Skip to main content

Insulin, Insulin Resistance, and Cancer Associations

  • Chapter
  • First Online:
Insulin Resistance and Cancer

Part of the book series: Energy Balance and Cancer ((EBAC,volume 1))

Abstract

There have been long-standing attempts to elucidate the causes of cancer through observational research. While causation can never be definitively established based on this type of evidence, the impossibility of conducting experimental studies forces us to rely on epidemiologic studies to generate hypotheses regarding key risk factors for cancers. Initially, potential risk factors are considered based on biological hypo-theses, preliminary in vitro or animal studies, ecologic observations, or anecdotal evidence. Associations between risk factors and cancer outcomes are then sought through more rigorous observational studies. We must then determine whether such associations represent causative relationships, based on well-established criteria such as biologic plausibility, the strength, specificity and consistency of the association, temporality, and demonstration of a biologic gradient [1]. Recently, epidemiologic associations have emerged between obesity, diabetes, and certain forms of cancer such as those of the breast, colon, and pancreas. Since these conditions are associated with insulin resistance and compensatory hyperinsulinemia, it has been hypothesized that insulin may be a common mediator in these relationships due to its cancer-promoting properties. This chapter will review the growing body of evidence linking obesity and diabetes to the risk of certain cancers and the potential role of hyperinsulinemia in these associations, with a particular focus on cancer of the breast, colon, pancreas, and prostate. As a framework, this review consider these cancers separately, and will discuss the epidemiological evidence linking cancer risk first to obesity, then to insulin resistance and diabetes, followed by a discussion of direct and indirect evidence of the role of hyperinsulinemia in these associations.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Bradford-Hill A (1966) The environment and disease: association or causation? Proc Roy Soc Med 58:295

    Article  Google Scholar 

  2. Cleary MP, Maihle NJ (1997) The role of body mass index in the relative risk of developing premenopausal versus postmenopausal breast cancer. Proc Soc Exp Biol Med 216:28–43

    Article  CAS  PubMed  Google Scholar 

  3. Stephenson GD, Rose DP (2003) Breast cancer and obesity: an update. Nutr Cancer 45:1–16

    Article  CAS  PubMed  Google Scholar 

  4. Renehan AG, Tyson M, Egger M, Heller RF, Zwahlen M (2008) Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet 371:569–578

    Article  PubMed  Google Scholar 

  5. van den Brandt PA, Spiegelman D, Yaun SS, Adami HO, Beeson L, Folsom AR, Fraser G, Goldbohm RA, Graham S, Kushi L, Marshall JR, Miller AB, Rohan T, Smith-Warner SA, Speizer FE, Willett WC, Wolk A, Hunter DJ (2000) Pooled analysis of prospective cohort studies on height, weight, and breast cancer risk. Am J Epidemiol 152:514–527

    Article  PubMed  Google Scholar 

  6. Ursin G, Longnecker MP, Haile RW, Greenland S (1995) A meta-analysis of body mass index and risk of premenopausal breast cancer. Epidemiology 6:137–141

    Article  CAS  PubMed  Google Scholar 

  7. Lake JK, Power C, Cole TJ (1997) Women’s reproductive health: the role of body mass index in early and adult life. Int J Obes Relat Metab Disord 21:432–438

    Article  CAS  PubMed  Google Scholar 

  8. Bray GA (2002) The underlying basis for obesity: relationship to cancer. J Nutr 132:3451S–3455S

    Article  CAS  PubMed  Google Scholar 

  9. Bulun SE, Mahendroo MS, Simpson ER (1994) Aromatase gene expression in adipose tissue: relationship to breast cancer. J Steroid Biochem Mol Biol 49:319–326

    Article  CAS  PubMed  Google Scholar 

  10. Lawlor DA, Smith GD, Ebrahim S (2004) Hyperinsulinaemia and increased risk of breast cancer: findings from the British Women’s Heart and Health Study. Cancer Causes Control 15:267–275

    Article  PubMed  Google Scholar 

  11. Renehan AG, Zwahlen M, Minder C, O’Dwyer ST, Shalet SM, Egger M (2004) Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis. The Lancet 363(9418):1346–1353

    Article  CAS  Google Scholar 

  12. Nyholm H, Djursing H, Hagen C, Agner T, Bennett P, Svenstrup B (1989) Androgens and estrogens in postmenopausal insulin-treated diabetic women. J Clin Endocrinol Metab 69:946–949

    Article  CAS  PubMed  Google Scholar 

  13. Alexander CM, Landsman PB, Teutsch SM, Haffner SM, Third National H, Nutrition Examination S, National Cholesterol Education P (2003) NCEP-defined metabolic syndrome, diabetes, and prevalence of coronary heart disease among NHANES III participants age 50 years and older. Diabetes 52:1210–1214

    Article  CAS  PubMed  Google Scholar 

  14. Folsom AR, Kaye SA, Prineas RJ, Potter JD, Gapstur SM, Wallace RB (1990) Increased incidence of carcinoma of the breast associated with abdominal adiposity in postmenopausal women. Am J Epidemiol 131:794–803

    Article  CAS  PubMed  Google Scholar 

  15. Huang Z, Willett WC, Colditz GA, Hunter DJ, Manson JE, Rosner B, Speizer FE, Hankinson SE (1999) Waist circumference, waist:hip ratio, and risk of breast cancer in the Nurses’ Health Study. Am J Epidemiol 150:1316–1324

    Article  CAS  PubMed  Google Scholar 

  16. Kaaks R, van Noord PA, Den Tonkelaar I, Peeters PH, Riboli E, Grobbee DE (1998) Breast-cancer incidence in relation to height, weight and body-fat distribution in the Dutch “DOM” cohort. Int J Cancer 76:647–651

    Article  CAS  PubMed  Google Scholar 

  17. den Tonkelaar I, Seidell JC, Collette HJ (1995) Body fat distribution in relation to breast cancer in women participating in the DOM-project. Breast Cancer Res Treat 34:55–61

    Article  Google Scholar 

  18. Lahmann PH, Hoffmann K, Allen N, Van Gils CH, Khaw KT, Tehard B, Berrino F, Tjonneland A, Bigaard J, Olsen A, Overvad K, Clavel-Chapelon F, Nagel G, Boeing H, Trichopoulos D, Economou G, Bellos G, Palli D, Tumino R, Panico S, Sacerdote C, Krogh V, Peeters PH, Bueno-de-Mesquita HB, Lund E, Ardanaz E, Amiano P, Pera G, Quiros JR, Martinez C, Tormo MJ, Wirfalt E, Berglund G, Hallmans G, Key TJ, Reeves G, Bingham S, Norat T, Biessy C, Kaaks R, Riboli E (2004) Body size and breast cancer risk: findings from the European Prospective Investigation into Cancer And Nutrition (EPIC). Int J Cancer 111:762–771

    Article  CAS  PubMed  Google Scholar 

  19. Morimoto LM, White E, Chen Z, Chlebowski RT, Hays J, Kuller L, Lopez AM, Manson J, Margolis KL, Muti PC, Stefanick ML, McTiernan A (2002) Obesity, body size, and risk of postmenopausal breast cancer: the Women’s Health Initiative (United States). Cancer Causes Control 13:741–751

    Article  PubMed  Google Scholar 

  20. Sonnenschein E, Toniolo P, Terry MB, Bruning PF, Kato I, Koenig KL, Shore RE (1999) Body fat distribution and obesity in pre- and postmenopausal breast cancer. Int J Epidemiol 28:1026–1031

    Article  CAS  PubMed  Google Scholar 

  21. Harvie M, Hooper L, Howell AH (2003) Central obesity and breast cancer risk: a systematic review. Obes Rev 4:157–173

    Article  CAS  PubMed  Google Scholar 

  22. Tornberg SA, Holm LE, Carstensen JM (1988) Breast cancer risk in relation to serum cholesterol, serum beta-lipoprotein, height, weight, and blood pressure. Acta Oncol 27:31–37

    Article  CAS  PubMed  Google Scholar 

  23. Soler M, Chatenoud L, Negri E, Parazzini F, Franceschi S, La VC (1999) Hypertension and hormone-related neoplasms in women. Hypertension 34:320–325

    Article  CAS  PubMed  Google Scholar 

  24. Largent JA, McEligot AJ, Ziogas A, Reid C, Hess J, Leighton N, Peel D, Anton-Culver H (2006) Hypertension, diuretics and breast cancer risk. J Hum Hypertens 20:727–732

    Article  CAS  PubMed  Google Scholar 

  25. Manjer J, Kaaks R, Riboli E, Berglund G (2001) Risk of breast cancer in relation to anthropometry, blood pressure, blood lipids and glucose metabolism: a prospective study within the Malmo Preventive Project. Eur J Cancer Prev 10:33–42

    Article  CAS  PubMed  Google Scholar 

  26. Peeters PH, van Noord PA, Hoes AW, Fracheboud J, Gimbrere CH, Grobbee DE (2000) Hypertension and breast cancer risk in a 19-year follow-up study (the DOM cohort). Diagnostic investigation into mammarian cancer. J Hypertens 18:249–254

    Article  CAS  PubMed  Google Scholar 

  27. Lindgren AM, Nissinen AM, Tuomilehto JO, Pukkala E (2005) Cancer pattern among hypertensive patients in North Karelia, Finland. Hum Hypertens 19:373–379

    Article  CAS  Google Scholar 

  28. Basu TK, Williams DC (1975) Plasma and body lipids in patients with carcinoma of the breast. Oncology 31:172–176

    Article  CAS  PubMed  Google Scholar 

  29. Bani IA, Williams CM, Boulter PS, Dickerson JW (1986) Plasma lipids and prolactin in patients with breast cancer. Br J Cancer 54:439–446

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Alexopoulos CG, Blatsios B, Avgerinos A (1987) Serum lipids and lipoprotein disorders in cancer patients. Cancer 60:3065–3070

    Article  CAS  PubMed  Google Scholar 

  31. Kumar K, Sachdanandam P, Arivazhagan R (1991) Studies on the changes in plasma lipids and lipoproteins in patients with benign and malignant breast cancer. Biochem Int 23:581–589

    CAS  PubMed  Google Scholar 

  32. Kaye JA, Meier CR, Walker AM, Jick H (2002) Statin use, hyperlipidaemia, and the risk of breast cancer. Br J Cancer 86:1436–1439

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Gerber M, Cavallo F, Marubini E, Richardson S, Barbieri A, Capitelli E, Costa A, de Crastes PA, de Crastes PP, Decarli A (1988) Liposoluble vitamins and lipid parameters in breast cancer. A joint study in northern Italy and southern France. Int J Cancer 42:489–494

    Article  CAS  PubMed  Google Scholar 

  34. Kokoglu E, Karaarslan I, Karaarslan HM, Baloglu H (1994) Alterations of serum lipids and lipoproteins in breast cancer. Cancer Lett 82:175–178

    Article  CAS  PubMed  Google Scholar 

  35. Dyer AR, Stamler J, Paul O, Shekelle RB, Schoenberger JA, Berkson DM, Lepper M, Collette P, Shekelle S, Lindberg HA (1981) Serum cholesterol and risk of death from cancer and other causes in three Chicago epidemiological studies. J Chron Dis 34:249–260

    Article  CAS  PubMed  Google Scholar 

  36. Vatten LJ, Foss OP (1990) Total serum cholesterol and triglycerides and risk of breast cancer: a prospective study of 24,329 Norwegian women. Cancer Res 50:2341–2346

    CAS  PubMed  Google Scholar 

  37. Williams RR, Sorlie PD, Feinleib M, McNamara PM, Kannel WB, Dawber TR (1981) Cancer incidence by levels of cholesterol. JAMA 245:247–252

    Article  CAS  PubMed  Google Scholar 

  38. Hiatt RA, Friedman GD, Bawol RD, Ury HK (1982) Breast cancer and serum cholesterol. J Natl Cancer Inst 68:885–889

    CAS  PubMed  Google Scholar 

  39. Morris DL, Borhani NO, Fitzsimons E, Hardy RJ, Hawkins CM, Kraus JF, Labarthe DR, Mastbaum L, Payne GH (1983) Serum cholesterol and cancer in the Hypertension Detection and Follow-up Program. Cancer 52:1754–1759

    Article  CAS  PubMed  Google Scholar 

  40. Schatzkin A, Hoover RN, Taylor PR, Ziegler RG, Carter CL, Albanes D, Larson DB, Licitra LM (1988) Site-specific analysis of total serum cholesterol and incident cancer in the National Health and Nutrition Examination Survey I Epidemiologic Follow-up Study. Cancer Res 48:452–458

    CAS  PubMed  Google Scholar 

  41. Gaard M, Tretli S, Urdal P (1994) Risk of breast cancer in relation to blood lipids: a prospective study of 31,209 Norwegian women. Cancer Causes Control 5:501–509

    Article  CAS  PubMed  Google Scholar 

  42. Elkhadrawy TM, Ahsan H, Neugut AI (1998) Serum cholesterol and the risk of ductal carcinoma in situ: a case-control study. Eur J Cancer Prev 7:393–396

    Article  CAS  PubMed  Google Scholar 

  43. Eliassen AH, Colditz GA, Rosner B, Willett WC, Hankinson SE (2005) Serum lipids, lipid-lowering drugs, and the risk of breast cancer. Arch Intern Med 165:2264–2271

    Article  CAS  PubMed  Google Scholar 

  44. Hoyer AP, Engholm G (1992) Serum lipids and breast cancer risk: a cohort study of 5,207 Danish women. Cancer Causes Control 3:403–408

    Article  CAS  PubMed  Google Scholar 

  45. Sinagra D, Amato C, Scarpilta AM, Brigandi M, Amato M, Saura G, Latteri MA, Caimi G (2002) Metabolic syndrome and breast cancer risk. Eur Rev Med Pharmacol Sci 6:55–59

    CAS  PubMed  Google Scholar 

  46. Lipscombe LL, Goodwin PJ, Zinman B, McLaughlin JR, Hux JE (2006) Diabetes mellitus and breast cancer: a retrospective population-based cohort study. Breast Cancer Res Treat 98:349–356

    Article  PubMed  Google Scholar 

  47. Baron JA, Weiderpass E, Newcomb PA, Stampfer M, Titus-Ernstoff L, Egan KM, Greenberg ER (2001) Metabolic disorders and breast cancer risk (United States). Cancer Causes Control 12:875–880

    Article  CAS  PubMed  Google Scholar 

  48. Michels KB, Solomon CG, Hu FB, Rosner BA, Hankinson SE, Colditz GA, Manson JE (2003) Type 2 diabetes and subsequent incidence of breast cancer in the Nurses’ Health Study. Diabetes Care 26:1752–1758

    Article  PubMed  Google Scholar 

  49. Mink PJ, Shahar E, Rosamond WD, Alberg AJ, Folsom AR (2002) Serum insulin and glucose levels and breast cancer incidence: the atherosclerosis risk in communities study. Am J Epidemiol 156:349–352

    Article  PubMed  Google Scholar 

  50. O’Mara BA, Byers T, Schoenfeld E (1985) Diabetes mellitus and cancer risk: a multisite case-control study. J Chron Dis 38:435–441

    Article  PubMed  Google Scholar 

  51. Ragozzino M, Melton LJ III, Chu CP, Palumbo PJ (1982) Subsequent cancer risk in the incidence cohort of Rochester, Minnesota, residents with diabetes mellitus. J Chron Dis 35:13–19

    Article  CAS  PubMed  Google Scholar 

  52. Sellers TA, Sprafka JM, Gapstur SM, Rich SS, Potter JD, Ross JA, McGovern PG, Nelson CL, Folsom AR (1994) Does body fat distribution promote familial aggregation of adult onset diabetes mellitus and postmenopausal breast cancer? Epidemiology 5:102–108

    Article  CAS  PubMed  Google Scholar 

  53. Weiss HA, Brinton LA, Potischman NA, Brogan D, Coates RJ, Gammon MD, Malone KE, Schoenberg JB (1999) Breast cancer risk in young women and history of selected medical conditions. Int J Epidemiol 28:816–823

    Article  CAS  PubMed  Google Scholar 

  54. Moseson M, Koenig KL, Shore RE, Pasternack BS (1993) The influence of medical conditions associated with hormones on the risk of breast cancer. Int J Epidemiol 22:1000–1009

    Article  CAS  PubMed  Google Scholar 

  55. Swerdlow AJ, Laing SP, Qiao Z, Slater SD, Burden AC, Botha JL, Waugh NR, Morris AD, Gatling W, Gale EA, Patterson CC, Keen H (2005) Cancer incidence and mortality in patients with insulin-treated diabetes: a UK cohort study. Br J Cancer 92:2070–2075

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Franceschi S, La Vecchia C, Negri E, Parazzini F, Boyle P (1990) Breast cancer risk and history of selected medical conditions linked with female hormones. Eur J Cancer 26:781–785

    Article  CAS  PubMed  Google Scholar 

  57. Talamini R, Franceschi S, Favero A, Negri E, Parazzini F, La Vecchia C (1997) Selected medical conditions and risk of breast cancer. Br J Cancer 75:1699–1703

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Resta F, Triggiani V, Sabba C, Licchelli B, Ghiyasaldin S, Liso A, Schittulli F, Quaranta M, Paradiso A, Tafaro E, Guastamacchia E (2004) The impact of body mass index and type 2 diabetes on breast cancer: current therapeutic measures of prevention. Curr Drug Targets Immune Endocr Metabol Disord 4:327–333

    Article  CAS  PubMed  Google Scholar 

  59. Goodman MT, Cologne JB, Moriwaki H, Vaeth M, Mabuchi K (1997) Risk factors for primary breast cancer in Japan: 8-year follow-up of atomic bomb survivors. Prev Med 26:144–153

    Article  CAS  PubMed  Google Scholar 

  60. Inoue M, Iwasaki M, Otani T, Sasazuki S, Noda M, Tsugane S (2006) Diabetes mellitus and the risk of cancer: results from a large-scale population-based cohort study in Japan. Arch Intern Med 166:1871–1877

    Article  PubMed  Google Scholar 

  61. Khan M, Mori M, Fujino Y, Shibata A, Sakauchi F, Washio M, Tamakoshi A (2006) Site-specific cancer risk due to diabetes mellitus history: evidence from the Japan Collaborative Cohort (JACC) Study. Asian Pac J Cancer Prev 7:253–259

    PubMed  Google Scholar 

  62. Adami HO, Rimsten A (1978) Prevalence of hypertension and diabetes in breast cancer: a case-control study in 179 patients and age-matched, non-hospitalized controls. Clin Oncol 4:243–249

    CAS  PubMed  Google Scholar 

  63. Weiderpass E, Gridley G, Persson I, Nyren O, Ekbom A, Adami HO (1997) Risk of endometrial and breast cancer in patients with diabetes mellitus. Int J Cancer 71:360–363

    Article  CAS  PubMed  Google Scholar 

  64. Hjalgrim H, Frisch M, Ekbom A, Kyvik KO, Melbye M, Green A (1997) Cancer and diabetes – a follow-up study of two population-based cohorts of diabetic patients. J Intern Med 241:471–475

    Article  CAS  PubMed  Google Scholar 

  65. Wideroff L, Gridley G, Mellemkjaer L, Chow WH, Linet M, Keehn S, Borch-Johnsen K, Olsen JH (1997) Cancer incidence in a population-based cohort of patients hospitalized with diabetes mellitus in Denmark. J Natl Cancer Inst 89:1360–1365

    Article  CAS  PubMed  Google Scholar 

  66. Muck BR, Trotnow S, Hommel G (1975) Cancer of the breast, diabetes and pathological glucose tolerance. Arch Gynäkol 220:73–81

    Article  CAS  PubMed  Google Scholar 

  67. de Waard F, Baanders-van Halewijn EA (1974) A prospective study in general practice on breast-cancer risk in postmenopausal women. Int J Cancer 14:153–160

    Article  PubMed  Google Scholar 

  68. Jee SH, Ohrr H, Sull JW, Yun JE, Ji M, Samet JM (2005) Fasting serum glucose level and cancer risk in Korean men and women. JAMA 293:194–202

    Article  CAS  PubMed  Google Scholar 

  69. Larsson SC, Mantzoros CS, Wolk A (2007) Diabetes mellitus and risk of breast cancer: a meta-analysis. Int J Cancer 121:856–862

    Article  CAS  PubMed  Google Scholar 

  70. Xue F, Michels KB (2007) Diabetes, metabolic syndrome, and breast cancer: a review of the current evidence. Am J Clin Nutr 86:s823–s835

    Article  PubMed  Google Scholar 

  71. van der Burg B, Rutteman GR, Blankenstein MA, de Laat SW, van Zoelen EJ (1988) Mitogenic stimulation of human breast cancer cells in a growth factor-defined medium: synergistic action of insulin and estrogen. J Cell Physiol 134:101–108

    Article  PubMed  Google Scholar 

  72. Chappell J, Leitner JW, Solomon S, Golovchenko I, Goalstone ML, Draznin B (2001) Effect of insulin on cell cycle progression in MCF-7 breast cancer cells. Direct and potentiating influence. J Biol Chem 276:38023–38028

    Article  CAS  PubMed  Google Scholar 

  73. Belfiore A, Frittitta L, Costantino A, Frasca F, Pandini G, Sciacca L, Goldfine ID, Vigneri R (1996) Insulin receptors in breast cancer. Ann NY Acad Sci 784:173–188

    Article  CAS  PubMed  Google Scholar 

  74. Papa V, Belfiore A (1996) Insulin receptors in breast cancer: biological and clinical role. J Endocrinol Invest 19:324–333

    Article  CAS  PubMed  Google Scholar 

  75. Dang CV, Semenza GL (1999) Oncogenic alterations of metabolism. Trends Biochem Sci 24:68–72

    Article  CAS  PubMed  Google Scholar 

  76. Buchanan TA (2003) Pancreatic beta-cell loss and preservation in type 2 diabetes. Clin Ther 25(Suppl B):32–46

    Article  Google Scholar 

  77. Steppel JH, Horton ES (2004) Beta-cell failure in the pathogenesis of type 2 diabetes mellitus. Curr Diab Rep 4:169–175

    Article  PubMed  Google Scholar 

  78. Lipscombe LL, Goodwin PJ, Zinman B, McLaughlin JR, Hux JE (2006) Increased prevalence of prior breast cancer in women with newly diagnosed diabetes. Breast Cancer Res Treat 98:303–309

    Article  PubMed  Google Scholar 

  79. Dawson SI (2004) Long-term risk of malignant neoplasm associated with gestational glucose intolerance. Cancer 100:149–155

    Article  PubMed  Google Scholar 

  80. Balen A (2001) Polycystic ovary syndrome and cancer. Hum Reprod Update 7:522–525

    Article  CAS  PubMed  Google Scholar 

  81. Chittenden BG, Fullerton G, Maheshwari A, Bhattacharya S (2009) Polycystic ovary syndrome and the risk of gynaecological cancer: a systematic review. Reprod Biomed Online 19(3):398–405

    Article  CAS  PubMed  Google Scholar 

  82. Bowker SL, Majumdar SR, Veugelers P, Johnson JA (2006) Increased cancer-related mortality for patients with type 2 diabetes who use sulfonylureas or insulin. Diabetes Care 29:254–258

    Article  PubMed  Google Scholar 

  83. Colhoun HM (2009) Use of insulin glargine and cancer incidence in Scotland: a study from the Scottish Diabetes Research Network Epidemiology Group. Diabetologia 52(9):1755–1765

    Article  PubMed  PubMed Central  Google Scholar 

  84. Currie CJ, Poole CD, Gale EA (2009) The influence of glucose-lowering therapies on cancer risk in type 2 diabetes. Diabetologia 52(9):1766–1777

    Article  CAS  PubMed  Google Scholar 

  85. Hemkens LG, Grouven U, Bender R, Gunster C, Gutschmidt S, Selke GW et al (2009) Risk of malignancies in patients with diabetes treated with human insulin or insulin analogues: a cohort study. Diabetologia 52(9):1732–1744

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Jonasson JM, Ljung R, Talback M, Haglund B, Gudbjornsdottir S, Steineck G (2009) Insulin glargine use and short-term incidence of malignancies-a population-based follow-up study in Sweden. Diabetologia 52(9):1745–1754

    Article  CAS  PubMed  Google Scholar 

  87. Suissa S, Azoulay L, Dell’aniello S, Evans M, Vora J, Pollak M (2011) Long-term effects of insulin glargine on the risk of breast cancer. Diabetologia; On-line first May 26th

    Google Scholar 

  88. McFarland MS, Cripps R (2010) Diabetes mellitus and increased risk of cancer: focus on metformin and the insulin analogs. Pharmacotherapy 30(11):1159–1178

    Article  CAS  PubMed  Google Scholar 

  89. Evans JM, Donnelly LA, Emslie-Smith AM, Alessi DR, Morris AD (2005) Metformin and reduced risk of cancer in diabetic patients. BMJ 330:1304–1305

    Article  PubMed  PubMed Central  Google Scholar 

  90. Decensi A, Puntoni M, Goodwin P, Cazzaniga M, Gennari A, Bonanni B et al (2010) Metformin and cancer risk in diabetic patients: a systematic review and meta-analysis. Cancer Prev Res (Phila) 3(11):1451–1461

    Article  CAS  Google Scholar 

  91. Jiralerspong S, Palla SL, Giordano SH, Meric-Bernstam F, Liedtke C, Barnett CM et al (2009) Metformin and pathologic complete responses to neoadjuvant chemotherapy in diabetic patients with breast cancer. J Clin Oncol 27(20):3297–3302

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Zakikhani M, Dowling R, Fantus IG, Sonenberg N, Pollak M (2006) Metformin is an AMP kinase-dependent growth inhibitor for breast cancer cells. Cancer Res 66:10269–10273

    Article  CAS  PubMed  Google Scholar 

  93. Del Giudice ME, Fantus IG, Ezzat S, McKeown-Eyssen G, Page D, Goodwin PJ (1998) Insulin and related factors in premenopausal breast cancer risk. Breast Cancer Res Treat 47:111–120

    Article  PubMed  Google Scholar 

  94. Hirose K, Toyama T, Iwata H, Takezaki T, Hamajima N, Tajima K (2003) Insulin, insulin-like growth factor-I and breast cancer risk in Japanese women. Asian Pac J Cancer Prev 4:239–246

    PubMed  Google Scholar 

  95. Yam D, Fink A, Mashiah A, Ben-Hur E (1996) Hyperinsulinemia in colon, stomach and breast cancer patients. Cancer Lett 104:129–132

    Article  CAS  PubMed  Google Scholar 

  96. Gamayunova VB (1997) Comparative study of blood insulin levels in breast and endometrial cancer patients. Neoplasma 44:123–126

    CAS  PubMed  Google Scholar 

  97. Jernstrom H, Barrett-Connor E (1999) Obesity, weight change, fasting insulin, proinsulin, C-peptide, and insulin-like growth factor-1 levels in women with and without breast cancer: the Rancho Bernardo Study. J Womens Health Gend Based Med 8:1265–1272

    Article  CAS  PubMed  Google Scholar 

  98. Kaaks R, Lundin E, Rinaldi S, Manjer J, Biessy C, Soderberg S, Lenner P, Janzon L, Riboli E, Berglund G, Hallmans G (2002) Prospective study of IGF-I, IGF-binding proteins, and breast cancer risk, in northern and southern Sweden. Cancer Causes Control 13:307–316

    Article  PubMed  Google Scholar 

  99. Muti P, Quattrin T, Grant BJ, Krogh V, Micheli A, Schunemann HJ, Ram M, Freudenheim JL, Sieri S, Trevisan M, Berrino F (2002) Fasting glucose is a risk factor for breast cancer: a prospective study. Cancer Epidemiol Biomarkers Prev 11:1361–1368

    CAS  PubMed  Google Scholar 

  100. Bruning PF, Bonfrer JM, van Noord PA, Hart AA, de Jong-Bakker M, Nooijen WJ (1992) Insulin resistance and breast-cancer risk. Int J Cancer 52:511–516

    Article  CAS  PubMed  Google Scholar 

  101. Verheus M, Peeters PH, Rinaldi S, Dossus L, Biessy C, Olsen A, Tjonneland A, Overvad K, Jeppesen M, Clavel-Chapelon F, Tehard B, Nagel G, Linseisen J, Boeing H, Lahmann PH, Arvaniti A, Psaltopoulou T, Trichopoulou A, Palli D, Tumino R, Panico S, Sacerdote C, Sieri S, Van Gils CH, Bueno-de-Mesquita BH, Gonzalez CA, Ardanaz E, Larranaga N, Garcia CM, Navarro C, Quiros JR, Key T, Allen N, Bingham S, Khaw KT, Slimani N, Riboli E, Kaaks R (2006) Serum C-peptide levels and breast cancer risk: results from the European Prospective Investigation into Cancer and Nutrition (EPIC). Int J Cancer 119:659–667

    Article  CAS  PubMed  Google Scholar 

  102. Malin A, Dai Q, Yu H, Shu XO, Jin F, Gao YT, Zheng W (2004) Evaluation of the synergistic effect of insulin resistance and insulin-like growth factors on the risk of breast carcinoma. Cancer 100:694–700

    Article  CAS  PubMed  Google Scholar 

  103. Yang G, Lu G, Jin F, Dai Q, Best R, Shu XO, Chen JR, Pan XY, Shrubsole M, Zheng W (2001) Population-based, case-control study of blood C-peptide level and breast cancer risk. Cancer Epidemiol Biomarkers Prev 10:1207–1211

    CAS  PubMed  Google Scholar 

  104. Keinan-Boker L, Bueno De Mesquita HB, Kaaks R, Van Gils CH, van Noord PA, Rinaldi S, Riboli E, Seidell JC, Grobbee DE, Peeters PH (2003) Circulating levels of insulin-like growth factor I, its binding proteins -1,-2, -3, C peptide risk postmenopausal breast cancer. Int J Cancer 106:90–95

    Article  CAS  PubMed  Google Scholar 

  105. Schairer C, Hill D, Sturgeon SR, Fears T, Pollak M, Mies C, Ziegler RG, Hoover RN, Sherman ME (2004) 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

    Article  CAS  PubMed  Google Scholar 

  106. Toniolo P, Bruning PF, Akhmedkhanov A, Bonfrer JM, Koenig KL, Lukanova A, Shore RE, Zeleniuch-Jacquotte A (2000) Serum insulin-like growth factor-I and breast cancer. Int J Cancer 88:828–832

    Article  CAS  PubMed  Google Scholar 

  107. Pisani P (2008) Hyper-insulinaemia and cancer, meta-analyses of epidemiological studies. Arch Physiol Biochem 114:63–70

    Article  CAS  PubMed  Google Scholar 

  108. Williams CL, Hayman LL, Daniels SR, Robinson TN, Steinberger J, Paridon S, Bazzarre T (2002) Cardiovascular health in childhood: A statement for health professionals from the Committee on Atherosclerosis, Hypertension, and Obesity in the Young (AHOY) of the Council on Cardiovascular Disease in the Young, American Heart Association. Circulation 106:143–160

    Article  PubMed  Google Scholar 

  109. Warburg O (1956) On the origin of cancer cells. Science 123:309–314

    Article  CAS  PubMed  Google Scholar 

  110. Zendehdel K, Nyren O, Ostenson CG, Adami HO, Ekbom A, Ye W (2003) Cancer incidence in patients with type 1 diabetes mellitus: a population-based cohort study in Sweden. J Natl Cancer Inst 95:1797–1800

    Article  PubMed  Google Scholar 

  111. Rapp K, Schroeder J, Klenk J, Ulmer H, Concin H, Diem G, Oberaigner W, Weiland SK (2006) Fasting blood glucose and cancer risk in a cohort of more than 140,000 adults in Austria. Diabetologia 49:945–952

    Article  CAS  PubMed  Google Scholar 

  112. Mathieu MC, Clark GM, Allred DC, Goldfine ID, Vigneri R (1997) Insulin receptor expression and clinical outcome in node-negative breast cancer. Proc Assoc Am Physicians 109:565–571

    CAS  PubMed  Google Scholar 

  113. Frasca F, Pandini G, Scalia P, Sciacca L, Mineo R, Costantino A, Goldfine ID, Belfiore A, Vigneri R (1999) Insulin receptor isoform A, a newly recognized, high-affinity insulin-like growth factor II receptor in fetal and cancer cells. Mol Cell Biol 19:3278–3288

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Goodwin PJ, Ennis M, Pritchard KI, Trudeau ME, Koo J, Madarnas Y, Hartwick W, Hoffman B, Hood N (2002) Fasting insulin and outcome in early-stage breast cancer: results of a prospective cohort study. J Clin Oncol 20:42–51

    Article  CAS  PubMed  Google Scholar 

  115. Coughlin SS, Calle EE, Teras LR, Petrelli J, Thun MJ (2004) Diabetes mellitus as a predictor of cancer mortality in a large cohort of US adults. Am J Epidemiol 159:1160–1167

    Article  PubMed  Google Scholar 

  116. Verlato G, Zoppini G, Bonora E, Muggeo M (2003) Mortality from site-specific malignancies in type 2 diabetic patients from verona. Diabetes Care 26:1047–1051

    Article  PubMed  Google Scholar 

  117. Kessler II (1970) Cancer mortality among diabetics. J Natl Cancer Inst 44:673–686

    CAS  PubMed  Google Scholar 

  118. Du W, Simon MS (2005) Racial disparities in treatment and survival of women with stage I-III breast cancer at a large academic medical center in metropolitan Detroit. Breast Cancer Res Treat 91:243–248

    Article  PubMed  Google Scholar 

  119. Lipscombe LL, Goodwin PJ, Zinman B, McLaughlin JR, Hux JE (2008) The impact of diabetes on survival following breast cancer. Breast Cancer Res Treat 109:389–395

    Article  PubMed  Google Scholar 

  120. Tammemagi CM, Nerenz D, Neslund-Dudas C, Feldkamp C, Nathanson D (2005) Comorbidity and survival disparities among black and white patients with breast cancer. JAMA 294:1765–1772

    Article  CAS  PubMed  Google Scholar 

  121. van de Poll-Franse LV, Houterman S, Janssen-Heijnen ML, Dercksen MW, Coebergh JW, Haak HR (2007) Less aggressive treatment and worse overall survival in cancer patients with diabetes: a large population based analysis. Int J Cancer 120:1986–1992

    Article  PubMed  CAS  Google Scholar 

  122. Yancik R, Wesley MN, Ries LA, Havlik RJ, Edwards BK, Yates JW (2001) Effect of age and comorbidity in postmenopausal breast cancer patients aged 55 years and older. JAMA 285:885–892

    Article  CAS  PubMed  Google Scholar 

  123. Barone BB, Yeh HC, Snyder CF, Peairs KS, Stein KB, Derr RL, Wolff AC, Brancati FL (2008) Long-term all-cause mortality in cancer patients with preexisting diabetes mellitus: a systematic review and meta-analysis. JAMA 300:2754–2764

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Louwman WJ, Janssen-Heijnen ML, Houterman S, Voogd AC, van der Sangen MJ, Nieuwenhuijzen GA, Coebergh JW (2005) Less extensive treatment and inferior prognosis for breast cancer patient with comorbidity: A population-based study. Eur J Cancer 41:779–785

    Article  CAS  PubMed  Google Scholar 

  125. Lipscombe LL, Hux JE, Booth GL (2005) Reduced screening mammography among women with diabetes. Arch Intern Med 165:2090–2095

    Article  PubMed  Google Scholar 

  126. Giovannucci E, Michaud D (2007) The role of obesity and related metabolic disturbances in cancers of the colon, prostate, and pancreas. Gastroenterology 132:2208–2225

    Article  CAS  PubMed  Google Scholar 

  127. Pischon T, Lahmann PH, Boeing H, Friedenreich C, Norat T, Tjonneland A, Halkjaer J, Overvad K, Clavel-Chapelon F, Boutron-Ruault MC, Guernec G, Bergmann MM, Linseisen J, Becker N, Trichopoulou A, Trichopoulos D, Sieri S, Palli D, Tumino R, Vineis P, Panico S, Peeters PH, Bueno-de-Mesquita HB, Boshuizen HC, Van GB, Palmqvist R, Berglund G, Gonzalez CA, Dorronsoro M, Barricarte A, Navarro C, Martinez C, Quiros JR, Roddam A, Allen N, Bingham S, Khaw KT, Ferrari P, Kaaks R, Slimani N, Riboli E (2006) Body size and risk of colon and rectal cancer in the European Prospective Investigation Into Cancer and Nutrition (EPIC). J Natl Cancer Inst 98:920–931

    Article  PubMed  Google Scholar 

  128. Schoen RE, Tangen CM, Kuller LH, Burke GL, Cushman M, Tracy RP, Dobs A, Savage PJ (1999) Increased blood glucose and insulin, body size, and incident colorectal cancer. J Natl Cancer Inst 91:1147–1154

    Article  CAS  PubMed  Google Scholar 

  129. Giovannucci E, Ascherio A, Rimm EB, Colditz GA, Stampfer MJ, Willett WC (1995) Physical activity, obesity, and risk for colon cancer and adenoma in men. Ann Intern Med 122:327–334

    Article  CAS  PubMed  Google Scholar 

  130. Bostick RM, Potter JD, Kushi LH, Sellers TA, Steinmetz KA, McKenzie DR, Gapstur SM, Folsom AR (1994) Sugar, meat, and fat intake, and non-dietary risk factors for colon cancer incidence in Iowa women (United States). Cancer Causes Control 5:38–52

    Article  CAS  PubMed  Google Scholar 

  131. Russo A, Franceschi S, La VC, Dal ML, Montella M, Conti E, Giacosa A, Falcini F, Negri E (1998) Body size and colorectal-cancer risk. Int J Cancer 78:161–165

    Article  CAS  PubMed  Google Scholar 

  132. Martinez ME, Giovannucci E, Spiegelman D, Stampfeer MJ, Hunter DJ, Speizer FE, Willett WC, Colditz GA (1996) Physical activity, body size, and colorectal cancer in women. Am J Epidemiol 143:S73

    Article  Google Scholar 

  133. Giovannucci E, Colditz GA, Stampfer MJ, Willett WC (1996) Physical activity, obesity, and risk of colorectal adenoma in women (United States). Cancer Causes Control 7:253–263

    Article  CAS  PubMed  Google Scholar 

  134. Trevisan M, Liu J, Muti P, Misciagna G, Menotti A, Fucci F (2001) Markers of insulin resistance and colorectal cancer mortality. Cancer Epidemiol Biomarkers Prev 10:937–941

    CAS  PubMed  Google Scholar 

  135. Colangelo LA, Gapstur SM, Gann PH, Dyer AR, Liu K (2002) Colorectal cancer mortality and factors related to the insulin resistance syndrome. Cancer Epidemiol Biomarkers Prev 11:385–391

    PubMed  Google Scholar 

  136. Ahmed RL, Schmitz KH, Anderson KE, Rosamond WD, Folsom AR (2006) The metabolic syndrome and risk of incident colorectal cancer. Cancer 107:28–36

    Article  PubMed  Google Scholar 

  137. Bowers K, Albanes D, Limburg P, Pietinen P, Taylor PR, Virtamo J, Stolzenberg-Solomon R (2006) A prospective study of anthropometric and clinical measurements associated with insulin resistance syndrome and colorectal cancer in male smokers. Am J Epidemiol 164:652–664

    Article  PubMed  Google Scholar 

  138. Yamada K, Araki S, Tamura M, Sakai I, Takahashi Y, Kashihara H, Kono S (1998) Relation of serum total cholesterol, serum triglycerides and fasting plasma glucose to colorectal carcinoma in situ. Int J Epidemiol 27:794–798

    Article  CAS  PubMed  Google Scholar 

  139. Saydah SH, Platz EA, Rifai N, Pollak MN, Brancati FL, Helzlsouer KJ (2003) Association of markers of insulin and glucose control with subsequent colorectal cancer risk. Cancer Epidemiol Biomarkers Prev 12:412–418

    CAS  PubMed  Google Scholar 

  140. Tsushima M, Nomura AM, Lee J, Stemmermann GN (2005) Prospective study of the association of serum triglyceride and glucose with colorectal cancer. Dig Dis Sci 50:499–505

    Article  PubMed  Google Scholar 

  141. Saydah SH, Loria CM, Eberhardt MS, Brancati FL (2003) Abnormal glucose tolerance and the risk of cancer death in the United States. Am J Epidemiol 157:1092–1100

    Article  PubMed  Google Scholar 

  142. Bayerdorffer E, Mannes GA, Richter WO, Ochsenkuhn T, Seeholzer G, Kopcke W, Wiebecke B, Paumgartner G (1993) Decreased high-density lipoprotein cholesterol and increased low-density cholesterol levels in patients with colorectal adenomas. Ann Intern Med 118:481–487

    Article  CAS  PubMed  Google Scholar 

  143. Park SK, Joo JS, Kim DH, Kim YE, Kang D, Yoo KY (2000) Association of serum lipids and glucose with the risk of colorectal adenomatous polyp in men: a case-control study in Korea. J Korean Med Sci 15:690–695

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Tabuchi M, Kitayama J, Nagawa H (2006) Hypertriglyceridemia is positively correlated with the development of colorectal tubular adenoma in Japanese men. World J Gastroenterol 12:1261–1264

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Wang YY, Lin SY, Lai WA, Liu PH, Sheu WH (2005) Association between adenomas of rectosigmoid colon and metabolic syndrome features in a Chinese population. J Gastroenterol Hepatol 20:1410–1415

    Article  PubMed  Google Scholar 

  146. Yang YX, Hennessy S, Lewis JD (2005) Type 2 diabetes mellitus and the risk of colorectal cancer. Clin Gastroenterol Hepatol 3:587–594

    Article  PubMed  Google Scholar 

  147. Kune GA, Kune S, Watson LF (1988) Colorectal cancer risk, chronic illnesses, operations, and medications: case control results from the Melbourne Colorectal Cancer Study. Cancer Res 48:4399–4404

    CAS  PubMed  Google Scholar 

  148. Le Marchand L, Wilkens LR, Kolonel LN, Hankin JH, Lyu LC (1997) Associations of sedentary lifestyle, obesity, smoking, alcohol use, and diabetes with the risk of colorectal cancer. Cancer Res 57:4787–4794

    PubMed  Google Scholar 

  149. La Vecchia C, Negri E, Decarli A, Franceschi S (1997) Diabetes mellitus and colorectal cancer risk. Cancer Epidemiol Biomarkers Prev 6:1007–1010

    PubMed  Google Scholar 

  150. Levi F, Pasche C, Lucchini F, La VC (2002) Diabetes mellitus, family history, and colorectal cancer. J Epidemiol Community Health 56:479–480

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Hu FB, Manson JE, Liu S, Hunter D, Colditz GA, Michels KB, Speizer FE, Giovannucci E (1999) Prospective study of adult onset diabetes mellitus (type 2) and risk of colorectal cancer in women. J Natl Cancer Inst 91:542–547

    Article  CAS  PubMed  Google Scholar 

  152. Weiderpass E, Gridley G, Nyren O, Ekbom A, Persson I, Adami HO (1997) Diabetes mellitus and risk of large bowel cancer. J Natl Cancer Inst 89:660–661

    Article  CAS  PubMed  Google Scholar 

  153. Steenland K, Hu S, Walker J (2004) All-cause and cause-specific mortality by socioeconomic status among employed persons in 27 US states, 1984–1997. Am J Public Health 94:1037–1042

    Article  PubMed  PubMed Central  Google Scholar 

  154. Will JC, Galuska DA, Vinicor F, Calle EE (1998) Colorectal cancer: another complication of diabetes mellitus? Am J Epidemiol 147:816–825

    Article  CAS  PubMed  Google Scholar 

  155. Nilsen TI, Vatten LJ (2001) Prospective study of colorectal cancer risk and physical activity, diabetes, blood glucose and BMI: exploring the hyperinsulinaemia hypothesis. Br J Cancer 84:417–422

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Seow A, Yuan JM, Koh WP, Lee HP, Yu MC (2006) Diabetes mellitus and risk of colorectal cancer in the Singapore Chinese Health Study. J Natl Cancer Inst 98:135–138

    Article  PubMed  Google Scholar 

  157. Khaw KT, Wareham N, Bingham S, Luben R, Welch A, Day N (2004) Preliminary communication: glycated hemoglobin, diabetes, and incident colorectal cancer in men and women: a prospective analysis from the European prospective investigation into cancer-Norfolk study. Cancer Epidemiol Biomarkers Prev 13:915–919

    PubMed  Google Scholar 

  158. Limburg PJ, Anderson KE, Johnson TW, Jacobs DR Jr, Lazovich D, Hong CP, Nicodemus KK, Folsom AR (2005) Diabetes mellitus and subsite-specific colorectal cancer risks in the Iowa Women’s Health Study. Cancer Epidemiol Biomarkers Prev 14:133–137

    PubMed  Google Scholar 

  159. Larsson SC, Giovannucci E, Wolk A (2005) Diabetes and colorectal cancer incidence in the cohort of Swedish men. Diabetes Care 28:1805–1807

    Article  PubMed  Google Scholar 

  160. Palmqvist R, Stattin P, Rinaldi S, Biessy C, Stenling R, Riboli E, Hallmans G, Kaaks R (2003) Plasma insulin, IGF-binding proteins-1 and -2 and risk of colorectal cancer: a prospective study in northern Sweden. Int J Cancer 107:89–93

    Article  CAS  PubMed  Google Scholar 

  161. Bonser AM, Garcia-Webb P (1984) C-peptide measurement: methods and clinical utility. Crit Rev Clin Lab Sci 19:297–352

    Article  CAS  PubMed  Google Scholar 

  162. Kaaks R, Toniolo P, Akhmedkhanov A, Lukanova A, Biessy C, Dechaud H, Rinaldi S, Zeleniuch-Jacquotte A, Shore RE, Riboli E (2000) 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

    Article  CAS  PubMed  Google Scholar 

  163. Ma J, Giovannucci E, Pollak M, Leavitt A, Tao Y, Gaziano JM, Stampfer MJ (2004) A prospective study of plasma C-peptide and colorectal cancer risk in men. J Natl Cancer Inst 96:546–553

    Article  CAS  PubMed  Google Scholar 

  164. Wei EK, Ma J, Pollak MN, Rifai N, Fuchs CS, Hankinson SE, Giovannucci E (2005) A prospective study of C-peptide, insulin-like growth factor-I, insulin-like growth factor binding protein-1, and the risk of colorectal cancer in women. Cancer Epidemiol Biomarkers Prev 14:850–855

    Article  CAS  PubMed  Google Scholar 

  165. Yang YX, Hennessy S, Lewis JD (2004) Insulin therapy and colorectal cancer risk among type 2 diabetes mellitus patients. Gastroenterology 127:1044–1050

    Article  CAS  PubMed  Google Scholar 

  166. Platz EA, Hankinson SE, Rifai N, Colditz GA, Speizer FE, Giovannucci E (1999) Glycosylated hemoglobin and risk of colorectal cancer and adenoma (United States). Cancer Causes Control 10:379–386

    Article  CAS  PubMed  Google Scholar 

  167. Smith GD, Egger M, Shipley MJ, Marmot MG (1992) Post-challenge glucose concentration, impaired glucose tolerance, diabetes, and cancer mortality in men. Am J Epidemiol 136:1110–1114

    Article  CAS  PubMed  Google Scholar 

  168. Shonka NA, Anderson JR, Panwalkar AW, Reed EC, Steen PD, Ganti AK (2006) Effect of diabetes mellitus on the epidemiology and outcomes of colon cancer. Med Oncol 23:515–519

    Article  PubMed  Google Scholar 

  169. Gross CP, Guo Z, McAvay GJ, Allore HG, Young M, Tinetti ME (2006) Multimorbidity and survival in older persons with colorectal cancer. J Am Geriatr Soc 54:1898–1904

    Article  PubMed  Google Scholar 

  170. Polednak AP (2006) Comorbid diabetes mellitus and risk of death after diagnosis of colorectal cancer: a population-based study. Cancer Detect Prev 30:466–472

    Article  PubMed  Google Scholar 

  171. Park SM, Lim MK, Shin SA, Yun YH (2006) Impact of prediagnosis smoking, alcohol, obesity, and insulin resistance on survival in male cancer patients: National Health Insurance Corporation Study. J Clin Oncol 24:5017–5024

    Article  PubMed  Google Scholar 

  172. Meyerhardt JA, Catalano PJ, Haller DG, Mayer RJ, Macdonald JS, Benson AB III, Fuchs CS (2003) Impact of diabetes mellitus on outcomes in patients with colon cancer. J Clin Oncol 21:433–440

    Article  PubMed  Google Scholar 

  173. Bardeesy N, DePinho RA (2002) Pancreatic cancer biology and genetics. Nat Rev Cancer 2:897–909

    Article  CAS  PubMed  Google Scholar 

  174. Bueno De Mesquita HB, Moerman CJ, Runia S, Maisonneuve P (1990) Are energy and energy-providing nutrients related to exocrine carcinoma of the pancreas? Int J Cancer 46:435–444

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  176. Howe GR, Ghadirian P, Bueno De Mesquita HB, Zatonski WA, Baghurst PA, Miller AB, Simard A, Baillargeon J, de Waard F, Przewozniak K (1992) A collaborative case-control study of nutrient intake and pancreatic cancer within the search programme. Int J Cancer 51:365–372

    Article  CAS  PubMed  Google Scholar 

  177. Michaud DS, Giovannucci E, Willett WC, Colditz GA, Stampfer MJ, Fuchs CS (2001) Physical activity, obesity, height, and the risk of pancreatic cancer. JAMA 286:921–929

    Article  CAS  PubMed  Google Scholar 

  178. Coughlin SS, Calle EE, Patel AV, Thun MJ (2000) Predictors of pancreatic cancer mortality among a large cohort of United States adults. Cancer Causes Control 11:915–923

    Article  CAS  PubMed  Google Scholar 

  179. Samanic C, Gridley G, Chow WH, Lubin J, Hoover RN, Fraumeni JF Jr (2004) Obesity and cancer risk among white and black United States veterans. Cancer Causes Control 15:35–43

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  181. Wolk A, Gridley G, Svensson M, Nyren O, McLaughlin JK, Fraumeni JF, Adam HO (2001) A prospective study of obesity and cancer risk (Sweden). Cancer Causes Control 12:13–21

    Article  CAS  PubMed  Google Scholar 

  182. Larsson SC, Permert J, Hakansson N, Naslund I, Bergkvist L, Wolk A (2005) Overall obesity, abdominal adiposity, diabetes and cigarette smoking in relation to the risk of pancreatic cancer in two Swedish population-based cohorts. Br J Cancer 93:1310–1315

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  183. Rapp K, Schroeder J, Klenk J, Stoehr S, Ulmer H, Concin H, Diem G, Oberaigner W, Weiland SK (2005) Obesity and incidence of cancer: a large cohort study of over 145,000 adults in Austria. Br J Cancer 93:1062–1067

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  184. Gapstur SM, Gann PH, Lowe W, Liu K, Colangelo L, Dyer A (2000) Abnormal glucose metabolism and pancreatic cancer mortality. JAMA 283:2552–2558

    Article  CAS  PubMed  Google Scholar 

  185. Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ (2003) Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med 348:1625–1638

    Article  PubMed  Google Scholar 

  186. Patel AV, Rodriguez C, Bernstein L, Chao A, Thun MJ, Calle EE (2004) Obesity, location of weight gain, and risk of pancreatic cancer in a large United States cohort. Am J Epidemiol 159:S67

    Article  Google Scholar 

  187. Silverman DT, Swanson CA, Gridley G, Wacholder S, Greenberg RS, Brown LM, Hayes RB, Swanson GM, Schoenberg JB, Pottern LM, Schwartz AG, Fraumeni JF Jr, Hoover RN (1998) Dietary and nutritional factors and pancreatic cancer: a case-control study based on direct interviews. J Natl Cancer Inst 90:1710–1719

    Article  CAS  PubMed  Google Scholar 

  188. Hanley AJ, Johnson KC, Villeneuve PJ, Mao Y (2001) Physical activity, anthropometric factors and risk of pancreatic cancer: results from the Canadian enhanced cancer surveillance system. Int J Cancer 94:140–147

    Article  CAS  PubMed  Google Scholar 

  189. Eberle CA, Bracci PM, Holly EA (2005) Anthropometric factors and pancreatic cancer in a population-based case-control study in the San Francisco Bay area. Cancer Causes Control 16:1235–1244

    Article  PubMed  Google Scholar 

  190. Pan SY, Johnson KC, Ugnat AM, Wen SW, Mao Y (2004) Association of obesity and cancer risk in Canada. Am J Epidemiol 159:259–268

    Article  PubMed  Google Scholar 

  191. Stolzenberg-Solomon RZ, Pietinen P, Taylor PR, Virtamo J, Albanes D (2002) A prospective study of medical conditions, anthropometry, physical activity, and pancreatic cancer in male smokers (Finland). Cancer Causes Control 13:417–426

    Article  PubMed  Google Scholar 

  192. Sinner PJ, Schmitz KH, Anderson KE, Folsom AR (2005) Lack of association of physical activity and obesity with incident pancreatic cancer in elderly women. Cancer Epidemiol Biomarkers Prev 14:1571–1573

    Article  PubMed  Google Scholar 

  193. de Berrington GA, Spencer EA, Bueno-de-Mesquita HB, Roddam A, Stolzenberg-Solomon R, Halkjaer J, Tjonneland A, Overvad K, Clavel-Chapelon F, Boutron-Ruault MC, Boeing H, Pischon T, Linseisen J, Rohrmann S, Trichopoulou A, Benetou V, Papadimitriou A, Pala V, Palli D, Panico S, Tumino R, Vineis P, Boshuizen HC, Ocke MC, Peeters PH, Lund E, Gonzalez CA, Larranaga N, Martinez-Garcia C, Mendez M, Navarro C, Quiros JR, Tormo MJ, Hallmans G, Ye W, Bingham SA, Khaw KT, Allen N, Key TJ, Jenab M, Norat T, Ferrari P, Riboli E (2006) Anthropometry, physical activity, and the risk of pancreatic cancer in the European prospective investigation into cancer and nutrition. Cancer Epidemiol Biomarkers Prev 15:879–885

    Article  Google Scholar 

  194. Isaksson B, Jonsson F, Pedersen NL, Larsson J, Feychting M, Permert J (2002) Lifestyle factors and pancreatic cancer risk: a cohort study from the Swedish Twin Registry. Int J Cancer 98:480–482

    Article  CAS  PubMed  Google Scholar 

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

    Article  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  197. Huxley R, Ansary-Moghaddam A, de GA Berrington, Barzi F, Woodward M (2005) Type-II diabetes and pancreatic cancer: a meta-analysis of 36 studies. Br J Cancer 92:2076–2083

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  198. Fisher WE, Muscarella P, Boros LG, Schirmer WJ (1998) Variable effect of streptozotocin-diabetes on the growth of hamster pancreatic cancer (H2T) in the Syrian hamster and nude mouse. Surgery 123:315–320

    Article  CAS  PubMed  Google Scholar 

  199. Fisher WE, Boros LG, Schirmer WJ (1996) Insulin promotes pancreatic cancer: evidence for endocrine influence on exocrine pancreatic tumors. J Surg Res 63:310–313

    Article  CAS  PubMed  Google Scholar 

  200. Pour PM, Stepan K (1984) Modification of pancreatic carcinogenesis in the hamster model. VIII. Inhibitory effect of exogenous insulin. J Natl Cancer Inst 72:1205–1208

    Article  CAS  PubMed  Google Scholar 

  201. Stolzenberg-Solomon RZ, Graubard BI, Chari S, Limburg P, Taylor PR, Virtamo J, Albanes D (2005) Insulin, glucose, insulin resistance, and pancreatic cancer in male smokers. JAMA 294:2872–2878

    Article  CAS  PubMed  Google Scholar 

  202. Michaud DS, Wolpin B, Giovannucci E, Liu S, Cochrane B, Manson JE, Pollak MN, Ma J, Fuchs CS (2007) Prediagnostic plasma C-peptide and pancreatic cancer risk in men and women. Cancer Epidemiol Biomarkers Prev 16:2101–2109

    Article  CAS  PubMed  Google Scholar 

  203. Pour PM, Kazakoff K (1996) Stimulation of islet cell proliferation enhances pancreatic ductal carcinogenesis in the hamster model. Am J Pathol 149:1017–1025

    CAS  PubMed  PubMed Central  Google Scholar 

  204. Schneider MB, Matsuzaki H, Haorah J, Ulrich A, Standop J, Ding XZ, Adrian TE, Pour PM (2001) Prevention of pancreatic cancer induction in hamsters by metformin. Gastroenterology 120:1263–1270

    Article  CAS  PubMed  Google Scholar 

  205. Pour PM, Donnelly K, Stepan K (1983) Modification of pancreatic carcinogenesis in the hamster model. 3. Inhibitory effect of alloxan. Am J Pathol 110:310–314

    CAS  PubMed  PubMed Central  Google Scholar 

  206. Nishikawa T, Edelstein D, Du XL, Yamagishi S, Matsumura T, Kaneda Y, Yorek MA, Beebe D, Oates PJ, Hammes HP, Giardino I, Brownlee M (2000) Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage. Nature 404:787–790

    Article  CAS  PubMed  Google Scholar 

  207. Cullen JJ, Weydert C, Hinkhouse MM, Ritchie J, Domann FE, Spitz D, Oberley LW (2003) The role of manganese superoxide dismutase in the growth of pancreatic adenocarcinoma. Cancer Res 63:1297–1303

    CAS  PubMed  Google Scholar 

  208. Cullen JJ, Mitros FA, Oberley LW (2003) Expression of antioxidant enzymes in diseases of the human pancreas: another link between chronic pancreatitis and pancreatic cancer. Pancreas 26:23–27

    Article  CAS  PubMed  Google Scholar 

  209. Batty GD, Shipley MJ, Marmot M, Smith GD (2004) Diabetes status and post-load plasma glucose concentration in relation to site-specific cancer mortality: findings from the original Whitehall study. Cancer Causes Control 15:873–881

    Article  PubMed  Google Scholar 

  210. Lew EA, Garfinkel L (1979) Variations in mortality by weight among 750,000 men and women. J Chron Dis 32:563–576

    Article  CAS  PubMed  Google Scholar 

  211. Snowdon DA, Phillips RL, Choi W (1984) Diet, obesity, and risk of fatal prostate cancer. Am J Epidemiol 120:244–250

    Article  CAS  PubMed  Google Scholar 

  212. Chyou PH, Nomura AM, Stemmermann GN (1994) A prospective study of weight, body mass index and other anthropometric measurements in relation to site-specific cancers. Int J Cancer 57:313–317

    Article  CAS  PubMed  Google Scholar 

  213. Thune I, Lund E (1994) Physical activity and the risk of prostate and testicular cancer: a cohort study of 53,000 Norwegian men. Cancer Causes Control 5:549–556

    Article  CAS  PubMed  Google Scholar 

  214. Cerhan JR, Torner JC, Lynch CF, Rubenstein LM, Lemke JH, Cohen MB, Lubaroff DM, Wallace RB (1997) Association of smoking, body mass, and physical activity with risk of prostate cancer in the Iowa 65+ Rural Health Study (United States). Cancer Causes Control 8:229–238

    Article  CAS  PubMed  Google Scholar 

  215. Veierod MB, Laake P, Thelle DS (1997) Dietary fat intake and risk of prostate cancer: a prospective study of 25,708 Norwegian men. Int J Cancer 73:634–638

    Article  CAS  PubMed  Google Scholar 

  216. Thompson MM, Garland C, Barrett-Connor E, Khaw KT, Friedlander NJ, Wingard DL (1989) Heart disease risk factors, diabetes, and prostatic cancer in an adult community. Am J Epidemiol 129:511–517

    Article  CAS  PubMed  Google Scholar 

  217. Whittemore AS, Paffenbarger RS Jr, Anderson K, Lee JE (1985) Early precursors of site-specific cancers in college men and women. J Natl Cancer Inst 74:43–51

    CAS  PubMed  Google Scholar 

  218. Greenwald P, Damon A, Kirmss V, Polan AK (1974) Physical and demographic features of men before developing cancer of the prostate. J Natl Cancer Inst 53:341–346

    Article  CAS  PubMed  Google Scholar 

  219. Le ML, Kolonel LN, Wilkens LR, Myers BC, Hirohata T (1994) Animal fat consumption and prostate cancer: a prospective study in Hawaii. Epidemiology 5:276–282

    Article  Google Scholar 

  220. Mills PK, Beeson WL, Phillips RL, Fraser GE (1989) Cohort study of diet, lifestyle, and prostate cancer in Adventist men. Cancer 64:598–604

    Article  CAS  PubMed  Google Scholar 

  221. Giovannucci E, Rimm EB, Stampfer MJ, Colditz GA, Willett WC (1997) Height, body weight, and risk of prostate cancer. Cancer Epidemiol Biomarkers Prev 6:557–563

    CAS  PubMed  Google Scholar 

  222. Putnam SD, Cerhan JR, Parker AS, Bianchi GD, Wallace RB, Cantor KP, Lynch CF (2000) Lifestyle and anthropometric risk factors for prostate cancer in a cohort of Iowa men. Ann Epidemiol 10:361–369

    Article  CAS  PubMed  Google Scholar 

  223. Habel LA, Van Den Eeden SK, Friedman GD (2000) Body size, age at shaving initiation, and prostate cancer in a large, multiracial cohort. Prostate 43:136–143

    Article  CAS  PubMed  Google Scholar 

  224. Nilsen TI, Vatten LJ (1999) Anthropometry and prostate cancer risk: a prospective study of 22,248 Norwegian men. Cancer Causes Control 10:269–275

    Article  CAS  PubMed  Google Scholar 

  225. Gapstur SM, Gann PH, Colangelo LA, Barron-Simpson R, Kopp P, Dyer A, Liu K (2001) Postload plasma glucose concentration and 27-year prostate cancer mortality (United States). Cancer Causes Control 12:763–772

    Article  CAS  PubMed  Google Scholar 

  226. Macinnis RJ, English DR (2006) Body size and composition and prostate cancer risk: systematic review and meta-regression analysis. Cancer Causes Control 17:989–1003

    Article  PubMed  Google Scholar 

  227. Macinnis RJ, English DR, Gertig DM, Hopper JL, Giles GG (2003) Body size and composition and prostate cancer risk. Cancer Epidemiol Biomarkers Prev 12:1417–1421

    PubMed  Google Scholar 

  228. Gong Z, Neuhouser ML, Goodman PJ, Albanes D, Chi C, Hsing AW, Lippman SM, Platz EA, Pollak MN, Thompson IM, Kristal AR (2006) Obesity, diabetes, and risk of prostate cancer: results from the prostate cancer prevention trial. Cancer Epidemiol Biomarkers Prev 15:1977–1983

    Article  PubMed  Google Scholar 

  229. Bradbury BD, Wilk JB, Kaye JA (2005) Obesity and the risk of prostate cancer (United States). Cancer Causes Control 16:637–641

    Article  PubMed  Google Scholar 

  230. Robinson WR, Stevens J, Gammon MD, John EM (2005) Obesity before age 30 years and risk of advanced prostate cancer. Am J Epidemiol 161:1107–1114

    Article  PubMed  Google Scholar 

  231. Porter MP, Stanford JL (2005) Obesity and the risk of prostate cancer. Prostate 62:316–321

    Article  PubMed  Google Scholar 

  232. Giovannucci E, Rimm EB, Liu Y, Leitzmann M, Wu K, Stampfer MJ, Willett WC (2003) Body mass index and risk of prostate cancer in U.S. health professionals. J Natl Cancer Inst 95:1240–1244

    Article  PubMed  Google Scholar 

  233. Schuurman AG, Goldbohm RA, Dorant E, van den Brandt PA (2000) Anthropometry in relation to prostate cancer risk in the Netherlands Cohort Study. Am J Epidemiol 151:541–549

    Article  CAS  PubMed  Google Scholar 

  234. Tan RS, Pu SJ (2002) Impact of obesity on hypogonadism in the andropause. Int J Androl 25:195–201

    Article  CAS  PubMed  Google Scholar 

  235. Thompson IM, Goodman PJ, Tangen CM, Lucia MS, Miller GJ, Ford LG, Lieber MM, Cespedes RD, Atkins JN, Lippman SM, Carlin SM, Ryan A, Szczepanek CM, Crowley JJ, Coltman CA Jr (2003) The influence of finasteride on the development of prostate cancer. N Engl J Med 349:215–224

    Article  CAS  PubMed  Google Scholar 

  236. Schatzl G, Madersbacher S, Thurridl T, Waldmuller J, Kramer G, Haitel A, Marberger M (2001) High-grade prostate cancer is associated with low serum testosterone levels. Prostate 47:52–58

    Article  CAS  PubMed  Google Scholar 

  237. Platz EA, Leitzmann MF, Rifai N, Kantoff PW, Chen YC, Stampfer MJ, Willett WC, Giovannucci E (2005) Sex steroid hormones and the androgen receptor gene CAG repeat and subsequent risk of prostate cancer in the prostate-specific antigen era. Cancer Epidemiol Biomarkers Prev 14:1262–1269

    Article  CAS  PubMed  Google Scholar 

  238. Severi G, Morris HA, Macinnis RJ, English DR, Tilley W, Hopper JL, Boyle P, Giles GG (2006) Circulating steroid hormones and the risk of prostate cancer. Cancer Epidemiol Biomarkers Prev 15:86–91

    Article  CAS  PubMed  Google Scholar 

  239. Adami HO, McLaughlin J, Ekbom A, Berne C, Silverman D, Hacker D, Persson I (1991) Cancer risk in patients with diabetes mellitus. Cancer Causes Control 2:307–314

    Article  CAS  PubMed  Google Scholar 

  240. Giovannucci E, Rimm EB, Stampfer MJ, Colditz GA, Willett WC (1998) Diabetes mellitus and risk of prostate cancer (United States). Cancer Causes Control 9:3–9

    Article  CAS  PubMed  Google Scholar 

  241. Weiderpass E, Ye W, Vainio H, Kaaks R, Adami HO (2002) Reduced risk of prostate cancer among patients with diabetes mellitus. Int J Cancer 102:258–261

    Article  CAS  PubMed  Google Scholar 

  242. Kasper JS, Giovannucci E (2006) A meta-analysis of diabetes mellitus and the risk of prostate cancer. Cancer Epidemiol Biomarkers Prev 15:2056–2062

    Article  PubMed  Google Scholar 

  243. Ando S, Rubens R, Rottiers R (1984) Androgen plasma levels in male diabetics. J Endocrinol Invest 7:21–24

    Article  CAS  PubMed  Google Scholar 

  244. Tavani A, Gallus S, Bosetti C, Tzonou A, Lagiou P, Negri E, Trichopoulos D, La VC (2002) Diabetes and the risk of prostate cancer. Eur J Cancer Prev 11:125–128

    Article  CAS  PubMed  Google Scholar 

  245. Rodriguez C, Patel AV, Mondul AM, Jacobs EJ, Thun MJ, Calle EE (2005) Diabetes and risk of prostate cancer in a prospective cohort of US men. Am J Epidemiol 161:147–152

    Article  PubMed  Google Scholar 

  246. Lund HL, Wisloff TF, Holme I, Nafstad P (2006) Metabolic syndrome predicts prostate cancer in a cohort of middle-aged Norwegian men followed for 27 years. Am J Epidemiol 164:769–774

    Article  Google Scholar 

  247. Laukkanen JA, Laaksonen DE, Niskanen L, Pukkala E, Hakkarainen A, Salonen JT (2004) Metabolic syndrome and the risk of prostate cancer in Finnish men: a population-based study. Cancer Epidemiol Biomarkers Prev 13:1646–1650

    CAS  PubMed  Google Scholar 

  248. Hsing AW, Chua S Jr, Gao YT, Gentzschein E, Chang L, Deng J, Stanczyk FZ (2001) Prostate cancer risk and serum levels of insulin and leptin: a population-based study. J Natl Cancer Inst 93:783–789

    Article  CAS  PubMed  Google Scholar 

  249. Hammarsten J, Hogstedt B (2005) Hyperinsulinaemia: a prospective risk factor for lethal clinical prostate cancer. Eur J Cancer 41:2887–2895

    Article  CAS  PubMed  Google Scholar 

  250. Lehrer S, Diamond EJ, Stagger S, Stone NN, Stock RG (2002) Increased serum insulin associated with increased risk of prostate cancer recurrence. Prostate 50:1–3

    Article  PubMed  Google Scholar 

  251. Stattin P, Bylund A, Rinaldi S, Biessy C, Dechaud H, Stenman UH, Egevad L, Riboli E, Hallmans G, Kaaks R (2000) 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

    Article  CAS  PubMed  Google Scholar 

  252. Tande AJ, Platz EA, Folsom AR (2006) The metabolic syndrome is associated with reduced risk of prostate cancer. Am J Epidemiol 164:1094–1102

    Article  PubMed  Google Scholar 

  253. Larsson SC, Orsini N, Brismar K, Wolk A (2006) Diabetes mellitus and risk of bladder cancer: a meta-analysis. Diabetologia 49:2819–2823

    Article  CAS  PubMed  Google Scholar 

  254. Dunn SE, Kari FW, French J, Leininger JR, Travlos G, Wilson R, Barrett JC (1997) Dietary restriction reduces insulin-like growth factor I levels, which modulates apoptosis, cell proliferation, and tumor progression in p53-deficient mice. Cancer Res 57:4667–4672

    CAS  PubMed  Google Scholar 

  255. Zhao H, Grossman HB, Spitz MR, Lerner SP, Zhang K, Wu X (2003) Plasma levels of insulin-like growth factor-1 and binding protein-3, and their association with bladder cancer risk. J Urol 169:714–717

    Article  CAS  PubMed  Google Scholar 

  256. Tripathi A, Folsom AR, Anderson KE (2002) Risk factors for urinary bladder carcinoma in postmenopausal women. The Iowa Women’s Health Study. Cancer 95:2316–2323

    Article  PubMed  Google Scholar 

  257. Joshi N, Caputo GM, Weitekamp MR, Karchmer AW (1999) Infections in patients with diabetes mellitus. N Engl J Med 341:1906–1912

    Article  CAS  PubMed  Google Scholar 

  258. Kravchick S, Gal R, Cytron S, Peled R, Weissman Y, Mukamel E, Koren R (2001) Increased incidence of diabetes mellitus in the patients with transitional cell carcinoma of urinary bladder. Pathol Oncol Res 7:56–59

    Article  CAS  PubMed  Google Scholar 

  259. Friberg E, Orsini N, Mantzoros CS, Wolk A (2007) Diabetes mellitus and risk of endometrial cancer: a meta-analysis. Diabetologia 50:1365–1374

    Article  CAS  PubMed  Google Scholar 

  260. Key TJ, Pike MC (1988) The dose-effect relationship between ‘unopposed’ oestrogens and endometrial mitotic rate: its central role in explaining and predicting endometrial cancer risk. Br J Cancer 57:205–212

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  261. Ferenczy A, Bertrand G, Gelfand MM (1979) Proliferation kinetics of human endometrium during the normal menstrual cycle. Am J Obstet Gynecol 133:859–867

    Article  CAS  PubMed  Google Scholar 

  262. Lukanova A, Zeleniuch-Jacquotte A, Lundin E, Micheli A, Arslan AA, Rinaldi S, Muti P, Lenner P, Koenig KL, Biessy C, Krogh V, Riboli E, Shore RE, Stattin P, Berrino F, Hallmans G, Toniolo P, Kaaks R (2004) Prediagnostic levels of C-peptide, IGF-I, IGFBP -1, -2 and -3 and risk of endometrial cancer. Int J Cancer 108:262–268

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Lorraine Lipscombe .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Lipscombe, L. (2011). Insulin, Insulin Resistance, and Cancer Associations. In: Fantus, I. (eds) Insulin Resistance and Cancer. Energy Balance and Cancer, vol 1. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-9911-5_5

Download citation

  • DOI: https://doi.org/10.1007/978-1-4419-9911-5_5

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4419-9910-8

  • Online ISBN: 978-1-4419-9911-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics