Skip to main content
Environmental Health Perspectives logoLink to Environmental Health Perspectives
. 2002 Jun;110(6):555–558. doi: 10.1289/ehp.02110555

Teen smoking, field cancerization, and a "critical period" hypothesis for lung cancer susceptibility.

John K Wiencke 1, Karl T Kelsey 1
PMCID: PMC1240869  PMID: 12055044

Abstract

Cigarette smoking by children and adolescents continues to be prevalent, and this fact represents a major public health problem and challenge. Epidemiologic work has previously suggested that exposure of the lung to tobacco carcinogens at an early age may be an independent risk factor for lung cancer. Recent studies at the molecular and cellular levels are consistent with this, now suggesting that early exposure enhances DNA damage and is associated with the induction of DNA alterations in specific chromosomal regions. In this paper we hypothesize that adolescence, which is known to be the period of greatest development for the lung, may constitute a "critical period" in which tobacco carcinogens can induce fields of genetic alterations that make the early smoker more susceptible to the damaging effects of continued smoking. The fact that lung development differs by sex might also contribute to apparent gender differences in lung cancer susceptibility. Because this hypothesis has important implications for health policy and tobacco control, additional resources need to be devoted to its further evaluation. Targeted intervention in adolescent smoking may yield even greater reductions in lung cancer occurrence than otherwise anticipated.

Full Text

The Full Text of this article is available as a PDF (511.9 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Autier P., Doré J. F., Gefeller O., Cesarini J. P., Lejeune F., Koelmel K. F., Lienard D., Kleeberg U. R. Melanoma risk and residence in sunny areas. EORTC Melanoma Co-operative Group. European Organization for Research and Treatment of Cancer. Br J Cancer. 1997;76(11):1521–1524. doi: 10.1038/bjc.1997.588. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Benhamou S., Benhamou E., Tirmarche M., Flamant R. Lung cancer and use of cigarettes: a French case-control study. J Natl Cancer Inst. 1985 Jun;74(6):1169–1175. [PubMed] [Google Scholar]
  3. Doll R., Peto R. Cigarette smoking and bronchial carcinoma: dose and time relationships among regular smokers and lifelong non-smokers. J Epidemiol Community Health. 1978 Dec;32(4):303–313. doi: 10.1136/jech.32.4.303. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Doll R., Peto R. Mortality in relation to smoking: 20 years' observations on male British doctors. Br Med J. 1976 Dec 25;2(6051):1525–1536. doi: 10.1136/bmj.2.6051.1525. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Dunnill M. S. The problem of lung growth. Thorax. 1982 Aug;37(8):561–563. doi: 10.1136/thx.37.8.561. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Endo C., Sato M., Fujimura S., Sakurada A., Aikawa H., Takahashi S., Usuda K., Saito Y., Sagawa M. Allelic loss on 17p13 (TP53) and allelic loss on 3p21 in early squamous cell carcinoma of the lung. Surg Today. 2000;30(8):695–699. doi: 10.1007/s005950070079. [DOI] [PubMed] [Google Scholar]
  7. Franklin W. A., Gazdar A. F., Haney J., Wistuba I. I., La Rosa F. G., Kennedy T., Ritchey D. M., Miller Y. E. Widely dispersed p53 mutation in respiratory epithelium. A novel mechanism for field carcinogenesis. J Clin Invest. 1997 Oct 15;100(8):2133–2137. doi: 10.1172/JCI119748. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gold D. R., Wang X., Wypij D., Speizer F. E., Ware J. H., Dockery D. W. Effects of cigarette smoking on lung function in adolescent boys and girls. N Engl J Med. 1996 Sep 26;335(13):931–937. doi: 10.1056/NEJM199609263351304. [DOI] [PubMed] [Google Scholar]
  9. Hegmann K. T., Fraser A. M., Keaney R. P., Moser S. E., Nilasena D. S., Sedlars M., Higham-Gren L., Lyon J. L. The effect of age at smoking initiation on lung cancer risk. Epidemiology. 1993 Sep;4(5):444–448. doi: 10.1097/00001648-199309000-00010. [DOI] [PubMed] [Google Scholar]
  10. Hirao T., Nelson H. H., Ashok T. D., Wain J. C., Mark E. J., Christiani D. C., Wiencke J. K., Kelsey K. T. Tobacco smoke-induced DNA damage and an early age of smoking initiation induce chromosome loss at 3p21 in lung cancer. Cancer Res. 2001 Jan 15;61(2):612–615. [PubMed] [Google Scholar]
  11. Jackson C., Henriksen L., Dickinson D., Messer L., Robertson S. B. A longitudinal study predicting patterns of cigarette smoking in late childhood. Health Educ Behav. 1998 Aug;25(4):436–447. doi: 10.1177/109019819802500403. [DOI] [PubMed] [Google Scholar]
  12. Jemal A., Chu K. C., Tarone R. E. Recent trends in lung cancer mortality in the United States. J Natl Cancer Inst. 2001 Feb 21;93(4):277–283. doi: 10.1093/jnci/93.4.277. [DOI] [PubMed] [Google Scholar]
  13. Khlat M., Vail A., Parkin M., Green A. Mortality from melanoma in migrants to Australia: variation by age at arrival and duration of stay. Am J Epidemiol. 1992 May 15;135(10):1103–1113. doi: 10.1093/oxfordjournals.aje.a116210. [DOI] [PubMed] [Google Scholar]
  14. Lerman M. I., Minna J. D. The 630-kb lung cancer homozygous deletion region on human chromosome 3p21.3: identification and evaluation of the resident candidate tumor suppressor genes. The International Lung Cancer Chromosome 3p21.3 Tumor Suppressor Gene Consortium. Cancer Res. 2000 Nov 1;60(21):6116–6133. [PubMed] [Google Scholar]
  15. Merkus P. J., Borsboom G. J., Van Pelt W., Schrader P. C., Van Houwelingen H. C., Kerrebijn K. F., Quanjer P. H. Growth of airways and air spaces in teenagers is related to sex but not to symptoms. J Appl Physiol (1985) 1993 Nov;75(5):2045–2053. doi: 10.1152/jappl.1993.75.5.2045. [DOI] [PubMed] [Google Scholar]
  16. Merkus P. J., ten Have-Opbroek A. A., Quanjer P. H. Human lung growth: a review. Pediatr Pulmonol. 1996 Jun;21(6):383–397. doi: 10.1002/(SICI)1099-0496(199606)21:6<383::AID-PPUL6>3.0.CO;2-M. [DOI] [PubMed] [Google Scholar]
  17. Mitsudomi T., Oyama T., Nishida K., Ogami A., Osaki T., Sugio K., Yasumoto K., Sugimachi K., Gazdar A. F. Loss of heterozygosity at 3p in non-small cell lung cancer and its prognostic implication. Clin Cancer Res. 1996 Jul;2(7):1185–1189. [PubMed] [Google Scholar]
  18. Moolgavkar S. H., Dewanji A., Luebeck G. Cigarette smoking and lung cancer: reanalysis of the British doctors' data. J Natl Cancer Inst. 1989 Mar 15;81(6):415–420. doi: 10.1093/jnci/81.6.415. [DOI] [PubMed] [Google Scholar]
  19. Page W. F., Whiteman D., Murphy M. A comparison of melanoma mortality among WWII veterans of the Pacific and European theaters. Ann Epidemiol. 2000 Apr;10(3):192–195. doi: 10.1016/s1047-2797(99)00050-2. [DOI] [PubMed] [Google Scholar]
  20. Park I. W., Wistuba I. I., Maitra A., Milchgrub S., Virmani A. K., Minna J. D., Gazdar A. F. Multiple clonal abnormalities in the bronchial epithelium of patients with lung cancer. J Natl Cancer Inst. 1999 Nov 3;91(21):1863–1868. doi: 10.1093/jnci/91.21.1863. [DOI] [PubMed] [Google Scholar]
  21. Rosenthal M., Bain S. H., Cramer D., Helms P., Denison D., Bush A., Warner J. O. Lung function in white children aged 4 to 19 years: I--Spirometry. Thorax. 1993 Aug;48(8):794–802. doi: 10.1136/thx.48.8.794. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. SLAUGHTER D. P., SOUTHWICK H. W., SMEJKAL W. Field cancerization in oral stratified squamous epithelium; clinical implications of multicentric origin. Cancer. 1953 Sep;6(5):963–968. doi: 10.1002/1097-0142(195309)6:5<963::aid-cncr2820060515>3.0.co;2-q. [DOI] [PubMed] [Google Scholar]
  23. Tager I. B., Segal M. R., Speizer F. E., Weiss S. T. The natural history of forced expiratory volumes. Effect of cigarette smoking and respiratory symptoms. Am Rev Respir Dis. 1988 Oct;138(4):837–849. doi: 10.1164/ajrccm/138.4.837. [DOI] [PubMed] [Google Scholar]
  24. Tokunaga M., Land C. E., Yamamoto T., Asano M., Tokuoka S., Ezaki H., Nishimori I. Incidence of female breast cancer among atomic bomb survivors, Hiroshima and Nagasaki, 1950-1980. Radiat Res. 1987 Nov;112(2):243–272. [PubMed] [Google Scholar]
  25. Vulimiri S. V., Wu X., Baer-Dubowska W., de Andrade M., Detry M., Spitz M. R., DiGiovanni J. Analysis of aromatic DNA adducts and 7,8-dihydro-8-oxo- 2'-deoxyguanosine in lymphocyte DNA from a case-control study of lung cancer involving minority populations. Mol Carcinog. 2000 Jan;27(1):34–46. doi: 10.1002/(sici)1098-2744(200001)27:1<34::aid-mc6>3.3.co;2-7. [DOI] [PubMed] [Google Scholar]
  26. Wiencke J. K., Thurston S. W., Kelsey K. T., Varkonyi A., Wain J. C., Mark E. J., Christiani D. C. Early age at smoking initiation and tobacco carcinogen DNA damage in the lung. J Natl Cancer Inst. 1999 Apr 7;91(7):614–619. doi: 10.1093/jnci/91.7.614. [DOI] [PubMed] [Google Scholar]
  27. Wistuba I. I., Behrens C., Milchgrub S., Bryant D., Hung J., Minna J. D., Gazdar A. F. Sequential molecular abnormalities are involved in the multistage development of squamous cell lung carcinoma. Oncogene. 1999 Jan 21;18(3):643–650. doi: 10.1038/sj.onc.1202349. [DOI] [PubMed] [Google Scholar]
  28. Zang E. A., Wynder E. L. Differences in lung cancer risk between men and women: examination of the evidence. J Natl Cancer Inst. 1996 Feb 21;88(3-4):183–192. doi: 10.1093/jnci/88.3-4.183. [DOI] [PubMed] [Google Scholar]

Articles from Environmental Health Perspectives are provided here courtesy of National Institute of Environmental Health Sciences

RESOURCES