Increased Adiposity and Colorectal Cancer



It has been clinically well established in the last years that obesity and obesity-related disorders, such as nonalcoholic fatty liver diseases, metabolic syndrome, and type 2 diabetes, are characterized by an increased risk of developing colorectal polyps and colorectal cancer. All other things equal, this risk appears to be strongest with an increased waist circumference and waist-to-hip ratios compared to one’s body mass index. In addition, obese men seem to be more at risk for colon cancer than obese women. Interestingly, among colon cancer patients, epidemiologic studies suggest that obesity is also associated with increased rates for death and disease relapse compared to patients of normal weight. The increased risk of cancer in the obese suggests that weight loss could reduce this risk or improve survival in individual diagnosed with colon cancer, but this remain to be fully investigated. Importantly, the associations between anthropometric measurements and cancer are very clinically relevant as it might affect our colon cancer screening strategies suggesting screening certain populations earlier than recommended for the general population. The pathophysiology behind this association is still not understood but might involve mediators derived from the adipose tissue. Obesity is commonly associated with adipose tissue inflammation, systemic inflammation, and release of numerous adipocytokines into the circulation. An imbalance in these fundamentally important adipose tissue-derived factors could contribute to disease manifestation beyond the adipose tissue including colorectal cancer. Cells other than adipocytes, including adipose stromal cells and monocytes accumulating in adipose tissue, have surfaced as important contributors to the adipocytokine pool. Finally, recently discovered trafficking of adipose stromal cells suggests paracrine adipocytokine signaling in tumor microenvironment.


Colon Cancer White Adipose Tissue Distal Colon Adenomatous Polyp Nonalcoholic Fatty Liver Disease 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Berrington de Gonzalez A, Hartge P, Cerhan JR, et al. Body-mass index and mortality among 1.46 million white adults. N Engl J Med. 2010;363:2211–9.PubMedGoogle Scholar
  2. 2.
    Donohoe CL, Pidgeon GP, Lysaght J, et al. Obesity and gastrointestinal cancer. Br J Surg. 2010;97:628–42.PubMedGoogle Scholar
  3. 3.
    Renehan AG, Soerjomataram I, Tyson M, et al. Incident cancer burden attributable to excess body mass index in 30 European countries. Int J Cancer. 2010;126:692–702.PubMedGoogle Scholar
  4. 4.
    Morois S, Mesrine S, Josset M, et al. Anthropometric factors in adulthood and risk of colorectal adenomas: the French E3N-EPIC prospective cohort. Am J Epidemiol. 2010;172:1166–80.PubMedGoogle Scholar
  5. 5.
    Dehal A, Garrett T, Tedders SH, et al. Body mass index and death rate of colorectal cancer among a national cohort of U.S. adults. Nutr Cancer. 2011;63:1218–25.PubMedGoogle Scholar
  6. 6.
    Zauber AG, Winawer SJ, O’Brien MJ, et al. Colonoscopic polypectomy and long-term prevention of colorectal-cancer deaths. N Engl J Med. 2012;366:687–96.PubMedGoogle Scholar
  7. 7.
    Ferlitsch M, Reinhart K, Pramhas S, et al. Sex-specific prevalence of adenomas, advanced adenomas, and colorectal cancer in individuals undergoing screening colonoscopy. JAMA. 2011;306:1352–8.PubMedGoogle Scholar
  8. 8.
    Ning Y, Wang L. Giovannucci ELA quantitative analysis of body mass index and colorectal cancer: findings from 56 observational studies. Obes Rev. 2010;11(1):19–30.PubMedGoogle Scholar
  9. 9.
    Chyou PH, Nomura AM, Stemmermann GN. A prospective study of weight, body mass index and other anthropometric measurements in relation to site-specific cancers. Int J Cancer. 1994;57(3):313–7.PubMedGoogle Scholar
  10. 10.
    Lin J, Zhang SM, Cook NR, Rexrode KM, Lee IM, Buring JE. Body mass index and risk of colorectal cancer in women (United States). Cancer Causes Control. 2004;15(6):581–9.PubMedGoogle Scholar
  11. 11.
    Moore LL, Bradlee ML, Singer MR, Splansky GL, Proctor MH, Ellison RC, et al. BMI and waist circumference as predictors of lifetime colon cancer risk in Framingham Study adults. Int J Obes Relat Metab Disord. 2004;28:559–67.PubMedGoogle Scholar
  12. 12.
    Ford ES. Body mass index and colon cancer in a national sample of adult US men and women. Am J Epidemiol. 1999;150:390–8.PubMedGoogle Scholar
  13. 13.
    Murphy TK, Calle EE, Rodriguez C, Kahn HS, Thun MJ. Body mass index and colon cancer mortality in a large prospective study. Am J Epidemiol. 2000;152:847–54.PubMedGoogle Scholar
  14. 14.
    Le Marchand L, Wilkens LR, Mi MP. Obesity in youth and middle age and risk of colorectal cancer in men. Cancer Causes Control. 1992;3:349–54.PubMedGoogle Scholar
  15. 15.
    Caan BJ, Coates AO, Slattery ML, Potter JD, Quesenberry Jr CP, Edwards SM. Body size and the risk of colon cancer in a large case-control study. Int J Obes Relat Metab Disord. 1998;22:178–84.PubMedGoogle Scholar
  16. 16.
    Dietz AT, Newcomb PA, Marcus PM, Storer BE. The association of body size and large bowel cancer risk in Wisconsin (United States) women. Cancer Causes Control. 1995;6:30–6.PubMedGoogle Scholar
  17. 17.
    Russo A, Franceschi S, La Vecchia C, et al. Body size and colorectal-cancer risk. Int J Cancer. 1998;78:161–5.PubMedGoogle Scholar
  18. 18.
    Larsson SC, Wolk A. Obesity and colon and rectal cancer risk: a meta-analysis of prospective studies. Am J Clin Nutr. 2007;86:556–65.PubMedGoogle Scholar
  19. 19.
    Harriss DJ, Atkinson G, George K, et al. Lifestyle factors and colorectal cancer risk (1): systematic review and meta-analysis of associations with body mass index. Colorectal Dis. 2009;11:547–63.PubMedGoogle Scholar
  20. 20.
    Terry P, Giovannucci E, Bergkvist L, et al. Body weight and colorectal cancer risk in a cohort of Swedish women: relation varies by age and cancer site. Br J Cancer. 2001;85:346–9.PubMedGoogle Scholar
  21. 21.
    Terry PD, Miller AB, Rohan TE. Obesity and colorectal cancer risk in women. Gut. 2002;51:191–4.PubMedGoogle Scholar
  22. 22.
    Meyerhardt JA et al. Influence of body mass index on outcomes and treatment-related toxicity in patients with colon carcinoma. Cancer. 2003;98:484–95.PubMedGoogle Scholar
  23. 23.
    Dignam JJ, Polite BN, Yothers G, Raich P, Colangelo L, O’Connell MJ, et al. Body mass index and outcomes in patients who receive adjuvant chemotherapy for colon cancer. J Natl Cancer Inst. 2006;98:1647–54.PubMedGoogle Scholar
  24. 24.
    Sinicrope FA et al. Obesity is an independent prognostic variable in colon cancer survivors. Clin Cancer Res. 2010;16:1884–93.PubMedGoogle Scholar
  25. 25.
    Healy LA et al. Impact of obesity on surgical and oncological outcomes in the management of colorectal cancer. Int J Colorectal Dis. 2010;25:1293–9.PubMedGoogle Scholar
  26. 26.
    Meyerhardt JA et al. Impact of body mass index and weight change after treatment on cancer recurrence and survival in patients with stage III colon cancer: findings from Cancer and Leukemia Group B 89803. J Clin Oncol. 2008;26:4109–15.PubMedGoogle Scholar
  27. 27.
    Roxburgh CS et al. Relationship between preoperative comorbidity, systemic inflammatory response, and survival in patients undergoing curative resection for colorectal cancer. Ann Surg Oncol. 2011;18:997–1005.PubMedGoogle Scholar
  28. 28.
    Slattery ML et al. Diet and survival of patients with colon cancer in Utah: is there an association? Int J Epidemiol. 1989;18:792–7.PubMedGoogle Scholar
  29. 29.
    Prizment AE, Flood A, Anderson KE, Folsom AR. Survival of women with colon cancer in relation to precancer anthropometric characteristics: the Iowa Women’s Health Study. Cancer Epidemiol Biomarkers Prev. 2010;19:2229–37.PubMedGoogle Scholar
  30. 30.
    Haydon AM, Macinnis RJ, English DR, Giles GG. Effect of physical activity and body size on survival after diagnosis with colorectal cancer. Gut. 2006;55:62–7.PubMedGoogle Scholar
  31. 31.
    Park SM et al. Impact of prediagnosis smoking, alcohol, obesity, and insulin resistance on survival in male cancer patients: National Health Insurance Corporation Study. J Clin Oncol. 2006;24:5017–24.PubMedGoogle Scholar
  32. 32.
    Campbell PT et al. Impact of body mass index on survival after colorectal cancer diagnosis: the Cancer Prevention Study-II Nutrition Cohort. J Clin Oncol. 2011;30(1):42–52.PubMedGoogle Scholar
  33. 33.
    Moon HG et al. Visceral obesity may affect oncologic outcome in patients with colorectal cancer. Ann Surg Oncol. 2008;15:1918–22.PubMedGoogle Scholar
  34. 34.
    Doria-Rose VP et al. Body mass index and the risk of death following the diagnosis of colorectal cancer in postmenopausal women (United States). Cancer Causes Control. 2006;17:63–70.PubMedGoogle Scholar
  35. 35.
    Asghari-Jafarabadi M et al. Site-specific evaluation of prognostic factors on survival in Iranian colorectal cancer patients: a competing risks survival analysis. Asian Pac J Cancer Prev. 2009;10:815–21.PubMedGoogle Scholar
  36. 36.
    Shibakita M et al. Body mass index influences long-term outcome in patients with colorectal cancer. Hepatogastroenterology. 2010;57:62–9.PubMedGoogle Scholar
  37. 37.
    Hines RB et al. Effect of comorbidity and body mass index on the survival of African-American and Caucasian patients with colon cancer. Cancer. 2009;115:5798–806.PubMedGoogle Scholar
  38. 38.
    Simkens LH et al. Influence of body mass index on outcome in advanced colorectal cancer patients receiving chemotherapy with or without targeted therapy. Eur J Cancer. 2011;47:2560–7.PubMedGoogle Scholar
  39. 39.
    Pathak S et al. Hepatic steatosis, body mass index and long term outcome in patients undergoing hepatectomy for colorectal liver metastases. Eur J Surg Oncol. 2010;36:52–7.PubMedGoogle Scholar
  40. 40.
    West DW, Slattery ML, Robison LM, et al. Dietary intake and colon cancer: sex- and anatomic site-specific associations. Am J Epidemiol. 1989;130:883–94.PubMedGoogle Scholar
  41. 41.
    Laake I, Thune I, Selmer R, et al. A prospective study of body mass index, weight change, and risk of cancer in the proximal and distal colon. Cancer Epidemiol Biomarkers Prev. 2010;19:1511–22.PubMedGoogle Scholar
  42. 42.
    Shin A, Joo J, Bak J, Yang HR, Kim J, Park S, et al. Site-specific risk factors for colorectal cancer in a Korean population. PLoS One. 2011;6:e23196.PubMedGoogle Scholar
  43. 43.
    Hughes LA, Simons CC, van den Brandt PA, Goldbohm RA, van Engeland M, Weijenberg MP. Body size and colorectal cancer risk after 16.3 years of follow-up: an analysis from the Netherlands Cohort Study. Am J Epidemiol. 2011;174:1127–39.PubMedGoogle Scholar
  44. 44.
    Oxentenko AS, Bardia A, Vierkant RA, et al. Body size and incident colorectal cancer: a prospective study of older women. Cancer Prev Res (Phila). 2010;3:1608–20.Google Scholar
  45. 45.
    Offerhaus GJ, De Feyter EP, Cornelisse CJ, et al. The relationship of DNA aneuploidy to molecular genetic alterations in colorectal carcinoma. Gastroenterology. 1992;102:1612–9.PubMedGoogle Scholar
  46. 46.
    Bell SM, Scott N, Cross D, et al. Prognostic value of p53 over-expression and c-Ki-ras gene mutations in colorectal cancer. Gastroenterology. 1993;104:57–64.PubMedGoogle Scholar
  47. 47.
    Wolin KY, Yan Y, Colditz GA. Physical activity and risk of colon adenoma: a meta-analysis. Br J Cancer. 2011;104:882–5.PubMedGoogle Scholar
  48. 48.
    Wolin KY, Yan Y, Colditz GA, Lee IM. Physical activity and colon cancer prevention: meta-analysis. Br J Cancer. 2009;100:611–6.PubMedGoogle Scholar
  49. 49.
    Pham NM, Mizoue T, Tanaka K, Tsuji I, Tamakoshi A, Matsuo K, et al. Physical activity and colorectal cancer risk: an evaluation based on a systematic review of epidemiologic evidence among the Japanese population. Jpn J Clin Oncol. 2012;42:2–13.PubMedGoogle Scholar
  50. 50.
    Nilsen TIL, PlR R, Petersen H, Gunnell D, Vatten LJ. Recreational physical activity and cancer risk in subsites of the colon (the Nord-Trøndelag Health Study). Cancer Epidemiol Biomarkers Prev. 2008;17:183–8.PubMedGoogle Scholar
  51. 51.
    Wolin KY, Lee IM, Colditz GA, Glynn RJ, Fuchs C, Giovannucci E. Leisure-time physical activity patterns and risk of colon cancer in women. Int J Cancer. 2007;121(12):2776–81.PubMedGoogle Scholar
  52. 52.
    International Agency for Research on Cancer WHO. IARC Handbooks of cancer prevention: weight control and physical activity, vol. 6. Lyon: International Agency for Research on Cancer; 2002.Google Scholar
  53. 53.
    Denlinger CS, Engstrom PF. Colorectal cancer survivorship: movement matters. Cancer Prev Res (Phila). 2011;4:502–11.Google Scholar
  54. 54.
    Meyerhardt JA et al. Physical activity and survival after colorectal cancer diagnosis. J Clin Oncol. 2006;24:3527–34.PubMedGoogle Scholar
  55. 55.
    Meyerhardt JA et al. Physical activity and male colorectal cancer survival. Arch Intern Med. 2009;169:2102–8.PubMedGoogle Scholar
  56. 56.
    Meyerhardt JA et al. Impact of physical activity on cancer recurrence and survival in patients with stage III colon cancer: findings from CALGB 89803. J Clin Oncol. 2006;24:3535–41.PubMedGoogle Scholar
  57. 57.
    Satia JA, Campbell MK, Galanko JA, James A, Carr C, Sandler RS. Longitudinal changes in lifestyle behaviors and health status in colon cancer survivors. Cancer Epidemiol Biomarkers Prev. 2004;13:1022–31.PubMedGoogle Scholar
  58. 58.
    Kaplan RN, Riba RD, Zacharoulis S, Bramley AH, Vincent L, Costa C, et al. VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature. 2005;438:820–7.PubMedGoogle Scholar
  59. 59.
    Carmeliet P, Luttun A. The emerging role of the bone marrow-derived stem cells in (therapeutic) angiogenesis. Thromb Haemost. 2001;86:289–97.PubMedGoogle Scholar
  60. 60.
    Shaked Y, Ciarrocchi A, Franco M, Lee CR, Man S, Cheung AM, et al. Therapy-induced acute recruitment of circulating endothelial progenitor cells to tumors. Science. 2006;313:1785–7.PubMedGoogle Scholar
  61. 61.
    Bergers G, Song S. The role of pericytes in blood-vessel formation and maintenance. Neuro Oncol. 2005;7:452–64.PubMedGoogle Scholar
  62. 62.
    Nilsson SK, Simmons PJ. Transplantable stem cells: home to specific niches. Curr Opin Hematol. 2004;11:102–6.PubMedGoogle Scholar
  63. 63.
    Prockop DJ. Marrow stromal cells as stem cells for nonhematopoietic tissues. Science. 1997;276:71–4.PubMedGoogle Scholar
  64. 64.
    Hung SC, Deng WP, Yang WK, Liu RS, Lee CC, Su TC, et al. Mesenchymal stem cell targeting of microscopic tumors and tumor stroma development monitored by noninvasive in vivo positron emission tomography imaging. Clin Cancer Res. 2005;11:7749–56.PubMedGoogle Scholar
  65. 65.
    Studeny M, Marini FC, Dembinski JL, Zompetta C, Cabreira-Hansen M, Bekele BN, et al. Mesenchymal stem cells: potential precursors for tumor stroma and targeted-delivery vehicles for anticancer agents. J Natl Cancer Inst. 2004;96:1593–603.PubMedGoogle Scholar
  66. 66.
    Liu JW, Dunoyer-Geindre S, Serre-Beinier V, Mai G, Lambert JF, Fish RJ, et al. Characterization of endothelial-like cells derived from human mesenchymal stem cells. J Thromb Haemost. 2007;5:826–34.PubMedGoogle Scholar
  67. 67.
    Fernández M, Simon V, Herrera G, Cao C, Del Favero H, Minguell JJ. Detection of stromal cells in peripheral blood progenitor cell collections from breast cancer patients. Bone Marrow Transplant. 1997;20:265–71.PubMedGoogle Scholar
  68. 68.
    Gao D, Nolan DJ, Mellick AS, Bambino K, McDonnell K, Mittal V. Endothelial progenitor cells control the angiogenic switch in mouse lung metastasis. Science. 2008;319:195–8.PubMedGoogle Scholar
  69. 69.
    Aicher A, Rentsch M, Sasaki K, Ellwart JW, Fändrich F, Siebert R, et al. Nonbone marrow-derived circulating progenitor cells contribute to postnatal neovascularization following tissue ischemia. Circ Res. 2007;100:581–9.PubMedGoogle Scholar
  70. 70.
    Zuk PA, Zhu M, Mizuno H, Huang J, Futrell JW, Katz AJ, et al. Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng. 2001;7:211–28.PubMedGoogle Scholar
  71. 71.
    Traktuev DO, Merfeld-Clauss S, Li J, Kolonin M, Arap W, Pasqualini R, et al. A population of multipotent CD34-positive adipose stromal cells share pericyte and mesenchymal surface markers, reside in a periendothelial location, and stabilize endothelial networks. Circ Res. 2008;102:77–85.PubMedGoogle Scholar
  72. 72.
    Gimble JM, Guilak F, Nuttall ME, Sathishkumar S, Vidal M, Bunnell BA. In vitro differentiation potential of mesenchymal stem cells. Transfus Med Hemother. 2008;35:228–38.PubMedGoogle Scholar
  73. 73.
    Rehman J, Traktuev D, Li J, Merfeld-Clauss S, Temm-Grove CJ, Bovenkerk JE, et al. Secretion of angiogenic and antiapoptotic factors by human adipose stromal cells. Circulation. 2004;109:1292–8.PubMedGoogle Scholar
  74. 74.
    Kucerova L, Altanerova V, Matuskova M, Tyciakova S, Altaner C. Adipose tissue-derived human mesenchymal stem cells mediated prodrug cancer gene therapy. Cancer Res. 2007;67:6304–13.PubMedGoogle Scholar
  75. 75.
    Martin-Padura I, Gregato G, Marighetti P, Mancuso P, Calleri A, Corsini C, et al. The white adipose tissue used in lipotransfer procedures is a rich reservoir of CD34+ progenitors able to promote cancer progression. Cancer Res. 2012;72:325–34.PubMedGoogle Scholar
  76. 76.
    Van Harmelen V, Röhrig K, Hauner H. Comparison of proliferation and differentiation capacity of human adipocyte precursor cells from the omental and subcutaneous adipose tissue depot of obese subjects. Metabolism. 2004;53:632–7.PubMedGoogle Scholar
  77. 77.
    Cartwright MJ, Tchkonia T, Kirkland JL. Aging in adipocytes: potential impact of inherent, depot-specific mechanisms. Exp Gerontol. 2007;42:463–71.PubMedGoogle Scholar
  78. 78.
    Yang RZ, Lee MJ, Hu H, Pray J, Wu HB, Hansen BC, et al. Identification of omentin as a novel depot-specific adipokine in human adipose tissue: possible role in modulating insulin action. Am J Physiol Endocrinol Metab. 2006;290(6):E1253–61.PubMedGoogle Scholar
  79. 79.
    Karnoub AE, Dash AB, Vo AP, Sullivan A, Brooks MW, Bell GW, et al. Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature. 2007;449:557–63.PubMedGoogle Scholar
  80. 80.
    Cawthorn WP, Scheller EL, Macdougald OA. Adipose tissue stem cells: the great WAT hope. Trends Endocrinol Metab. 2012;23:270–7.PubMedGoogle Scholar
  81. 81.
    Hursting SD, Lavigne JA, Berrigan D, Perkins SN, Barrett JC. Calorie restriction, aging, and cancer prevention: mechanisms of action and applicability to humans. Annu Rev Med. 2003;54:131–52.PubMedGoogle Scholar
  82. 82.
    Adams TD, Stroup AM, Gress RE, Adams KF, Calle EE, Smith SC, et al. Cancer incidence and mortality after gastric bypass surgery. Obesity (Silver Spring). 2009;17:796–802.Google Scholar
  83. 83.
    Zhang Y, Bellows CF, Kolonin MG. Adipose tissue-derived progenitor cells and cancer. World J Stem Cells. 2010;2:103–13.PubMedGoogle Scholar
  84. 84.
    Bellows CF, Zhang Y, Chen J, Frazier ML, Kolonin MG. Circulation of progenitor cells in obese and lean colorectal cancer patients. Cancer Epidemiol Biomarkers Prev. 2011;20:2461–8.PubMedGoogle Scholar
  85. 85.
    Kolonin MG, Saha PK, Chan L, Pasqualini R, Arap W. Reversal of obesity by targeted ablation of adipose tissue. Nat Med. 2004;10:625–32.PubMedGoogle Scholar
  86. 86.
    Daquinag AC, Zhang Y, Kolonin MG. Vascular targeting of adipose tissue as an anti-obesity approach. Trends Pharmacol Sci. 2011;32:300–7.PubMedGoogle Scholar
  87. 87.
    Sun K, Kusminski CM, Scherer PE. Adipose tissue remodeling and obesity. J Clin Invest. 2011;121:2094–101.PubMedGoogle Scholar
  88. 88.
    Tilg H, Moschen AR. Adipocytokines: mediators linking adipose tissue, inflammation and immunity. Nat Rev Immunol. 2006;6:772–83.PubMedGoogle Scholar
  89. 89.
    Shetty S, Kusminski CM, Scherer PE. Adiponectin in health and disease: evaluation of adiponectin-targeted drug development strategies. Trends Pharmacol Sci. 2009;30:234–9.PubMedGoogle Scholar
  90. 90.
    Tilg H, Moschen AR. Role of adiponectin and PBEF/visfatin as regulators of inflammation: involvement in obesity-associated diseases. Clin Sci (Lond). 2008;114:275–88.Google Scholar
  91. 91.
    Wei EK, Giovannucci E, Fuchs CS, et al. Low plasma adiponectin levels and risk of colorectal cancer in men: a prospective study. J Natl Cancer Inst. 2005;97:1688–94.PubMedGoogle Scholar
  92. 92.
    Kaklamani VG, Wisinski KB, Sadim M, et al. Variants of the adiponectin (ADIPOQ) and adiponectin receptor 1 (ADIPOR1) genes and colorectal cancer risk. JAMA. 2008;300:1523–31.PubMedGoogle Scholar
  93. 93.
    Ishikawa M, Kitayama J, Kazama S, et al. Plasma adiponectin and gastric cancer. Clin Cancer Res. 2005;11:466–72.PubMedGoogle Scholar
  94. 94.
    Pinthus JH, Kleinmann N, Tisdale B, et al. Lower plasma adiponectin levels are associated with larger tumor size and metastasis in clear-cell carcinoma of the kidney. Eur Urol. 2008;54:866–73.PubMedGoogle Scholar
  95. 95.
    Cust AE, Stocks T, Lukanova A, et al. The influence of overweight and insulin resistance on breast cancer risk and tumour stage at diagnosis: a prospective study. Breast Cancer Res Treat. 2009;113:567–76.PubMedGoogle Scholar
  96. 96.
    An W, Bai Y, Deng SX, et al. Adiponectin levels in patients with colorectal cancer and adenoma: a meta-analysis. Eur J Cancer Prev. 2012;21:126–33.PubMedGoogle Scholar
  97. 97.
    Aleksandrova K, Boeing H, Jenab M, et al. Total and high-molecular weight adiponectin and risk of colorectal cancer: the European Prospective Investigation into Cancer and Nutrition Study. Carcinogenesis. 2012;33(2):1211–8.PubMedGoogle Scholar
  98. 98.
    Lysaght J, van der Stok EP, Allott EH, et al. Pro-inflammatory and tumour proliferative properties of excess visceral adipose tissue. Cancer Lett. 2011;312:62–72.PubMedGoogle Scholar
  99. 99.
    Gialamas SP, Petridou ET, Tseleni-Balafouta S, et al. Serum adiponectin levels and tissue expression of adiponectin receptors are associated with risk, stage, and grade of colorectal cancer. Metabolism. 2011;60:1530–8.PubMedGoogle Scholar
  100. 100.
    Ho GY, Wang T, Gunter MJ, et al. Adipokines linking obesity with colorectal cancer risk in postmenopausal women. Cancer Res. 2012;72(12):3029–37.PubMedGoogle Scholar
  101. 101.
    Pechlivanis S, Bermejo JL, Pardini B, et al. Genetic variation in adipokine genes and risk of colorectal cancer. Eur J Endocrinol. 2009;160:933–40.PubMedGoogle Scholar
  102. 102.
    Liu L, Zhong R, Wei S, et al. Interactions between genetic variants in the adiponectin, adiponectin receptor 1 and environmental factors on the risk of colorectal cancer. PLoS One. 2011;6:e27301.PubMedGoogle Scholar
  103. 103.
    Yamaji T, Iwasaki M, Sasazuki S, et al. Interaction between adiponectin and leptin influences the risk of colorectal adenoma. Cancer Res. 2010;70:5430–7.PubMedGoogle Scholar
  104. 104.
    Larsson SC, Orsini N, Wolk A. Diabetes mellitus and risk of colorectal cancer: a meta-analysis. J Natl Cancer Inst. 2005;97:1679–87.PubMedGoogle Scholar
  105. 105.
    Danese S, Fiocchi C. Ulcerative colitis. N Engl J Med. 2011;365:1713–25.PubMedGoogle Scholar
  106. 106.
    Fujisawa T, Endo H, Tomimoto A, et al. Adiponectin suppresses colorectal carcinogenesis under the high-fat diet condition. Gut. 2008;57:1531–8.PubMedGoogle Scholar
  107. 107.
    Sugiyama M, Takahashi H, Hosono K, et al. Adiponectin inhibits colorectal cancer cell growth through the AMPK/mTOR pathway. Int J Oncol. 2009;34:339–44.PubMedGoogle Scholar
  108. 108.
    Kim AY, Lee YS, Kim KH, et al. Adiponectin represses colon cancer cell proliferation via AdipoR1- and -R2-mediated AMPK activation. Mol Endocrinol. 2010;24:1441–52.PubMedGoogle Scholar
  109. 109.
    Brakenhielm E, Veitonmaki N, Cao R, et al. Adiponectin-induced antiangiogenesis and antitumor activity involve caspase-mediated endothelial cell apoptosis. Proc Natl Acad Sci USA. 2004;101:2476–81.PubMedGoogle Scholar
  110. 110.
    Ealey KN, Archer MC. Elevated circulating adiponectin and elevated insulin sensitivity in adiponectin transgenic mice are not associated with reduced susceptibility to colon carcinogenesis. Int J Cancer. 2009;124:2226–30.PubMedGoogle Scholar
  111. 111.
    Saxena A, Chumanevich A, Fletcher E, et al. Adiponectin deficiency: role in chronic inflammation induced colon cancer. Biochim Biophys Acta. 2012;1822:527–36.PubMedGoogle Scholar
  112. 112.
    Mutoh M, Teraoka N, Takasu S, et al. Loss of adiponectin promotes intestinal carcinogenesis in Min and wild-type mice. Gastroenterology. 2011;140:2000-8, 8 e1-2.Google Scholar
  113. 113.
    Otani K, Kitayama J, Yasuda K, et al. Adiponectin suppresses tumorigenesis in Apc(Min)(/+) mice. Cancer Lett. 2010;288:177–82.PubMedGoogle Scholar
  114. 114.
    La Cava A, Matarese G. The weight of leptin in immunity. Nat Rev Immunol. 2004;4:371–9.PubMedGoogle Scholar
  115. 115.
    Procaccini C, Galgani M, De Rosa V, et al. Leptin: the prototypic adipocytokine and its role in NAFLD. Curr Pharm Des. 2010;16:1902–12.PubMedGoogle Scholar
  116. 116.
    Endo H, Hosono K, Uchiyama T, et al. Leptin acts as a growth factor for colorectal tumours at stages subsequent to tumour initiation in murine colon carcinogenesis. Gut. 2011;60:1363–71.PubMedGoogle Scholar
  117. 117.
    Hirosumi J, Tuncman G, Chang L, et al. A central role for JNK in obesity and insulin resistance. Nature. 2002;420:333–6.PubMedGoogle Scholar
  118. 118.
    Fang JY, Richardson BC. The MAPK signalling pathways and colorectal cancer. Lancet Oncol. 2005;6:322–7.PubMedGoogle Scholar
  119. 119.
    Endo H, Hosono K, Fujisawa T, et al. Involvement of JNK pathway in the promotion of the early stage of colorectal carcinogenesis under high-fat dietary conditions. Gut. 2009;58:1637–43.PubMedGoogle Scholar
  120. 120.
    Tsugane S, Inoue M. Insulin resistance and cancer: epidemiological evidence. Cancer Sci. 2010;101:1073–9.PubMedGoogle Scholar
  121. 121.
    Jung TW, Lee YJ, Lee MW, et al. Full-length adiponectin protects hepatocytes from palmitate-induced apoptosis via inhibition of c-Jun NH2 terminal kinase. FEBS J. 2009;276:2278–84.PubMedGoogle Scholar
  122. 122.
    Kim KY, Kim JK, Jeon JH, et al. c-Jun N-terminal kinase is involved in the suppression of adiponectin expression by TNF-alpha in 3T3-L1 adipocytes. Biochem Biophys Res Commun. 2005;327:460–7.PubMedGoogle Scholar
  123. 123.
    Stickel F, Hellerbrand C. Non-alcoholic fatty liver disease as a risk factor for hepatocellular carcinoma: mechanisms and implications. Gut. 2010;59:1303–7.PubMedGoogle Scholar
  124. 124.
    Wong VW, Wong GL, Tsang SW, et al. High prevalence of colorectal neoplasm in patients with non-alcoholic steatohepatitis. Gut. 2011;60:829–36.PubMedGoogle Scholar
  125. 125.
    Stadlmayr A, Aigner E, Steger B, et al. Nonalcoholic fatty liver disease: an independent risk factor for colorectal neoplasia. J Intern Med. 2011;270:41–9.PubMedGoogle Scholar
  126. 126.
    Hwang ST, Cho YK, Park JH, et al. Relationship of non-alcoholic fatty liver disease to colorectal adenomatous polyps. J Gastroenterol Hepatol. 2010;25:562–7.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Department of SurgeryTulane UniversityNew OrleansUSA
  2. 2.Christian Doppler Research Laboratory for Gut InflammationMedical University InnsbruckInnsbruckAustria

Personalised recommendations