The role of obesity in gastrointestinal cancer: Evidence and opinion

Therapeutic Advances in Gastroenterology

Volumn 7, Issue 1, 2014, Pages 38-50

  Donohoe, Claire L ^a   Ofarrell, Naoimh J ^a   Doyle, Suzanne L ^a   Reynolds, John V ^a  

^a TRINITY COLLEGE DUBLIN   (Ireland)

Author keywords

adipose tissue, carcinogenesis; inflammation; signalling pathways; visceral adiposity

Indexed keywords

ADIPOCYTOKINE;

CANCER EPIDEMIOLOGY; CHRONIC INFLAMMATION; DIGESTIVE SYSTEM CANCER; DISEASE ASSOCIATION; HUMAN; OBESITY; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION; SYSTEMIC DISEASE;

EID: 84891046577     PISSN: 1756283X     EISSN: 17562648     Source Type: Journal    
DOI: 10.1177/1756283X13501786     Document Type: Review

References (128)

1. Adams T. Stroup A. Gress R. Adams K. Calle E. Smith S. et al. (2009) Cancer incidence and mortality after gastric bypass surgery. Obesity (Silver Spring) 17: 796–802.
2. Aggarwal B. Kunnumakkara A. Harikumar K. Gupta S. Tharakan S. Koca C. et al. (2009) Signal Transducer and Activator of Transcription-3, Inflammation, and Cancer. Ann NY Acad Sci 1171 (1): 59–76.
3. Akiyama T. Yoneda M. Inamori M. Iida H. Endo H. Hosono K. et al. (2009) Visceral obesity and the risk of Barrett's esophagus in Japanese patients with non-alcoholic fatty liver disease. BMC Gastroenterol 9: 56.
4. Algire C. Amrein L. Zakikhani M. Panasci L. Pollak M. (2010) Metformin blocks the stimulative effect of a high-energy diet on colon carcinoma growth in vivo and is associated with reduced expression of fatty acid synthase. Endocrine-Related Cancer 17: 351–360.
5. Bassols J. Ortega F. Moreno-Navarrete J. Peral B. Ricart W. Fernandez-Real J. (2009) Study of the proinflammatory role of human differentiated omental adipocytes. J Cell Biochem 107: 1107–1117.
6. Bergman R. Ader M. (2000) Free fatty acids and pathogenesis of type 2 diabetes mellitus. Trends Endocrinol Metab 11: 351–356.
7. Bergström A. Pisani P. Tenet V. Wolk A. Adami H. (2001) Overweight as an avoidable cause of cancer in Europe. Int J Cancer 91: 421–430.
8. Brakenhielm E. Veitonmaki N. Cao R. Kihara S. Matsuzawa Y. Zhivotovsky B. et al. (2004) Adiponectin-induced antiangiogenesis and antitumor activity involve caspase-mediated endothelial cell apoptosis. Proc Natl Acad Sci U S A 101: 2476–2481.
9. Brown L. Swanson C. Gridley G. Swanson G. Schoenberg J. Greenberg R. et al. (1995) Adenocarcinoma of the esophagus: role of obesity and diet. J Natl Cancer Inst 87: 104–109.
10. Calle E. (2007) Obesity and cancer. BMJ 335: 1107–1108.
11. Calle E. Kaaks R. (2004) Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Nat Rev Cancer 4: 579–591.
12. Calle E. Rodriguez C. Walker-Thurmond K. Thun M. (2003) Overweight, obesity, and mortality from cancer in a prospectively studied cohort of US adults. N Engl J Med 348: 1625–1638.
13. Chow W. Blot W. Vaughan T. Risch H. Gammon M. Stanford J. et al. (1998) Body mass index and risk of adenocarcinomas of the esophagus and gastric cardia. J Natl Cancer Inst 90: 150–155.
14. Christou N. Lieberman M. Sampalis F. Sampalis J. (2008) Bariatric surgery reduces cancer risk in morbidly obese patients. Surg Obes Relat Dis 4: 691–695.
15. Colangelo L. Gapstur S. Gann P. Dyer A. Liu K. (2002) Colorectal cancer mortality and factors related to the insulin resistance syndrome. Cancer Epidemiol Biomarkers Prev 11: 385–391.
16. Cook M. Greenwood D. Hardie L. Wild C. Forman D. (2008) A systematic review and meta-analysis of the risk of increasing adiposity on Barrett's esophagus. Am J Gastroenterol 103: 292–300.
17. Corley D. Kubo A. Levin T. Block G. Habel L. Zhao W. et al. (2007 a) Abdominal obesity and body mass index as risk factors for Barrett's esophagus. Gastroenterology 133: 34–41; quiz 311.
18. Corley D. Kubo A. Zhao W. (2007 b) Abdominal obesity, ethnicity and gastro-oesophageal reflux symptoms. Gut 56: 756–762.
19. Creighton C. Sada Y. Zhang Y. Tsimelzon A. Wong H. Dave B. et al. (2012) A gene transcription signature of obesity in breast cancer. Breast Cancer Res Treat 132: 993–1000.
20. Cummings D. Foster K. (2003) Ghrelin-leptin tango in body-weight regulation. Gastroenterology 124: 1532–1535.
21. Curat C. Miranville A. Sengenes C. Diehl M. Tonus C. Busse R. et al. (2004) From blood monocytes to adipose tissue-resident macrophages: induction of diapedesis by human mature adipocytes. Diabetes 53: 1285–1292.
22. Dai Z. Xu Y. Niu L. (2007) Obesity and colorectal cancer risk: a meta-analysis of cohort studies. World J Gastroenterol 13: 4199–4206.
23. Das U. (2001) Is obesity an inflammatory condition? Nutrition 17: 953–966.
24. de Gonzalez A. Sweetland S. Spencer E. (2003) A meta-analysis of obesity and the risk of pancreatic cancer. Br J Cancer 89: 519–523.
25. Despres J. Lemieux I. (2006) Abdominal obesity and metabolic syndrome. Nature 444: 881–887.
26. Despres J. Moorjani S. Lupien P. Tremblay A. Nadeau A. Bouchard C. (1990) Regional distribution of body fat, plasma lipoproteins, and cardiovascular disease. Arteriosclerosis 10: 497–511.
27. Dieudonne M. Bussiere M. Dos Santos E. Leneveu M. Giudicelli Y. Pecquery R. (2006) Adiponectin mediates antiproliferative and apoptotic responses in human MCF 7 breast cancer cells. Biochem Biophys Res Commun 345: 271–279.
28. Donohoe C. Doyle S. McGarrigle S. Cathcart M. Daly E. O'Grady A. et al. (2012) Role of the insulin-like growth factor 1 axis and visceral adiposity in oesophageal adenocarcinoma. Br J Surg 99: 387–396.
29. Donohoe C. Doyle S. Reynolds J. (2011) Visceral adiposity, insulin resistance and cancer risk. Diabetol Metab Syndr 3: 12.
30. Doyle S. Donohoe C. Finn S. Howard J. Lithander F. Reynolds J. et al. (2012) IGF-1 and its receptor in esophageal cancer: association with adenocarcinoma and visceral obesity. Am J Gastroenterol 107:196–204.
31. Dunstan D. Zimmet P. Welborn T. de Courten M. Cameron A. Sicree R. et al. (2002) The rising prevalence of diabetes and impaired glucose tolerance: The Australian Diabetes, Obesity and Lifestyle Study. Diabetes Care 25: 829–834.
32. Edelstein Z. Farrow D. Bronner M. Rosen S. Vaughan T. (2007) Central adiposity and risk of Barrett's esophagus. Gastroenterology 133: 403–411.
33. Engel L. Chow W. Vaughan T. Gammon M. Risch H. Stanford J. et al. (2003) Population attributable risks of esophageal and gastric cancers.J Natl Cancer Inst 95: 1404–1413.
34. Engelman J. (2009) Targeting PI3K signalling in cancer: opportunities, challenges and limitations. Nat Rev Cancer 9: 550–562.
35. Esposito K. Giugliano D. (2004) The metabolic syndrome and inflammation: association or causation? Nutr Metab Cardiovasc Dis 14: 228–232.
36. Feldser D. Agani F. Iyer N. Pak B. Ferreira G. Semenza G. (1999) Reciprocal positive regulation of hypoxia-inducible factor 1alpha and insulin-like growth factor 2. Cancer Res 59: 3915–3918.
37. Ford E. Li C. Zhao G. Tsai J. (2011) Trends in obesity and abdominal obesity among adults in the United States from 1999–2008. Int J Obes 35: 736–743.
38. Fukuda R. Hirota K. Fan F. Jung Y. Ellis L. Semenza G. (2002) Insulin-like growth factor 1 induces hypoxia-inducible factor 1-mediated vascular endothelial growth factor expression, which is dependent on MAP kinase and phosphatidylinositol 3-kinase signaling in colon cancer cells. J Biol Chem 277: 38205–38211.
39. World Cancer Research Fund (2007) Food, Nutrition, Physical Activity and the Prevention of Cancer: A Global Perspective, Second Expert Report. Washington: American Institute for Cancer Research. Available at: http://www.dietandcancerreport.org/expert_report/
40. Galic S. Oakhill J. Steinberg G. (2010) Adipose tissue as an endocrine organ. Mol Cell Endocrinol 316: 129–139.
41. Garcia R. Jove R. (1998) Activation of STAT transcription factors in oncogenic tyrosine kinase signaling. J Biomed Sci 5 (2): 79–85.
42. Ghanim H. Aljada A. Hofmeyer D. Syed T. Mohanty P. Dandona P. (2004) Circulating mononuclear cells in the obese are in a proinflammatory state. Circulation 110: 1564–1571.
43. Giovannucci E. Colditz G. Stampfer M. Willett W. (1996) Physical activity, obesity, and risk of colorectal adenoma in women (United States). Cancer Causes and Control 7: 253–263.
44. Greenberg A. McDaniel M. (2002) Identifying the links between obesity, insulin resistance and beta-cell function:potential role of adipocyte-derived cytokines in the pathogenesis of type 2 diabetes. Eur J Clin Invest 32(Suppl. 3): 24–34.
45. Guh D. Zhang W. Bansback N. Amarsi Z. Birmingham C. Anis A. (2009) The incidence of co-morbidities related to obesity and overweight: A systematic review and meta-analysis. BMC Public Health 9 (1): 88.
46. Harriss D. Atkinson G. George K. Cable N. Reilly T. Haboubi N. et al. (2009) Lifestyle factors and colorectal cancer risk (1): systematic review and meta-analysis of associations with body mass index. Colorectal Disease 11: 547–563.
47. Haura E. Turkson J. Jove R. (2005) Mechanisms of disease: Insights into the emerging role of signal transducers and activators of transcription in cancer. Nat Clin Practice Oncol 2: 315–324.
48. Healy L. Ryan A. Pidgeon G. Ravi N. Reynolds J. (2010) Lack of differential pattern in central adiposity and metabolic syndrome in Barrett's esophagus and gastroesophageal reflux disease. Dis Esophagus 23: 386–391.
49. Howard J. Beddy P. Ennis D. Keogan M. Pidgeon G. Reynolds J. (2010) Associations between leptin and adiponectin receptor upregulation, visceral obesity and tumour stage in oesophageal and junctional adenocarcinoma. Br J Surg 97: 1020–1027.
50. Huang P. Han J. Hui L. (2010) MAPK signaling in inflammation-associated cancer development. Protein Cell 1: 218–226.
51. Huffman D. Augenlicht L. Zhang X. Lofrese J. Atzmon G. Chamberland J. et al. (2013) Abdominal obesity, independent from caloric intake, accounts for the development of intestinal tumors in Apc1638N/+ female mice. Cancer Prev Res 6: 177–187.
52. Jain S. Bird R. (2010) Elevated expression of tumor necrosis factor-alpha signaling molecules in colonic tumors of Zucker obese (fa/fa) rats. Int J Cancer 127: 2042–2050.
53. Jing N. Tweardy D. (2005) Targeting Stat 3 in cancer therapy. Anti-Cancer Drugs 16: 601–607.
54. Kadowaki T. Yamauchi T. (2005) Adiponectin and adiponectin receptors. Endocr Rev 26: 439–451.
55. Kalaany N. Sabatini D. (2009) Tumours with PI3K activation are resistant to dietary restriction. Nature 458: 725–731.
56. Katiyar S. Meeran S. (2007) Obesity increases the risk of UV radiation-induced oxidative stress and activation of MAPK and NF-[kappa]B signaling. Free Radical Biol Med 42: 299–310.
57. Kershaw E. Flier J. (2004) Adipose tissue as an endocrine organ. J Clin Endocrinol Metab 89: 2548–2556.
58. Kim Y. Kim Y. Lee S. (2009) An association between colonic adenoma and abdominal obesity: a cross-sectional study. BMC Gastroenterology 9 (1): 4.
59. Kissebah A. Vydelingum N. Murray R. Evans D. Kalkhoff R. Adams P. (1982) Relation of body fat distribution to metabolic complications of obesity. J Clin Endocrinol Metab 54: 254–260.
60. Kodelja V. Muller C. Tenorio S. Schebesch C. Orfanos C. Goerdt S. (1997) Differences in angiogenic potential of classically vs alternatively activated macrophages. Immunobiology 197: 478–493.
61. Kono S. Handa K. Hayabuchi H. Kiyohara C. Inoue H. Marugame T. et al. (1999) Obesity, weight gain and risk of colon adenomas in Japanese men. Jpn J Cancer Res 90: 805–811.
62. Kopfstein L. Christofori G. (2006) Metastasis: cell-autonomous mechanisms versus contributions by the tumor microenvironment. Cell Mol Life Sci 63: 449–468.
63. Kortylewski M. Kujawski M. Wang T. Wei S. Zhang S. Pilon-Thomas S. et al. (2005) Inhibiting Stat 3 signaling in the hematopoietic system elicits multicomponent antitumor immunity. Nat Med 11: 1314–1321.
64. Lagergren J. Bergstrom R. Lindgren A. Nyren O. (1999 a) Symptomatic gastroesophageal reflux as a risk factor for esophageal adenocarcinoma. N Engl J Med 340: 825–831.
65. Lagergren J. Bergstrom R. Nyren O. (1999 b) Association between body mass and adenocarcinoma of the esophagus and gastric cardia. Ann Intern Med 130: 883–890.
66. Larsson S. Orsini N. Wolk A. (2007) Body mass index and pancreatic cancer risk: A meta-analysis of prospective studies. Int J Cancer 120: 1993–1998.
67. Larsson S. Wolk A. (2007 a) Obesity and colon and rectal cancer risk: a meta-analysis of prospective studies. Am J Clin Nutr 86: 556–565.
68. Larsson S. Wolk A. (2007 b) Obesity and the risk of gallbladder cancer: a meta-analysis. Br J Cancer 96: 1457–1461.
69. Larsson S. Wolk A. (2007 c) Overweight, obesity and risk of liver cancer: a meta-analysis of cohort studies. Br J Cancer 97: 1005–1008.
70. Li D. Morris J. Liu J. Hassan M. Day R. Bondy M. et al. (2009) Body mass index and risk, age of onset, and survival in patients with pancreatic cancer. JAMA 301: 2553–2562.
71. Liu P. Cheng H. Roberts T. Zhao J. (2009) Targeting the phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug Discov 8: 627–644.
72. Lynch T. Bell D. Sordella R. Gurubhagavatula S. Okimoto R. Brannigan B. et al. (2004) Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 350: 2129–2139.
73. Lysaght J. van der Stok E. Allott E. Casey R. Donohoe C. Howard J. et al. (2011) Pro-inflammatory and tumour proliferative properties of excess visceral adipose tissue. Cancer Lett 312: 62–72.
74. Mendall M. Patel P. Asante M. Ballam L. Morris J. Strachan D. et al. (1997) Relation of serum cytokine concentrations to cardiovascular risk factors and coronary heart disease. Heart 78: 273–277.
75. Moghaddam A. Woodward M. Huxley R. (2007) Obesity and risk of colorectal cancer: a meta-analysis of 31 studies with 70,000 events. Cancer Epidemiol Biomarkers Prev 16: 2533–2547.
76. Moller D. Flier J. (1991) Insulin resistance–mechanisms, syndromes, and implications. N Engl J Med 325: 938–948.
77. Moore L. Bradlee M. Singer M. Splansky G. Proctor M. Ellison R. et al. (2004) BMI and waist circumference as predictors of lifetime colon cancer risk in Framingham Study adults. Int J Obes Relat Metab Disord 28: 559–567.
78. Moore T. Beltran L. Carbajal S. Strom S. Traag J. Hursting S. et al. (2008) Dietary energy balance modulates signaling through the Akt/mammalian target of rapamycin pathways in multiple epithelial tissues. Cancer Prev Res 1: 65–76.
79. Nedungadi T. Clegg D. (2009) Sexual dimorphism in body fat distribution and risk for cardiovascular diseases. J Cardiovasc Transl Res 2: 321–327.
80. Neels J. Olefsky J. (2006) Inflamed fat: what starts the fire? J Clin Invest 116: 33–35.
81. Nieman D. Henson D. Nehlsen-Cannarella S. Ekkens M. Utter A. Butterworth D. et al. (1999) Influence of obesity on immune function. J Am Dietetic Assoc 99: 294–299.
82. Nishimura S. Manabe I. Nagasaki M. Eto K. Yamashita H. Ohsugi M. et al. (2009) CD8+ effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity. Nat Med 15: 914–920.
83. Oberlin D. Fellbaum C. Eppler E. (2009) Insulin-like growth factor I messenger RNA and protein are expressed in the human lymph node and distinctly confined to subtypes of macrophages, antigen-presenting cells, lymphocytes and endothelial cells. Immunology 128: 342–350.
84. Ogden C. Carroll M. Curtin L. McDowell M. Tabak C. Flegal K. (2006) Prevalence of overweight and obesity in the United States, 1999–2004. JAMA 295: 1549–1555.
85. Park E. Lee J. Yu G. He G. Ali S. Holzer R. et al. (2010) Dietary and genetic obesity promote liver inflammation and tumorigenesis by enhancing IL-6 and TNF expression. Cell 140: 197–208.
86. Pischon T. Lahmann P. Boeing H. Friedenreich C. Norat T. Tjonneland A. et al. (2006) body size and risk of colon and rectal cancer in the European Prospective Investigation Into Cancer and Nutrition (EPIC). J Natl Cancer Inst 98: 920–931.
87. Pollak M. (2012) The insulin and insulin-like growth factor receptor family in neoplasia: an update. Nat Rev Cancer 12: 159–169.
88. Quesnelle K. Boehm A. Grandis J. (2007) STAT-mediated EGFR signaling in cancer. J Cellular Biochem 102: 311–319.
89. Renehan A. Roberts D. Dive C. (2008 a) Obesity and cancer: pathophysiological and biological mechanisms. Arch Physiol Biochem 114: 71–83.
90. Renehan A. Tyson M. Egger M. Heller R. Zwahlen M. (2008 b) Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet 371: 569–578.
91. Roberts D. Dive C. Renehan A. (2010) Biological mechanisms linking obesity and cancer risk: new perspectives. Annu Rev Med 61: 301–316.
92. Ryan A. Rowley S. Fitzgerald A. Ravi N. Reynolds J. (2006) Adenocarcinoma of the oesophagus and gastric cardia: male preponderance in association with obesity. Eur J Cancer 42: 1151–1158.
93. Sartipy P. Loskutoff D. (2003) Monocyte chemoattractant protein 1 in obesity and insulin resistance. Proc Natl Acad Sci U S A 100: 7265–7270.
94. Schaffler A. Muller-Ladner U. Scholmerich J. Buchler C. (2006) Role of adipose tissue as an inflammatory organ in human diseases. Endocr Rev 27: 449–467.
95. Schaffler A. Scholmerich J. Buchler C. (2005) Mechanisms of Disease: adipocytokines and visceral adipose tissue–emerging role in intestinal and mesenteric diseases. Nat Clin Pract Gastroenterol Hepatol 2: 103–111.
96. Schindler C. Darnell J. Jr (1995) Transcriptional responses to polypeptide ligands: the JAK-STAT pathway. Ann Rev Biochem 64: 621–651.
97. Schoen R. Tangen C. Kuller L. Burke G. Cushman M. Tracy R. et al. (1999) Increased blood glucose and insulin, body size, and incident colorectal cancer. J Natl Cancer Inst 91: 1147–1154.
98. Sebolt-Leopold J. Herrera R. (2004) Targeting the mitogen-activated protein kinase cascade to treat cancer. Nat Rev Cancer 4: 937–947.
99. Serdula M. Ivery D. Coates R. Freedman D. Williamson D. Byers T. (1993) Do obese children become obese adults? A review of the literature. Prev Med 22: 167–177.
100. Sharma S. Katiyar S. (2010) Leptin deficiency-induced obesity exacerbates ultraviolet B radiation-induced cyclooxygenase-2 expression and cell survival signals in ultraviolet B-irradiated mouse skin. Toxicol Appl Pharmacol 244: 328–335.
101. Shoelson S. Lee J. Goldfine A. (2006) Inflammation and insulin resistance. J Clin Invest 116: 1793–1801.
102. Siddiquee K. Zhang S. Guida W. Blaskovich M. Greedy B. Lawrence H. et al. (2007) Selective chemical probe inhibitor of Stat3, identified through structure-based virtual screening, induces antitumor activity. Proc Natl Acad Sci U S A 104: 7391–7396.
103. Sjostrom L. Gummesson A. Sjostrom C. Narbro K. Peltonen M. Wedel H. 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: 653–662.
104. Snijder M. Dam R. Visser M. Seidell J. (2006) What aspects of body fat are particularly hazardous and how do we measure them? Int J Epidemiol 35: 83–92.
105. Spiotto M. Chung T. (2000) STAT 3 mediates IL-6-induced neuroendocrine differentiation in prostate cancer cells. Prostate 42: 186–195.
106. Steffen A. Schulze M. Pischon T. Dietrich T. Molina E. Chirlaque M. et al. (2009) Anthropometry and esophageal cancer risk in the European prospective investigation into cancer and nutrition. Cancer Epidemiol Biomarkers Prev 18: 2079–2089.
107. Sunderkotter C. Steinbrink K. Goebeler M. Bhardwaj R. Sorg C. (1994) Macrophages and angiogenesis. J Leukoc Biol 55: 410–422.
108. Taron M. Ichinose Y. Rosell R. Mok T. Massuti B. Zamora L. et al. (2005) Activating mutations in the tyrosine kinase domain of the epidermal growth factor receptor are associated with improved survival in gefitinib-treated chemorefractory lung adenocarcinomas. Clin Cancer Res 11: 5878–5885.
109. Trayhurn P. Wood I. (2004) Adipokines: inflammation and the pleiotropic role of white adipose tissue. Br J Nutr 92: 347–355.
110. Trevisan M. Liu J. Muti P. Misciagna G. Menotti A. Fucci F. (2001) Markers of insulin resistance and colorectal cancer mortality. Cancer Epidemiol Biomarkers Prev 10: 937–941.
111. Troiano R. Flegal K. (1999) Overweight prevalence among youth in the United States: why so many different numbers? Int J Obes Relat Metab Disord 23(Suppl. 2): S22–S27.
112. Turkson J. (2004) STAT proteins as novel targets for cancer drug discovery. Expert opinion on therapeutic targets 8: 409–422.
113. van Kruijsdijk R. van der Wall E. Visseren F. (2009) Obesity and cancer: the role of dysfunctional adipose tissue. Cancer Epidemiol Biomarkers Prev 18: 2569–2578.
114. Vaughan T. Davis S. Kristal A. Thomas D. (1995) Obesity, alcohol, and tobacco as risk factors for cancers of the esophagus and gastric cardia: adenocarcinoma versus squamous cell carcinoma. Cancer Epidemiol Biomarkers Prev 4: 85–92.
115. Vohl M. Sladek R. Robitaille J. Gurd S. Marceau P. Richard D. et al. (2004) A survey of genes differentially expressed in subcutaneous and visceral adipose tissue in men. Obes Res 12: 1217–1222.
116. Wajchenberg B. (2000) Subcutaneous and visceral adipose tissue: their relation to the metabolic syndrome. Endocr Rev 21: 697–738.
117. Wang Y. Jacobs E. Patel A. Rodriguez C. McCullough M. Thun M. et al. (2008) A prospective study of waist circumference and body mass index in relation to colorectal cancer incidence. Cancer Causes Control 19: 783–792.
118. Wang Y. Lam K. Xu A. (2007) Adiponectin as a negative regulator in obesity-related mammary carcinogenesis. Cell Res 17: 280–282.
119. Weerasinghe P. Garcia G.E. Zhu Q. Yuan P. Feng L. Mao L. et al. (2007) Inhibition of Stat 3 activation and tumor growth suppression of non-small cell lung cancer by G-quartet oligonucleotides. Int J Oncol 31: 129–136.
120. Weisberg S. McCann D. Desai M. Rosenbaum M. Leibel R. Ferrante A. Jr (2003) Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 112: 1796–1808.
121. Wellen K. Hotamisligil G. (2003) Obesity-induced inflammatory changes in adipose tissue. J Clin Invest 112: 1785–1788.
122. WHO (2000) Obesity: preventing and managing the global epidemic. Report of a WHO consultation. World Health Organ Tech Rep Ser 894: i–xii, 1–253.
123. Xu H. Barnes G. Yang Q. Tan G. Yang D. Chou C. et al. (2003) Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest 112: 1821–1830.
124. Ya-Yu W. Shih-Yi L. Wen-An L. Pi-Hwa L. Wayne Huey-Herng S. (2005) Association between adenomas of rectosigmoid colon and metabolic syndrome features in a Chinese population. J Gastroenterol Hepatol 20: 1410–1415.
125. Yamauchi T. Kamon J. Waki H. Terauchi Y. Kubota N. Hara K. et al. (2001) The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med 7: 941–946.
126. Yu H. Pardoll D. Jove R. (2009) STATs in cancer inflammation and immunity: a leading role for STAT3. Nat Rev Cancer 9: 798–809.
127. Yue P. Turkson J. (2009) Targeting STAT 3 in cancer: how successful are we? Exp Opin Invest Drugs 18: 45–56.
128. Zaninotto P. Wardle H. Stamatakis E. Mindell J. Head J. (2006) Forecasting Obesity to 2010. National Centre for Social research, Department of Health, London. Available at: http://www.erpho.org.uk/Download/Public/15199/1/ForecastingObesityTo2010.pdf.