It has been almost 25 years since Doll and Peto performed their landmark analysis of epidemiological data to identify the causes of cancers and possible modes of cancer prevention. Since then, there have been many additional studies of cancer incidence using various epidemiological techniques. These studies revealed expanded opportunities for cancer prevention through approaches that include vaccination, increased physical activity, weight control and avoidance of post-menopausal hormone therapy.
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World Health Organization. Prevention of Cancer (WHO, Geneva, 1964).
Doll, R. Prevention of Cancer — Pointers from Epidemiology (Nuffield Hospital Trust, London, 1967).
Wynder, E. L. & Gori, G. B. Contribution of the environment to cancer incidence: an epidemiologic exercise. J. Natl Cancer Inst. 58, 825–832 (1977).
Higginson, J. & Muir, C. S. Environmental carcinogenesis: misconceptions and limitations to cancer control. J. Natl Cancer Inst. 63, 1291–1298 (1979).
Doll, R. & Peto, R. The Causes of Cancer: Quantitative Estimates of Avoidable Risks of Cancer in the United States Today (Oxford University Press, New York, 1981).
Epstein, S. & Swartz, J. Fallacies of lifestyle cancer theories. Nature 289, 127–130 (1981).
Weil, D. OSHA: Beyond the politics. Frontline (online), http://www.pbs.org/wgbh/pages/frontline/shows/workplace/osha/weil.html (2003).
Xu, Z. et al. Cancer risks among iron and steel workers in Anshan, China, part II: case–control studies of lung and stomach cancer. Am. J. Ind. Med. 30, 7–15 (1996).
Monson, R. R. & Christiani, D. C. Summary of the evidence: occupation and environment and cancer. Cancer Causes Control 8, 529–531 (1997).
Willett, W., Colditz, G. & Mueller, N. Strategies for minimizing cancer risk. Sci. Amer. 275, 88–95 (1996).
Prevention Working Group. Cancer control objectives for the nation: 1985–2000. NCI Monogr. 2, 3–11 (1986).
Byers, T. et al. The American Cancer Society challenge goals. How far can cancer rates decline in the U.S. by the year 2015? Cancer 86, 715–727 (1999).
Colditz, G. A., DeJong, D., Hunter, D. J., Trichopoulos, D. & Willett, W. C. Harvard report on cancer prevention. Volume 1. Causes of human cancer. Cancer Causes Control 7, 1–59 (1996).
Collaborative Group on Hormonal Factors in Breast Cancer. Breast cancer and hormone replacement therapy. Combined reanalysis of data from 51 epidemiological studies involving 52,705 women with breast cancer and 108,411 women without breast cancer. Lancet 350, 1047–1059 (1997).
Rossouw, J. E. et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial. JAMA 288, 321–333 (2002).
US Public Health Service. Smoking and Health. Report of the Advisory Committee to the Surgeon General of the Public Health Service (US Department of Health, Education, and Welfare, Public Health Service, Centers for Disease Control, Washington DC, 1964).
Angell, M. The interpretation of epidemiologic studies. N. Engl. J. Med. 323, 782–788 (1990).
Hill, A. B. The environment and disease: association or causation? Proc. R. Soc. Med. 58, 295–300 (1965).
Fletcher, S. W. & Colditz, G. A. Failure of estrogen plus progestin therapy for prevention. JAMA 288, 366–368 (2002).
Benson, K. & Hartz, A. J. A comparison of observational studies and randomized, controlled trials. N. Engl. J. Med. 342, 1878–1886 (2000).
Concato, J., Shah, N. & Horwitz, R. I. Randomized, controlled trials, observational studies, and the hierarchy of research designs. N. Engl. J. Med. 342, 1887–1892 (2000).
Ahmad, N. & Mukhtar, H. Green tea polyphenols and cancer: biologic mechanisms and practical implications. Nutr. Rev. 57, 78–83 (1999).
Peto, R. et al. Smoking, smoking cessation, and lung cancer in the UK since 1950: combination of national statistics with two case–control studies. Br. Med. J. 321, 323–329 (2000).
US Department of Health and Human Services. Preventing Tobacco Use among Young People. A Report of the Surgeon General (US Department of Health and Human Services, Public Health Service, Centers for Disease Control, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, Atlanta, Georgia, 1994).
Pierce, J. P., Fiore, M. C., Novotny, T. E., Hatziandreu, E. J. & Davis, R. M. Trends in cigarette smoking in the United States. Projections to the year 2000. JAMA 261, 61–65 (1989).
Hecht, S. Tobacco smoke carcinogens and lung cancer. J. Natl Cancer Inst. 91, 1194–1210 (1999).
Hecht, S. S. Tobacco carcinogens, their biomarkers and tobacco-induced cancer. Nature Rev. Cancer 3, 733–744 (2003).
Ezzati, M. & Lopez, A. D. Estimates of global mortality attributable to smoking in 2000. Lancet 362, 847–852 (2003).
Peto, R. et al. Mortality from smoking worldwide. Br. Med. Bull. 52, 12–21 (1996).
Committee on the Biologic Effects of Ionizing Radiation. Health Effects of Low Levels of Ionizing Radiation. BEIR V (National Academy Press, Washington DC, 1990).
Armstrong, B. & Kricker, A. The epidemiology of UV induced skin cancer. J. Photochem. Photobiol. B. 63, 8–18 (2001).
Parkin, D. M., Pisani, P. & Ferlay, J. Estimates of the worldwide incidence of 25 major cancers in 1990. Int. J. Cancer 80, 827–841 (1999).
Ahlbom, A. et al. Epidemiology of health effects of radiofrequency exposure. Environ. Health Perspect. 112, 1741–1754 (2004).
Bernstein, J. L. et al. Study design: evaluating gene–environment interactions in the etiology of breast cancer — the WECARE study. Breast Cancer Res. 6, R199–R214 (2004).
Polednak, A. Trends in incidence rates for obesity-related cancers in the US. Cancer Detect. Prev. 27, 415–421 (2003).
Hedley, A. A. et al. Prevalence of overweight and obesity among US children, adolescents, and adults, 1999–2002. JAMA 291, 2847–2850 (2004).
International Agency for Research on Cancer. in Weight Control and Physical Activity 315 (International Agency for Research on Cancer, Lyon, 2002).
Calle, E. E. & Kaaks, R. Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Nature Rev. Cancer 4, 579–591 (2004).
Calle, E. E., Rodriguez, C., Walker-Thurmond, K. & Thun, M. J. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N. Engl. J. Med. 348, 1625–1638 (2003).
Schiffman, M. H. et al. Epidemiologic evidence showing that human papillomavirus infection causes most cervical intrepthelial neoplasia. J. Natl Cancer Inst. 85, 958–964 (1993).
Franco, E., Rohan, T. & Villa, L. Epidemiologic evidence and human papillomavirus infection as a necessary cause of cervical cancer. J. Natl Cancer Inst. 91, 506–511 (1999).
Buchschacher, G. & Wong-Staal, F. in Cancer Principles and Practice of Oncology (eds DeVita, V., Hellman, S. & Rosenberg, S.) 165–173 (Lippincott Williams & Wilkins, Philadelphia, 2005).
Howley, P., Ganem, D. & E, K. in Cancer Principles and Practice of Oncology (eds DeVita, V., Hellman, S. & Rosenberg, S.) 173–184 (Lippincott Williams & Wilkins, Philadelphia, 2005).
International Agency for Research on Cancer Working Group on the Evaluation of Carcinogenic Risks to Humans. in Schistosomes, liver flukes and heicobacter pylori: views and expert opinions of an IARC working grooup on the evaluation of carcinogenic risks to humans 177–240 (IARC Press, Lyon, France, 1994).
Webb PM & Forman D. Helicobacter pylori as a risk factor for cancer. Baillieres Clin. Gastroenterol. 9, 563–582 (1995).
Correa, P. Is gastric cancer preventable? Gut 53, 1217–1219 (2004).
US Institute of Medicine. The Hidden Epidemic: Confronting Sexually Transmitted Diseases (National Academy Press, Washington DC, 1997).
Stuver, S. Towards the global control of liver cancer. Semin. Cancer Biol. 8, 299–306 (1998).
Koutsky, L. A. et al. A controlled trial of a human papillomavirus type 16 vaccine. N. Engl. J. Med. 347, 1645–1651 (2002).
Chang, M. H. et al. Universal hepatitis B vaccination in Taiwan and the incidence of hepatocellular carcinoma in children. Taiwan Childhood Hepatoma Study Group. N. Engl J. Med. 336, 1855–1859 (1997).
Breast cancer and hormonal contraceptives: collaborative reanalysis of individual data on 53,297 women with breast cancer and 100,239 women without breast cancer from 54 epidemiological studies. Collaborative Group on Hormonal Factors in Breast Cancer. Lancet 347, 1713–1727 (1996).
Rich, S. S. & Sellers, T. A. in The Genetic Basis of Common Diseases. (eds King, R. A., Rotter, J. & Motulsky, A. G.) 39–49 (Oxford University Press, Inc., New York, 2002).
Slye, M. Biological evidence for the inheritability of cancer in man: studies in the incidence and inheritability of spontaneous tumors in mice. Eighteenth report. J. Cancer Res. 7, 107–147 (1922).
Jacobsen, O. Heredity in Breast Cancer (H. K. Lewis, London, 1946).
Anderson, V. E., Goodman, H. O. & Reed, S. C. Variables Related to Human Breast Cancer (University of Minnesota Press, Minneapolis, 1958).
Claus, E. B., Risch, N. J. & Thompson, W. D. Age at onset as an indicator of familial risk of breast cancer. Am. J. Epidemiol. 131, 961–972 (1990).
Claus, E. B., Risch, N. & Thompson, W. D. Genetic analysis of breast cancer in the cancer and steroid hormone study. Am. J. Hum. Genet. 48, 232–242 (1991).
Hall, J. M. et al. Linkage of early-onset familial breast cancer to chromosome 17q21. Science 250, 1684–1689 (1990).
Miki, Y. et al. A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science 266, 66–71 (1994).
Li, F. et al. A cancer family syndrome in twenty-four kindreds. Cancer Res. 48, 5358–5362 (1988).
Peto, J. Cancer epidemiology in the last century and the next decade. Nature 411, 390–395 (2001).
Atwood, K., Colditz, G. & Kawachi, I. Implementing prevention policies: relevance of the Richmond model to health policy judgments. Am. J. Public Health 87, 1603–1606 (1997).
Peto, R., Lopez, A. D., Boreham, J., Thun, M. & Heath, C. J. Mortality from tobacco in development countries: indirect estimation from national vital statistics. Lancet 339, 1268–1278 (1992).
Curry, S., Byers, T. & Hewitt, M. Fulfilling the Potential of Cancer Prevention and Early Detection (National Academy Press, Washington DC, 2003).
Hiatt, R. & Rimer, B. A new strategy for cancer control research. Cancer Epidemiol. Biol. Prev. 8, 957–964 (1999).
Giovino, G. Epidemiology of tobacco use in the United States. Oncogene 21, 7326–7340 (2002).
Warner, K. Effects of the antismoking campaign: an update. Am. J. Public Health 79, 144–151 (1989).
Centers for Disease Control and Prevention. Annual smoking-attributable mortality, years of potential life lost, and economic costs — United States, 1995–1999. MMWR Morb. Mortal. Wkly Rep. 51, 300–303 (2002).
Tengs, T. et al. Five hundred life saving interventions and thier cost-effectiveness. Risk Analysis 15, 369–390 (1995).
Etzioni, R., Urban, N. & Ramsey, S. The case for early detection. Nature Rev. Cancer 3, 243–252 (2003).
Smith, R. A. et al. American Cancer Society guidelines for breast cancer screening: update 2003. CA Cancer J. Clin. 53, 141–169 (2003).
Smith, R. A. et al. American Cancer Society guidelines for the early detection of cancer: update of early detection guidelines for prostate, colorectal, and endometrial cancers. Also: update 2001 — testing for early lung cancer detection. CA Cancer J. Clin. 51, 38–75; quiz 77–80 (2001).
Saslow, D. et al. American Cancer Society guideline for the early detection of cervical neoplasia and cancer. CA Cancer J. Clin. 52, 342–362 (2002).
Mushlin, A. I., Kouides, R. W. & Shapiro, D. E. Estimating the accuracy of screening mammography: a meta-analysis. Am. J. Prev. Med. 14, 143–153 (1998).
Kouskos, E. et al. Missed cancers on mammograms: causes and measures of prevention. Eur. J. Gynaecol. Oncol. 25, 230–232 (2004).
Elmore, J. G., Armstrong, K., Lehman, C. D. & Fletcher, S. W. Screening for breast cancer. JAMA 293, 1245–1256 (2005).
Minardi, D. et al. Diagnostic accuracy of percent free prostate-specific antigen in prostatic pathology and its usefulness in monitoring prostatic cancer patients. Urol. Int. 67, 272–282 (2001).
Seeff, L. C. et al. Patterns and predictors of colorectal cancer test use in the adult U.S. population. Cancer 100, 2093–2103 (2004).
Frazier, A., Colditz, G., Fuchs, C. & Kuntz, K. Cost-effectiveness of screening for colorectal cancer in the general population. JAMA 284, 1954–1961 (2000).
Schwartz, L., Woloshin, S., Fowler, F. Jr & Welch, H. Enthusiasm for cancer screening in the United States. JAMA 291, 71–78 (2004).
Gorga, F. The Molecular Basis of Cancer (Bridgewater Review, 1998).
Spencer, S. L., Berryman, M. J., Garcia, J. A. & Abbot, D. An ordinary differential equation model for the multistep transformation to cancer. J. Theor. Biol. 231, 515–524 (2004).
Abdel-Rahman, W. M. & Peltomaki, P. Molecular basis and diagnostics of hereditary colorectal cancers. Ann. Med. 36, 379–388 (2004).
Garnis, C., Buys, T. P. & Lam, W. L. Genetic alteration and gene expression modulation during cancer progression. Mol. Cancer 3, 9 (2004).
Sung, J. et al. Oncogene regulation of tumor suppressor genes in tumorigenesis. Carcinogenesis 26, 487–494 (2005).
Misek, D. E., Imafuku, Y. & Hanash, S. M. Application of proteomic technologies to tumor analysis. Pharmacogenomics 5, 1129–1137 (2004).
Cowherd, S. M., Espina, V. A., Petricoin, E. F. 3rd & Liotta, L. A. Proteomic analysis of human breast cancer tissue with laser-capture microdissection and reverse-phase protein microarrays. Clin. Breast Cancer 5, 385–392 (2004).
Okuda T et al. The profile of Hmlh1 methylation and microsatellite instability in colorectal and non-small cell lung cancer. Int. J. Mol. Med. 15, 85–90 (2005).
Rook, M. S., Delach, S. M., Deyneko, G., Worlock, A. & Wolfe, J. L. Whole genome amplification of DNA from laser capture-microdissected tissue for high-throughput single nucleotide polymorphism and short tandem repeat genotyping. Am. J. Pathol. 164, 23–33 (2004).
Grieu, F., Joseph, D., Norman, P. & Iacopetta, B. Development of a rapid genotyping method for single nucleotide polymorphisms and its application in cancer studies. Oncol. Rep. 11, 501–504 (2004).
Ohno, M. et al. Lymphagenesis correlates with expression of vascular endothelial growth factor-C in colorectal cancer. Oncol. Rep. 10, 939–943 (2003).
Hicklin, D. J. & Ellis, L. M. Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J. Clin. Oncol. 23, 1011–1027 (2005).
Demel, U. et al. Detection of tumor cells in the peripheral blood of patients with breast cancer, development of a new sensitive and specific immunomolecular assay. J. Exp. Clin. Cancer Res. 23, 465–468 (2004).
Muller, V. & Pantel, K. Bone marrow micrometastases and circulating tumor cells: current aspects and future perspectives. Breast Cancer Res. 6, 258–261 (2004).
Eissa, S. et al. Diagnostic value of urinary molecular markers in bladder cancer. Anticancer Res. 23, 4347–4355 (2003).
Pepe, M. S. et al. Phases of biomarker development for early detection of cancer. J. Natl Cancer Inst. 93, 1054–1061 (2001).
Colditz, G. A. & Hankinson, S. E. The Nurses' Health Study: lifestyle and health among women. Nature Rev. Cancer 5, 388–396 (2005).
Hirschhorn, J. N. & Daly, M. J. Genome-wide association studies for common diseases and complex traits. Nature Rev. Genet. 6, 95–108 (2005).
Ransohoff, D. F. Rules of evidence for cancer molecular-marker discovery and validation. Nature Rev. Cancer 4, 309–314 (2004).
The National Cancer Institute Breast and Prostate Cancer Cohort Consortium. A candidate gene approach to searching for low-penetrance breast and prostate cancer genes. Nature Rev. Cancer 5, 977–985 (2005).
Mosteller, F. & Colditz, G. Understanding research synthesis (meta-analysis). Ann. Rev. Public Health 17, 1–32 (1996).
Webb, P., Bain, C. & Pirozzo, S. Esential Epidemiology (Cambridge University Press, Cambridge, 2005).
Whittemore, A. S., Harris, R. & Itnyre, J. Characteristics relating to ovarian cancer risk: collaborative analysis of 12 US case–control studies. II. Invasive epithelial ovarian cancers in white women. Am. J. Epidemiol. 136, 1184–1203 (1992).
Grodstein, F. et al. Postmenopausal hormone use and risk of colorectal cancer and adenoma. Ann. Intern. Med. 128, 705–712 (1998).
Herbst, A., Kurman, R., Scully, R. & Poskanzer, D. Clear-cell adenocarcinoma of the genital tract in young females: registry report. N. Engl. J. Med. 287, 1259–1264 (1972).
Thun, M. J., Henley, S. & Patrono, C. Nonsteroidal anti-inflammatory drugs as anticancer agents: mechanistic, pharmacologic, and clincal issues. J. Natl Cancer Inst. 94, 252–266 (2002).
Bernstein, L. et al. Tamoxifen therapy for breast cancer and endometrial cancer risk. J. Natl Cancer Inst. 91, 1654–1662 (1999).
Bergman-Jungestrom, M., Gentile, M., Lundin, A. C. & Wingren, S. Association between CYP17 gene polymorphism and risk of breast cancer in young women. Int. J. Cancer 84, 350–353 (1999).
United States Department of Health and Human Services. in Reducing Tobacco Use: A Report of the Surgeon General — Executive Summary. 7 (United States Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, Atlanta, Georgia, 2000).
We are most thankful for the critical contribution of peer reviewers.
The authors declare no competing financial interests.
National Cancer Institute
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