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Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms

Key Points

  • The International Agency for Research on Cancer has determined that, based on results from epidemiological studies, people who are overweight or obese are at increased risk of developing several cancer types, including adenocarcinoma of the oesophagus, colon cancer, breast cancer (in postmenopausal women), endometrial cancer and kidney (renal-cell) cancer.

  • Epidemiological evidence also indicates that cancers of the liver, gallbladder and pancreas are obesity related, and that obesity might also increase risk for haematopoietic cancers and for aggressive prostate cancer. No association is seen between obesity and lung cancer. Results for other cancers have been inconsistent.

  • Insulin resistance develops as a metabolic adaptation to increased levels of circulating free fatty acids released from adipose tissue, especially intra-abdominal adipose. Insulin resistance is generally compensated by increased pancreatic insulin secretion. There is mounting epidemiological and experimental evidence to indicate that chronic hyperinsulinaemia increases risk of cancers of the colon and endometrium, and probably other tumours (for example, of the pancreas and kidney).

  • Serum levels of insulin-like growth factor 1 (IGF1) are also associated with different forms of cancer. However, there is no simple, direct relationship between circulating levels of IGF1 and the degree of adiposity.

  • Circulating levels of oestrogens are strongly related to adiposity. For cancers of the breast (in postmenopausal women) and endometrium, the effects of overweight and obesity on cancer risk are largely mediated by increased oestrogen levels.

  • In 4–8% of premenopausal women, obesity and ensuing insulin resistance can either cause or aggravate syndromes of ovarian androgen excess (polycystic ovary syndrome) and chronic progesterone deficiency. There is strong evidence that such syndromes, along with reduced progesterone production, increase the risk of endometrial cancer.

  • Successful intervention strategies for weight loss and maintenance at the individual and community level are needed to reduce cancer risk.

Abstract

The prevalence of obesity is rapidly increasing globally. Epidemiological studies have associated obesity with a range of cancer types, although the mechanisms by which obesity induces or promotes tumorigenesis vary by cancer site. These include insulin resistance and resultant chronic hyperinsulinaemia, increased bioavailability of steroid hormones and localized inflammation. Gaining a better understanding of the relationship between obesity and cancer can provide new insight into mechanisms of cancer pathogenesis.

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Figure 1: Obesity trends.
Figure 2: Effects of obesity on growth-factor production.
Figure 3: Effects of obesity on hormone production.
Figure 4: Obesity, hormones and endometrial cancer.

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References

  1. Heymsfield, S. B. et al. in Handbook of Obesity: Etiology and Pathophysiology (eds. Bray, G. & Bouchard, C.) 33–79 (Marcel Dekker, New York, 2004).

    Google Scholar 

  2. Flegal, K. M., Carroll, M. D., Ogden, C. L. & Johnson, C. L. Prevalence and trends in obesity among US adults, 1999–2000. JAMA 288 1723–1727 (2002).

    PubMed  Google Scholar 

  3. Mokdad, A. H. et al. Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001. JAMA 289, 76–79 (2003).

    PubMed  Google Scholar 

  4. 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). A landmark epidemiological study indicating that overweight and obesity are associated with mortality from a wide range of cancer types, and might explain 14% and 20% of all deaths from cancer in men and women from the United States, respectively.

    PubMed  Google Scholar 

  5. International Agency for Reasearch on Cancer. IARC Handbooks of Cancer Prevention. Weight Control and Physical Activity (International Agency for Research on Cancer, Lyon, 2002). An extensive report, prepared by an international expert panel, reviewing and summarizing epidemiological and experimental evidence relating increased cancer risk of excess weight. The report also includes a detailed discussion of hormonal and other mechanisms that might provide the physiological link between excess weight and tumour development.

  6. Willett, W. C. in Nutritional Epidemiology (ed. Willett, W.) 244–273 (Oxford University Press, New York, 1998).

    Google Scholar 

  7. Kuczmarski, R. J. & Flegal, K. M. Criteria for definition of overweight in transition: background and recommendations for the United States. Am. J. Clin. Nutr. 72, 1074–1081 (2000).

    CAS  PubMed  Google Scholar 

  8. James, P. T., Leach, R., Kalamara, E. & Shayeghi, M. The worldwide obesity epidemic. Obes. Res. 9 (Suppl. 4), 228–233 (2001).

    Google Scholar 

  9. Seidell, J. C. in Progress in Obesity Research (eds. Medeiros-Neto, G., Halpern, A. & Bouchard, C.) 571–578 (John Libbey and Company, London, 2003).

    Google Scholar 

  10. Seidell, J. & Rissanen, A. in Handbook of Obesity: Etiology and Pathophysiology (eds. Bray, G. & Bouchard, C.) 93–107 (Marcel Dekker, New York, 2004).

    Google Scholar 

  11. Bjorntorp, P. Obesity. Lancet 350, 423–426 (1997).

    CAS  PubMed  Google Scholar 

  12. Giovannucci, E., Colditz, G. A., Stampfer, M. J. & Willett, W. C. Physical activity, obesity, and risk of colorectal adenoma in women (United States). Cancer Causes Control 7, 253–263 (1996).

    CAS  PubMed  Google Scholar 

  13. Giovannucci, E. et al. Physical activity, obesity, and risk for colon cancer and adenoma in men. Ann. Intern. Med. 122, 327–334 (1995).

    CAS  PubMed  Google Scholar 

  14. Calle, E. E., Miracle-McMahill, H. L., Thun, M. J. & Heath, C. W. Jr. Estrogen replacement therapy and risk of fatal colon cancer in a prospective cohort of postmenopausal women. J. Natl Cancer Inst. 87, 517–523 (1995).

    CAS  PubMed  Google Scholar 

  15. Writing Group for the Women's Health Initiative Investigators. 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).

  16. Tchernof, A. & Despres, J. P. Sex steroid hormones, sex hormone-binding globulin, and obesity in men and women. Horm. Metab. Res. 32, 526–536 (2000).

    CAS  PubMed  Google Scholar 

  17. Stephenson, G. D. & Rose, D. P. Breast cancer and obesity: an update. Nutr. Cancer 45, 1–16 (2003). An excellent and comprehensive review of the impact of adiposity on both breast cancer risk and the clinical behaviour of the established disease.

    CAS  PubMed  Google Scholar 

  18. Potischman, N., Swanson, C. A., Siiteri, P. & Hoover, R. N. Reversal of relation between body mass and endogenous estrogen concentrations with menopausal status. J. Natl Cancer Inst. 88, 756–758 (1996).

    CAS  PubMed  Google Scholar 

  19. Ballard-Barbash, R. & Swanson, C. A. Body weight: estimation of risk for breast and endometrial cancer. Am. J. Clin. Nutr. 63 (Suppl. 3), 437–441 (1996).

    Google Scholar 

  20. Galanis, D. J. et al. Anthropometric predictors of breast cancer incidence and survival in a multi-ethnic cohort of female residents of Hawaii, United States. Cancer Causes Control 9, 217–224 (1998).

    CAS  PubMed  Google Scholar 

  21. Trentham-Dietz, A. et al. Body size and risk of breast cancer. Am. J. Epidemiol. 145, 1011–1119 (1997).

    CAS  PubMed  Google Scholar 

  22. Hunter, D. J. & Willett, W. C. Diet, body size and breast cancer. Epidemiol. Rev. 15, 110–132 (1993).

    CAS  PubMed  Google Scholar 

  23. Harvie, M., Hooper, L. & Howell, A. H. Central obesity and breast cancer risk: a systematic review. Obesity Rev. 4, 157–173 (2003).

    CAS  Google Scholar 

  24. Folsom, A. R. et al. Increased incidence of carcinoma of the breast associated with abdominal adiposity in postmenopausal women. Am. J. Epidemiol. 131, 794–803 (1990).

    CAS  PubMed  Google Scholar 

  25. Huang, Z. et al. Dual effects of weight and weight gain on breast cancer risk. JAMA 278, 1407–1411 (1997).

    CAS  PubMed  Google Scholar 

  26. Barnes-Josiah, D., Potter, J. D., Sellers, T. A. & Himes, J. H. Early body size and subsequent weight gain as predictors of breast cancer incidence (Iowa, United States). Cancer Causes Control 6, 112–118 (1995).

    CAS  PubMed  Google Scholar 

  27. Feigelson, H. S., Jonas, C. R., Teras, L. R., Thun, M. J. & Calle, E. E. Weight gain, body mass index, hormone replacement therapy, and postmenopausal breast cancer in a large prospective study. Cancer Epidemiol. Biomark. Prev. 13, 220–224 (2004).

    Google Scholar 

  28. Collaborative Group on Hormonal Factors in Breast Cancer. Breast cancer and hormone replacement therapy: collaborative reanalysis of data from 51 epidemiological studies of 52 705 women with breast cancer and 108 411 women without breast cancer. Lancet 350, 1047–1059 (1997).

  29. Schairer, C. et al. Menopausal estrogen and estrogen-progestin replacement therapy and breast cancer risk. JAMA 283, 485–491 (2000).

    CAS  PubMed  Google Scholar 

  30. Rock, C. L. & Demark-Wahnefried, W. Nutrition and survival after the diagnosis of breast cancer: a review of the evidence. J. Clin. Oncol. 20, 3302–3316 (2002).

    PubMed  Google Scholar 

  31. Chlebowski, R. T., Aiello, E. & McTiernan, A. Weight loss in breast cancer patient management. J. Clin. Oncol. 20, 1128–1143 (2002).

    PubMed  Google Scholar 

  32. Petrelli, J. M., Calle, E. E., Rodriguez, C. & Thun, M. J. Body mass index, height, and postmenopausal breast cancer mortality in a prospective cohort of U. S. women. Cancer Causes Control 13, 325–332 (2002).

    PubMed  Google Scholar 

  33. Wee, C., McCarthy, E., Davis, R. & Phillips, R. Screening for cervical and breast cancer: is obesity an unrecognized barrier to preventive care? Ann. Intern. Med. 132, 697–704 (2000).

    CAS  PubMed  Google Scholar 

  34. Reeves, M., Newcomb, P. A., Remington, P., Marcus, P. M. & MacKenzie, W. Body mass and breast cancer, relationship between method of detection and stage of disease. Cancer 77, 301–307 (1996).

    CAS  PubMed  Google Scholar 

  35. Kaaks, R., Lukanova, A. & Kurzer, M. A. Obesity, endogenous hormones, and endometrial cancer risk: a synthetic review. Cancer Epidemiol. Biomark. Prev. 11, 1531–1543 (2002).

    CAS  Google Scholar 

  36. Lew, E. A. & Garfinkel, L. Variations in mortality by weight among 750,000 men and women. J. Chron. Dis. 32, 563–576 (1979).

    CAS  PubMed  Google Scholar 

  37. Bergstrom, A. et al. Obesity and renal cell cancer — a quantitative review. Br. J. Cancer 85, 984–990 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Hu, J., Mao, Y., White, K. & The Canadian Cancer Registries Epidemiology Research Group. Overweight and obesity in adults and risk of renal cell carcinoma in Canada. Soz Praventivmed. 48, 178–185 (2003).

    PubMed  Google Scholar 

  39. Pan, S. Y. et al. Association of obesity and cancer risk in Canada. Am. J. Epidemiol. 159, 259–268 (2004).

    PubMed  Google Scholar 

  40. Samanic, C. et al. Obesity and cancer risk among white and black United States veterans. Cancer Causes Control 15, 35–43 (2004).

    PubMed  Google Scholar 

  41. World Cancer Research Fund & American Institute for Cancer Research. in Food, Nutrition and the Prevention of Cancer: a global perspective 371–373 (Am. Instit. Cancer Res., Washington, 1997).

  42. Hill, H. A. & Austin, H. Nutrition and endometrial cancer. Cancer Causes Control 7, 19–32 (1996).

    CAS  PubMed  Google Scholar 

  43. Wolk, A., Lindblad, P. & Adami, H. -O. Nutrition and renal cell cancer. Cancer Causes Control 7, 5–18 (1996).

    CAS  PubMed  Google Scholar 

  44. Chow, W. H. et al. Obesity and risk of renal cell cancer. Cancer Epidemiol. Biomarkers Prev. 5, 17–21 (1996).

    CAS  PubMed  Google Scholar 

  45. Mellemgaard, A., Engholm, G., McLaughlin, J. K. & Olsen, J. H. Risk factors for renal-cell carcinoma in Denmark. III. Role of weight, physical activity and reproductive factors. Int. J. Cancer 56, 66–71 (1994).

    CAS  PubMed  Google Scholar 

  46. McLaughlin, J. et al. A population-based case-control study of renal cell carcinoma. J. Natl Cancer Inst. 72, 275–284 (1984).

    CAS  PubMed  Google Scholar 

  47. McLaughlin, J. K. et al. Risk factors for renal-cell cancer in Shanghai, China. Int. J. Cancer 52, 562–565 (1992).

    CAS  PubMed  Google Scholar 

  48. Chow, W. H., Gridley, G., Fraumeni, J. F. & Jarvholm, B. Obesity, hypertension, and the risk of kidney cancer in men. N. Engl. J. Med. 343, 1305–1311 (2000).

    CAS  PubMed  Google Scholar 

  49. Devesa, S. S., Blot, W. J. & Fraumeni, J. F. Changing patterns in the incidence of esophageal and gastric carcinoma in the United States. Cancer 83, 2049–2053 (1998).

    CAS  PubMed  Google Scholar 

  50. Wild, C. P. & Hardie, L. J. Reflux, Barrett's oesophagus and adenocarcinoma: burning questions. Nature Rev. Cancer 3, 676–685 (2003).

    CAS  Google Scholar 

  51. Wu, A. H. & Bernstein, L. A multiethnic population-based study of smoking, alcohol and body size and risk of adenocarcinomas of the stomach and esophagus. Cancer Causes Control 12, 721–732 (2001).

    CAS  PubMed  Google Scholar 

  52. Lagergren, J., Bergstrom, R., Lindgren, A. & Nyren, O. Symptomatic gastroesophageal reflux as a risk factor for esophageal adenocarcinoma. N. Engl. J. Med. 340, 825–831 (1999).

    CAS  PubMed  Google Scholar 

  53. Chow, W. H. et al. The relation of gastroesophageal reflux disease and its treatment to adenocarcinomas of the esophagus and gastric cardia. JAMA 274, 474–477 (1995).

    CAS  PubMed  Google Scholar 

  54. Nilsson, M., Johnsen, R., Weimin, Y., Hveem, K. & Lagergren, J. Obesity and estrogen as risk factors for gastroesophageal reflux symptoms. JAMA 290, 66–72 (2003).

    CAS  PubMed  Google Scholar 

  55. Lagergren, J., Bergstrom, R. & Nyren, O. No relation between body mass and gastro-esophageal reflux symptoms in a Swedish population based study. Gut 47, 26–29 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Chow, W. H. et al. Body mass index and risk of adenocarcinomas of the esophagus and gastric cardia. J. Natl Cancer Inst. 90, 150–55 (1998).

    CAS  PubMed  Google Scholar 

  57. Lagergren, J., Bergstrom, R., Adami, H. O. & Nyren, O. Association between medications that relax the lower esophageal sphincter and risk for esophageal adenocarcinoma. Ann. Intern. Med. 133, 165–175 (2000).

    CAS  PubMed  Google Scholar 

  58. Moller, H., Mellemgaard, A., Lindvig, K. & Olsen, J. H. Obesity and cancer risk: a Danish record-linkage study. Eur. J. Cancer 30A, 344–350 (1994).

    CAS  PubMed  Google Scholar 

  59. Gapstur, S. M. et al. Abnormal glucose metabolism and pancreatic cancer mortality. JAMA 283, 2552–2558 (2000).

    CAS  PubMed  Google Scholar 

  60. Michaud, D. S. et al. Physical activity, obesity, height, and the risk of pancreatic cancer. JAMA 286, 921–929 (2001).

    CAS  PubMed  Google Scholar 

  61. Silverman, D. T. et al. Dietary and nutritional factors and pancreatic cancer: a case-control study based on direct interviews. J. Natl Cancer Inst. 90, 1710–1719 (1998).

    CAS  PubMed  Google Scholar 

  62. Hanley, A. J. G., Johnson, K. C., Villeneuve, P. J. & Mao, Y. Physical activity, anthropometric factors and risk of pancreatic cancer: results from the Canadian enhanced cancer surveillance system. Int. J. Cancer 94, 140–147 (2001).

    CAS  PubMed  Google Scholar 

  63. Berrington de Gonzalez, A., Sweetland, S. & Spencer, E. A meta-analysis of obesity and the risk of pancreatic cancer. Br. J. Cancer 89, 519–523 (2003).

    CAS  PubMed  Google Scholar 

  64. Lee, I. -M., Sesso, H. D., Oguma, Y. & Paffenbarger, R. S. Physical activity, body weight, and pancreatic cancer mortality. Br. J. Cancer 88, 679–683 (2003).

    PubMed  PubMed Central  Google Scholar 

  65. Zatonski, W. et al. Nutritional factors and pancreatic cancer: a case-control study from south-west Poland. Int. J. Cancer 48, 390–394 (1991).

    CAS  PubMed  Google Scholar 

  66. Howe, G. R., Jain, M. & Miller, A. B. Dietary factors and risk of pancreatic cancer: results of a Canadian population-based case-control study. Int. J. Cancer 45, 604–608 (1990).

    CAS  PubMed  Google Scholar 

  67. Ghadirian, P., Simard, A., Baillargeon, J., Maisonneuve, P. & Boyle, P. Nutritional factors and pancreatic cancer in the francophone community in Montreal, Canada. Int. J. Cancer 47, 1–6 (1991).

    CAS  PubMed  Google Scholar 

  68. Bueno de Mesquita, H. B., Moerman, C. J., Runia, S. & Maisonneuve, P. Are energy and energy-providing nutrients related to exocrine carcinoma of the pancreas? Int. J. Cancer 46, 435–444 (1990).

    CAS  PubMed  Google Scholar 

  69. Wolk, A. et al. A prospective study of obesity and cancer risk (Sweden). Cancer Causes Control 12, 13–21 (2001).

    CAS  PubMed  Google Scholar 

  70. Strom, B. L. et al. Risk factors for gallbladder cancer. Cancer 76, 1747–1756 (1995).

    CAS  PubMed  Google Scholar 

  71. Zatonski, W. A. et al. Epidemiologic aspects of gallbladder cancer: a case-control study of the SEARCH Program of the International Agency for Research on Cancer. J. Natl Cancer Inst. 89, 1132–1138 (1997).

    CAS  PubMed  Google Scholar 

  72. Ji, B. -T. et al. Body mass index and the risk of cancers of the gastric cardia and distal stomach in Shanghai, China. Cancer Epidemiol. Biomarkers Prev. 6, 481–485 (1997).

    CAS  PubMed  Google Scholar 

  73. Vaughan, T. L., Davis, S., Kristal, A. & Thomas, D. B. Obesity, alcohol, and tobacco as risk factors fo cancers of the esophagus and gastric cardia: adenocarcinoma versus squamous cell carcinoma. Cancer Epidemiol. Biomarkers Prev. 4, 85–92 (1995).

    CAS  PubMed  Google Scholar 

  74. Henley, S. J., Flanders, W. D., Manatunga, A. & Thun, M. J. Leanness and lung cancer risk: fact or artifact? Epidemiology 13, 268–276 (2002).

    PubMed  Google Scholar 

  75. Tornberg, S. A. & Carstensen, J. M. Relationship between Quetelet's index and cancer of breast and female genital tract in 47,000 women followed for 25 years. Br. J. Cancer 69, 358–361 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  76. Lacey, J. V. et al. Obesity as a potential risk factor for adenocarcinomas and squamous cell carcinomas of the uterine cervix. Cancer 98, 814–821 (2003).

    PubMed  Google Scholar 

  77. Risch, H. A. Hormonal etiology of epithelial ovarian cancer, with a hypothesis concerning the role of androgens and progesterone. J. Natl Cancer Inst. 90, 1774–1786 (1998).

    CAS  PubMed  Google Scholar 

  78. Rodriguez, C., Calle, E. E., Fakhrabadi-Shokoohi, D., Jacobs, E. J. & Thun, M. J. Body mass index, height, and the risk of ovarian cancer mortality in a prospective cohort of postmenopausal women. Cancer Epidemiol. Biomark. Prev. 11, 822–828 (2002).

    Google Scholar 

  79. Engeland, A., Tretli, S. & Bjorge, T. Height, body mass index, and ovarian cancer: a follow-up of 1. 1 million Norwegian women. J. Natl Cancer Inst. 95, 1244–1248 (2003).

    PubMed  Google Scholar 

  80. Fairfield, K. M. et al. Obesity, weight gain, and ovarian cancer. Obstet. Gynecol. 100, 288–296 (2002).

    PubMed  Google Scholar 

  81. Kuper, H., Cramer, D. W. & Titus-Ernstoff, L. Risk of ovarian cancer in the United States in relation to anthropometric measures: does the association depend on menopausal status? Cancer Causes Control 13, 455–463 (2002).

    PubMed  Google Scholar 

  82. Lubin, F. et al. Body mass index at age 18 years and during adult life and ovarian cancer risk. Am. J. Epidemiol. 157, 113–120 (2003).

    CAS  PubMed  Google Scholar 

  83. Schouten, L. J., Goldbohm, A. & van den Brandt, P. A. Height, weight, weight change, and ovarian cancer risk in the Netherlands cohort study on diet and cancer. Am. J. Epidemiol. 157, 424–433 (2003).

    PubMed  Google Scholar 

  84. Calle, E. E. Invited commentary: Do anthropometric measures predict risk of prostate cancer? Am. J. Epidemiol. 151, 550–553 (2000).

    CAS  PubMed  Google Scholar 

  85. Engeland, A., Tretli, S. & Bjorge, T. Height, body mass index, and prostate cancer: a follow-up of 950,000 Norwegian men. Br. J. Cancer 89, 1237–1242 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Giovannucci, E., Rimm, E. B., Stampfer, M. J., Colditz, G. A. & Willett, W. C. Height, body weight, and risk of prostate cancer. Cancer Epidemiol. Biomark. Prev. 6, 557–563 (1997).

    CAS  Google Scholar 

  87. Andersson, S. O. et al. Body size and prostate cancer: a 20-year follow-up study among 135,006 Swedish construction workers. J. Natl Cancer Inst. 89, 385–389 (1997).

    CAS  PubMed  Google Scholar 

  88. Rodriguez, C. et al. Body mass index, height, and prostate cancer mortality in two large cohorts of adult men in the United States. Cancer Epidemiol. Biomark. Prev. 10, 345–353 (2001).

    CAS  Google Scholar 

  89. Amling, C. L. et al. Pathologic variables and recurrence rates as related to obesity and race in men with prostate cancer undergoing radical prostatectomy. J. Clin. Oncol. 22, 439–445 (2004).

    PubMed  Google Scholar 

  90. Freedland, S. J. et al. Impact of obesity on biochemical control after radical prostatectomy for clinically localized prostate cancer: a report by the Shared Equal Access Regional Cancer Hospital Database Study Group. J. Clin. Oncol. 22, 446–453 (2004).

    PubMed  Google Scholar 

  91. Holly, E. A., Lele, C., Bracci, P. M. & McGrath, M. S. Case-control study of non-Hodgkin's lymphoma among women and heterosexual men in the San Francisco Bay area, California. Am. J. Epidemiol. 150, 375–389 (1999).

    CAS  PubMed  Google Scholar 

  92. Cerhan, J. R. et al. Anthropometric characteristics, physical activity and risk of non-Hodgkin's lymphoma subtypes and B-cell lymphocytic leukemia: a prospective study. Am. J. Epidemiol. 156, 527–535 (2003).

    Google Scholar 

  93. Rajala, M. W. & Scherer, P. E. Minireview: the adipocyte — at the crossroads of energy homeostasis, inflammation, and atherosclerosis. Endocrinology 144, 3765–3773 (2003).

    CAS  PubMed  Google Scholar 

  94. Reaven, G. M. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes 37, 1595–1607 (1988).

    CAS  PubMed  Google Scholar 

  95. Wajchenberg, B. L. Subcutaneous and visceral adipose tissue: their relation to the metabolic syndrome. Endocr. Rev. 21, 697–738 (2000).

    CAS  PubMed  Google Scholar 

  96. McKeown-Eyssen, G. Epidemiology of colorectal cancer revisited: are serum triglycerides and/or plasma glucose associated with risk? Cancer Epidemiol. Biomarkers Prev. 3, 687–695 (1994).

    CAS  PubMed  Google Scholar 

  97. Giovannucci, E. Insulin and colon cancer. Cancer Causes Control 6, 164–179 (1995).

    CAS  PubMed  Google Scholar 

  98. Kaaks, R. Nutrition, hormones, and breast cancer: is insulin the missing link? Cancer Causes Control 7, 605–625 (1996).

    CAS  PubMed  Google Scholar 

  99. Stoll, B. A. Western nutrition and the insulin resistance syndrome: a link to breast cancer. Eur. J. Clin. Nutr. 53, 83–87 (1999).

    CAS  PubMed  Google Scholar 

  100. Weiderpass, E. et al. Occurrence, trends and environment etiology of pancreatic cancer. Scand. J. Work Environ. Health 24, 165–174 (1998).

    CAS  PubMed  Google Scholar 

  101. Lawlor, M. A. & Alessi, D. R. PKB/Akt: a key mediator of cell proliferation, survival and insulin responses? J. Cell Sci. 114, 2903–2910 (2001).

    CAS  PubMed  Google Scholar 

  102. Prisco, M., Romano, G., Peruzzi, F., Valentinis, B. & Baserga, R. Insulin and IGF-I receptors signaling in protection from apoptosis. Horm. Metab. Res. 31, 80–89 (1999).

    CAS  PubMed  Google Scholar 

  103. Ish-Shalom, D. et al. Mitogenic properties of insulin and insulin analogues mediated by the insulin receptor. Diabetologia 40 (Suppl. 2), 25–31 (1997).

    Google Scholar 

  104. Le Roith, D. Regulation of proliferation and apoptosis by the insulin-like growth factor I receptor. Growth Horm. IGF Res. 10 (Suppl. A), 12–13 (2000).

    Google Scholar 

  105. Khandwala, H. M., McCutcheon, I. E., Flyvbjerg, A. & Friend, K. E. The effects of insulin-like growth factors on tumorigenesis and neoplastic growth. Endocr. Rev. 21, 215–244 (2000).

    CAS  PubMed  Google Scholar 

  106. Shafie, S. M. & Grantham, F. H. Role of hormones in the growth and regression of human breast cancer cells (MCF-7) transplanted into athymic nude mice. J. Natl Cancer Inst. 67, 51–56 (1981).

    CAS  PubMed  Google Scholar 

  107. Shafie, S. M. & Hilf, R. Insulin receptor levels and magnitude of insulin-induced responses in 7,12-dimethylbenz(a)-anthracene-induced mammary tumors in rats. Cancer Res. 41, 826–829 (1981).

    CAS  PubMed  Google Scholar 

  108. Heuson, J. C. & Legros, N. Effect of insulin and of alloxan diabetes on growth of the rat mammary carcinoma in vivo. Eur. J. Cancer 6, 349–351 (1970).

    CAS  PubMed  Google Scholar 

  109. Heuson, J. C. & Legros, N. Influence of insulin deprivation on growth of the 7,12-dimethylbenz(a)anthracene-induced mammary carcinoma in rats subjected to alloxan diabetes and food restriction. Cancer Res. 32, 226–232 (1972).

    CAS  PubMed  Google Scholar 

  110. Cocca, C. et al. An experimental model of diabetes and cancer in rats. Eur. J. Cancer 34, 889–894 (1998).

    CAS  PubMed  Google Scholar 

  111. Cocca, C. et al. Suppression of mammary gland tumorigenesis in diabetic rats. Cancer Detect. Prev. 27, 37–46 (2003).

    PubMed  Google Scholar 

  112. LeRoith, D. & Roberts, C. T. Jr. The insulin-like growth factor system and cancer. Cancer Lett. 195, 127–137 (2003).

    CAS  PubMed  Google Scholar 

  113. Wideroff, L. et al. Cancer incidence in a population-based cohort of patients hospitalized with diabetes mellitus in Denmark. J. Natl Cancer Inst. 89, 1360–1365 (1997).

    CAS  PubMed  Google Scholar 

  114. Lindblad, P. et al. The role of diabetes mellitus in the aetiology of renal cell cancer. Diabetologia 42, 107–112 (1999).

    CAS  PubMed  Google Scholar 

  115. Everhart, J. & Wright, D. Diabetes mellitus as a risk factor for pancreatic cancer. A meta-analysis. JAMA 273, 1605–1609 (1995).

    CAS  PubMed  Google Scholar 

  116. Kaaks, R. et al. Serum C-peptide, insulin-like growth factor (IGF)-I, Igf-binding proteins, and colorectal cancer risk in women. J. Natl Cancer Inst. 92, 1592–1600 (2000). Provides the first concrete evidence, from a prospective cohort study, that increased circulating insulin levels are a risk factor for the development of colon cancer.

    CAS  PubMed  Google Scholar 

  117. Stattin, P. et al. Obesity and colon cancer: does leptin provide a link? Int. J. Cancer 109, 149–152 (2004).

    CAS  PubMed  Google Scholar 

  118. Schoen, R. E. et al. Increased blood glucose and insulin, body size, and incident colorectal cancer. J. Natl Cancer Inst. 91, 1147–1154 (1999).

    CAS  PubMed  Google Scholar 

  119. Lukanova, A. et al. Prediagnostic levels of C-peptide, IGF-I, IGFBP-1-2 and-3 and risk of endometrial cancer. Int. J. Cancer 108, 262–268 (2004). Gives the first solid evidence, from a prospective cohort study, that increased circulating insulin levels are a risk factor for the development of endometrial cancer.

    CAS  PubMed  Google Scholar 

  120. Bruning, P. F. et al. Insulin resistance and breast cancer risk. Int. J. Cancer 52, 511–516 (1992).

    CAS  PubMed  Google Scholar 

  121. Del Giudice, M. E. et al. Insulin and related factors in premenopausal breast cancer. Breast Cancer Res. Treat. 47, 111–120 (1998).

    CAS  PubMed  Google Scholar 

  122. Hirose, K. et al. Insulin, insulin-like growth factor-I and breast cancer risk in Japanese women. Asian Pac. J. Cancer Prev. 4, 239–246 (2003).

    PubMed  Google Scholar 

  123. Yang, G. et al. Population-based, case-control study of blood C-peptide level and breast cancer risk. Cancer Epidemiol. Biomarkers Prev. 10, 1207–1211 (2001).

    CAS  PubMed  Google Scholar 

  124. Schairer, C. et al. Serum concentrations of IGF-I, IGFBP-3 and c-peptide and risk of hyperplasia and cancer of the breast in postmenopausal women. Int. J. Cancer 108, 773–779 (2004).

    CAS  PubMed  Google Scholar 

  125. Kaaks, R. et al. Prospective study of IGF-I, IGF-binding proteins, and breast cancer risk, in northern and southern Sweden. Cancer Causes Control 13, 307–316 (2002).

    PubMed  Google Scholar 

  126. Keinan-Boker, L. et al. Circulating levels of insulin-like growth factor I, its binding proteins-1,-2,-3, C-peptide and risk of postmenopausal breast cancer. Int. J. Cancer 106, 90–95 (2003).

    CAS  PubMed  Google Scholar 

  127. Muti, P. et al. Fasting glucose is a risk factor for breast cancer: a prospective study. Cancer Epidemiol. Biomarkers Prev. 11, 1361–1368 (2002).

    CAS  PubMed  Google Scholar 

  128. Toniolo, P. et al. Serum insulin-like growth factor-I and breast cancer. Int. J. Cancer 88, 828–832 (2000).

    CAS  PubMed  Google Scholar 

  129. Clemmons, D. R. Role of insulin-like growth factor binding proteins in controlling IGF actions. Mol. Cell Endocrinol. 140, 19–24 (1998).

    CAS  PubMed  Google Scholar 

  130. Kaaks, R. & Lukanova, A. Energy balance and cancer: the role of insulin and insulin-like growth factor-I. Proc. Nutr. Soc. 60, 91–106 (2001).

    CAS  PubMed  Google Scholar 

  131. Thissen, J. P., Ketelslegers, J. M. & Underwood, L. E. Nutritional regulation of the insulin-like growth factors. Endocr. Rev. 15, 80–101 (1994).

    CAS  PubMed  Google Scholar 

  132. Allen, N. E. et al. Lifestyle determinants of serum insulin-like growth-factor-I (IGF-I), C-peptide and hormone binding protein levels in British women. Cancer Causes Control 14, 65–74 (2003).

    PubMed  Google Scholar 

  133. Holmes, M. D., Pollak, M. N. & Hankinson, S. E. Lifestyle correlates of plasma insulin-like growth factor I and insulin-like growth factor binding protein 3 concentrations. Cancer Epidemiol. Biomarkers Prev. 11, 862–867 (2002).

    CAS  PubMed  Google Scholar 

  134. Lukanova, A. et al. Circulating levels of insulin-like growth factor-I and risk of ovarian cancer. Int. J. Cancer 101, 549–554 (2002).

    CAS  PubMed  Google Scholar 

  135. Chapman, I. M. et al. Recovery of growth hormone release from suppression by exogenous insulin-like growth factor I (IGF-I): evidence for a suppressive action of free rather than bound IGF-I. J. Clin. Endocrinol. Metab. 83, 2836–2842 (1998).

    CAS  PubMed  Google Scholar 

  136. Tannenbaum, G. S., Guyda, H. J. & Posner, B. I. Insulin-like growth factors: a role in growth hormone negative feedback and body weight regulation via brain. Science 220, 77–79 (1983).

    CAS  PubMed  Google Scholar 

  137. Hankinson, S. E. et al. Circulating concertrations of insulin-like growth factor-I and risk of breast cancer. Lancet 351, 1393–1396 (1998).

    CAS  PubMed  Google Scholar 

  138. Stattin, P. et al. Plasma insulin-like growth factor-I, insulin-like growth factor-binding proteins, and prostate cancer risk: a prospective study. J. Natl Cancer Inst. 92, 1910–1917 (2000).

    CAS  PubMed  Google Scholar 

  139. Chan, J. M. et al. Plasma insulin-like growth factor-I and prostate cancer risk: a prospective study. Science 279, 563–566 (1998).

    CAS  PubMed  Google Scholar 

  140. Giovannucci, E. et al. A prospective study of plasma insulin-like growth factor-1 and binding protein-3 and risk of colorectal neoplasia in women. Cancer Epidemiol. Biomark. Prev. 9, 345–349 (2000).

    CAS  Google Scholar 

  141. Ma, J. et al. A prospective study of plasma levels of insulin-like growth factor I, insulin-like growth factor binding protein 3 and colorectal cancer risk among men. J. Natl Cancer Inst. 91, 620–625 (1999).

    CAS  PubMed  Google Scholar 

  142. Palmqvist, R. et al. Plasma insulin-like growth factor 1, insulin-like growth factor binding protein 3, and risk of colorectal cancer: a prospective study in northern Sweden. Gut 50, 642–646 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  143. Key, T. J., Allen, N. E., Verkasalo, P. K. & Banks, E. Energy balance and cancer: the role of sex hormones. Proc. Nutr. Soc. 60, 81–89 (2001).

    CAS  PubMed  Google Scholar 

  144. Key, T. J. et al. Body mass index, serum sex hormones, and breast cancer risk in postmenopausal women. J. Natl Cancer Inst. 95, 1218–1226 (2003). This paper presents a re-analysis of the original data from nine prospective cohort studies on the relationships between excess weight, alterations in circulating sex-hormone levels and breast cancer risk.

    CAS  PubMed  Google Scholar 

  145. Pugeat, M. et al. Pathophysiology of sex hormone binding globulin (SHBG): relation to insulin. J. Steroid Biochem. Mol. Biol. 40, 841–849 (1991).

    CAS  PubMed  Google Scholar 

  146. Kokkoris, P. & Pi-Sunyer, F. X. Obesity and endocrine disease. Endocrinol. Metab. Clin. North Am. 32, 895–914 (2003).

    CAS  PubMed  Google Scholar 

  147. Kaaks, R., Lukanova, A. & Sommersberg, B. Plasma androgens, IGF-1, body size, and prostate cancer risk: a synthetic review. Prostate Cancer Prostatic Dis. 3, 157–172 (2000).

    CAS  PubMed  Google Scholar 

  148. Strain, G. W. et al. Mild hypogonadotropic hypogonadism in obese men. Metabolism 31, 871–875 (1982).

    CAS  PubMed  Google Scholar 

  149. Amatruda, J. M., Harman, S. M., Pourmotabbed, G. & Lockwood, D. H. Depressed plasma testosterone and fractional binding of testosterone in obese males. J. Clin. Endocrinol. Metab. 47, 268–271 (1978).

    CAS  PubMed  Google Scholar 

  150. Poretsky, L., Cataldo, N. A., Rosenwaks, Z. & Giudice, L. C. The insulin-related ovarian regulatory system in health and disease. Endocr. Rev. 20, 535–582 (1999).

    CAS  PubMed  Google Scholar 

  151. Ehrmann, D. A., Barnes, R. B. & Rosenfield, R. L. Polycystic ovary syndrome as a form of functional ovarian hyperandrogenism due to dysregulation of androgen secretion. Endocr. Rev. 16, 322–353 (1995).

    CAS  PubMed  Google Scholar 

  152. Dunaif, A. Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis. Endocr. Rev. 18, 774–800 (1997).

    CAS  PubMed  Google Scholar 

  153. Robinson, S. et al. The relationship of insulin insensitivity to menstrual pattern in women with hyperandrogenism and polycystic ovaries. Clin. Endocrinol. 39, 351–355 (1993).

    CAS  Google Scholar 

  154. Dickson, R. B. & Stancel, G. M. Estrogen receptor-mediated processes in normal and cancer cells. J. Natl Cancer Inst. Monogr. 27, 135–145 (2000).

    CAS  Google Scholar 

  155. Flototto, T. et al. Hormones and hormone antagonists: mechanisms of action in carcinogenesis of endometrial and breast cancer. Horm. Metab. Res. 33, 451–457 (2001).

    CAS  PubMed  Google Scholar 

  156. Key, T. J. & Pike, M. C. The dose-effect relationship between 'unopposed' estrogens and endometrial mitotic rate: its central role in explaining and predicting endometrial cancer. Br. J. Cancer 57, 205–212 (1988).

    CAS  PubMed  PubMed Central  Google Scholar 

  157. Endogenous Hormones and Breast Cancer Collaborative Group. Endogenous sex hormones and breast cancer in postmenopausal women: reanalysis of nine prospective studies. J. Natl Cancer Inst. 94, 606–616 (2002).

  158. Zeleniuch-Jacquotte, A. et al. Postmenopausal levels of oestrogen, androgen, and SHBG and breast cancer: long-term results of a prospective study. Br. J. Cancer 90, 153–159 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  159. Coates, R. J. et al. Race, nutritional status, and survival from breast cancer. J. Natl Cancer Inst. 82, 1684–1692 (1990).

    CAS  PubMed  Google Scholar 

  160. Tretli, S., Haldorsen, T. & Ottestad, L. The effect of pre-morbid height and weight on the survival of breast cancer patients. Br. J. Cancer 62, 299–303 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  161. Maehle, B. O. & Tretli, S. Pre-morbid body-mass-index in breast cancer: reversed effect on survival in hormone receptor negative patients. Breast Cancer Res. Treat. 41, 123–130 (1996).

    CAS  PubMed  Google Scholar 

  162. Lukanova, A. et al. Circulating levels of sex steroid hormones and risk of endometrial cancer in postmenopausal women. Int. J. Cancer 108, 425–432 (2004).

    CAS  PubMed  Google Scholar 

  163. Zeleniuch-Jacquotte, A. et al. Postmenopausal endogenous oestrogens and risk of endometrial cancer: results of a prospective study. Br. J. Cancer 84, 975–981 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  164. Hsing, A. W., Reichardt, J. K. & Stanczyk, F. Z. Hormones and prostate cancer: current perspectives and future directions. Prostate 52, 213–235 (2002).

    CAS  PubMed  Google Scholar 

  165. Bosland, M. C. The role of steroid hormones in prostate carcinogenesis. J. Natl Cancer Inst. Monogr. 27, 39–66 (2000).

    CAS  Google Scholar 

  166. Harrison, S. A. & Diehl, A. M. Fat and the liver: a molecular overview. Semin. Gastroint. Dis. 13, 3–16 (2002).

    Google Scholar 

  167. Festi, D. et al. Hepatic steatosis in obese patients: clinical aspects and prognostic significance. Obes. Rev. 5, 27–42 (2004).

    CAS  PubMed  Google Scholar 

  168. Hill, J. O., Wyatt, H. R., Reed, G. W. & Peters, J. C. Obesity and the environment: where do we go from here? Science 299, 853–855 (2003).

    CAS  PubMed  Google Scholar 

  169. Allison, D. B., Fontaine, K. R., Manson, J. E., Stevens, J. & VanItallie, T. B. Annual deaths attributable to obesity in the United States. JAMA 282, 1530–1538 (1999).

    CAS  PubMed  Google Scholar 

  170. Banegas, J. R., Lopez-Garcia, E., Gutierriz-Fisac, J. L., Guallar-Castillon, P. & Rodriguez-Artalejo, F. A simple estimate of mortality attributable to excess weight in the European Union. Eur. J. Clin. Nutr. 57, 201–208 (2003).

    CAS  PubMed  Google Scholar 

  171. Finkelstein, E. A., Fiebelkorn, I. C. & Wang, G. State-level estimates of annual medical expenditures attributable to obesity. Obes. Res. 12, 18–24 (2004).

    PubMed  Google Scholar 

  172. Sturm, R. The effects of obesity, smoking, and drinking on medical problems and costs. Health Affairs 21, 245–253 (2002).

    PubMed  Google Scholar 

  173. Mokdad, A., Marks, J., Stroup, D. & Gerberding, J. Actual causes of death in the United States, 2000. JAMA 291, 1238–1245 (2004).

    PubMed  Google Scholar 

  174. McTigue, K. M. et al. Screening and interventions for obesity in adults: summary of the evidence for the U. S. Preventive Services Task Force. Ann. Intern. Med. 139, 933–949 (2003). Current clinical guidelines to promote effective screening and intervention for obesity in adult populations, based on systematic reviews of all trials and observation studies of the health outcomes of obesity and efficacy of obesity treatment.

    PubMed  Google Scholar 

  175. Chopra, M., Galbraith, S. & Darnton-Hill, I. A global response to a global problem: the epidemic of overnutrition. Bull. World Health Organ. 80, 952–958 (2002).

    PubMed  Google Scholar 

  176. Byers, T. et al. American Cancer Society guidelines on nutrition and physical activity for cancer prevention: reducing the risk of cancer with healthy food choices and physical activity. CA Cancer J. Clin. 52, 92–119 (2002).

    PubMed  Google Scholar 

  177. Royal College of Physicians, Royal College of Paediatrics and Child Health, and Faculty of Public Health Medicine. Storing up problems: the medical case for a slimmer nation [online], <www.rcplondon.ac.uk/pubs/brochures/pub_print_SUP.htm> (2004).

  178. Mercer, J. G., O'Reilly, J. M. & Morgan, P. J. Increasing the impact of European obesity research in preparation for the European research area: a report on the 2003 European Commission obesity workshop. Obes. Rev. 5, 79–86 (2004).

    CAS  PubMed  Google Scholar 

  179. World Health Organization. Global strategy on diet, physical activity and health [online], <www.who.int/dietphysicalactivity/strategy/eb11344/en/> (2004).

  180. Borkan, G., Hultz, D., Gerzof, S., Robbins, A. H. & Silbert, C. K. Age changes in body composition revealed by computed tomography. J. Gerontol. 38, 673–677 (1983).

    CAS  PubMed  Google Scholar 

  181. US Department of Agriculture and US Department of Health and Human Services. Nutrition and your health: dietary guidelines for Americans (US Government Printing Office, Washington, DC, 2000).

  182. WHO Expert Committee. Physical Status: the Use and Interpretation of Anthropometry. WHO Technical Report Series 854 (World Health Organization, Geneva, 1995).

  183. National Institutes of Health and National Heart Lung and Blood Institute. Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults — the evidence report. Obes. Res. 6 (Suppl. 2), 51–209 (1998).

  184. Rockhill, B., Newman, B. & Weinberg, C. Use and misuse of population attributable fractions. Am. J. Public Health 88, 15–19 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  185. Bergman, R. N. & Ader, M. Free fatty acids and pathogenesis of type 2 diabetes mellitus. Trends Endocrinol. Metab. 11, 351–356 (2000).

    CAS  PubMed  Google Scholar 

  186. Ebeling, P. & Koivisto, V. A. Non-esterified fatty acids regulate lipid and glucose oxidation and glycogen synthesis in healthy man. Diabetologia 37, 202–209 (1994).

    CAS  PubMed  Google Scholar 

  187. Randle, P. J. Regulatory interactions between lipids and carbohydrates: the glucose fatty acid cycle after 35 years. Diabetes Metab. Rev. 14, 263–283 (1998).

    CAS  PubMed  Google Scholar 

  188. Havel, P. J. Control of energy homeostasis and insulin action by adipocyte hormones: leptin, acylation stimulating protein, and adiponectin. Curr. Opin. Lipidol. 13, 51–59 (2002).

    CAS  PubMed  Google Scholar 

  189. Hotamisligil, G. S. Molecular mechanisms of insulin resistance and the role of the adipocyte. Int. J. Obes. Relat. Metab. Disord. 24 (Suppl. 4), 23–27 (2000).

    Google Scholar 

  190. Kahn, B. B. & Flier, J. S. Obesity and insulin resistance. J. Clin. Invest. 106, 473–481 (2000). An excellent review of the physiological mechanisms leading to insulin resistance.

    CAS  PubMed  PubMed Central  Google Scholar 

  191. Steppan, C. M. & Lazar, M. A. Resistin and obesity-associated insulin resistance. Trends Endocrinol. Metab. 13, 18–23 (2002).

    CAS  PubMed  Google Scholar 

  192. Trayhurn, P. & Beattie, J. H. Physiological role of adipose tissue: white adipose tissue as an endocrine and secretory organ. Proc. Nutr. Soc. 60, 329–339 (2001).

    CAS  PubMed  Google Scholar 

  193. Ukropec, J., Sebokova, E. & Klimes, I. Nutrient sensing, leptin and insulin action. Arch. Physiol. Biochem. 109, 38–51 (2001).

    CAS  PubMed  Google Scholar 

  194. Le Roith, D. & Zick, Y. Recent advances in our understanding of insulin action and insulin resistance. Diabetes Care 24, 588–597 (2001).

    CAS  PubMed  Google Scholar 

  195. Moller, D. E. & Flier, J. S. Insulin resistance — mechanisms, syndromes, and implications. N. Engl. J. Med. 325, 938–948 (1991).

    CAS  PubMed  Google Scholar 

  196. Virkamaki, A., Ueki, K. & Kahn, C. R. Protein–protein interaction in insulin signaling and the molecular mechanisms of insulin resistance. J. Clin. Invest. 103, 931–943 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  197. Henriksen, E. J. Invited review: Effects of acute exercise and exercise training on insulin resistance. J. Appl. Physiol. 93, 788–796 (2002).

    CAS  PubMed  Google Scholar 

  198. Borghouts, L. B. & Keizer, H. A. Exercise and insulin sensitivity: a review. Int. J. Sports Med. 21, 1–12 (2000).

    CAS  PubMed  Google Scholar 

  199. Pedersen, O. Genetics of insulin resistance. Exp. Clin. Endocrinol. Diabetes 107, 113–118 (1999).

    CAS  PubMed  Google Scholar 

  200. Grundy, S. M., Abate, N. & Chandalia, M. Diet composition and the metabolic syndrome: what is the optimal fat intake? Am. J. Med. 113 (Suppl. 9B), 25–29 (2002).

    Google Scholar 

  201. Kopp, W. High-insulinogenic nutrition — an etiologic factor for obesity and the metabolic syndrome? Metabolism 52, 840–844 (2003).

    CAS  PubMed  Google Scholar 

  202. Vessby, B. Dietary fat, fatty acid composition in plasma and the metabolic syndrome. Curr. Opin. Lipidol. 14, 15–19 (2003).

    CAS  PubMed  Google Scholar 

  203. Grundy, S. M., Brewer, H. B. Jr., Cleeman, J. I., Smith, S. C. Jr. & Lenfant, C. Definition of metabolic syndrome: report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition. Circulation 109, 433–438 (2004).

    PubMed  Google Scholar 

  204. Reaven, G. M. Pathophysiology of insulin resistance in human disease. Physiol. Rev. 75, 473–486 (1995).

    CAS  PubMed  Google Scholar 

  205. National Center for Health Statistics, Centers for Disease Control and Prevention. National Health and Nutrition Examination Survey 1999–2000 [online], <www.cdc.gov/nchs/about/major/nhanes/NHANES99_00.htm.> (2004)

  206. Bergstrom, A., Pisani, P., Tenet, V., Wolk, A. & Adami, H. O. Overweight as an avoidable cause of cancer in Europe. Int. J. Cancer 91, 421–430 (2001).

    CAS  PubMed  Google Scholar 

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Correspondence to Eugenia E. Calle.

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DATABASES

Cancer.gov

cervical cancer

colon cancer

endometrial cancer

breast cancer

gallbladder cancer

gastric cancer

kidney cancer

liver cancer

lung cancer

multiple myeloma

non-Hodgkin's lymphoma

oesophageal cancer

ovarian cancer

pancreatic cancer

prostate cancer

Entrez Gene

adiponectin

GH

IGF1

IGF1 receptor

IGFBP1

IGFBP2

IGFBP3

IGFBP4

IGFBP5

IGFBP6

leptin

resistin

SHBG

OMIM

gastro-oesophageal reflux disease

polycystic ovary syndrome

type-II diabetes

FURTHER INFORMATION

International Agency for Research on Cancer

National Center for Health Statistics

Royal College of Physicians

US Preventive Services Task Force

World Health Organization Global Strategy on Diet, Physical Activity and Health

World Health Organization site on the epidemic of obesity

Glossary

TRIGLYCERIDE

A fat that is synthesized from carbohydrates and stored in animal adipose cells. On hydrolysis, it releases free fatty acids into the blood.

ANTHROPOMETRIC

A measurement of the size or proportions of the human body; for example, weight, height and waist circumference.

RELATIVE RISK

The risk of cancer (or other disease) in a group of exposed persons divided by the risk in a group of unexposed persons. The relative risk is a commonly used measure of association in epidemiological studies.

CENTRAL ADIPOSITY

The storage of adipose tissue preferentially in adipocytes on or within the trunk rather than the extremities.

ANOVULATORY

A menstrual cycle that is not accompanied by the discharge of an egg from the ovary.

PROXY RESPONDERS

Also called surrogate responders, individuals who provide information regarding exposure in place of the individual involved in the study.

SEX STEROIDS

A family of hormones that all share a basic chemical (steroidal) structure. These hormones include androgens, oestrogens and progesterone, and have important effects on sexual development and reproductive functions.

FASTING AND NON-FASTING GLUCOSE LEVELS

Glucose is the end product of carbohydrate metabolism and the chief source of energy for living organisms; its utilization is controlled by insulin. It is found in the blood of all animals. Fasting plasma glucose levels are a measurement of the concentration of glucose in the plasma after the patient has not eaten for at least 8 hours.

BIOAVAILABLE

The portion of a substance that can be used physiologically by target tissues.

NON-ALCOHOLIC STEATOHEPATITIS.

A liver lesion characterized by liver cell injury and death, and hepatic inflammation that can be accompanied by progressive hepatic fibrosis.

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Calle, E., Kaaks, R. Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Nat Rev Cancer 4, 579–591 (2004). https://doi.org/10.1038/nrc1408

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