• 1
    Hirsch FR, Lippman SM. Advances in the biology of lung cancer chemoprevention. J Clin Oncol 2005; 23: 318697.
  • 2
    Ginsberg RJ, Vokes EE, Rosenzweig K. Non-small cell lung cancer. In: DeVitaVT, HellmannS, RosenbergSA, eds. Cancer: principles and practice of oncology, Vol. 1. Philadelphia: Lippincott, 6th edn, 2001. 92583.
  • 3
    Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, Zhu J, Johnson DH for the Eastern Cooperative Oncology Group. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med 2002; 346: 928.
  • 4
    Coleman MP, Rachet B, Woods LM, Mitry E, Riga M, Cooper N, Quinn MJ, Brenner H, Esteve J. Trends and socioeconomic inequalities in cancer survival in England and Wales up to 2001. Br J Cancer 2004; 90: 136773.
  • 5
    Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin 2005; 55: 74108.
  • 6
    Ganti AK, Mulshine JL. Lung cancer screening: panacea or pipe dream? Ann Oncol 2005; 16 ( Suppl 2): ii215ii219.
  • 7
    Mulshine JL, Sullivan DC. Clinical practice. Lung cancer screening. N Engl J Med 2005; 352: 271420.
  • 8
    National Cancer Institute. The nation's investment in cancer research. A plan and budget proposal for the year 2006. National cancer Institute, Bethesda, MD. Available at
  • 9
    Kannel WB, McGee D, Gordon T. A general cardiovascular risk profile: the Framingham study. Am J Cardiol 1976; 38: 4651.
  • 10
    Gail MH, Brinton LA, Byar DP, Corle DK, Green SB, Schairer C, Mulvihill JJ. Projecting individualized probabilities of developing breast cancer for white females who are being examined annually. J Natl Cancer Inst 1989; 81: 187986.
  • 11
    Taplin SH, Thompson RS, Schnitzer F, Anderman C, Immanuel V. Revisions in the risk-based breast cancer screening program at group health cooperative. Cancer 1990; 66: 81218.
  • 12
    Claus EB, Risch N, Thompson WD. Autosomal dominant inheritance of early-onset breast cancer. Implications for risk prediction. Cancer 1994; 73: 64351.
  • 13
    Ueda K, Tsukuma H, Tanaka H, Ajiki W, Oshima A. Estimation of individualized probabilities of developing breast cancer for Japanese women. Breast Cancer 2003; 10: 5462.
  • 14
    Tyrer J, Duffy SW, Cuzick J. A breast cancer prediction model incorporating familial and personal risk factors. Stat Med 2004; 23: 111130.
  • 15
    Tice JA, Cummings SR, Ziv E, Kerlikowske K. Mammographic breast density and the Gail model for breast cancer risk prediction in a screening population. Breast Cancer Res Treat 2005; 94: 11522.
  • 16
    Wijnen JT, Vasen HF, Khan PM, Zwinderman AH, van der Klift H, Mulder A, Tops C, Moller P, Fodde R. Clinical findings with implications for genetic testing in families with clustering of colorectal cancer. N Engl J Med 1998; 339: 51118.
  • 17
    Selvachandran SN, Hodder RJ, Ballal MS, Jones P, Cade D. Prediction of colorectal cancer by a patient consultation questionnaire and scoring system: a prospective study. Lancet 2002; 360: 27883.
  • 18
    Imperiale TF, Wagner DR, Lin CY, Larkin GN, Rogge JD, Ransohoff DF. Using risk for advanced proximal colonic neoplasia to tailor endoscopic screening for colorectal cancer. Ann Intern Med 2003; 139: 95965.
  • 19
    Cho E, Rosner BA, Feskanich D, Colditz GA. Risk factors and individual probabilities of melanoma for whites. J Clin Oncol 2005; 23: 266975.
  • 20
    Whiteman DC, Green AC. A risk prediction tool for melanoma? Cancer Epidemiol Biomarkers Prev 2005; 14: 7613.
  • 21
    Bach PB, Kattan MW, Thornquist MD, Kris MG, Tate RC, Barnett MJ, Hsieh LJ, Begg CB. Variations in lung cancer risk among smokers. J Natl Cancer Inst 2003; 95: 4708.
  • 22
    Hartge P, Whittemore AS, Itnyre J, McGowan L, Cramer D. Rates and risks of ovarian cancer in subgroups of white women in the United States. The Collaborative Ovarian Cancer Group. Obstet Gynecol 1994; 84: 7604.
  • 23
    Eastham JA, May R, Robertson JL, Sartor O, Kattan MW. Development of a nomogram that predicts the probability of a positive prostate biopsy in men with an abnormal digital rectal examination and a prostate-specific antigen between 0 and 4 ng/mL. Urology 1999; 54: 70913.
  • 24
    Ohori M, Swindle P. Nomograms and instruments for the initial prostate evaluation: the ability to estimate the likelihood of identifying prostate cancer. Semin Urol Oncol 2002; 20: 11622.
  • 25
    Colditz GA, Atwood KA, Emmons K, Monson RR, Willett WC, Trichopoulos D, Hunter DJ. Harvard report on cancer prevention volume 4: Harvard cancer risk index. Risk Working Group, Harvard Center for Cancer Prevention. Cancer Causes Control 2000; 11: 47788.
  • 26
    Freedman AN, Seminara D, Gail MH, Hartge P, Colditz GA, Ballard-Barbash R, Pfeiffer RM. Cancer risk prediction models: a workshop on development, evaluation and application. J Natl Cancer Inst 2005; 97: 71523.
  • 27
    McTiernan A, Gilligan MA, Redmond C. Assessing individual risk for breast cancer: risky business. J Clin Epidemiol 1997; 50: 54756.
  • 28
    Lutz WK. Susceptibility differences in chemical carcinogenesis linearize the dose-response relationship: threshold doses can be defined only for individuals. Mutat Res 2001; 482: 716.
  • 29
    Day NE. Time as a determinant of risk in cancer epidemiology: the role of multi-stage models. Cancer Surv 1983; 2: 57793.
  • 30
    Shields PG, Harris CC. Cancer risk and low-penetrance susceptibility genes in gene-environment interactions. J Clin Oncol 2000; 18: 230915.
  • 31
    Lutz WK. Carcinogens in the diet vs. overnutrition. Individual dietary habits, malnutrition and genetic susceptibility modify carcinogenic potency and cancer risk. Mutat Res 1999; 443: 2518.
  • 32
    van Zandwijk N. Chemoprevention in lung carcinogenesis—an overview. Eur J Cancer 2005; 41: 19902002.
  • 33
    Schwartz AG. Genetic predisposition to lung cancer. Chest 2004; 125( 5 Suppl): 86S89S.
  • 34
    Lichtenstein P, Holm NV, Verkasalo PK, Iliadou A, Kaprio J, Koskenvuo M, Pukkala E, Skytthe A, Hemminki K. Environmental and heritable factors in the causation of cancer—analyses of cohorts of twins from Sweden, Denmark and Finland. N Engl J Med 2000; 343: 7885.
  • 35
    Siemiatycki J, Richardson L, Straif K, Latreille B, Lakhani R, Campbell S, Rousseau MC, Boffetta P. Listing occupational carcinogens. Environ Health Perspect 2004; 112: 144759.
  • 36
    Doll R. Mortality from lung cancer in asbestos workers. Br J Ind Med 1955; 12: 816.
  • 37
    Saracci R, Boffetta P. Interactions of tobacco smoking and other causes of lung cancer. In: SametJM, ed. Epidemiology of lung cancer. New York: Marcel Dekker, 1994. 46593.
  • 38
    Balkwill F, Mantovani A. Inflammation and cancer: back to Virchow? Lancet 2001; 357: 53945.
  • 39
    Coussens LM, Werb Z. Inflammation and cancer. Nature 2002; 420: 8607.
  • 40
    Littman AJ, Thornquist MD, White E, Jackson LA, Goodman GE, Vaughan TL. Prior lung disease and risk of lung cancer in a large prospective study. Cancer Causes Control 2004; 15: 81927.
  • 41
    Schabath MB, Delclos GL, Martynowicz MM, Greisinger AJ, Lu C, Wu X, Spitz MR. Opposing effects of emphysema, hay fever and select genetic variants on lung cancer risk. Am J Epidemiol 2005; 161: 41222.
  • 42
    Skillrud DM, Offord KP, Miller RD. Higher risk of lung cancer in chronic obstructive pulmonary disease. A prospective, matched, controlled study. Ann Intern Med 1986; 105: 5037.
  • 43
    Islam SS, Schottenfeld D. Declining FEV1 and chronic productive cough in cigarette smokers: a 25-year prospective study of lung cancer incidence in Tecumseh, Michigan. Cancer Epidemiol Biomarkers Prev 1994; 3: 28998.
  • 44
    Eberly LE, Ockene J, Sherwin R, Yang L, Kuller L for the Multiple Risk Factor Intervention Trial Research Group. Pulmonary function as a predictor of lung cancer mortality in continuing cigarette smokers and in quitters. Int J Epidemiol 2003; 32: 5929.
  • 45
    Mannino DM, Buist AS, Petty TL, Enright PL, Redd SC. Lung function and mortality in the United States: data from the first national health and nutrition examination survey follow up study. Thorax 2003; 58: 38893.
  • 46
    Alberg AJ, Brock MV, Samet JM. Epidemiology of lung cancer: looking to the future. J Clin Oncol 2005; 23: 317585.
  • 47
    Michels KB. Nutritional epidemiology—past, present, future. Int J Epidemiol 2003; 32: 4868.
  • 48
    Matakidou A, Eisen T, Houlston RS. Systematic review of the relationship between family history and lung cancer risk. Br J Cancer 2005; 93: 82533.
  • 49
    Amos CI, Xu W, Spitz MR. Is there a genetic basis for lung cancer susceptibility? Recent Results Cancer Res 1999; 151: 312.
  • 50
    Bailey-Wilson JE, Amos CI, Pinney SM, Petersen GM, de Andrade M, Wiest JS, Fain P, Schwartz AG, You M, Franklin W, Klein C, Gazdar A, et al. A major lung cancer susceptibility locus maps to chromosome 6q23–25. Am J Hum Genet 2004; 75: 46074.
  • 51
    Cancer GeneticsWeb. Available at [Last accessed: July 7, 2006]
  • 52
    Belinsky SA. Gene-promoter hypermethylation as a biomarker in lung cancer. Nat Rev Cancer 2004; 4: 70717.
  • 53
    Peto R, Darby S, Deo H, Silcocks P, Whitley E, Doll R. Smoking, smoking cessation, and lung cancer in the UK since 1950: combination of national statistics with two case-control studies. Br Med J 2000; 321: 3239.
  • 54
    Prindiville SA, Byers T, Hirsch FR, Franklin WA, Miller YE, Vu KO, Wolf HJ, Baron AE, Shroyer KR, Zeng C, Kennedy TC, Bunn PA. Sputum cytological atypia as a predictor of incident lung cancer in a cohort of heavy smokers with airflow obstruction. Cancer Epidemiol Biomarkers Prev 2003; 12: 98793.
  • 55
    Cassidy A, Myles JP, Liloglou T, Duffy SW, Field JK. Defining high-risk individuals in a population-based molecular-epidemiological study of lung cancer. Int J Oncol 2006; 28: 1295302.
  • 56
    Crispo A, Brennan P, Jockel KH, Schaffrath-Rosario A, Wichmann HE, Nyberg F, Simonato L, Merletti F, Forastiere F, Boffetta P, Darby S. The cumulative risk of lung cancer among current, ex- and never-smokers in European men. Br J Cancer 2004; 91: 12806.
  • 57
    Cronin KA, Gail MH, Zou Z, Bach PB, Virtamo J, Albanes D. Validation of a model of lung cancer risk prediction among smokers. J Natl Cancer Inst 2006; 98: 63740.
  • 58
    Tockman MS, Anthonisen NR, Wright EC, Donithan MG. Airways obstruction and the risk for lung cancer. Ann Intern Med 1987; 106: 51218.
  • 59
    Papi A, Casoni G, Caramori G, Guzzinati I, Boschetto P, Ravenna F, Calia N, Petruzzelli S, Corbetta L, Cavallesco G, Forini E, Saetta M, et al. COPD increases the risk of squamous histological subtype in smokers who develop non-small cell lung carcinoma. Thorax 2004; 59: 67981.
  • 60
    Keith RL, Miller YE. Lung cancer: genetics of risk and advances in chemoprevention. Curr Opin Pulm Med 2005; 11: 26571.
  • 61
    Chanin TD, Merrick DT, Franklin WA, Hirsch FR. Recent developments in biomarkers for the early detection of lung cancer: perspectives based on publications 2003 to present. Curr Opin Pulm Med 2004; 10: 2427.
  • 62
    Field JK, Smith DL, Duffy S, Cassidy A. The Liverpool lung project research protocol. Int J Oncol 2005; 27: 163345.
  • 63
    Franco EL, Correa P, Santella RM, Wu X, Goodman SN, Petersen GM. Role and limitations of epidemiology in establishing a causal association. Semin Cancer Biol 2004; 14: 41326.
  • 64
    Grundy SM, Balady GJ, Criqui MH, Fletcher G, Greenland P, Hiratzka LF, Houston-Miller N, Kris-Etherton P, Krumholz HM, LaRosa J, Ockene IS, Pearson TA, et al. Primary prevention of coronary heart disease: guidance from Framingham: a statement for healthcare professionals from the AHA task force on risk reduction. Circulation 1998; 97: 187687.
  • 65
    Pepe MS, Etzioni R, Feng Z, Potter JD, Thompson ML, Thornquist M, Winget M, Yasui Y. Phases of biomarker development for early detection of cancer. J Natl Cancer Inst 2001; 93: 105461.
  • 66
    Rockhill B, Spiegelman D, Byrne C, Hunter DJ, Colditz GA. Validation of the Gail, et al. model of breast cancer risk prediction and implications for chemoprevention. J Natl Cancer Inst 2001; 93: 35866.
  • 67
    Duffy SW, Tabar L, Smith RA, Krusemo UB, Prevost TC, Chen HH. Risk of breast cancer and risks with breast cancer: the relationship of histologic type with epidemiology, disease progression and survival. Semin Breast Dis 1999; 2: 292300.
  • 68
    Hoover RN. Cancer–nature, nurture, or both. N Engl J Med 2000; 343: 1356.
  • 69
    Cuzick J. Keynote comment: chemoprevention of cancer—time to catch up with the cardiologists. Lancet Oncol 2006; 7: 989.
  • 70
    Shaw AT, Kirsch DG, Jacks T. Future of early detection of lung cancer: the role of mouse models. Clin Cancer Res 2005; 11: 4999s5003s.
  • 71
    Maruvada P, Srivastava S. Joint national cancer institute-food and drug administration workshop on research strategies, study designs, and statistical approaches to biomarker validation for cancer diagnosis and detection. Cancer Epidemiol Biomarkers Prev 2006; 15: 107882.
  • 72
    Spitz MR, Wu X, Mills G. Integrative epidemiology: from risk assessment to outcome prediction. J Clin Oncol 2005; 23: 26775.
  • 73
    Lader D, Meltzer H, Office for National Statistics. Smoking related behaviour and attitudes, 2002. London: The Stationary Office, 2003.
  • 74
    National Cancer Institute. Cancer Intervention and Surveillance Modeling Network (CISNET). National Cancer Institute, Bethesda, MD. Available at
  • 75
    Colditz GA, Sellers TA, Trapido E. Epidemiology—identifying the causes and preventability of cancer? Nat Rev Cancer 2006; 6: 7583.
  • 76
    Weissleder R. Molecular imaging in cancer. Science 2006; 312: 116871.
  • 77
    Sweet-Cordero A, Mukherjee S, Subramanian A, You H, Roix JJ, Ladd-Acosta C, Mesirov J, Golub TR, Jacks T. An oncogenic KRAS2 expression signature identified by cross-species gene-expression analysis. Nat Genet 2005; 37: 4855.
  • 78
    Grimm J, Kirsch DG, Windsor SD, Kim CF, Santiago PM, Ntziachristos V, Jacks T, Weissleder R. Use of gene expression profiling to direct in vivo molecular imaging of lung cancer. Proc Natl Acad Sci USA 2005; 102: 144049.