Cancer Causes & Control

, Volume 14, Issue 4, pp 327–334 | Cite as

A meta-analysis of asthma and risk of lung cancer (United States)

  • Alfredo A. Santillan
  • Carlos A. CamargoJr
  • Graham A. ColditzEmail author


Objective: To review epidemiologic evidence that asthma is a risk factor for lung cancer, with particular attention to the role of smoking on this association. Methods: Through MEDLINE computer searches (January 1966 to April 2002) and a review of references, we identified studies with quantitative data on the relation of asthma to lung cancer. Summary estimates of relative risks (RR) were calculated using the fixed-effects model or the random-effects model as appropriate. Results: The combined results from five case–control studies – that presented data limited to individuals who had never smoked – showed a 1.8-fold increase in lung cancer risk among asthmatics (95% confidence interval (CI) = 1.3–2.3). The results from six case–control and four cohort studies, which controlled for smoking history also were significant (RR = 1.7; 95% CI = 1.3–2.2). Finally, to illustrate the potential confounding by tobacco, we combined data from seven cohort studies that did not control for smoking history and found an overall RR of 1.4 (95% CI = 1.2–1.6). Conclusions: The increased risk of lung cancer among never smoking individuals with asthma supports a direct relation between asthma and lung cancer. There is biological evidence to support this association.

asthma epidemiology lung neoplasm meta-analysis smoking 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Jemal A, Thomas A, Murray T, Thun M (2002) Cancer Statistics, 2002. CA Cancer J Clin 52: 23-47.Google Scholar
  2. 2.
    Parkin DM (2001) Global cancer statistics in the year 2000. Lancet Oncol 2: 533-543.Google Scholar
  3. 3.
    US Department of Health and Human Services(1989) Reducing the Health Consequences of Smoking: 25 years of Progress. A Report of the Surgeon General. Washington, DC: US GPO (DHHS publication no. (CDC) 89-8411).Google Scholar
  4. 4.
    International Agency for Research on Cancer(1986). IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans: Tobacco Smoking. Vol. 38. Lyon, France: International Agency for Research on Cancer.Google Scholar
  5. 5.
    US Department of Health and Human Services(2001) Women and Smoking: A Report of the Surgeon General. Rockville, MD: US Department of Health and Human Services, Public Health Service, Office of the Surgeon General.Google Scholar
  6. 6.
    Thun MJ, Day-Lally C, Myers DG, et al. (1997) Trends in tobacco smoking and mortality from cigarette use in cancer prevention studies I (1959-1965) and II (1982-1988). In: National Cancer Institute, Smoking and Tobacco Control, Monograph 8: Changes in Cigarette-Related Disease Risks and their Implication for Prevention and Control. Bethesda, MD: US Department of Health and Human Services, Public Health Service, National Institutes of Health, National Cancer Institute. NIH Publ No. 97-1213, pp. 305-382.Google Scholar
  7. 7.
    Wingo PA, Ries LA, Giovino GA, et al. (1999) Annual report to the nation on the status of cancer, 1973-1996, with a special section on lung cancer and tobacco smoking. J Natl Cancer Inst 91: 675-690.Google Scholar
  8. 8.
    Zheng W, Blot WJ, Liao ML, et al. (1987) Lung cancer and prior tuberculosis infection in Shanghai. Br J Cancer 56: 501-504.Google Scholar
  9. 9.
    Ko YC, Lee C-H, Chen M-J, et al. (1997) Risk factors for primary lung cancer among non-smoking women in Taiwan. Int J Epidemiol 26: 24-31.Google Scholar
  10. 10.
    Alavanja MCR, Brownson RC, Boice Jr JD, Hock E (1992) Preexisting lung disease and lung cancer among nonsmoking women. Am J Epidemiol 136: 623-632.Google Scholar
  11. 11.
    Wu AH, Fontham ETH, Reynolds P, et al. (1995) Previous lung disease and risk of lung cancer among lifetime nonsmoking women in the United States. Am J Epidemiol 141: 1023-1032.Google Scholar
  12. 12.
    Mayne ST, Buenconsejo J, Janerich DT (1999) Previous lung disease and risk of lung cancer among men and women nonsmokers. Am J Epidemiol 149: 13-20.Google Scholar
  13. 13.
    Gabriel R, Dudley BM, Alexander WD (1972) Lung cancer and allergy. Br J Clin Pract 26: 202-204.Google Scholar
  14. 14.
    Alderson M (1974) Mortality from malignant disease in patients with asthma. Lancet ii: 1475-1477.Google Scholar
  15. 15.
    Ford MR (1978) Primary lung cancer and asthma. Ann Allergy 40: 240-242.Google Scholar
  16. 16.
    Markowe HL, Bulpitt CJ, Shipley MJ, Rose G, Crombie DL, Fleming DM (1987) Prognosis in adult asthma: a national study. BMJ 295: 949-952.Google Scholar
  17. 17.
    Osann KE (1991) Lung cancer in women: the importance of smoking, family history of cancer, and medical history of respiratory disease. Cancer Res 51: 4893-4897.Google Scholar
  18. 18.
    Eriksson NE, Holmen A, Hogstedt B, Mikoczy Z, Hagmar L (1995) A prospective study of cancer incidence in a cohort examined for allergy. Allergy 50: 718-722.Google Scholar
  19. 19.
    Vena JE, Bona JR, Byers TE, Middleton E, Swanson MK, Graham S (1985) Allergy-related diseases and cancer: an inverse association. Am J Epidemiol 122: 66-74.Google Scholar
  20. 20.
    Vena JE, Byers TE, Middleton E, Graham S (1987) Re: ‘Asthma and cancer.’ The authors reply. Am J Epidemiol 125: 540.Google Scholar
  21. 21.
    Brenner AV, Wang A, Kleinerman RA, et al. (2001) Previous pulmonary diseases and risk of lung cancer in Gansu Province, China. Int J Epidemiol 30: 118-124.Google Scholar
  22. 22.
    Brownson RC, Alavanja MCR (2000) Previous lung disease and lung cancer risk among women (United States). Cancer Causes Control 11: 853-858.Google Scholar
  23. 23.
    Osann KE, Lowery JT, Schell MJ (2000) Small cell lung cancer in women: risk associated with smoking, prior respiratory disease, and occupation. Lung Cancer 28: 1-10.Google Scholar
  24. 24.
    Wu AH, Yu MC, Thomas DC, Pike MC, Henderson BE (1988) Personal and family history of lung disease as risk factors for adenocarcinoma of the lung. Cancer Res 48: 7279-7284.Google Scholar
  25. 25.
    Reynolds P, Kaplan GA (1987) Asthma and cancer. Am J Epidemiol 125: 539-540.Google Scholar
  26. 26.
    Mills PK, Beeson L, Fraser GE, Phillips RL (1992) Allergy and cancer: organ site-specific results from the Adventist Health Study. Am J Epidemiol 136: 287-292.Google Scholar
  27. 27.
    Lange P, Ulrik CS, Vestbo J (1996) Mortality in adults with selfreported asthma. Lancet 347: 1285-1289.Google Scholar
  28. 28.
    Houvinen E, Kaprio J, Vesterinen E, Koskenvuo M (1997) Mortality of adults with asthma: a prospective cohort study. Thorax 52: 49-54.Google Scholar
  29. 29.
    Boffetta P, Ye W, Boman G, Nyren O (2002) Lung cancer risk in a population-based cohort of patients hospitalized for asthma in Sweden. Eur Respir J 19: 127-133.Google Scholar
  30. 30.
    Musk AW, Ryan GF, Perera DM, D'souza BPJ, Hockey RL, Hobbs MST (1987) Mortality from asthma in Western Australia. Med J Aust 147: 423-427.Google Scholar
  31. 31.
    Vesterinen E, Pukkala E, Timonen T, Aromaa A (1993) Cancer incidence among 78,000 asthmatic patients. Int J Epidemiol 22: 976-982.Google Scholar
  32. 32.
    Robinette CD, Fraumeni Jr JF (1978) Asthma and subsequent mortality in World War II veterans. J Chron Dis 31: 619-624.Google Scholar
  33. 33.
    Alavanja MCR, Brownson RC, Benichou J, Swanson C, Boice JD (1995) Attributable risk of lung cancer in lifetime nonsmokers and long-term ex-smokers (Missouri, United States). Cancer Causes Control 6: 209-216.Google Scholar
  34. 34.
    Samet JM, Humble CH, Pathak DR (1986) Personal and family history of respiratory disease and lung cancer risk. Am Rev Respir Dis 134: 466-470.Google Scholar
  35. 35.
    Polednak AP (1975) Asthma and cancer mortality. Lancet i: 1147-1148.Google Scholar
  36. 36.
    Wu AH, Henderson BE, Pike MC, Yu MC (1985) Smoking and other risk factors for lung cancer in women. J Natl Cancer Inst 74: 747-751.Google Scholar
  37. 37.
    Ulrik CS, Frederiksen J (1995) Mortality and markers of risk of asthma death among 1075 outpatients with asthma. Chest 108: 10-15.Google Scholar
  38. 38.
    Kallen B, Gunnarskog J, Conradson T-B (1993) Cancer risk in asthmatic subjects selected from hospital discharge registry. Eur Respir J 6: 694-697.Google Scholar
  39. 39.
    DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Controlled Clin Trials 7: 177-188.Google Scholar
  40. 40.
    Colditz GA, Burdick E, Mosteller F (1995) Heterogeneity in metaanalysis of data from epidemiologic studies: a commentary. Am J Epidemiol 142: 371-382.Google Scholar
  41. 41.
    Begg CB, Mazumdar M (1994) Operating characteristics of a rank correlation test for publication bias. Biometrics 50: 1088-1101.Google Scholar
  42. 42.
    Egger M, Smith GD, Schneider M, et al. (1997) Bias in metaanalysis detected by a simple, graphical test. BMJ 315: 629-634.Google Scholar
  43. 43.
    Schlesselman JJ (1982) Case-Control Studies. New York, NY: Oxford University Press.Google Scholar
  44. 44.
    Vesterinen E, Kaprio J, Koskenvuo M (1988) Prospective study of asthma in relation to smoking habits among 14,729 adults. Thorax 43: 534-539.Google Scholar
  45. 45.
    American Thoracic Society(1995) Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 152: S77-S120.Google Scholar
  46. 46.
    Toren K, Brisman J, Jarvholm B (1993) Asthma and asthma-like symptoms in adults assessed by questionnaires: a literature review. Chest 104: 600-608.Google Scholar
  47. 47.
    Fontham ETH, Correa P, Reynolds P, et al. (1994) Environmental tobacco smoke and lung cancer in nonsmoking women: a multicenter study. JAMA 271: 1752-1759.Google Scholar
  48. 48.
    Burrows B, Barbee RA, Cline MG, Knudson RJ, Lebowitz MD (1991) Characteristics of asthma among elderly adults in a sample of the general population. Chest 100: 935-942.Google Scholar
  49. 49.
    Ben-Noun L (1999) Is there a relationship between smoking and asthma in adults? J Int Med Res 27: 15-21.Google Scholar
  50. 50.
    Lubin JH, Blot WJ (1984) Assessment of lung cancer risk factors by histologic category. J Natl Cancer Inst 73: 383-389.Google Scholar
  51. 51.
    Houtmeyers E, Gosselink R, Gayan-Ramirez G, Decramer M (1999) Regulation of mucociliary clearance in health and disease. Eur Respir J 13: 1177-1188.Google Scholar
  52. 52.
    Wanner A, Salathe M, O'Riordan TG (1996) Mucociliary clearance of the airways. Am J Respir Crit Care Med 154: 1868-1902.Google Scholar
  53. 53.
    American Thoracic Society(1987) Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease (COPD) and asthma. Am Rev Respir Dis 136: 225-244.Google Scholar
  54. 54.
    Cohen BH, Diamond EL, Graves CG, et al. (1977) A common familial component in lung cancer and chronic obstructive pulmonary disease. Lancet 2: 523-526.Google Scholar
  55. 55.
    Tekin D, Sin BA, Mungan D, Misirligil Z, Yavuzer S (2000) The antioxidative defense in asthma. J Asthma 37: 59-63.Google Scholar
  56. 56.
    Comhair SA, Bhathena PR, Dweik RA, Kavuru M, Erzurum SC (2000) Rapid loss of superoxide dismutase activity during antigeninduced asthmatic response. Lancet 355: 624.Google Scholar
  57. 57.
    Dreher D, Junod AF (1996) Role of oxygen free radicals in cancer development. Eur J Cancer 32A: 30-38.Google Scholar
  58. 58.
    Roche WR (1998) Inflammatory and structural changes in the small airways in bronchial asthma. Am J Respir Crit Care Med 157: S191-S194.Google Scholar
  59. 59.
    O'Byrne PM, Postma DS (1999) The many faces of airway inflammation: asthma and chronic obstructive pulmonary disease. Am J Respir Crit Care Med 159: S41-S66.Google Scholar
  60. 60.
    Mentzer SJ (1995) Immunoreactivity of lung cancer. Chest Surg Clin N Am 5: 57-71.Google Scholar
  61. 61.
    Oehling AG, Akdis CA, Schapowal A, Blaser K, Schmitz M, Simon HU (1997) Suppression of the immune system by oral glucocorticoid therapy in bronchial asthma. Allergy 52: 144-154.Google Scholar
  62. 62.
    Gemou-Engesaeth V, Bush A, Kay AB, Hamid Q, Corrigan CJ (1997) Inhaled glucocorticoid therapy of childhood asthma is associated with reduced peripheral blood T cell activation and Th2-type cytokine mRNA expression. Pediatrics 99: 695-703.Google Scholar
  63. 63.
    Druille A, Wallaert B, Tsicopoulos A, et al. (1998) Apoptosis, proliferation, and expression of Bcl-2, Fas, and Fas ligand in bronchial biopsies from asthmatics. Am J Respir Cell Mol Biol 19: 747-757.Google Scholar
  64. 64.
    Solary E, Dubrez L, Eymin B (1996) The role of apoptosis in the pathogenesis and treatment of diseases. Eur Respir J 9: 1293-1305.Google Scholar
  65. 65.
    Pezzella F, Turley H, Kuzu I, et al. (1993) Bcl-2 protein in nonsmall-cell lung carcinoma. N Engl J Med 329: 690-694.Google Scholar
  66. 66.
    Anonymous (2001) Self-reported asthma prevalence among adults-United States, 2000. MMWR Morb Mortal Wkly Rep 50: 682-686.Google Scholar
  67. 67.
    Camargo Jr CA, Richardson LD (1999) Epidemiology of asthma. In: Brenner BE, ed. Emergency Asthma. New York: Marcel Dekker, pp. 59-80.Google Scholar

Copyright information

© Kluwer Academic Publishers 2003

Authors and Affiliations

  • Alfredo A. Santillan
    • 1
  • Carlos A. CamargoJr
    • 1
    • 2
    • 3
  • Graham A. Colditz
    • 1
    Email author
  1. 1.Department of EpidemiologyHarvard School of Public HealthBostonUSA
  2. 2.Channing Laboratory, Department of Medicine, Brigham and Women's HospitalHarvard Medical SchoolBostonUSA
  3. 3.Department of Emergency MedicineMassachusetts General Hospital, Harvard Medical SchoolBostonUSA

Personalised recommendations