Skip to main content
SpringerLink
Log in

Obesity and Cancer: Overview of Mechanisms

  • Chapter
  • First Online:
Cancer and Energy Balance, Epidemiology and Overview

Part of the book series: Energy Balance and Cancer ((EBAC,volume 2))

Abstract

This chapter provides an overview of the putative pathophysiological mechanisms explaining the positive association between obesity and various cancers. After presenting each of the major factors and pathways involved in obesity-related carcinogenesis and their potential synergisms from a physiological, epidemiological and mechanistic perspective, we conclude with a discussion of the therapeutic opportunities to reduce obesity and obesity-related cancers.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
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. Caterson ID, Gill TP (2002). Obesity: epidemiology and possible prevention. Best Prac Res Clin Endocrinol Metab, 16:595–610.

    Google Scholar 

  2. Ogden CL, Carroll MD, Curtin LR et al. (2008). Prevalence of overweight and obesity in the United States, 1999–2004. JAMA, 295:1549–55.

    Google Scholar 

  3. World Health Organization (2003). World Cancer Report. IARC Nonserial Publication, Geneva, Switzerland.

    Google Scholar 

  4. Ogden CL, Yanvoski SZ, Carroll MD et al. (2007). The epidemiology of obesity. Gastroenterology, 132:2087–102.

    PubMed  Google Scholar 

  5. World Health Organization (2000). Obesity: Preventing and Managing the Global Epidemic. Report of a WHO Consultation. Rep. 894, World Health Organization, Geneva.

    Google Scholar 

  6. World Cancer Research Fund and American Institute for Cancer Research (2007). Food, Nutrition, Physical Activity, and the Prevention of Cancer: a Global Perspective. AICR, Washington, DC.

    Google Scholar 

  7. Renehan AG, Tyson M, Egger M et al. (2008). Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet. 371: 569–78.

    PubMed  Google Scholar 

  8. Calle EE, Rodriquez C, Walker-Thurmond K et al. (2003). Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med, 348:1625–38.

    PubMed  Google Scholar 

  9. Li D, Morris JS, Liu J et al. (2009). Body mass index and risk, age of onset, and survival in patients with pancreatic cancer. JAMA, 301:2553–62.

    CAS  PubMed  Google Scholar 

  10. Freedland SJ, Platz EA (2007). Obesity and prostate cancer: making sense out of apparently conflicting data. Epidemiol Rev, 29:88–97.

    PubMed  Google Scholar 

  11. Chia VM, Newcomb PA, Trentham-Dietz A et al. (2007). Obesity, diabetes, and other factors in relation to survival after endometrial cancer diagnosis. Int J Gynecol Cancer, 17: 441–6.

    CAS  PubMed  Google Scholar 

  12. Lane G (2008). Obesity and gynaecological cancer. Menopause Int, 14:33–7.

    PubMed  Google Scholar 

  13. Reeves GK, Pirie K, Beral V et al. (2007). Cancer incidence and mortality in relation to body mass index in the Million Women Study: cohort study. BMJ, 335:1134.

    PubMed  Google Scholar 

  14. Caan BJ, Kwan ML, Hartzell G et al. (2008). Pre-diagnosis body mass index, post-diagnosis weight change, and prognosis among women with early stage breast cancer. Cancer Causes Control, 19:1319–28.

    PubMed  Google Scholar 

  15. Carmichael AR (2006). Obesity and prognosis of breast cancer. Obesity Rev, 7:333–40.

    CAS  Google Scholar 

  16. Dignam JJ, Polite BN, Yothers G et al. (2006). Body mass index and outcomes in patients who receive adjuvant chemotherapy for colon cancer. J Natl Cancer Inst, 98:1647–54.

    PubMed  Google Scholar 

  17. Kristal AR, Gong Z (2007). Obesity and prostate cancer mortality. Future Oncol, 3:557–67.

    PubMed  Google Scholar 

  18. Dirx MJ, Zeegers MP, Dagnelie PC et al. (2003). Energy restriction and the risk of spontaneous mammary tumors in mice: a meta-analysis Int J Cancer, 106:766–70.

    CAS  PubMed  Google Scholar 

  19. Calle EE, Kaaks R (2004). Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Nat Rev Cancer, 4:579–91.

    CAS  PubMed  Google Scholar 

  20. Clark JM (2006). The epidemiology of nonalcoholic fatty liver disease in adults. J Clin Gastroenterol, 40:S5–S10.

    PubMed  Google Scholar 

  21. Anand G, Katz PO (2008). Gastroesophageal reflux disease and obesity. Rev Gastroenterol Disord, 8:233–9.

    PubMed  Google Scholar 

  22. Nordenstedt H, Lagergren J (2008). Environmental factors in the etiology of gastroesophageal reflux disease. Expert Rev Gastroenterol Hepatol, 2:93–103.

    PubMed  Google Scholar 

  23. Rabinowitz D, Zierler KL (1962). Forearm metabolism in obesity and its response to intra-arterial insulin. Characterization of insulin resistance and evidence for adaptive hyperinsulinism. J Clin Invest, 41:2173–81.

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  25. Allen NE, Appleby PN, Kaaks R et al. (2003). 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.

    PubMed  Google Scholar 

  26. Lukanova A, Zeleniuch-Jacquotte A, Lundin E et al. (2004). Prediagnostic levels of C-peptide, IGF-I, IGFBP -1, -2 and -3 and risk of endometrial cancer. Int J Cancer, 108:262–8.

    CAS  PubMed  Google Scholar 

  27. Schairer C, Hill D, Sturgeon SR et al. (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, 108:773–9.

    CAS  PubMed  Google Scholar 

  28. Ma J, Giovannucci E, Pollak M et al. (2004). A prospective study of plasma C-peptide and colorectal cancer risk in men. J Natl Cancer Inst, 96:546–53.

    CAS  PubMed  Google Scholar 

  29. Michaud DS, Wolpin B, Giovannucci E et al. (2007). Prediagnostic plasma C-peptide and pancreatic cancer risk in men and women. Cancer Epidemiol Biomarkers Prev, 16:2101–9.

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  31. Carling D (2004). The AMP-activated protein kinase cascade–a unifying system for energy control. Trends Biochem Sci, 29:18–24.

    CAS  PubMed  Google Scholar 

  32. Renehan AG, Frystyk J, Flyvbjerg A (2006). Obesity and cancer risk: the role of the insulin-IGF axis. Trends Endocrinol Metab, 17:328–36.

    CAS  PubMed  Google Scholar 

  33. Björnholm M, Al-Khalili L, Dicker A et al. (2002). Insulin signal transduction and glucose transport in human adipocytes: effects of obesity and low calorie diet. Diabetologia, 45:1128–35.

    PubMed  Google Scholar 

  34. Vanhaesebroeck B, Alessi DR (2000). The PI3K-PDK1 connection: more than just a road to PKB. Biochem J, 346:561–76.

    CAS  PubMed  Google Scholar 

  35. Rosner M, Hanneder M, Siegel N et al. (2008). The mTOR pathway and its role in human genetic diseases. Mutat Res, 659:284–92.

    CAS  PubMed  Google Scholar 

  36. Wang W, Guan KL (2009). AMP-activated protein kinase and cancer. Acta Physiol (Oxf), 196:55–63.

    CAS  Google Scholar 

  37. Singh A, Hamilton-Fairley D, Koistinen R et al. (1990). Effect of insulin-like growth factor-type I (IGF-I) and insulin on the secretion of sex hormone binding globulin and IGF-I binding protein (IBP-I) by human hepatoma cells. J Endocrinol, 124:3.

    Google Scholar 

  38. Marelli MM, Moretti RM, Procacci P et al. (2006). Insulin-like growth factor-I promotes migration in human androgen-independent prostate cancer cells via the alphavbeta3 integrin and PI3-K/Akt signaling. Int J Oncol, 28:723–30.

    CAS  Google Scholar 

  39. Clemmons DR (2006). Involvement of insulin-like growth factor-I in the control of glucose homeostasis. Curr Opin Pharmacol, 6:620–5.

    CAS  PubMed  Google Scholar 

  40. Le Roith D, Scavo L, Butler A (2001). What is the role of circulating IGF-I? Trends Endocrinol Metab, 12:48–52.

    CAS  PubMed  Google Scholar 

  41. Le Roith D, Bondy C, Yakar S et al. (2001). The somatomedin hypothesis: 2001. Endocr Rev, 22:53–74.

    PubMed  Google Scholar 

  42. Allen NE, Roddam AW, Allen DS, Fentiman IS et al. (2005). A prospective study of serum insulin-like growth factor-I (IGF-I), IGF-II, IGF-binding protein-3 and breast cancer risk Br J Cancer. 92:1283–7.

    CAS  PubMed  Google Scholar 

  43. Kim HS, Ingermann AR, Tsubaki J et al. (2004). Insulin-like growth factor binding protein 3 induces caspase-dependent apoptosis through a death receptor-mediated pathway in MCF-7 human breast cancer cells. Cancer Res. 64:2229–37.

    CAS  PubMed  Google Scholar 

  44. Sandhu MS, Gibson JM, Heald AH et al. (2004). Association between insulin-like growth factor-I: insulin-like growth factor-binding protein-1 ratio and metabolic and anthropometric factors in men and women. Cancer Epidemiol Biomarkers Prev, 13:166–70.

    CAS  PubMed  Google Scholar 

  45. Frystyk J, Skjaerbaek C, Vestbo E et al. (1999). Circulating levels of free insulin-like growth factors in obese subjects: the impact of type 2 diabetes. Diabetes Metab Res Rev, 15:314–22.

    CAS  PubMed  Google Scholar 

  46. Holmes MD, Pollak MN, Hankinson SE (2002). Lifestyle correlates of plasma insulin-like growth factor I and insulin-like growth factor binding protein 3 concentrations. Cancer Epidemiol Biomarkers Prev, 11:862–7.

    CAS  PubMed  Google Scholar 

  47. Renehan AG, Zwahlen M, Minder C et al. (2004). Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis. Lancet, 363:1346–53.

    CAS  PubMed  Google Scholar 

  48. Giovannucci E (2001). Insulin, insulin-like growth factors and colon cancer: a review of the evidence. J Nutr, 131:3109S–20S.

    CAS  PubMed  Google Scholar 

  49. Renehan AG, Harvie M, Howell A (2006). Insulin-like growth factor (IGF)-I, IGF binding protein-3, and breast cancer risk: eight years on. Endocr Relat Cancer, 13:273–8.

    CAS  PubMed  Google Scholar 

  50. Nakae J, Kido Y, Accili D (2001). Distinct and overlapping functions of insulin and IGF-I receptors. Endocr Rev, 22:818–35.

    CAS  PubMed  Google Scholar 

  51. Hursting SD, Lavigne JA, Berrigan D et al. (2003). Calorie restriction, aging, and cancer prevention: mechanisms of action and applicability to humans. Annu Rev Med, 54:131–52.

    CAS  PubMed  Google Scholar 

  52. LeRoith D, Roberts CT Jr. (2003). The insulin-like growth factor system and cancer. Cancer Lett, 195:127–37.

    CAS  PubMed  Google Scholar 

  53. Buckbinder L, Talbott R, Velasco-Miguel S et al. (1995). Induction of the growth inhibitor IGF-binding protein 3 by p53. Nature, 377:646–9.

    CAS  PubMed  Google Scholar 

  54. Takahashi K, Suzuki K (1993). Association of insulin-like growth-factor-I-induced DNA synthesis with phosphorylation and nuclear exclusion of p53 in human breast cancer MCF-7 cells. Int J Cancer, 55:453–8.

    CAS  PubMed  Google Scholar 

  55. Karver KC, Schuler LA (2008). Prolactin does not require insulin-like growth factor intermediates but synergizes with insulin-like growth factor I in human breast cancer cells. Mol Cancer Res, 6:634–43.

    Google Scholar 

  56. Saxena NK, Taliaferro-Smith L, Knight BB et al. (2008). Bidirectional crosstalk between leptin and insulin-like growth factor-I signaling promotes invasion and migration of breast cancer cells via transactivation of epidermal growth factor receptor. Cancer Res, 68:9712–22.

    CAS  PubMed  Google Scholar 

  57. Yee D, Lee AV (2000). Crosstalk between the insulin-like growth factors and estrogens in breast cancer. Mammary Gland Biol Neoplasia, 5:107–15.

    CAS  Google Scholar 

  58. Lee AV, Jackson JG, Gooch JL et al. (1999). Enhancement of insulin-like growth factor signaling in human breast cancer: estrogen regulation of insulin receptor substrate-1 expression in vitro and in vivo. Mol Endocrinol, 13:787–96.

    CAS  PubMed  Google Scholar 

  59. Sinha-Hikim I, Taylor WE, Gonzalez-Cadavid NF et al. (2004). Androgen Receptor in Human Skeletal Muscle and Cultured Muscle Satellite Cells: Up-Regulation by Androgen Treatment. J Clin Endocrinol Metab, 89:5245–55.

    CAS  PubMed  Google Scholar 

  60. Ray R, Novotny NM, Crisostomo PR et al. (2008). Sex steroids and stem cell function. Mol Med, 14:493–501.

    CAS  PubMed  Google Scholar 

  61. Key TJ, Allen NE, Verkasalo PK et al. (2001). Energy balance and cancer: the role of sex hormones. Proc Nutr Soc, 60:81–9.

    CAS  PubMed  Google Scholar 

  62. Key TJ, Appleby PN, Reeves GK et al. (2003). Body mass index, serum sex hormones, and breast cancer risk in postmenopausal women. J Natl Cancer Inst, 95:1218–26.

    CAS  PubMed  Google Scholar 

  63. Derby CA, Zilber S, Brambilla D et al. (2006). Body mass index, waist circumference and waist to hip ratio and change in sex steroid hormones: the Massachusetts Male Ageing Study. Clin Endocrinol (Oxf), 65:125–31.

    CAS  Google Scholar 

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

    Google Scholar 

  65. Franks S, Kiddy DS, Hamilton-Fairley D et al. (1991). The role of nutrition and insulin in the regulation of sex hormone binding globulin. J Steroid Biochem Mol Biol, 39:835–8.

    CAS  PubMed  Google Scholar 

  66. McTiernan A, Rajan KB, Tworoger SS et al. (2003). Adiposity and sex hormones in postmenopausal breast cancer survivors. J Clin Oncol, 21:1961–6.

    CAS  PubMed  Google Scholar 

  67. Jen KL, Djuric Z, DiLaura NM et al. (2004). Improvement of metabolism among obese breast cancer survivors in differing weight loss regimens. Obes Res, 12:306–12.

    PubMed  Google Scholar 

  68. Kaaks R, Berrino F, Key T et al. (2005). Serum sex steroids in premenopausal women and breast cancer risk within the European Prospective Investigation into Cancer and Nutrition (EPIC). J Natl Cancer Inst, 97:755–65.

    CAS  PubMed  Google Scholar 

  69. Kaaks R, Lukanova A, Kurzer MS (2002). Obesity, endogenous hormones, and endometrial cancer risk: a synthetic review. Cancer Epidemiol Biomarkers Prev, 11:1531–43.

    CAS  PubMed  Google Scholar 

  70. Endogenous Hormones and Prostate Cancer Collaborative Group, Roddam AW, Allen NE et al. (2008). Endogenous sex hormones and prostate cancer: a collaborative analysis of 18 prospective studies. J Natl Cancer Inst, 100:170–83.

    Google Scholar 

  71. Hsing AW, Chu LW, Stanczyk FZ (2008). Androgen and prostate cancer: is the hypothesis dead? Cancer Epidemiol Biomarkers Prev, 17:2525–30.

    CAS  PubMed  Google Scholar 

  72. Hsing AW, Sakoda LC, Chua SC Jr. (2007). Obesity, metabolic syndrome, and prostate cancer. Am J Clin Nutr, 86:S857.

    Google Scholar 

  73. O’Connor KA, Ferrell RJ, Brindle E et al. (2009). Total and unopposed estrogen exposure across stages of the transition to menopause. Cancer Epidemiol Biomarkers Prev, 18:828–36.

    PubMed  Google Scholar 

  74. Liao DJ, Dickson RB (2002). Roles of androgens in the development, growth, and carcinogenesis of the mammary gland. J Steroid Biochem Mol Biol, 80:175–89.

    CAS  PubMed  Google Scholar 

  75. Risch HA (1998). Hormonal etiology of epithelial ovarian cancer, with a hypothesis concerning the role of androgens and progesterone. J Natl Cancer Inst, 90:1774–86.

    CAS  PubMed  Google Scholar 

  76. Olsen CM, Green AC, Nagle CM et al. (2008). Epithelial ovarian cancer: testing the ‘androgens hypothesis’. Endocr Relat Cancer, 15:1061–8.

    CAS  PubMed  Google Scholar 

  77. Debes JD, Tindall DJ (2002). The role of androgens and the androgen receptor in prostate cancer. Cancer Lett, 187:1–7.

    CAS  PubMed  Google Scholar 

  78. Mellado B, Codony J, Ribal MJ et al. (2009). Molecular biology of androgen-independent prostate cancer: the role of the androgen receptor pathway. Clin Transl Oncol, 11:5–10.

    CAS  PubMed  Google Scholar 

  79. Zhang J, Sun Y, Liu Y et al. (2004). Synergistic effects of androgen and estrogen on the mouse uterus and mammary gland. Oncol Rep, 12:709–16.

    CAS  PubMed  Google Scholar 

  80. Ho SM, Leav I, Merk FB et al. (1995). Induction of atypical hyperplasia, apoptosis, and type II estrogen-binding sites in the ventral prostates of Noble rats treated with testosterone and pharmacologic doses of estradiol-17 beta. Lab Invest, 73:356–65.

    CAS  PubMed  Google Scholar 

  81. Mawson A, Lai A, Carroll JS et al. (2005). Estrogen and insulin/IGF-1 cooperatively stimulate cell cycle progression in MCF-7 breast cancer cells through differential regulation of c-My and cyclin D1. Mol Cell Endocrinol, 229:161–73.

    CAS  PubMed  Google Scholar 

  82. MacDougald OA, Burant CF (2007). The rapidly expanding family of adipokines. Cell Metab, 6:159–61.

    CAS  PubMed  Google Scholar 

  83. Considine RV, Sinha MK, Heiman ML et al. (1996). Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med, 334:292–5.

    CAS  PubMed  Google Scholar 

  84. Guerra B, Santana A, Fuentes T et al. (2007). Leptin receptors in human skeletal muscle. J Appl Physiol, 102:1786–92.

    CAS  PubMed  Google Scholar 

  85. Trayhurn P, Bing C (2006). Appetite and energy balance signals from adipocytes. Philos Trans R Soc Lond B Biol Sci, 361:1237–49.

    CAS  PubMed  Google Scholar 

  86. Blüher S, Mantzoros CS (2007). Leptin in reproduction. Curr Opin Endocrinol Diabetes Obes, 14:458–64.

    PubMed  Google Scholar 

  87. Maya-Monteiro CM, Bozza PT (2008). Leptin and mTOR: partners in metabolism and inflammation. Cell Cycle, 7:1713–7.

    CAS  PubMed  Google Scholar 

  88. Baratta M (2002). Leptin – from a signal of adiposity to a hormonal mediator in peripheral tissues. Med Sci Monit, 8:RA282–RA292.

    CAS  PubMed  Google Scholar 

  89. Zhang Y, Proenca R, Maffei M et al. (1994). Positional cloning of the mouse obese gene and its human homologue. Nature, 372:425–32.

    CAS  PubMed  Google Scholar 

  90. Ingalls AM, Dickie MM, Snell GD (1950). Obese, a new mutation in the house mouse. J Hered, 41:317–8.

    CAS  PubMed  Google Scholar 

  91. Considine RV, Sinha MK, Heiman ML et al. (1996). Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med, 334:292–5.

    CAS  PubMed  Google Scholar 

  92. Schäffler A, Schölmerich J, Buechler C (2007). Mechanisms of disease: adipokines and breast cancer – endocrine and paracrine mechanisms that connect adiposity and breast cancer. Nat Clin Pract Endocrinol Metab, 3:345–54.

    PubMed  Google Scholar 

  93. Magni P, Liuzzi A, Ruscica M et al. (2005). Free and bound plasma leptin in normal weight and obese men and women: relationship with body composition, resting energy expenditure, insulin-sensitivity, lipid profile and macronutrient preference. Clin Endocrinol (Oxf), 62:189–96.

    CAS  Google Scholar 

  94. Smith SR, Lovejoy JC, Greenway F et al. (2001). Contributions of total body fat, abdominal subcutaneous adipose tissue compartments, and visceral adipose tissue to the metabolic complications of obesity. Metabolism, 50:425–35.

    CAS  PubMed  Google Scholar 

  95. Vona-Davis L, Rose DP (2007). Adipokines as endocrine, paracrine, and autocrine factors in breast cancer risk and progression. Endocr Relat Cancer, 14:189–206.

    CAS  PubMed  Google Scholar 

  96. Cymbaluk A, Chudecka-Glaz A, Rzepka-Górska I (2008). Leptin levels in serum depending on Body Mass Index in patients with endometrial hyperplasia and cancer. Eur J Obstet Gynecol Reprod Biol, 136:74–7.

    CAS  PubMed  Google Scholar 

  97. Mistry T, Digby JE, Desai KM et al. (2007). Obesity and prostate cancer: a role for adipokines. Eur Urol, 52:46–53.

    CAS  PubMed  Google Scholar 

  98. Stattin P, Kaaks R, Johansson R et al. (2003). Plasma leptin is not associated with prostate cancer risk. Cancer Epidemiol Biomarkers Prev, 12:474–5.

    CAS  PubMed  Google Scholar 

  99. Stattin P, Palmqvist R, Söderberg S et al. (2003). Plasma leptin and colorectal cancer risk: a prospective study in Northern Sweden. Oncol Rep, 10:2015–21.

    PubMed  Google Scholar 

  100. Stattin P, Lukanova A, Biessy C et al. (2004). Obesity and colon cancer: does leptin provide a link? Int J Cancer, 109:149–52.

    CAS  PubMed  Google Scholar 

  101. Chia VM, Newcomb PA, Lampe JW et al. (2007). Leptin concentrations, leptin receptor polymorphisms, and colorectal adenoma risk. Cancer Epidemiol Biomarkers Prev, 16:2697–703.

    CAS  PubMed  Google Scholar 

  102. Kumor A, Daniel P, Pietruczuk M et al. (2009). Serum leptin, adiponectin, and resistin concentration in colorectal adenoma and carcinoma (CC) patients. Int J Colorectal Dis, 24:275–81.

    PubMed  Google Scholar 

  103. Hoda MR, Keely SJ, Bertelsen LS et al. (2007). Leptin acts as a mitogenic and antiapoptotic factor for colonic cancer cells. Br J Surg, 94:346–54.

    CAS  PubMed  Google Scholar 

  104. Birmingham JM, Busik JV, Hansen-Smith FM et al. (2009). Novel mechanism for obesity-induced colon cancer progression. Carcinogenesis, 30:690–7.

    CAS  PubMed  Google Scholar 

  105. Kendall BJ, Macdonald GA, Hayward NK et al. (2008). Leptin and the risk of Barrett’s oesophagus. Gut, 57:448–54.

    CAS  PubMed  Google Scholar 

  106. Orel M, Lichnovská R, Gwozdziewiczová S et al. (2004). Gender differences in tumor necrosis factor alpha and leptin secretion from subcutaneous and visceral fat tissue. Physiol Res, 53:501–5.

    CAS  PubMed  Google Scholar 

  107. Catalona S, Marsico S, Giordano C et al. (2003). Leptin enhances via AP-1 expression of aromatase in MCF-7 cell line. J Biol Chem, 278:28668–76.

    Google Scholar 

  108. Machinal-Quélin F, Dieudonné MN, Leneveu MC et al. (2002). Direct in vitro effects of androgens and estrogens on ob gene expression and leptin secretion in human adipose tissue. Endocrine, 18:179–84.

    PubMed  Google Scholar 

  109. Hu X, Juneja SC, Maihle NJ et al. (2002). Leptin-a growth factor in normal and malignant breast cancer cells and for normal mammary gland development. J Natl Cancer Inst, 94:1704–11.

    CAS  PubMed  Google Scholar 

  110. Hardwick JC, Van Den Brink GR, Offerhaus GJ et al. (2001). Leptin is a growth factor for colonic epithelial cells. Gastroenterology, 121:79–90.

    CAS  PubMed  Google Scholar 

  111. Sharma D, Saxena NK, Vertino PM et al. (2006). Leptin promotes the proliferative response and invasiveness in human endometrial cancer cells by activating multiple signal-transduction pathways. Endocr Relat Cancer, 13:629–40.

    CAS  PubMed  Google Scholar 

  112. Hursting SD, Nunez NP, Varticovski L et al. (2007). The obesity-cancer link: lessons learned from a fatless mouse. Cancer Res, 67:2391–3.

    CAS  PubMed  Google Scholar 

  113. Kantartzis K, Staiger H, Machann J et al. (2009). Adiponectin oligomers and ectopic fat in liver and skeletal muscle in humans. Obesity (Silver Spring), 17:390–2.

    CAS  Google Scholar 

  114. Haluzík M, Parízková J, Haluzík MM (2004). Adiponectin and its role in the obesity-induced insulin resistance and related complications. Physiol Res, 53:123–9.

    PubMed  Google Scholar 

  115. Yamauchi T, Karmon J, Ito Y et al. (2003). Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature, 423:762–9.

    CAS  PubMed  Google Scholar 

  116. Gil-Campos M, Cañete RR, Gil A (2004). Adiponectin, the missing link in insulin resistance and obesity. Clin Nutr, 23:963–74.

    CAS  PubMed  Google Scholar 

  117. Yamauchi T, Kamon J, Minokoshi Y et al. (2002). Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-protein kinase. Nat Med, 8:1288–95.

    CAS  PubMed  Google Scholar 

  118. Steffes MW, Gross MD, Schreiner PJ et al. (2004). Serum adiponectin in young adults – interactions with central adiposity, circulating levels of glucose and insulin resistance: the CARDIA study. Ann Epidemiol, 14:492–8.

    PubMed  Google Scholar 

  119. Coppola A, Marfella R, Coppola L et al. (2009). Effect of weight loss on coronary circulation and adiponectin levels in obese women. Int J Cardiol, 134(3):414–6.

    Google Scholar 

  120. Wedick NM, Snijder MB, Dekker JM et al. (2009). Prospective investigation of metabolic characteristics in relation to weight gain in older adults: the Hoorn study. Obesity (Silver Spring), 17(8):1609–14.

    Google Scholar 

  121. Cust AE, Kaaks R, Friedenreich C et al. (2007). Plasma adiponectin levels and endometrial cancer risk in pre- and postmenopausal women. J Clin Endocrinol Metab, 92:255–63.

    CAS  PubMed  Google Scholar 

  122. Rzepka-Górska I, Bedner R, Cymbaluk-Ploska A et al. (2008). Serum adiponectin in relation to endometrial cancer and endometrial hyperplasia with atypia in obese women. Eur J Gynaecol Oncol, 29:594–7.

    PubMed  Google Scholar 

  123. Tian YF, Chu CH, Wu MH et al. (2007). Anthropometric measures, plasma adiponectin, and breast cancer risk. Endocr Relat Cancer, 14:669–77.

    CAS  PubMed  Google Scholar 

  124. Mantzoros C, Petridou E, Dessypris N et al. (2004). Adiponectin and breast cancer risk. Clin Endocrinol Metab, 89:1102–7.

    CAS  Google Scholar 

  125. Wei EK, Giovannucci E, Fuchs CS et al. (2005). Low plasma adiponectin levels and risk of colorectal cancer in men: a prospective study. J Natl Cancer Inst, 97:1688–94.

    CAS  PubMed  Google Scholar 

  126. Ferroni P, Palmirotta R, Spila A et al. (2007). Prognostic significance of adiponectin levels in non-metastatic colorectal cancer. Anticancer Res, 27:483–9.

    CAS  PubMed  Google Scholar 

  127. Nishihara T, Baba M, Matsuda M et al. (2008). Adiponectin deficiency enhances colorectal carcinogenesis and liver tumor formation induced by azoxymethane in mice. World J Gastroenterol, 14:6473–80.

    CAS  PubMed  Google Scholar 

  128. Sher DJ, Oh WK, Jacobus S et al. (2008). Relationship between serum adiponectin and prostate cancer grade. Prostate, 68:1592–8.

    CAS  PubMed  Google Scholar 

  129. Goktas S, Yilmaz MI, Caglar K et al. (2005). Prostate cancer and adiponectin. Urology. 65:1168–72.

    PubMed  Google Scholar 

  130. Bråkenhielm E, Veitonmäki N, Cao R et al. (2004). Adiponectin-induced antiangiogenesis and antitumor activity involve caspase-mediated endothelial cell apoptosis. Proc Natl Acad Sci U S A, 101:2476–81.

    PubMed  Google Scholar 

  131. Kappes A, Loffler G (2000). Influences of ionomycin, dibutyryl-cycloAMP and tumor necrosis factor-alpha on intracellular amount and secretion of apM1 in differentiating primary human adipocytes. Hormone Metabolic Res, 32:548–54.

    CAS  Google Scholar 

  132. Fasshauer M, Kralisch S, Klier M et al. (2003). Adiponectin gene expression and secretion is inhibited by interleukin-6 in 3T3-L1 adipocytes. Biochem Biophys Res Comm, 301:1045–50.

    CAS  PubMed  Google Scholar 

  133. Steppan CM, Brown EJ, Wright CM et al. (2001). A family of tissue-specific resistin-like molecules. Proc Natl Acad Sci U S A, 98:502–6.

    CAS  PubMed  Google Scholar 

  134. Haluzik M, Haluzikova D. 2006. The role of resistin in obesity-induced insulin resistance. Curr Opin Investig Drugs, 7:306–11.

    CAS  PubMed  Google Scholar 

  135. Silswal N, Singh AK, Aruna B et al. (2005). Human resistin stimulates the pro-inflammatory cytokines TNF-alpha and IL-12 in macrophages by NF-kappaB-dependent pathway. Biochem Biophys Res Commun, 334:1092–101.

    CAS  PubMed  Google Scholar 

  136. Degawa-Yamauchi MBJE, Juliar BE, Watson W et al. (2003). Serum resistin (FIZZ3) protein is increased in obese humans. J Clin Endocrinol Metab, 88:5452–5.

    CAS  PubMed  Google Scholar 

  137. Silha JV, Krsek M, Skrha JV et al. (2003). Plasma resistin, adiponectin and leptin levels in lean and obese subjects: correlations with insulin resistance. Eur J Endocrinol, 149:331–5.

    CAS  PubMed  Google Scholar 

  138. Chen BH, Song Y, Ding EL et al. (2009). Circulating levels of resistin and risk of type 2 diabetes in men and women: results from two prospective cohorts. Diabetes Care, 32: 329–34.

    CAS  PubMed  Google Scholar 

  139. Kang JH, Yu BY, Youn DS (2007). Relationship of serum adiponectin and resistin levels with breast cancer risk. J Korean Med Sci, 22:117–21.

    CAS  PubMed  Google Scholar 

  140. Hou WK, Xu YX, Yu T et al. (2007). Adipocytokines and breast cancer risk. Chin Med J (Engl), 120:1592–6.

    CAS  Google Scholar 

  141. Housa D, Vernerova Z, Heracek J et al. (2008). Serum resistin levels in benign prostate hyperplasia and non-metastatic prostate cancer: possible role in cancer progression. Neoplasma, 55:442–6.

    CAS  PubMed  Google Scholar 

  142. Mu H, Ohashi R, Yan S et al. (2006). Adipokine resistin promotes in vitro angiogenesis of human endothelial cells. Cardiovasc Res, 70:146–57.

    CAS  PubMed  Google Scholar 

  143. Fukuhara AM, Matsuda M, Nishizawa K et al. (2005). Visfatin: a protein secreted by visceral fat that mimics the effects of insulin. Science, 307:426–30.

    CAS  PubMed  Google Scholar 

  144. Garten A, Petzold S, Korner A et al. (2009). Nampt: linking NAD biology, metabolism and cancer. Trends Endocrinol. Metab, 20:130–8.

    CAS  PubMed  Google Scholar 

  145. Kowalska I, Straczkowski M, Nikolajuk A et al. (2007). Serum visfatin in relation to insulin resistance and markers of hyperandrogenism in lean and obese women with polycystic ovary syndrome. Hum. Reprod, 22:1824–9.

    CAS  PubMed  Google Scholar 

  146. Tilg H, Moschen AR (2008). Role of adiponectin and PBEF/visfatin as regulators of inflammation: involvement in obesity-associated diseases. Clin Sci (Lond), 114:275–88.

    CAS  Google Scholar 

  147. Hufton SE, Moerkerk PT, Brandwijk R et al. (1999). A profile of differentially expressed genes in primary colorectal cancer using suppression subtractive hybridization FEBS Lett, 463:77–82.

    CAS  PubMed  Google Scholar 

  148. Van B, Jr., Moerkerk PT, Gerbers AJ et al. (2002). Target validation for genomics using peptide-specific phage antibodies: a study of five gene products overexpressed in colorectal cancer. Int, J, Cancer, 101:118–27.

    Google Scholar 

  149. Ramsey KM, Yoshino J, Brace CS et al. (2009). Circadian clock feedback cycle through NAMPT-mediated NAD+ biosynthesis, Science, 324:651–4.

    CAS  PubMed  Google Scholar 

  150. Nakahata Y, Kaluzova M, Grimaldi B et al. (2008). The NAD+-dependent deacetylase SIRT1 modulates CLOCK-mediated chromatin remodeling and circadian control, Cell, 134:329–40.

    CAS  PubMed  Google Scholar 

  151. Katergari SA, Milousis A, Pagonopoulou O et al. (2008). Ghrelin in pathological conditions. Endocr J, 55:439–53.

    CAS  PubMed  Google Scholar 

  152. Soares JB, Leite-Moreira AF (2008). Ghrelin, des-acyl ghrelin and obestatin: three pieces of the same puzzle. Peptides, 29:1255–70.

    CAS  PubMed  Google Scholar 

  153. Beasley JM, Ange BA, Anderson CA et al. (2009). Characteristics associated with fasting appetite hormones (obestatin, ghrelin, and leptin). Obesity (Silver Spring), 17:349–54.

    CAS  Google Scholar 

  154. Shak JR, Roper J, Perez-Perez GI et al. (2009). The effect of laparoscopic gastric banding surgery on plasma levels of appetite-control, insulinotropic, and digestive hormones. Obes Surg, 18:1089–96.

    Google Scholar 

  155. Roth CL, Reinehr T, Schernthaner GH et al. (2009). Ghrelin and obestatin levels in severely obese women before and after weight loss after Roux-en-Y gastric bypass surgery. Obes Surg, 19:29–35.

    PubMed  Google Scholar 

  156. Mungan NA, Eminferzane S, Mungan AG et al. (2008). Diagnostic value of serum ghrelin levels in prostate cancer. Urol Int, 80:245–8.

    CAS  PubMed  Google Scholar 

  157. Wolf I, Sadetzki S, Kanety H et al. (2006). Adiponectin, ghrelin, and leptin in cancer cachexia in breast and colon cancer patients. Cancer, 106:966–73.

    CAS  PubMed  Google Scholar 

  158. Lanfranco F, Baldi M, Cassoni P et al. (2008). Ghrelin and prostate cancer. Vitam Horm, 77:301–24.

    PubMed  Google Scholar 

  159. Hotamisligil GS, Shargill NS, Spiegelman BM (1993). Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science, 259:87–91.

    CAS  PubMed  Google Scholar 

  160. Rhodes JM, Campbell BJ (2002). Inflammation and colorectal cancer: IBD-associated and sporadic cancer compared. Trends Mol Med, 8:10–6.

    CAS  PubMed  Google Scholar 

  161. Nelson WG, De Marzo AM, DeWeese TL et al. (2004). The role of inflammation in the pathogenesis of prostate cancer. J Urol, 172:S6–S11.

    PubMed  Google Scholar 

  162. McCann J (1999). Esophageal cancers: changing character, increasing incidence. J Natl Cancer Inst, 91:497–8.

    CAS  PubMed  Google Scholar 

  163. Heilbronn LK, Campbell LV (2008). Adipose tissue macrophages, low grade inflammation and insulin resistance in human obesity. Curr Pharm Des, 14:1225–30.

    CAS  PubMed  Google Scholar 

  164. Kanda H, Tateya S, Tamori Y et al. (2006). MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity. J Clin Invest, 116:1494–505.

    CAS  PubMed  Google Scholar 

  165. Trayhurn P, Wood IS (2004). Adipokines: inflammation and the pleiotropic role of white adipose tissue. Br J Nutr, 92:347–55.

    CAS  PubMed  Google Scholar 

  166. Uysal KT, Wiesbrock SM, Marino MW et al. (1997). Protection from obesity-induced insulin resistance in mice lacking TNF-alpha function. Nature, 389:610–4.

    CAS  PubMed  Google Scholar 

  167. Coppak SW (2001). Pro-inflammatory cytokines and adipose tissue. Proc Nutr Soc, 60:349–56.

    Google Scholar 

  168. Bahceci M, Gokalp D, Bahceci S et al. (2007). The correlation between adiposity and adiponectin, tumor necrosis factor alpha, interleukin-6 and high sensitivity C-reactive protein levels. Is adipocyte size associated with inflammation in adults? J Endocrinol Invest, 30:210–4.

    CAS  PubMed  Google Scholar 

  169. Hotamisligil GS, Arner P, Caro JF et al. (1995). Increased adipose expression of tumor necrosis factor- in human obesity and insulin resistance. J Clin Invest, 95:2409–15.

    CAS  PubMed  Google Scholar 

  170. Kern PA, Saghizadeh M, Ong JM et al. (1995). The expression of tumor necrosis factor in human adipose tissue. Regulation by obesity, weight loss, and relationship to lipoprotein lipase. J Clin Invest, 95:2111–9.

    CAS  PubMed  Google Scholar 

  171. Il’yasova D, Colbert LH, Harris TB et al. (2005). Circulating levels of inflammatory markers and cancer risk in the health aging and body composition cohort. Cancer Epidemiol Biomarkers Prev, 14:2413–8.

    PubMed  Google Scholar 

  172. Kim S, Keku TO, Martin C et al. (2008). Circulating levels of inflammatory cytokines and risk of colorectal adenomas. Cancer Res, 68:323–8.

    CAS  PubMed  Google Scholar 

  173. Michalaki V, Syrigos K, Charles P et al. (2004). Serum levels of IL-6 and TNF-alpha correlate with clinicopathological features and patient survival in patients with prostate cancer. Br J Cancer, 90:2312–6.

    CAS  PubMed  Google Scholar 

  174. Gonullu G, Ersoy C, Evrensel T et al. (2005). Relation between insulin resistance and serum concentrations of IL-6 and TNF-alpha in overweight or obese women with early stage breast cancer. Cytokine, 31:264–9.

    CAS  PubMed  Google Scholar 

  175. Carswell EA, Old LJ, Kassel RL et al. (1975). An endotoxin-induced serum factor that causes necrosis of tumors. Proc Natl Acad Sci U S A, 72:3666–70.

    CAS  PubMed  Google Scholar 

  176. Nieto-Vazquez I, Fernández-Veledo S, Krämer DK et al. (2008). Insulin resistance associated to obesity: the link TNF-alpha. Arch Physiol Biochem, 114:183–94.

    CAS  PubMed  Google Scholar 

  177. Osawa Y, Nagaki M, Banno Y et al. 2002. Tumor necrosis factor alpha-induced interleukin-8 production via NF-kappaB and phosphatidylinositol 3-kinase/Akt pathways inhibits cell apoptosis in human hepatocytes. Infect Immun, 70:6294–301.

    CAS  PubMed  Google Scholar 

  178. Liu J, Lin A (2005). Role of JNK activation in apoptosis: a double-edged sword. Cell Res, 15:36–42.

    PubMed  Google Scholar 

  179. do Nascimento CO, Hunter L, Trayhurn P (2004). Regulation of haptoglobin gene expression in 3T3-L1 adipocytes by cytokines, catecholamines, and PPARgamma. Biochem Biophys Res Commun, 313:702–8.

    PubMed  Google Scholar 

  180. Purohit A, Newman SP, Reed MJ (2002). The role of cytokines in regulating estrogen synthesis: implications for the etiology of breast cancer. Breast Cancer Res, 4:65–9.

    CAS  PubMed  Google Scholar 

  181. Jansson JO, Wallenius K, Wernstedt I et al. (2003). On the site and mechanism of action of the anti-obesity effects of interleukin-6. Growth Horm IGF Res, 13:S28–S32.

    CAS  PubMed  Google Scholar 

  182. Wallenius K, Wallenius V, Sunter D et al. (2002). Intracerebroventricular interleukin-6 treatment decreases body fat in rats. Biochem Biophys Res Commun, 293:560–5.

    CAS  PubMed  Google Scholar 

  183. Vozarova B, Weyer C, Hanson K et al. (2001). Circulating interleukin-6 in relation to adiposity, insulin action, and insulin secretion. Obes Res, 9:414–7.

    CAS  PubMed  Google Scholar 

  184. Salgado R, Junius S, Benoy I et al. (2003). Circulating interleukin-6 predicts survival in patients with metastatic breast cancer. Int J Cancer, 103:642–6.

    CAS  PubMed  Google Scholar 

  185. Bachelot T, Ray-Coquard I, Menetrier-Caux C et al. (2003). Prognostic value of serum levels of interleukin 6 and of serum and plasma levels of vascular endothelial growth factor in hormone-refractory metastatic breast cancer patients. Br J Cancer, 88:1721–6.

    CAS  PubMed  Google Scholar 

  186. Lotem J, Sachs L (2001). Different mechanisms for suppression of apoptosis by cytokines and calcium mobilizing compounds. Proc Natl Acad Sci U S A, 95:4601–6.

    Google Scholar 

  187. Fenton JI, Hursting SD, Perkins SN et al. (2006). Interleukin-6 production induced by leptin treatment promotes cell proliferation in an Apc (Min/+) colon epithelial cell line. Carcinogenesis, 27:1507–15.

    CAS  PubMed  Google Scholar 

  188. Grano M, Mori G, Minielli V et al. (2000). Breast cancer cell line MDA-231 stimulates osteoclastogenesis and bone resorption in human osteoclasts. Biochem Biophys Res Commun, 270:1097–100.

    CAS  PubMed  Google Scholar 

  189. Ndumele CE, Pradhan AD, Ridker PM (2006). Interrelationships between inflammation, C-reactive protein, and insulin resistance. J Cardiometab Syndr, 1:190–6.

    PubMed  Google Scholar 

  190. Wee CC, Mukamal KJ, Huang A et al. (2008). Obesity and C-reactive protein levels among white, black, and hispanic US adults. Obesity (Silver. Spring), 16:875–80.

    CAS  Google Scholar 

  191. Marfella R, Esposito K, Siniscalchi M et al. (2004). Effect of weight loss on cardiac synchronization and proinflammatory cytokines in premenopausal obese women. Diabetes Care, 27:47–52.

    CAS  PubMed  Google Scholar 

  192. Tsilidis KK, Branchini C, Guallar E et al. (2008). C-reactive protein and colorectal cancer risk: a systematic review of prospective studies. Int J Cancer, 123:1133–40.

    CAS  PubMed  Google Scholar 

  193. Erlinger TP, Platz EA, Rifai N et al. (2004). C-reactive protein and the risk of incident colorectal cancer. JAMA, 291:585–90.

    CAS  PubMed  Google Scholar 

  194. Platz EA, De Marzo AM, Erlinger TP et al. (2004). No association between pre-diagnostic plasma C-reactive protein concentration and subsequent prostate cancer. Prostate, 59:393–400.

    CAS  PubMed  Google Scholar 

  195. Stark JR, Li H, Kraft P et al. (2009) Circulating prediagnostic interleukin-6 and C-reactive protein and prostate cancer incidence and mortality. Int J Cancer, 124(11):2683–9.

    Google Scholar 

  196. Heikkilä K, Ebrahim S, Lawlor DA (2007). A systematic review of the association between circulating concentrations of C reactive protein and cancer. J Epidemiol Community Health, 61:824–33.

    PubMed  Google Scholar 

  197. Pierce BL, Neuhouser ML, Wener MH et al. (2009). Correlates of circulating C-reactive protein and serum amyloid A concentrations in breast cancer survivors. Breast Cancer Res Treat, 114:155–67.

    CAS  PubMed  Google Scholar 

  198. Black S, Kushner I, Samols D (2004). C-reactive protein. J Biol Chem, 279:48487–90.

    CAS  PubMed  Google Scholar 

  199. Huber J, Kiefer FW, Zeyda M et al. (2008). CC chemokine and CC chemokine receptor profiles in visceral and subcutaneous adipose tissue are altered in human obesity. J Clin Endocrinol Metab, 93:3215–21.

    CAS  PubMed  Google Scholar 

  200. Harman-Boehm I, Blüher M, Redel H et al. (2007). Macrophage infiltration into omental versus subcutaneous fat across different populations: effect of regional adiposity and the comorbidities of obesity. J Clin Endocrinol Metab, 92:2240–7.

    CAS  PubMed  Google Scholar 

  201. Dehqanzada ZA, Storrer CE, Hueman MT et al. (2006). Correlations between serum monocyte chemotactic protein-1 levels, clinical prognostic factors, and HER-2/neu vaccine-related immunity in breast cancer patients. Clin Cancer Res, 12:478–86.

    CAS  PubMed  Google Scholar 

  202. Lu Y, Cai Z, Xiao G et al. (2007). Monocyte chemotactic protein-1 mediates prostate cancer-induced bone resorption. Cancer Res, 67:3646–53.

    CAS  PubMed  Google Scholar 

  203. Weisberg SP, Hunter D, Huber R et al. (2006). CCR2 modulates inflammatory and metabolic effects of high-fat feeding. J Clin Invest, 116:115–24.

    CAS  PubMed  Google Scholar 

  204. Li H, Kantoff PW, Ma J et al. (2005). Prediagnostic plasma vascular endothelial growth factor levels and risk of prostate cancer. Cancer Epidemiol Biomarkers Prev, 14:1557–61.

    CAS  PubMed  Google Scholar 

  205. Silha JV, Krsek M, Sucharda P et al. (2005). Angiogenic factors are elevated in overweight and obese individuals. Int J Obesity (Lond), 29:1308–14.

    CAS  Google Scholar 

  206. García de la Torre N, Rubio MA, Bordiú E et al. (2008). Effects of weight loss after bariatric surgery for morbid obesity on vascular endothelial growth factor-A, adipocytokines, and insulin. J Clin Endocrinol Metab, 93:4276–81.

    Google Scholar 

  207. Balasubramanian SP, Cox A, Cross SS et al. (2007). Influence of VEGF-A gene variation and protein levels in breast cancer susceptibility and severity. Int J Cancer, 121:1009–16.

    CAS  PubMed  Google Scholar 

  208. Reeves KW, Ness RB, Stone RA et al. (2009). Vascular endothelial growth factor and breast cancer risk. Cancer Causes Control, 20:375–86.

    PubMed  Google Scholar 

  209. Werther K, Christensen IJ, Nielsen HJ et al. (2002). Prognostic impact of matched preoperative plasma and serum VEGF in patients with primary colorectal carcinoma. Br J Cancer, 86:417–23.

    CAS  PubMed  Google Scholar 

  210. Powolny AA, Wang S, Carlton PS et al. (2008). Interrelationships between dietary restriction, the IGF-I axis, and expression of vascular endothelial growth factor by prostate adenocarcinoma in rats. Mol Carcinog, 47:458–65.

    CAS  PubMed  Google Scholar 

  211. Milne GL, Yin H, Morrow JD (2008). Human biochemistry of the isoprostane pathway J Biol Chem, 283:15533–7.

    CAS  PubMed  Google Scholar 

  212. Taketo MM (1998). Cyclooxygenase-2 inhibitors in tumorigenesis. J Natl Cancer Inst, 90:1529–36.

    CAS  PubMed  Google Scholar 

  213. Markowitz SD (2007). Aspirin and colon cancer – targeting prevention? N Engl J Med, 356:2195–8.

    CAS  PubMed  Google Scholar 

  214. Myung SJ, Rerko RM, Yan M et al. (2006). 15-Hydroxyprostaglandin dehydrogenase is an in vivo suppressor of colon tumorigenesis. Proc Natl Acad Sci U S A, 103:12098–102.

    CAS  PubMed  Google Scholar 

  215. Martínez ME, Heddens D, Earnest DL et al. (1999). Physical activity, body mass index, and prostaglandin E2 levels in rectal mucosa. J Natl Cancer Inst, 91:950–3.

    PubMed  Google Scholar 

  216. Fain JN, Kanu A, Bahouth SW et al. (2002). Comparison of PGE2, prostacyclin and leptin release by human adipocytes versus explants of adipose tissue in primary culture. Prostaglandins Leukot Essent Fatty Acids, 67:467–73.

    CAS  PubMed  Google Scholar 

  217. Hendrickse CW, Kelly RW, Radley S et al. (1994). Lipid peroxidation and prostaglandins in colorectal cancer. Br J Surg, 81:1219–23.

    CAS  PubMed  Google Scholar 

  218. Nicholson ML, Neoptolemos JP, Clayton HA et al. (1991). Increased cell membrane arachidonic acid in experimental colorectal tumors. Gut, 32:418.

    Google Scholar 

  219. Hughes D, Otani T, Yang P et al. (2008). NAD+-dependent 15-hydroxyprostaglandin dehydrogenase regulates levels of bioactive lipids in non-small cell lung cancer. Cancer Prev Res (Phila Pa), 1:241–9.

    CAS  Google Scholar 

  220. LeFever A, Funahashi A (1990). Elevated prostaglandin E2 levels in bronchoalveolar lavage fluid of patients with bronchogenic carcinoma. Chest, 98:1397–402.

    CAS  PubMed  Google Scholar 

  221. Larré S, Tran N, Fan C et al. (2008). PGE2 and LTB4 tissue levels in benign and cancerous prostates. Prostaglandins Other Lipid Mediat, 87:14–9.

    PubMed  Google Scholar 

  222. Sheng H, Shao J, Washington MK et al. (2001). Prostaglandin E2 increases growth and motility of colorectal carcinoma cells. J Biol Chem, 276:18075–81.

    CAS  PubMed  Google Scholar 

  223. Hinson RM, Williams JA, Shacter E (1996). Elevated interleukin 6 is induced by prostaglandin E2 in a murine model of inflammation: possible role of cyclooxygenase-2. Proc Natl Acad Sci U S A, 93:4885–90.

    CAS  PubMed  Google Scholar 

  224. Kawamori T, Rao CV, Seibert K et al. (1998). Chemopreventive activity of celecoxib, a specific cyclooxygenase-2 inhibitor, against colon carcinogenesis. Cancer Res, 58:409–12.

    CAS  PubMed  Google Scholar 

  225. Brueggemeier RW, Richards JA, Petrel TA (2003). Aromatase and cyclooxygenases: enzymes in breast cancer. J Steroid Biochem Mol Biol, 86:501–7.

    CAS  PubMed  Google Scholar 

  226. Le Bras M, Clément MV, Pervaiz S et al. (2005). Reactive oxygen species and the mitochondrial signaling pathway of cell death. Histol Histopathol, 20:205–19.

    PubMed  Google Scholar 

  227. Flowers L, Bleczinski WF, Burczynski ME et al. (1996). Disposition and biological activity of benzo[a]pyrene-7,8-dione. A genotoxic metabolite generated by dihydrodiol dehydrogenase. Biochemistry, 35:13664–72.

    CAS  PubMed  Google Scholar 

  228. Ghafourifar P, Cadenas E (2005). Mitochondrial nitric oxide synthase. Trends Pharmacol Sci, 26:190–5.

    CAS  PubMed  Google Scholar 

  229. Szabó C, Ischiropoulos H, Radi R (2007). Peroxynitrite: biochemistry, pathophysiology and development of therapeutics. Nat Rev Drug Discov, 6:662–80.

    PubMed  Google Scholar 

  230. Valko M, Izakovic M, Mazur M et al. (2004). Role of oxygen radicals in DNA damage and cancer incidence. Mol Cell Biochem, 266:37–56.

    CAS  PubMed  Google Scholar 

  231. Faraci FM, Didion SP (2004). Vascular protection: superoxide dismutase isoforms in the vessel wall. Arterioscler Thromb Vasc Biol, 24:1367–73.

    CAS  PubMed  Google Scholar 

  232. Brigelius-Flohé R (2006). Glutathione peroxidases and redox-regulated transcription factors. Biol Chem, 387:1329–35.

    PubMed  Google Scholar 

  233. Kehrer JP (2000). The Haber-Weiss reaction and mechanisms of toxicity. Toxicology, 149:43–50.

    CAS  PubMed  Google Scholar 

  234. Dean RT, Fu S, Stocker R et al. (1997). Biochemistry and pathology of radical-mediated protein oxidation. Biochem J, 324:1–18.

    CAS  PubMed  Google Scholar 

  235. Basu S (2008). F2-Isoprostanes in human health and diseases: From molecular mechanisms to clinical implications. Antioxid Redox Signal, 10:1405–34.

    CAS  PubMed  Google Scholar 

  236. Couillard C, Ruel G, Archer WR et al. (2005). Circulating levels of oxidative stress markers and endothelial adhesion molecules in men with abdominal obesity. J Clin Endocrinol Metab, 90:6454–9.

    CAS  PubMed  Google Scholar 

  237. Weinbrenner T, Schröder H, Escurriol V et al. (2006). Circulating oxidized LDL is associated with increased waist circumference independent of body mass index in men and women. Am J Clin Nutr, 83:30–5.

    CAS  PubMed  Google Scholar 

  238. Uzun H, Zengin K, Taskin M et al. (2004). Changes in leptin, plasminogen activator factor and oxidative stress in morbidly obese patients following open and laparoscopic Swedish adjustable gastric banding. Obes Surg, 14:659–65.

    PubMed  Google Scholar 

  239. Delimaris I, Faviou E, Antonakos G et al. (2007). Oxidized LDL, serum oxidizability and serum lipid levels in patients with breast or ovarian cancer. Clin Biochem, 40:1129–34.

    CAS  PubMed  Google Scholar 

  240. Suzuki K, Ito Y, Wakai K et al. (2004). Serum oxidized low-density lipoprotein levels and risk of colorectal cancer: a case-control study nested in the Japan Collaborative Cohort Study. Cancer Epidemiol Biomarkers Prev, 13:1781–7.

    CAS  PubMed  Google Scholar 

  241. Chen KH, Srivastava DK, Singhal RK et al. (2000). Modulation of base excision repair by low density lipoprotein, oxidized low density lipoprotein and antioxidants in mouse monocytes. Carcinogenesis, 21:1017–22.

    CAS  PubMed  Google Scholar 

  242. Haghdoost S, Czene S, Näslund I et al. (2005). Extracellular 8-oxo-dG as a sensitive parameter for oxidative stress in vivo and in vitro. Free Rad Res, 39:153–62.

    CAS  Google Scholar 

  243. Tsuzuki T, Nakatsu Y, Nakabeppu Y (2007). Significance of error-avoiding mechanisms for oxidative DNA damage in carcinogenesis. Cancer Sci, 98:465–70.

    CAS  PubMed  Google Scholar 

  244. Yamauchi M, Nakano H, Maekawa J et al. (2005). Oxidative stress in obstructive sleep apnea. Chest, 127:1674–9.

    CAS  PubMed  Google Scholar 

  245. de la Maza MP, Olivares D, Hirsch S et al. (2006). Weight increase and overweight are associated with DNA oxidative damage in skeletal muscle. Clin Nutr, 25:968–76.

    PubMed  Google Scholar 

  246. Azad MB, Chen Y, Gibson SB (2009). Regulation of autophagy by reactive oxygen species (ROS): implications for cancer progression and treatment. Antioxid Redox Signal, 11:777–90.

    CAS  PubMed  Google Scholar 

  247. Aykin-Burns N, Amhad IM, Zhu Y et al. (2009). Increased levels of superoxide and H2O2 mediate the differential susceptibility of cancer cells versus normal cells to glucose deprivation. Biochem J, 418:29–37.

    CAS  PubMed  Google Scholar 

  248. Valko M, Rhodes CJ, Moncol J et al. (2006). Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem Biol Interact, 160:1–40.

    CAS  PubMed  Google Scholar 

  249. Thomson CA, Giuliano AR, Shaw JW et al. (2007). Diet and biomarkers of oxidative damage in women previously treated for breast cancer. Nutr Cancer, 51:146–54.

    Google Scholar 

  250. Rossner P Jr, Gammon MD, Terry MB et al. (2006). Relationship between urinary 15-F2t-isoprostane and 8-oxodeoxyguanosine levels and breast cancer risk. Cancer Epidemiol Biomarkers Prev, 15:639–44.

    CAS  PubMed  Google Scholar 

  251. Leslie NR (2006). The redox regulation of PI 3-kinase-dependent signaling. Antioxid Redox Signal, 8:1765–74.

    CAS  PubMed  Google Scholar 

  252. Chen Y, Azad MB, Gibson SB (2009). Superoxide is the major reactive oxygen species regulating autophagy. Cell Death. Differ, 16:1040–52.

    CAS  PubMed  Google Scholar 

  253. McGill AT (2008). Malnutritive obesity (‘malnubesity’): is it driven by human brain evolution? Metab Syndr Relat Disord, 6:241–6.

    PubMed  Google Scholar 

  254. Reitman A, Friedrich I, Ben-Amotz A et al. (2002). Low plasma antioxidants and normal plasma B vitamins and homocysteine in patients with severe obesity. Isr Med Assoc J, 4:590–3.

    CAS  PubMed  Google Scholar 

  255. Zhu YG, Zhang SM, Wang JY et al. (2006). Overweight and obesity-induced oxidative stress in children. Biomed Environ Sci, 19:353–9.

    CAS  PubMed  Google Scholar 

  256. Lawson JA, Rokach J, FitzGerald GA (1999). Isoprostanes: formation, analysis and use as indices of lipid peroxidation in vivo. J Biol Chem, 274:24444.

    Google Scholar 

  257. Davi G, Guagnano MT, Ciabattoni G et al. (2002). Platelet activation in obese women: role of inflammation and oxidant stress. JAMA, 288:2008–14.

    CAS  PubMed  Google Scholar 

  258. Urakawa H, Katsuki A, Sumida Y et al. (2003). Oxidative stress is associated with adiposity and insulin resistance in men. J Clin Endocrinol Metab, 88:4673–6.

    CAS  PubMed  Google Scholar 

  259. Pou KM, Massaro JM, Hoffmann U et al. (2007). Visceral and subcutaneous adipose tissue volumes are cross-sectionally related to markers of inflammation and oxidative stress: the Framingham Heart Study. Circulation, 116:1234–41.

    CAS  PubMed  Google Scholar 

  260. Keaney JF, Jr., Larson MG, Vasan RS et al. (2003). Obesity and systemic oxidative stress: clinical correlates of oxidative stress in the Framingham Study Arterioscler. Thromb Vasc Biol, 23:434–9.

    CAS  Google Scholar 

  261. Dai Q, Gao YT, Shu XO et al. (2009). Oxidative stress, obesity, and breast cancer risk: results from the Shanghai Women’s Health Study. J Clin Oncol, 27:2482–8.

    PubMed  Google Scholar 

  262. Chen G, Heilbrun LK, Venkatramanamoorthy R et al. (2004). Effects of low-fat and/or high-fruit-and-vegetable diets on plasma levels of 8-isoprostane-F2alpha in the Nutrition and Breast Health study. Nutr Cancer, 50:155–60.

    CAS  PubMed  Google Scholar 

  263. Camphausen K, Ménard C, Sproull M et al. (2004). Isoprostane levels in the urine of patients with prostate cancer receiving radiotherapy are not elevated. Int J Radiat Oncol Biol Phys, 58:1536–9.

    CAS  PubMed  Google Scholar 

  264. Mense SM, Remotti F, Bhan A et al. (2008). Estrogen-induced breast cancer: alterations in breast morphology and oxidative stress as a function of estrogen exposure. Toxicol Appl Pharm, 232:78–85.

    CAS  Google Scholar 

  265. Fantuzzi G (2005). Adipose tissue, adipokines, and inflammation J Allergy Clin Immunol, 115:911–9.

    CAS  PubMed  Google Scholar 

  266. Shoelson SE, Lee J, Goldfine AB (2006). Inflammation and insulin resistance. J Clin Invest, 116:1793–801.

    CAS  PubMed  Google Scholar 

  267. Nock NL, Li L, Larkin EK et al. (2009). Empirical evidence for “syndrome Z”: a hierarchical 5-factor model of the metabolic syndrome incorporating sleep disturbance measures. Sleep, 32:615–22.

    PubMed  Google Scholar 

  268. Cowey S, Hardy RW (2006). The metabolic syndrome: A high-risk state for cancer? Am J Pathol, 169:1505–22.

    CAS  PubMed  Google Scholar 

  269. Pothiwala P, Jain SK, Yaturu S (2009). Metabolic syndrome and cancer. Metab Syndr Relat Disord, 7:279–88.

    CAS  PubMed  Google Scholar 

  270. Giovannucci E (2007). Metabolic syndrome, hyperinsulinemia, and colon cancer: a review. Am J Clin Nutr, 86:s836–s842.

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  272. Hill-Baskin AE, Markiewski MM, Buchner DA et al. (2009). Diet-induced hepatocellular carcinoma in genetically predisposed mice. Hum Mol Genet, 18: 2975–88.

    CAS  PubMed  Google Scholar 

  273. Sjostrom L, Narbro K, Sjostrom CD et al. (2007). Effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med, 357:741–52.

    PubMed  Google Scholar 

  274. Sjostrom L, Gummesson A, Sjostrom CD et al. (2009). Effects of bariatric surgery on cancer incidence in obese patients in Sweden (Swedish Obese Subjects Study): a prospective, controlled intervention trial. Lancet Oncol, 10:653–62.

    PubMed  Google Scholar 

  275. Adams TD, Hunt SC (2009). Cancer and obesity: effect of bariatric surgery. World J Surg, 33(10):2028–33.

    Google Scholar 

  276. Tang D, Liu JJ, Rundle A et al. (2007). Grilled meat consumption and PhIP-DNA adducts in prostate carcinogenesis. Cancer Epidemiol Biomarkers Prev, 16:803–8.

    CAS  PubMed  Google Scholar 

  277. Ericson U, Wirfält E, Mattisson I et al. (2007). Dietary intake of heterocyclic amines in relation to socio-economic, lifestyle and other dietary factors: estimates in a Swedish population. Public Health Nutr, 10:616–27.

    CAS  PubMed  Google Scholar 

  278. Larsson SC, Wolk A (2006). Meat consumption and risk of colorectal cancer: a meta-analysis of prospective studies. Int J Cancer, 119:2657–64.

    CAS  PubMed  Google Scholar 

  279. Rohrmann S, Hermann S, Linseisen J (2009). Heterocyclic aromatic amine intake increases colorectal adenoma risk: findings from a prospective European cohort study. Am J Clin Nutr, 89:1418–24.

    CAS  PubMed  Google Scholar 

  280. Koutros S, Cross AJ, Sandler DP et al. (2009). Meat and meat mutagens and risk of prostate cancer in the Agricultural Health Study. Cancer Epidemiol Biomarkers Prev, 17:80–7.

    Google Scholar 

  281. Michels KB, Mohllajee AP, Roset-Bahmanyar E et al. (2007). Diet and breast cancer: a review of the prospective observational studies. Cancer, 109:2712–49.

    CAS  PubMed  Google Scholar 

  282. Rybicki BA, Nock NL, Savera AT et al. (2006). Polycyclic aromatic hydrocarbon-DNA adduct formation in prostate carcinogenesis. Cancer Lett, 239:157–67.

    CAS  PubMed  Google Scholar 

  283. Phillips DH (1999). Polycyclic aromatic hydrocarbons in the diet. Mutat Res, 443:139–47.

    CAS  PubMed  Google Scholar 

  284. Sinha R, Cross A, Curtin J et al. (2005). Development of a food frequency questionnaire module and databases for compounds in cooked and processed meats. Mol Nutr Food Res, 49:648–55.

    CAS  PubMed  Google Scholar 

  285. Rundle A, Madsen A, Orjuela M et al. (2005). The association between benzo[a]pyrene-DNA adducts and body mass index, calorie intake and physical activity. Biomarkers, 12:123–32.

    Google Scholar 

  286. Nock NL, Tang D, Rundle A et al. (2007). Associations between smoking, polymorphisms in polycyclic aromatic hydrocarbon (PAH) metabolism and conjugation genes and PAH-DNA adducts in prostate tumors differ by race. Cancer Epidemiol Biomarkers Prev, 16:1236–45.

    CAS  PubMed  Google Scholar 

  287. Gammon MD, Sagiv SK, Eng SM et al. (2004). Polycyclic aromatic hydrocarbon-DNA adducts and breast cancer: a pooled analysis. Arch Environ Health, 59:640–9.

    CAS  PubMed  Google Scholar 

  288. Sinha R, Peters U, Cross AJ et al. (2005). Meat, meat cooking methods and preservation, and risk for colorectal adenoma. Cancer Res, 65:8034–41.

    CAS  PubMed  Google Scholar 

  289. Ivy JL (1997). Role of exercise training in the prevention and treatment of insulin resistance and non-insulin-dependent diabetes mellitus. Sports Med, 24:321–36.

    CAS  PubMed  Google Scholar 

  290. Schmitz KH, Ahmed RL, Yee D (2002). Effects of a 9-month strength training intervention on insulin, insulin-like growth factor (IGF)-I, IGF-binding protein (IGFBP)-1, and IGFBP-3 in 30–50-year-old women. Cancer Epidemiol Biomarkers Prev, 11:1597–604.

    CAS  PubMed  Google Scholar 

  291. Richter EA, Ruderman NB (2009). AMPK and the biochemistry of exercise: implications for human health and disease. Biochem J, 418:261–71.

    CAS  PubMed  Google Scholar 

  292. Bell RJ, Davison SL, Papalia MA et al. (2007). Endogenous androgen levels and cardiovascular risk profile in women across the adult life span. Menopause, 14:630–8.

    PubMed  Google Scholar 

  293. Plaisance EP, Grandjean PW (2006). Physical activity and high-sensitivity C-reactive protein. Sports Med, 36:443–58.

    PubMed  Google Scholar 

  294. Pedersen BK, Febbraio MA (2008). Muscle as an endocrine organ: focus on muscle-derived interleukin-6. Physiol Rev, 88:1379.

    CAS  PubMed  Google Scholar 

  295. Mathur N, Pedersen BK (2008). Exercise as a mean to control low-grade systemic inflammation. Mediators Inflamm, 2008:109502.

    Google Scholar 

  296. Petersen AM, Pedersen BK (2006). The role of IL-6 in mediating the anti-inflammatory effects of exercise. J Physiol Pharmacol, 57:43–51.

    PubMed  Google Scholar 

  297. Gu JW, Gadonski G, Wang J et al. (2004). Exercise increases endostatin in circulation of healthy volunteers. BMC Physiol, 4:2.

    PubMed  Google Scholar 

  298. Elosua R, Molina L, Fito M et al. (2003). Response of oxidative stress biomarkers to a 16-week aerobic physical activity program, and to acute physical activity, in healthy young men and women. Atherosclerosis, 167:327–34.

    CAS  PubMed  Google Scholar 

  299. Wang JS, Lee T, Chow SE (2008). Role of exercise intensities in oxidized low-density lipoprotein-mediated redox status of monocyte in men. J Appl Physiol, 101:740–4.

    Google Scholar 

  300. Woods JA, Davis JM, Smith JA et al. (1999). Exercise and cellular innate immune function. Med Sci Sports Exerc, 31:66.

    Google Scholar 

  301. Cordain L, Latin RW, Behnke JJ (1986). The effects of aeorobic running program in bowel transit time. J Sports Med Phys Fitness, 26:101–4.

    CAS  PubMed  Google Scholar 

  302. Holdstock DJ, Misiewicz JJ, Smith T et al. (1970). Propulsion (mass movements) in the human colon and its relationship to meals and somatic activity. Gut, 11:91–9.

    CAS  PubMed  Google Scholar 

  303. Qualtrough D, Kaidi A, Chell S et al. (2007). Prostaglandin F(2alpha) stimulates motility and invasion in colorectal tumor cells. Int J Cancer, 121:734–40.

    CAS  PubMed  Google Scholar 

  304. Mancini MC, Halpern A (2006). Investigational therapies in the treatment of obesity. Expert Opin Investig Drugs, 15:897–915.

    CAS  PubMed  Google Scholar 

  305. Jakicic JM, Clark K, Coleman E et al. (2001). American College of Sports Medicine position stand. Appropriate intervention strategies for weight loss and prevention of weight regain for adults. Med Sci Sports Exerc, 33:2145–56.

    CAS  PubMed  Google Scholar 

  306. Nissen SE, Wolski K (2007). Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med, 356:2457–71.

    CAS  PubMed  Google Scholar 

  307. Sachdev D, Li SL, Hartell JS et al. (2003). A chimeric humanized single-chain antibody against the type I insulin-like growth factor (IGF) receptor renders breast cancer cells refractory to the mitogenic effects of IGF-I. Cancer Res, 63:627–35.

    CAS  PubMed  Google Scholar 

  308. Pollak M (2008). Insulin and insulin-like growth factor signalling in neoplasia. Nat Rev Cancer, 8:915–28.

    CAS  PubMed  Google Scholar 

  309. Ryan PD, Goss PE (2008). The emerging role of the insulin-like growth factor pathway as a therapeutic target in cancer. Oncologist, 13:16–24.

    CAS  PubMed  Google Scholar 

  310. Zakikhani M, Dowling R, Fantus IG et al. (2006). Metformin is an AMP kinase-dependent growth inhibitor for breast cancer cells. Cancer Res, 66:1(0269)–73.

    Google Scholar 

  311. Goodwin PJ, Ligibel JA, Stambolic V (2009). Metformin in breast cancer: time for action. J Clin Oncol, 27:3271–3.

    CAS  PubMed  Google Scholar 

  312. Jiralerspong S, Palla SL, Giordano SH et al. (2009). Metformin and pathologic complete responses to neoadjuvant chemotherapy in diabetic patients with breast cancer. J Clin Oncol, 27:3297–302.

    CAS  PubMed  Google Scholar 

  313. Maira SM, Stauffer F, Schnell C et al. (2009). PI3K inhibitors for cancer treatment: where do we stand? Biochem Soc Trans, 37:265–72.

    CAS  PubMed  Google Scholar 

  314. Motzer RJ, Escudier B, Oudard S et al. (2008). Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet, 372:449–56.

    CAS  PubMed  Google Scholar 

  315. Schwab J, Antonescu C, Boland P et al. (2009). Combination of PI3K/mTOR inhibition demonstrates efficacy in human chordoma. Anticancer Res, 29:1867–71.

    CAS  PubMed  Google Scholar 

  316. Serra V, Markman B, Scaltriti M et al. (2008). NVP-BEZ235, a dual PI3K/mTOR inhibitor, prevents PI3K signaling and inhibits the growth of cancer cells with activating PI3K mutations. Cancer Res, 68:8022–30.

    CAS  PubMed  Google Scholar 

  317. Moore T, Beltran L, Carbajal S et al. (2009). Dietary energy balance modulates signaling through the Akt/mammalian target of rapamycin pathways in multiple epithelial tissues. Cancer Prev Res (Phila Pa), 1:65–76.

    Google Scholar 

Download references

Acknowledgments

Support for this work was derived in part from NIH Grants K07CA129162, to Nora Nock and U54 CA116867 and P30 CA043703 to Nathan Berger.

Author information

Authors and Affiliations

  1. Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, USA

    Nora L. Nock

  2. Center for Science, Health and Society, Case Western Reserve University, Cleveland, OH, USA

    Nathan A. Berger

Authors
  1. Nora L. Nock
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nathan A. Berger
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nora L. Nock .

Editor information

Editors and Affiliations

  1. School of Medicine, Center for Science, Health & Society, Case Western Reserve University, Euclid Ave. 10900, Cleveland, 44106, Ohio, USA

    Nathan A. Berger

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Nock, N.L., Berger, N.A. (2010). Obesity and Cancer: Overview of Mechanisms. In: Berger, N. (eds) Cancer and Energy Balance, Epidemiology and Overview. Energy Balance and Cancer, vol 2. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-5515-9_5

Download citation

  • DOI: https://doi.org/10.1007/978-1-4419-5515-9_5

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4419-5514-2

  • Online ISBN: 978-1-4419-5515-9

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation