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Chemoprevention of lung cancer


Lung cancer is the most common cancer worldwide, with an estimated 1,600,000 new cases and 1,380,000 deaths in 2008 [1].

The identification of the factors responsible for lung cancer permits targeted efforts at prevention. The main risk factor is cigarette smoking, which accounts for approximately 90 percent of cases in men and an estimated 70 to 85 percent of cases in women [2]. A variety of other environmental and occupational exposures, familial risk factors, dietary factors, and certain types of benign lung disease have also been associated with the development of lung cancer. The risk factors for lung cancer are discussed separately. (See "Cigarette smoking and other risk factors for lung cancer".)

The most important approach to lung cancer prevention is smoking cessation. However, even after people stop smoking, there is an increased risk of developing lung cancer for at least 30 to 40 years [3]. The limitations of smoking cessation are emphasized by the fact that ex-smokers make up nearly 50 percent of all new lung cancer cases in developed countries.

Chemoprevention can be classified as primary, secondary, or tertiary, based upon the target population:

Primary chemoprevention refers to preventing cancer in healthy individuals who are at high risk. This population primarily includes current and former smokers, as well as those with exposure to known carcinogens such as asbestos.


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Literature review current through: Mar 2014. | This topic last updated: Dec 12, 2013.
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  1. Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin 2011; 61:69.
  2. Shopland DR. Tobacco use and its contribution to early cancer mortality with a special emphasis on cigarette smoking. Environ Health Perspect 1995; 103 Suppl 8:131.
  3. McLaughlin JK, Hrubec Z, Blot WJ, Fraumeni JF Jr. Smoking and cancer mortality among U.S. veterans: a 26-year follow-up. Int J Cancer 1995; 60:190.
  4. Sporn MB. Approaches to prevention of epithelial cancer during the preneoplastic period. Cancer Res 1976; 36:2699.
  5. Salgia R, Skarin AT. Molecular abnormalities in lung cancer. J Clin Oncol 1998; 16:1207.
  6. The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. The Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group. N Engl J Med 1994; 330:1029.
  7. Virtamo J, Pietinen P, Huttunen JK, et al. Incidence of cancer and mortality following alpha-tocopherol and beta-carotene supplementation: a postintervention follow-up. JAMA 2003; 290:476.
  8. Woodson K, Tangrea JA, Barrett MJ, et al. Serum alpha-tocopherol and subsequent risk of lung cancer among male smokers. J Natl Cancer Inst 1999; 91:1738.
  9. Omenn GS, Goodman GE, Thornquist MD, et al. Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease. N Engl J Med 1996; 334:1150.
  10. Goodman GE, Thornquist MD, Balmes J, et al. The Beta-Carotene and Retinol Efficacy Trial: incidence of lung cancer and cardiovascular disease mortality during 6-year follow-up after stopping beta-carotene and retinol supplements. J Natl Cancer Inst 2004; 96:1743.
  11. Hennekens CH, Buring JE, Manson JE, et al. Lack of effect of long-term supplementation with beta carotene on the incidence of malignant neoplasms and cardiovascular disease. N Engl J Med 1996; 334:1145.
  12. Lee IM, Cook NR, Manson JE, et al. Beta-carotene supplementation and incidence of cancer and cardiovascular disease: the Women's Health Study. J Natl Cancer Inst 1999; 91:2102.
  13. Satia JA, Littman A, Slatore CG, et al. Long-term use of beta-carotene, retinol, lycopene, and lutein supplements and lung cancer risk: results from the VITamins And Lifestyle (VITAL) study. Am J Epidemiol 2009; 169:815.
  14. Kurie JM, Lee JS, Khuri FR, et al. N-(4-hydroxyphenyl)retinamide in the chemoprevention of squamous metaplasia and dysplasia of the bronchial epithelium. Clin Cancer Res 2000; 6:2973.
  15. Arnold AM, Browman GP, Levine MN, et al. The effect of the synthetic retinoid etretinate on sputum cytology: results from a randomised trial. Br J Cancer 1992; 65:737.
  16. Lee JS, Lippman SM, Benner SE, et al. Randomized placebo-controlled trial of isotretinoin in chemoprevention of bronchial squamous metaplasia. J Clin Oncol 1994; 12:937.
  17. Kelly K, Kittelson J, Franklin WA, et al. A randomized phase II chemoprevention trial of 13-CIS retinoic acid with or without alpha tocopherol or observation in subjects at high risk for lung cancer. Cancer Prev Res (Phila) 2009; 2:440.
  18. McLarty JW, Holiday DB, Girard WM, et al. Beta-Carotene, vitamin A, and lung cancer chemoprevention: results of an intermediate endpoint study. Am J Clin Nutr 1995; 62:1431S.
  19. Kurie JM, Lotan R, Lee JJ, et al. Treatment of former smokers with 9-cis-retinoic acid reverses loss of retinoic acid receptor-beta expression in the bronchial epithelium: results from a randomized placebo-controlled trial. J Natl Cancer Inst 2003; 95:206.
  20. Heimburger DC, Alexander CB, Birch R, et al. Improvement in bronchial squamous metaplasia in smokers treated with folate and vitamin B12. Report of a preliminary randomized, double-blind intervention trial. JAMA 1988; 259:1525.
  21. Lam S, MacAulay C, Le Riche JC, et al. A randomized phase IIb trial of anethole dithiolethione in smokers with bronchial dysplasia. J Natl Cancer Inst 2002; 94:1001.
  22. Mao JT, Fishbein MC, Adams B, et al. Celecoxib decreases Ki-67 proliferative index in active smokers. Clin Cancer Res 2006; 12:314.
  23. Kim ES, Hong WK, Lee JJ, et al. Biological activity of celecoxib in the bronchial epithelium of current and former smokers. Cancer Prev Res (Phila) 2010; 3:148.
  24. Keith, RL, Kittelson, JK, Blatchford, PJ, et al. Oral iloprost for the chemoprevention of lung cancer (Abstract). Presented at the American Thoracic Society meeting, 2010.
  25. Clark LC, Combs GF Jr, Turnbull BW, et al. Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. Nutritional Prevention of Cancer Study Group. JAMA 1996; 276:1957.
  26. Reid ME, Duffield-Lillico AJ, Garland L, et al. Selenium supplementation and lung cancer incidence: an update of the nutritional prevention of cancer trial. Cancer Epidemiol Biomarkers Prev 2002; 11:1285.
  27. Karp DD, Lee SJ, Keller SM, et al. 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 2013; 31:4179.
  28. Lippman SM, Lee JJ, Karp DD, et al. Randomized phase III intergroup trial of isotretinoin to prevent second primary tumors in stage I non-small-cell lung cancer. J Natl Cancer Inst 2001; 93:605.
  29. van Zandwijk N, Dalesio O, Pastorino U, et al. EUROSCAN, a randomized trial of vitamin A and N-acetylcysteine in patients with head and neck cancer or lung cancer. For the EUropean Organization for Research and Treatment of Cancer Head and Neck and Lung Cancer Cooperative Groups. J Natl Cancer Inst 2000; 92:977.
  30. Pastorino U, Infante M, Maioli M, et al. Adjuvant treatment of stage I lung cancer with high-dose vitamin A. J Clin Oncol 1993; 11:1216.