Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

Molecular epidemiology of smoking and lung cancer

Abstract

Lung cancer is the single most common cause of death, and almost all of it is due to tobacco smoking. Before the widespread use of cigarettes in this century, lung cancer was a rare illness. Tobacco smoke is a complex mixture of numerous mutagens and carcinogens. Over the last 40 years, the type of cigarettes most frequently used has been changing, namely the increased use of low tar and nicotine cigarettes. This has been accompanied by an increased risk of lung cancer due to a smokers' need to maintain blood nicotine levels, which in turn causes the need for smoking more cigarettes per day and deeper inhalation. This phenomena has led to the increasing rates of lung adenocarcinoma, compared to squamous cell carcinoma. It also probably explains, in part, the greater risk of lung cancer in women compared to men (in addition to some biological differences). The study of lung cancer involves many types of biomarkers, including those that measure exposure, the biologically effective dose and harm. The use of these has allowed us to understand many parts of lung carcinogenesis. Genetic susceptibilities play a large role in lung cancer risk. They govern smoking behavior (affecting dopamine reward mechanisms due to nicotine and nicotine metabolism), carcinogen metabolism and detoxification, DNA repair, cell cycle control and other cellular responses. The need for the study of lung cancer is highlighted by the need to improve cessation rates and reduce exposure among persons who cannot quit smoking, for better prevention strategies for former smokers and an understanding of environmental tobacco smoke risk.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  • Atawodi SE, Lea S, Nyberg F, Mukeria A, Constantinescu V, Ahrens W, Brueske-Hohlfeld I, Fortes C, Boffetta P, Friesen MD . 1998 Cancer Epidemiol. Biomarkers Prev. 7: 817–821

  • Auerbach O, Brewster G, Forman JB, Petrick TG, Smolin HJ, Meuhsam GE, Kassouny DY, Stout AP . 1957 New Engl. J. Med. 256: 97–104

  • Badawi AF, Hirvonen A, Bell DA, Lang NP, Kadlubar FF . 1995 Cancer Res. 55: 5230–5237

  • Bailar III JC . 1999 N. Engl. J. Med. 340: 958–959

  • Bardeesy N, Falkoff D, Petruzzi MJ, Nowak N, Zabel B, Adam M, Aguiar MC, Grundy P, Shows T, Pelletier J . 1994 Nat. Genet. 7: 91–97

  • Benowitz NL, Hall SM, Herning RI, Jacob III P, Jones RT, Osman AL . 1983 N. Engl. J. Med. 309: 139–142

  • Benowitz NL, Jacob III P, Kozlowski LT, Yu L . 1986b N. Engl. J. Med. 315: 1310–1313

  • Benowitz NL, Jacob III P, Yu L, Talcott R, Hall S, Jones RT . 1986a JAMA 256: 241–246

  • Benowitz NL, Zevin S, Jacob III P . 1998 J. Pharmacol. Exp. Ther. 287: 958–962

  • Brennan JA, Boyle JO, Koch WM, Goodman SN, Hruban RH, Eby YJ, Couch MJ, Forastiere AA, Sidransky D . 1995 N. Engl. J. Med. 332: 712–717

  • Brockmoller J, Cascorbi I, Kerb R, Sachse C, Roots I . 1998 Toxicol. Lett. 102–103: 173–183

  • Brownson RC, Alavanja MC, Caporaso N, Simoes EJ, Chang JC . 1998 Epidemiol. Rev. 20: 218–236

  • Brownson RC, Alavanja MC, Hock ET, Loy TS . 1992 Am. J. Public Health 82: 1525–1530

  • Brownson RC, Eriksen MP, Davis RM, Warner KE . 1997 Annu. Rev. Public Health 18: 163–185

  • Brunnemann KD, Prokopczyk B, Djordjevic MV, Hoffmann D . 1996 Crit. Rev. Toxicol. 26: 121–137

  • Burney LE . 1959 J. Am. Med. Assoc. 171: 1829–1837

  • Comings DE, Ferry L, Bradshaw-Robinson S, Burchette R, Chiu C, Muhleman D . 1996 Pharmacogenetics 6: 73–79

  • Cornfield J, Haenszel W, Hammond EC, Lilienfeld AM, Shimkin MB, Wynder EL . 1959 J. Natl. Cancer Inst. 22: 173–203

  • Darby SC, Pike MC . 1988 Br. J. Cancer 58: 825–831

  • Djordjevic MV, Fan J, Ferguson S, Hoffmann D . 1995 Carcinogenesis 16: 2015–2021

  • Djordjevic MV, Hoffmann D, Hoffmann I . 1997 Prev. Med. 26: 435–440

  • Djordjevic MV, Stellman SD, Zang E . 2000 J. Natl. Cancer Inst. 92: 106–111

  • Doll R, Peto R . 1976 Br. Med. J. 2: 1525–1536

  • Dunn BP, Vedal S, San RH, Kwan WF, Nelems B, Enarson DA, Stich HF . 1991 Int. J. Cancer 48: 485–492

  • Ebert RV, McNabb ME, McCusker KT, Snow SL . 1983 JAMA 250: 2840–2842

  • Ernster VL . 1996 Annu. Rev. Public Health 17: 97–114

  • Fischer S, Spiegelhalder B, Eisenbarth J, Preussmann R . 1990 Carcinogenesis 11: 723–730

  • Fischer S, Spiegelhalder B, Preussmann R . 1989 Carcinogenesis 10: 1511–1517

  • Gao YT, Blot WJ, Zheng W, Ershow AG, Hsu CW, Levin LI, Zhang R, Fraumeni Jr JF . 1987 Int. J. Cancer 40: 604–609

  • Grinberg-Funes RA, Singh VN, Perera FP, Bell DA, Young TL, Dickey C, Wang LW, Santella RM . 1994 Carcinogenesis 15: 2449–2454

  • Gritz ER, Rose JE, Jarvik ME . 1983 Pharmacol. Biochem. Behav. 18: 457–462

  • Haldorsen T, Grimsrud TK . 1999 Int. J. Epidemiol. 28: 1032–1036

  • Halpern MT, Gillespie BW, Warner KE . 1993 J. Natl. Cancer Inst. 85: 457–464

  • Harris CC, Genta VM, Frank AL, Kaufman DG, Barrett LA, McDowell EM, Trump BF . 1974 Nature 252: 68–69

  • Hartmann A, Blaszyk H, Kovach JS, Sommer SS . 1997 Trends Genet. 13: 27–33

  • Hecht SS . 1998 Chem. Res. Toxicol. 11: 559–603

  • Hecht SS . 1999a J. Natl. Cancer Inst. 91: 1194–1210

  • Hecht SS . 1999b Mutat. Res. 424: 127–142

  • Hecht SS, Carmella SG, Murphy SE, Akerkar S, Brunnemann KD, Hoffmann D . 1993 N. Engl. J. Med. 329: 1543–1546

  • Hegmann KT, Fraser AM, Keaney RP, Moser SE, Nilasena DS, Sedlars M, Higham-Gren L, Lyon JL . 1993 Epidemiology 4: 444–448

  • Hoffmann D, Hoffmann I . 1997 J. Toxicol. Environ. Health 50: 307–364

  • Hou SM, Yang K, Nyberg F, Hemminki K, Pershagen G, Lambert B . 1999 Carcinogenesis 20: 437–444

  • International Agency on the Research for Cancer. 1986 IARC monographs on the evaluation of the carcinogenic risk of chemicals to humans: tobacco smoking Vol 38: Lyon, France: IARC

  • Kaiser U, Hofmann J, Schilli M, Wegmann B, Klotz U, Wedel S, Virmani AK, Wollmer E, Branscheid D, Gazdar AF, Havemann K . 1996 Int. J. Cancer 67: 357–364

  • Kato S, Bowman ED, Harrington AM, Blomeke B, Shields PG . 1995 J. Natl. Cancer Inst. 87: 902–907

  • Kim JH, Stansbury KH, Walker NJ, Trush MA, Strickland PT, Sutter TR . 1998 Carcinogenesis 19: 1847–1853

  • Klein-Szanto AJ, Iizasa T, Momiki S, Garcia-Palazzo I, Caamano J, Metcalf R, Welsh J, Harris CC . 1992 Proc. Natl. Acad. Sci. USA 89: 6693–6697

  • Kondo K, Tsuzuki H, Sasa M, Sumitomo M, Uyama T, Monden Y . 1996 J. Surg. Oncol. 61: 20–26

  • Kure EH, Ryberg D, Hewer A, Phillips DH, Skaug V, Baera R, Haugen A . 1996 Carcinogenesis 17: 2201–2205

  • Lee PN . 1998 Stat. Meth. Med. Res. 7: 137–163

  • Lerman C, Caporaso N, Main D, Audrain J, Boyd NR, Bowman ED, Shields PG . 1998 Health Psychol. 17: 56–62

  • Lerman C, Caporaso NE, Main D, Audrain J, Bowman ED, Lockshin B, Boyd NR, Shields PG . 1999 Health Psychol. 18: 14–20

  • Levi F, La Vecchia C, Decarli A . 1987 Eur. J. Cancer Clin. Oncol. 23: 1025–1029

  • Lewis DF, Brantom PG, Ioannides C, Walker R, Parke DV . 1997 Drug Metab. Rev. 29: 1055–1078

  • Lodovici M, Akpan V, Giovannini L, Migliani F, Dolara P . 1998 Chem. Biol. Interact. 116: 199–212

  • Maclure M, Katz RB, Bryant MS, Skipper PL, Tannenbaum SR . 1989 Am. J. Public Health 79: 1381–1384

  • Mollerup S, Ryberg D, Hewer A, Phillips DH, Haugen A . 1999 Cancer Res. 59: 3317–3320

  • Mustonen R, Schoket B, Hemminki K . 1993 Carcinogenesis 14: 151–154

  • Nakachi K, Imai K, Hayashi S, Kawajiri K . 1993 Cancer Res. 53: 2994–2999

  • Nakachi K, Imai K, Hayashi S, Watanabe J, Kawajiri K . 1991 Cancer Res. 51: 5177–5180

  • NCI Expert Committee. 2000 The FTC cigarette test method for determining tar, nicotine and low yields of US cigarettes. Smoking and tobacco control monograph Washington, DC: US Department of Health pp. 238–247

  • Noble EP, St Jeor ST, Ritchie T, Syndulko K, St Jeor SC, Fitch RJ, Brunner RL, Sparkes RS . 1994 Med. Hypotheses 42: 257–260

  • Nyberg F, Isaksson I, Harris JR, Pershagen G . 1997 Epidemiology 8: 304–309

  • Okada T, Kawashima K, Fukushi S, Minakuchi T, Nishimura S . 1995 Pharmacogenetics 4: 333–340

  • Palmisano WA, Divine KK, Saccomanno G, Gilliland FD, Baylin SB, Herman JG, Belinsky SA . 2000 Cancer Res. 60: 5954–5958

  • Parsons WD, Carmella SG, Akerkar S, Bonilla LE, Hecht SS . 1998 Cancer Epidemiol. Biomarkers Prev. 7: 257–260

  • Pastorelli R, Guanci M, Cerri A, Negri E, La Vecchia C, Fumagalli F, Mezzetti M, Cappelli R, Panigalli T, Fanelli R, Airoldi L . 1998 Cancer Epidemiol. Biomarkers Prev. 7: 703–709

  • Peluso M, Airoldi L, Armelle M, Martone T, Coda R, Malaveille C, Giacomelli G, Terrone C, Casetta G, Vineis P . 1998 Cancer Epidemiol. Biomarkers Prev. 7: 341–346

  • Perera FP . 1987 J. Natl. Cancer Inst. 78: 887–898

  • Phillips DH, Hewer A, Martin CN, Garner RC, King MM . 1988 Nature 336: 790–792

  • Poli P, Buschini A, Spaggiari A, Rizzoli V, Carlo-Stella C, Rossi C . 1999 Toxicol. Lett. 108: 267–276

  • Prescott E, Osler M, Andersen PK, Hein HO, Borch-Johnsen K, Lange P, Schnohr P, Vestbo J . 1998 Int. J. Epidemiol. 27: 27–32

  • Rennard SI, Daughton D, Fujita J, Oehlerking MB, Dobson JR, Stahl MG, Robbins RA, Thompson AB . 1990 Eur. Respir. J. 3: 752–759

  • Repace JL, Lowrey AH . 1990 Risk Analysis 10: 27–37

  • Risch HA, Howe GR, Jain M, Burch JD, Holowaty EJ, Miller AB . 1993 Am. J. Epidemiol. 138: 281–293

  • Risch HA, Howe GR, Jain M, Burch JD, Holowaty EJ, Miller AB . 1994 Science 263: 1206–1208

  • Robertson IGC, Guthenberg C, Mannervik B, Jernstrom B . 1988 Polycarbon aromatic hydrocarbons Cooke M and Dennis AJ (eds) Columbus, OH: Batelle Press pp. 799–808

    Google Scholar 

  • Rojas M, Alexandrov K, Cascorbi I, Brockmoller J, Likhachev A, Pozharisski K, Bouvier G, Auburtin G, Mayer L, Kopp-Schneider A, Roots I, Bartsch H . 1998 Pharmacogenetics 8: 109–118

  • Ronai ZA, Gradia S, Peterson LA, Hecht SS . 1993 Carcinogenesis 14: 2419–2422

  • Ryberg D, Hewer A, Phillips DH, Haugen A . 1994 Cancer Res. 54: 5801–5803

  • Ryberg D, Skaug V, Hewer A, Phillips DH, Harries LW, Wolf CR, Ogreid D, Ulvik A, Vu P, Haugen A . 1997 Carcinogenesis 18: 1285–1289

  • Sabol SZ, Nelson ML, Fisher C, Gunzerath L, Brody CL, Hu S, Sirota LA, Marcus SE, Greenberg BD, Lucas FR4, Benjamin J, Murphy DL, Hamer DH . 1999 Health Psychol. 18: 7–13

  • Schmid W . 1975 9–15

  • Schoket B, Phillips DH, Kostic S, Vincze I . 1998 Carcinogenesis 19: 841–846

  • Scott FM, Modali R, Lehman TA, Seddon M, Kelly K, Dempsey EC, Wilson V, Tockman MS, Mulshine JL . 1997 Clin. Cancer Res. 3: 479–482

  • Seto H, Ohkubo T, Kanoh T, Koike M, Nakamura K, Kawahara Y . 1993 Arch. Environ. Contam. Toxicol. 24: 498–503

  • Shields PG . 1998 Medical and workplace applications of biomarkers 253–255

  • Shields PG, Lerman C, Audrain J, Bowman ED, Main D, Boyd NR, Caporaso NE . 1998 Cancer Epidemiol. Biomarkers Prev. 7: 453–458

  • Shimada T, Hayes CL, Yamazaki H, Amin S, Hecht SS, Guengerich FP, Sutter TR . 1996 Cancer Res. 56: 2979–2984

  • Shopland DR, Eyre HJ, Pechacek TF . 1991 J. Natl. Cancer Inst. 83: 1142–1148

  • Shriver SP, Bourdeau HA, Gubish CT, Tirpak DL, Davis AL, Luketich JD, Siegfried JM . 2000 J. Natl. Cancer Inst. 92: 24–33

  • Sidney S, Tekawa IS, Friedman GD, Sadler MC, Tashkin DP . 1995 Arch. Intern. Med. 155: 727–732

  • Slebos RJ, Hruban RH, Dalesio O, Mooi WJ, Offerhaus GJ, Rodenhuis S . 1991 J. Natl. Cancer Inst. 83: 1024–1027

  • Smith TJ, Guo Z, Gonzalez FJ, Guengerich FP, Stoner GD, Yang CS . 1992 Cancer Res. 52: 1757–1763

  • Smith TJ, Stoner GD, Yang CS . 1995 Cancer Res. 55: 5566–5573

  • Sorsa M, Falck K, Heinonen T, Vainio H, Norppa H, Rimpela M . 1984 Environ. Res. 33: 312–321

  • Speit G, Hartmann A . 1999 Methods Mol. Biol. 113: 203–212

  • Spitz MR, Shi H, Yang F, Hudmon KS, Jiang H, Chamberlain RM, Amos CI, Wan Y, Cinciripini P, Hong WK, Wu Z . 1998 J. Natl. Cancer Inst. 90: 358–363

  • Stern SJ, Degawa M, Martin MV, Guengerich FP, Kaderlik RK, Ilett KF, Breau R, McGhee M, Montague D, Lyn-Cook B . 1993 J. Cell. Biochem. Suppl 17F: 129–137

  • Stockwell HG, Goldman AL, Lyman GH, Noss CI, Armstrong AW, Pinkham PA, Candelora EC, Brusa MR . 1992 J. Natl. Cancer Inst. 84: 1417–1422

  • Sunyer J, Munoz A, Peng Y, Margolick J, Chmiel JS, Oishi J, Kingsley L, Samet JM . 1996 Am. J. Epidemiol. 144: 734–741

  • Takagi Y, Osada H, Kuroishi T, Mitsudomi T, Kondo M, Niimi T, Saji S, Gazdar AF, Takahashi T, Minna JD, Takahashi T . 1998 Br. J. Cancer 77: 1568–1572

  • Tang D, Phillips DH, Stampfer M, Mooney LA, Hsu Y, Cho S, Tsai WY, Ma J, Cole KJ, She MN, Perera FP . 2001 Cancer Res. 61: 6708–6712

  • Tang D, Santella RM, Blackwood AM, Young TL, Mayer J, Jaretzki A, Grantham S, Tsai WY, Perera FP . 1995 Cancer Epidemiol. Biomarkers Prev. 4: 341–346

  • Tang DL, Rundle A, Warburton D, Santella RM, Tsai WY, Chiamprasert S, Hsu YZ, Perera FP . 1998 Carcinogenesis 19: 1949–1953

  • Thun MJ, Lally CA, Flannery JT, Calle EE, Flanders WD, Heath Jr CW . 1997 J. Natl. Cancer Inst. 89: 1580–1586

  • Tiano HF, Wang RL, Hosokawa M, Crespi C, Tindall KR, Langenbach R . 1994 Carcinogenesis 15: 2859–2866

  • Tricker AR, Ditrich C, Preussmann R . 1991 Carcinogenesis 12: 257–261

  • Tweedie RL, Mengersen KL . 1992 Br. J. Cancer 66: 700–705

  • Valkonen M, Kuusi T . 1998 Circulation 97: 2012–2016

  • van Delft JH, Baan RA, Roza L . 1998 Crit. Rev. Toxicol. 28: 477–510

  • Van Schooten FJ, Hillebrand MJ, Van Leeuwen FE, Lutgerink JT, van Zandwijk N, Jansen HM, Kriek E . 1990 Carcinogenesis 11: 1677–1681

  • Vineis P, Bartsch H, Caporaso N, Harrington AM, Kadlubar FF, Landi MT, Malaveille C, Shields PG, Skipper P, Talaska G . 1994 Nature 369: 154–156

  • Wada M, Bartram CR, Nakamura H, Hachiya M, Chen DL, Borenstein J, Miller CW, Ludwig L, Hansen-Hagge TE, Ludwig WD, Reiter A, Mizoguchii H, Koeffler HP . 1993 Blood 82: 3163–3169

  • Wiencke JK, Kelsey KT, Varkonyi A, Semey K, Wain JC, Mark E, Christiani DC . 1995 Cancer Res. 55: 4910–4914

  • Wingo PA, Ries LA, Giovino GA, Miller DS, Rosenberg HM, Shopland DR, Thun MJ, Edwards BK . 1999 J. Natl. Cancer Inst. 91: 675–690

  • Xue KX, Wang S, Ma GJ, Zhou P, Wu PQ, Zhang RF, Xu Z, Chen WS, Wang YQ . 1992 Int. J. Cancer 50: 702–705

  • Yakubovskaya MS, Spiegelman V, Luo FC, Malaev S, Salnev A, Zborovskaya I, Gasparyan A, Polotsky B, Machaladze Z, Trachtenberg AC . 1995 Int. J. Cancer 63: 810–814

  • Zang EA, Wynder EL . 1996 J. Natl. Cancer Inst. 88: 183–192

  • Zaridze DG, Safaev RD, Belitsky GA, Brunnemann KD, Hoffmann D . 1991 IARC Sci. Publ. 105: 485–488

  • Zeise L, Dunn A, Haroun L, Ting D, Windham G, Golub M, Waller K, Lipsett M, Shusterman D, Mann J, Wu A . 1997 Washington, DC: Environmental Protection Agency Report

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Peter G Shields.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Shields, P. Molecular epidemiology of smoking and lung cancer. Oncogene 21, 6870–6876 (2002). https://doi.org/10.1038/sj.onc.1205832

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1205832

Keywords

This article is cited by

Search

Quick links