar
  108. Peto R, Darby S, Deo H, Silcocks P, Whitley E et al (2000) Smoking, smoking cessation, and lung cancer in the UK since 1950: combination of national statistics with two case-control studies. Br J Cancer 321:323–329Google Scholar
  109. Pope CA III, Burnett RT, Thun MJ et al (2002) Lung cancer, cardiopulmonary mortality, and long-term exposure to fine particulate air pollution. JAMA 287(9):1132–1141PubMedPubMedCentralCrossRefGoogle Scholar
  110. 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 101:554–559PubMedPubMedCentralCrossRefGoogle Scholar
  111. Ridker PM, MacFadyen JG, Thuren T, Everrett BM, Libby P et al (2017) Effect of interleukin-1β inhibition with canakinumab on incident lung cancer in patients with atherosclerosis: exploratory results from a randomised, double-blind, placebo-controlled trial. Lancet 390(10105):1833–1842PubMedCrossRefPubMedCentralGoogle Scholar
  112. Rivero L, Bunn C (2018) NELSON Study shows CT screening for nodule volume management reduces lung cancer mortality by 26 percent in men. Accessed 3 Aug 2019
  113. Rogot E, Murray J (1980) Cancer mortality among nonsmokers in an insured group of U.S. veterans. J Natl Cancer Inst 65(5):1163–1168PubMedPubMedCentralGoogle Scholar
  114. Rothwell PM, Fowkes FGR, Belch JF, Ogawa H, Warlow CP et al (2011) Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomized trials. Lancet 377:31–41PubMedCrossRefPubMedCentralGoogle Scholar
  115. Roy HK, Subramanian H, Damania D, Hensing TA, Rom WN et al (2010) Optical detection of buccal epithelial nanoarchitectural alterations in patients harboring lung cancer: implications for screening. Cancer Res 70:7748–7754PubMedPubMedCentralCrossRefGoogle Scholar
  116. Ru Zhao Y, Xie X, de Koning HJ, Mali WP, Vliegenthart R, Oudkerk M (2011) NELSON lung cancer screening study. Cancer Imaging 11:S79–S84PubMedCrossRefPubMedCentralGoogle Scholar
  117. Saccomanno G, Archer VE, Auerbach O, Saunders RP, Brennan LM (1974) Development of carcinoma of the lung as reflected in exfoliated cells. Cancer 33:256–270PubMedCrossRefPubMedCentralGoogle Scholar
  118. Saini RK, Sanyal SN (2009) Chemopreventive effect of nonsteroidal anti-inflammatory drugs on 9,10-dimethylbenz[a]anthracene-induced lung carcinogenesis in mice. Oncol Res 17:505–518PubMedCrossRefPubMedCentralGoogle Scholar
  119. Sakoda LC, Ferrara A, Achacoso NS, Peng T, Ehrlich SF et al (2015) Cancer Prev Res 8(2):174–179CrossRefGoogle Scholar
  120. Sayin VI, Ibrahim MX, Larsson E, Nilsson JA, Lindahl P et al (2014) Antioxidants accelerate lung cancer progression in mice. Sci Transl Med 6:221ra15PubMedCrossRefPubMedCentralGoogle Scholar
  121. Schatzkin A, Gail M (2002) The promise and peril of surrogate end points in cancer research. Nat Rev Cancer 2:1–9CrossRefGoogle Scholar
  122. Shopland DR (1995) Tobacco use and its contribution to early cancer mortality with a special emphasis on cigarette smoking. Environ Health Perspect 103(Suppl 8):131–142PubMedPubMedCentralCrossRefGoogle Scholar
  123. Siegel RL, Miller KD, Jemal A (2018) Cancer statistics, 2018. CA Cancer J Clin 68:7–30CrossRefGoogle Scholar
  124. Sivakumar S, San Lucas FA, McDowell TL, Lang W, Xu L et al (2017) Genomic landscape of atypical adenomatous hyperplasia reveals divergent modes to lung adenocarcinoma. Cancer Res 77(22):6119–6130PubMedPubMedCentralCrossRefGoogle Scholar
  125. Slaughter DP, Southwick HW, Smejkal W (1953) Field cancerization in oral stratified squamous epithelium; clinical implications of multicentric origin. Cancer 6:963–968CrossRefGoogle Scholar
  126. Soo RA, Loh M, Mok TS et al (2011) Ethnic differences in survival outcome in patients with advanced stage non-small cell lung cancer: results of a meta-analysis of randomized controlled trials. J Thorac Oncol 6:1030–1038PubMedCrossRefPubMedCentralGoogle Scholar
  127. Spira A, Beane J, Shah V, Liu G, Schembri F, Yang XM, Palma J, Brody JS (2004) Effects of cigarette smoke on the human airway epithelial cell transcriptome. Proc Natl Acad Sci U S A 101:10143–10148PubMedPubMedCentralCrossRefGoogle Scholar
  128. Sporn MB, Dunlop NM, Newton DL, Smith JM (1976) Prevention of chemical carcinogenesis by vitamin A and its synthetic analogs (retinoids). Fed Proc 35(6):1332–1338Google Scholar
  129. Sridhar S, Schembri F, Zeskind J, Shah V, Gustafson AM, Steiling K, Liu G, Dumas YM, Zhang XH, Brody JS, Lenburg ME, Spira A (2008) Smoking-induced gene expression changes in the bronchial airway are reflected in nasal and buccal epithelium. BMC Genomics 9:259PubMedPubMedCentralCrossRefGoogle Scholar
  130. Subbaramaiah K, Dannenberg AJ (2003) Cyclooxygenase 2: a molecular target for cancer prevention and treatment. Trends Pharmacol Sci 24:96–102CrossRefGoogle Scholar
  131. Szabo E (2010) Phase II cancer prevention clinical trials. Semin Oncol 37(4):359–366PubMedPubMedCentralCrossRefGoogle Scholar
  132. Szabo E, Mao JT, Lam S, Reid ME, Keith RL (2013) Chemoprevention of lung cancer: diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 143(5 Suppl):e40S–e60SPubMedPubMedCentralCrossRefGoogle Scholar
  133. Szabo E (2015) Biomarkers in phase I–II chemoprevention trials: lessons from the NCI experience. Ecancermedicalscience 9:599Google Scholar
  134. Takahashi H, Ogata H, Nishigaki R, Broide DH, Karin M (2010) Tobacco smoke promotes lung tumorigenesis by triggering IKKb- and JNK1-dependent inflammation. Cancer Cell 17:89–97PubMedPubMedCentralCrossRefGoogle Scholar
  135. Tammemagi CM, Pinsky P, Caporaso NE et al (2011) Lung cancer risk prediction: prostate, lung, colorectal and ovarian cancer screening trial models and validation. J Natl Cancer Inst 103(13):1058–1068PubMedPubMedCentralCrossRefGoogle Scholar
  136. Tammemagi MC, Schmidt H, Martel S, McWilliams A, Goffin JR et al (2017) Participant selection for lung cancer screening by risk modelling (the Pan-Canadian Early Detection of Lung Cancer [PanCan] study): a single-arm, prospective study. Lancet Oncol 18:1523–1531PubMedCrossRefPubMedCentralGoogle Scholar
  137. Tenkanen L, Hakulinen T et al (1987) The joint effect of smoking and respiratory symptoms on risk of lung cancer. Int J Epidemiol 16(4):509–515PubMedCrossRefPubMedCentralGoogle Scholar
  138. The Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group (1994) The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. N Engl J Med 330:1029–1035CrossRefGoogle Scholar
  139. Thorgeirsson TE, Geller F, Sulem P, Rafnar T, Wiste A et al (2008) A variant associated with nicotine dependence, lung cancer, and peripheral arterial disease. Nature 452(7187):638–642PubMedPubMedCentralCrossRefGoogle Scholar
  140. Tindle HA, Duncan MS, Greevy RA, Vasan RS, Kundu S et al (2018) Lifetime smoking history and risk of lung cancer: results from the Framingham Heart Study. J Natl Cancer Inst 110(11):1201–1207. Scholar
  141. Tockman M (1986) Survival and mortality from lung cancer in a screened population: the Johns Hopkins Study. Chest 89:325S–326SCrossRefGoogle Scholar
  142. Tockman MS, Anthonisen NR, Wright EC, Donithan MG (1987) Airways obstruction and the risk for lung cancer. Ann Intern Med 106(4):512–518PubMedCrossRefPubMedCentralGoogle Scholar
  143. Tokuhata GK, Lilienfeld AM (1963) Familial aggregation of lung cancer in humans. J Natl Cancer Inst 30:289–312PubMedPubMedCentralGoogle Scholar
  144. Turner MC, Chen Y, Krewski D, Calle EE, Thun MJ (2007) Chronic obstructive pulmonary disease is associated with lung cancer mortality in a prospective study of never smokers. Am J Respir Crit Care Med 176(3):285–290PubMedCrossRefPubMedCentralGoogle Scholar
  145. United States Department of Health and Human Services (2010) How tobacco smoke causes disease: the biology and behavioral basis for smoking-attributable disease: a report of the surgeon general. Ch. 5. U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, Atlanta (GA)Google Scholar
  146. US Environmental Protection Agency 2005. Accessed 10 Apr 2018)
  147. Venmans BJ, van BoxemTJ SEF, Postmus PE, Sutedja TG (2000) Outcome of bronchial carcinoma in situ. Chest 117:1572–1576PubMedCrossRefPubMedCentralGoogle Scholar
  148. Veronesi G, Szabo E, DeCensi A, Guerrieri-Gonzaga A, Bellomi M et al (2011) Randomized phase II trial of inhaled budesonide versus placebo in high-risk individuals with CT screen-detected lung nodules. Cancer Prev Res 4:34–42CrossRefGoogle Scholar
  149. Veronesi G, Lazzeroni M, Szabo E, Brown PH, DeCensi A et al (2015) Long-term effects of inhaled budesonide on screening-detected lung nodules. Ann Oncol 26:1025–1030PubMedPubMedCentralCrossRefGoogle Scholar
  150. Virtamo J, Pietinen P, Huttunen JK et al (2003) Incidence of cancer and mortality following alpha-tocopherol and beta-carotene supplementation: a postintervention follow-up. JAMA 290:476–485PubMedCrossRefPubMedCentralGoogle Scholar
  151. Wang XD, Russell RM (1999) Procarcinogenic and anticarcinogenic effects of beta-carotene. Nutr Rev 57(9 Pt 1):263–272PubMedPubMedCentralGoogle Scholar
  152. Wang Y, Broderick P, Webb E, Wu X, Vijayakrishnan J et al (2008) Common 5p15.33 and 6p21.33 variants influence lung cancer risk. Nat Genet 40(12):1407–1409PubMedPubMedCentralCrossRefGoogle Scholar
  153. Wang Y, James M, Wen W et al (2010) Chemopreventive effects of pioglitazone on chemically induced lung carcinogenesis in mice. Mol Cancer Ther 9:3074–3082PubMedCrossRefPubMedCentralGoogle Scholar
  154. Wattenberg LW, Estensen RD (1996) Chemopreventive effects of myo-inositol and dexamethasone on benzo(a)pyrene and 4-(methyl-nitrosamine)-1-(3-pyridyl)-1-butanone-induced pulmonary carcinogenesis in female A/J mice. Cancer Res 56:5132–5135PubMedPubMedCentralGoogle Scholar
  155. Wattenberg LW, Wiedmann TS, Estensen RD et al (2000) Chemoprevention of pulmonary carcinogenesis by brief exposures to aerosolized budesonide or beclomethasone diproprionate and by the combination of aerosolized budesonide and dietary myo-inositol. Carcinogenesis 21:179–182PubMedCrossRefPubMedCentralGoogle Scholar
  156. Wojtowicz ME, Dunn BK, Umar A (2016) Immunologic approaches to cancer prevention-current status, challenges, and future perspectives. Semin Oncol 43(1):161–172PubMedCrossRefPubMedCentralGoogle Scholar
  157. Wynder E, Graham EA (1950) Tobacco smoking as a possible etiologic factor in bronchogenic carcinoma: a study of 684 proved cases. JAMA 143:329–336CrossRefGoogle Scholar
  158. Yamamoto H, Yatabe Y, Toyooka S (2018) Inherited lung cancer syndromes targeting never smokers. Transl Lung Cancer Res 7(4):498–504PubMedPubMedCentralCrossRefGoogle Scholar
  159. Yang R, Cheung MC, Byrne MM et al (2010) Do racial or socioeconomic disparities exist in lung cancer treatment? Cancer 116:2437–2447PubMedPubMedCentralGoogle Scholar
  160. van Zandwijk N, Dalesio O, Pastorino U, de Vries N, van Tinteren H (2000) 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 92:977–986PubMedCrossRefPubMedCentralGoogle Scholar
  161. Zhang J, Jiang S et al (2001) Antioxidant supplementation prevents oxidation and inflammatory responses induced by sidestream cigarette smoke in old mice. Environ Health Perspect 109(10):1007–1009PubMedPubMedCentralCrossRefGoogle Scholar

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Lung and Upper Aerodigestive Cancer Research Group, Division of Cancer PreventionNational Cancer Institute, National Institutes of HealthBethesdaUSA

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