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Gastroenterology Research and Practice
Volume 2012 (2012), Article ID 483623, 10 pages
http://dx.doi.org/10.1155/2012/483623
Review Article

Metabolic Syndrome, Obesity, and Gastrointestinal Cancer

Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Takamatsu, Kagawa 761-0793, Japan

Received 29 June 2012; Revised 18 November 2012; Accepted 18 November 2012

Academic Editor: Dan L. Dumitrascu

Copyright © 2012 Shintaro Fujihara et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. D. L. Wingard, E. Barrett Connor, M. H. Criqui, and L. Suarez, “Clustering of heart disease risk factors in diabetic compared to nondiabetic adults,” American Journal of Epidemiology, vol. 117, no. 1, pp. 19–26, 1983. View at Scopus
  2. G. M. Reaven, “Role of insulin resistance in human disease,” Diabetes, vol. 37, no. 12, pp. 1595–1607, 1988. View at Scopus
  3. K. G. Alberti, P. Z. Zimmet, and WHO Consultation, “Definition, diagnosis, and classification of diabetes mellitus and its complications—part 1: diagnosis and classification of diabetes mellitus. Provisional report of a WHO consultation,” Diabetes Medicine, vol. 15, pp. 539–553, 1998.
  4. B. Isomaa, P. Almgren, T. Tuomi et al., “Cardiovascular morbidity and mortality associated with the metabolic syndrome,” Diabetes Care, vol. 24, no. 4, pp. 683–689, 2001. View at Scopus
  5. J. I. Cleeman, “Executive summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III),” Journal of the American Medical Association, vol. 285, no. 19, pp. 2486–2497, 2001. View at Scopus
  6. R. A. DeFronzo and E. Ferrannini, “Insulin resistance: a multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease,” Diabetes Care, vol. 14, no. 3, pp. 173–194, 1991. View at Scopus
  7. R. S. Lindsay and B. V. Howard, “Cardiovascular risk associated with the metabolic syndrome,” Current Diabetes Reports, vol. 4, no. 1, pp. 63–68, 2004. View at Scopus
  8. K. K. Koh, S. H. Han, and M. J. Quon, “Inflammatory markers and the metabolic syndrome: insights from therapeutic interventions,” Journal of the American College of Cardiology, vol. 46, no. 11, pp. 1978–1985, 2005. View at Publisher · View at Google Scholar · View at Scopus
  9. P. M. Ridker, J. E. Buring, N. R. Cook, and N. Rifai, “C-reactive protein, the metabolic syndrome, and risk of incident cardiovascular events: an 8-year follow-up of 14 719 initially healthy American women,” Circulation, vol. 107, no. 3, pp. 391–397, 2003. View at Scopus
  10. A. Festa, R. D'Agostino, G. Howard, L. Mykkänen, R. P. Tracy, and S. M. Haffner, “Chronic subclinical inflammation as part of the insulin resistance syndrome: the insulin resistance atherosclerosis study (IRAS),” Circulation, vol. 102, no. 1, pp. 42–47, 2000. View at Scopus
  11. P. M. Ridker, “Clinical application of C-reactive protein for cardiovascular disease detection and prevention,” Circulation, vol. 107, no. 3, pp. 363–369, 2003. View at Publisher · View at Google Scholar · View at Scopus
  12. A. D. Pradhan, J. E. Manson, N. Rifai, J. E. Buring, and P. M. Ridker, “C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus,” Journal of the American Medical Association, vol. 286, no. 3, pp. 327–334, 2001. View at Scopus
  13. A. Festa, R. D'Agostino, R. P. Tracy, and S. M. Haffner, “Elevated levels of acute-phase proteins and plasminogen activator inhibitor-1 predict the development of type 2 diabetes: the insulin resistance atherosclerosis study,” Diabetes, vol. 51, no. 4, pp. 1131–1137, 2002. View at Scopus
  14. “Obesity: preventing and managing the global epidemic. Report of a WHO consultation,” World Health Organization Technical Report Series, vol. 894, pp. 1–253, 2000.
  15. E. E. Kershaw and J. S. Flier, “Adipose tissue as an endocrine organ,” Journal of Clinical Endocrinology and Metabolism, vol. 89, no. 6, pp. 2548–2556, 2004. View at Publisher · View at Google Scholar · View at Scopus
  16. M. C. Vohl, R. Sladek, J. Robitaille et al., “A survey of genes differentially expressed in subcutaneous and visceral adipose tissue in men,” Obesity Research, vol. 12, no. 8, pp. 1217–1222, 2004. View at Scopus
  17. W. Zheng, D. F. McLerran, B. Rolland et al., “Association between body-mass index and risk of death in more than 1 million Asians,” New England Journal of Medicine, vol. 364, no. 8, pp. 719–729, 2011. View at Publisher · View at Google Scholar · View at Scopus
  18. R. C. M. Van Kruijsdijk, E. Van Der Wall, and F. L. J. Visseren, “Obesity and cancer: the role of dysfunctional adipose tissue,” Cancer Epidemiology Biomarkers and Prevention, vol. 18, no. 10, pp. 2569–2578, 2009. View at Publisher · View at Google Scholar · View at Scopus
  19. A. S. Gami, B. J. Witt, D. E. Howard et al., “Metabolic syndrome and risk of incident cardiovascular events and death. A systematic review and meta-analysis of longitudinal studies,” Journal of the American College of Cardiology, vol. 49, no. 4, pp. 403–414, 2007. View at Publisher · View at Google Scholar · View at Scopus
  20. E. S. Ford, “Prevalence of the metabolic syndrome defined by the international diabetes federation among adults in the U.S,” Diabetes Care, vol. 28, no. 11, pp. 2745–2749, 2005. View at Publisher · View at Google Scholar · View at Scopus
  21. S. M. Grundy, J. I. Cleeman, S. R. Daniels et al., “Diagnosis and management of the metabolic syndrome. An American Heart Association/National Heart, Lung, and Blood Institute scientific statement,” Circulation, vol. 112, no. 17, pp. 2735–2752, 2005. View at Publisher · View at Google Scholar · View at Scopus
  22. The Examination Committee of the Criteria for Metabolic Syndrome in Japan, “Definition and criteria of the metabolic syndrome in Japan,” Japan Internal Medicine, vol. 94, pp. 188–201, 2005 (Japanese).
  23. International Diabetes Federation, “The IDF Consensus Worldwide Definition of the Metabolic Syndrome,” International Diabetes Federation, Belgium, Brussels, 2006.
  24. C. Pelucchi, E. Negri, R. Talamini et al., “Metabolic syndrome is associated with colorectal cancer in men,” European Journal of Cancer, vol. 46, no. 10, pp. 1866–1872, 2010. View at Publisher · View at Google Scholar · View at Scopus
  25. R. L. Ahmed, K. H. Schmitz, K. E. Anderson, W. D. Rosamond, and A. R. Folsom, “The metabolic syndrome and risk of incident colorectal cancer,” Cancer, vol. 107, no. 1, pp. 28–36, 2006. View at Publisher · View at Google Scholar · View at Scopus
  26. M. Hamaguchi, T. Kojima, N. Takeda et al., “The metabolic syndrome as a predictor of nonalcoholic fatty liver disease,” Annals of Internal Medicine, vol. 143, no. 10, pp. 722–I70, 2005. View at Scopus
  27. G. Marchesini, E. Bugianesi, G. Forlani et al., “Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome,” Hepatology, vol. 37, no. 4, pp. 917–923, 2003. View at Publisher · View at Google Scholar · View at Scopus
  28. T. M. Welzel, B. I. Graubard, S. Zeuzem, H. B. El-Serag, J. A. Davila, and K. A. Mcglynn, “Metabolic syndrome increases the risk of primary liver cancer in the United States: a study in the SEER-medicare database,” Hepatology, vol. 54, no. 2, pp. 463–471, 2011. View at Publisher · View at Google Scholar · View at Scopus
  29. E. E. Calle, C. Rodriguez, K. Walker-Thurmond, and M. J. Thun, “Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. Adults,” New England Journal of Medicine, vol. 348, no. 17, pp. 1625–1638, 2003. View at Publisher · View at Google Scholar · View at Scopus
  30. E. S. Ford, W. H. Giles, and W. H. Dietz, “Prevalence of the metabolic syndrome among US adults. Findings from the Third National Health and Nutrition Examination Survey,” Journal of the American Medical Association, vol. 287, no. 3, pp. 356–359, 2002. View at Scopus
  31. E. S. Ford, “Prevalence of the metabolic syndrome defined by the international diabetes federation among adults in the U.S,” Diabetes Care, vol. 28, no. 11, pp. 2745–2749, 2005. View at Publisher · View at Google Scholar · View at Scopus
  32. P. W. F. Wilson, R. B. D'Agostino, H. Parise, L. Sullivan, and J. B. Meigs, “Metabolic syndrome as a precursor of cardiovascular disease and type 2 diabetes mellitus,” Circulation, vol. 112, no. 20, pp. 3066–3072, 2005. View at Publisher · View at Google Scholar · View at Scopus
  33. C. Invitti, L. Gilardini, G. Viberti et al., “Obesity and the metabolic syndrome in children and adolescents,” New England Journal of Medicine, vol. 351, no. 11, pp. 1146–1148, 2004. View at Publisher · View at Google Scholar · View at Scopus
  34. T. J. Roseboom, J. H. P. Van der Meulen, A. C. J. Ravelli, C. Osmond, D. J. P. Barker, and O. P. Bleker, “Effects of prenatal exposure to the Dutch famine on adult disease in later life: an overview,” Twin Research, vol. 185, no. 1-2, pp. 93–98, 2001.
  35. R. Barouki, P. D. Gluckman, and P. Grandjean, “Developmental origins of non-communicable disease: implications for research and public health,” Environmental Health, vol. 11, p. 42, 2012.
  36. M. K. Skinner, M. Manikkam, and C. Guerrero-Bosagna, “Epigenetic transgenerational actions of endocrine disruptors,” Reproductive Toxicology, vol. 31, no. 3, pp. 337–343, 2011. View at Publisher · View at Google Scholar · View at Scopus
  37. B. L. Wajchenberg, “Subcutaneous and visceral adipose tissue: their relation to the metabolic syndrome,” Endocrine Reviews, vol. 21, no. 6, pp. 697–738, 2000. View at Publisher · View at Google Scholar · View at Scopus
  38. B. J. John, S. Irukulla, A. M. Abulafi, D. Kumar, and M. A. Mendall, “Systematic review: adipose tissue, obesity and gastrointestinal diseases,” Alimentary Pharmacology and Therapeutics, vol. 23, no. 11, pp. 1511–1523, 2006. View at Publisher · View at Google Scholar · View at Scopus
  39. S. D. Hursting and M. J. Hursting, “Growth signals, inflammation, and vascular perturbations: mechanistic links between obesity, metabolic syndrome, and cancer,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 32, pp. 1766–1770, 2012.
  40. J. M. Argilés and F. J. López-Soriano, “Insulin and cancer,” International Journal of Oncology, vol. 18, no. 4, pp. 683–687, 2001. View at Scopus
  41. L. F. Watkins, L. R. Lewis, and A. E. Levine, “Characterization of the synergistic effect of insulin and transferrin and the regulation of their receptors on a human colon carcinoma cell line,” International Journal of Cancer, vol. 45, no. 2, pp. 372–375, 1990. View at Scopus
  42. M. Koenuma, T. Yamori, and T. Tsuruo, “Insulin and insulin-like growth factor 1 stimulate proliferation of metastatic variants of colon carcinoma 26,” Japanese Journal of Cancer Research, vol. 80, no. 1, pp. 51–58, 1989. View at Scopus
  43. J. Bjork, J. Nilsson, R. Hultcrantz, and C. Johansson, “Growth-regulatory effects of sensory neuropeptides, epidermal growth factor, insulin, and somatostatin on the non-transformed intestinal epithelial cell line IEC-6 and the colon cancer cell line HT29,” Scandinavian Journal of Gastroenterology, vol. 28, no. 10, pp. 879–884, 1993. View at Scopus
  44. R. Kaaks and A. Lukanova, “Energy balance and cancer: the role of insulin and insulin-like growth factor-I,” Proceedings of the Nutrition Society, vol. 60, no. 1, pp. 91–106, 2001. View at Scopus
  45. S. A. Aaronson, “Growth factors and cancer,” Science, vol. 254, no. 5035, pp. 1146–1153, 1991. View at Scopus
  46. M. V. Grau, J. R. Rees, and J. A. Baron, “Chemoprevention in gastrointestinal cancers: current status,” Basic and Clinical Pharmacology and Toxicology, vol. 98, no. 3, pp. 281–287, 2006. View at Publisher · View at Google Scholar · View at Scopus
  47. E. Giovannucci, E. B. Rimm, M. J. Stampfer, G. A. Colditz, A. Ascherio, and W. C. Willett, “Aspirin use and the risk for colorectal cancer and adenoma in male health professionals,” Annals of Internal Medicine, vol. 121, no. 4, pp. 241–246, 1994. View at Scopus
  48. A. Poullis, R. Foster, A. Shetty, M. K. Fagerhol, and M. A. Mendall, “Bowel inflammation as measured by fecal calprotectin: a link between lifestyle factors and colorectal cancer risk,” Cancer Epidemiology Biomarkers and Prevention, vol. 13, no. 2, pp. 279–284, 2004. View at Publisher · View at Google Scholar · View at Scopus
  49. T. Kadowaki, K. Hara, T. Yamauchi, Y. Terauchi, K. Tobe, and R. Nagai, “Molecular mechanism of insulin resistance and obesity,” Experimental Biology and Medicine, vol. 228, no. 10, pp. 1111–1117, 2003. View at Scopus
  50. E. Giovannucci, “Insulin and colen cancer,” Cancer Causes and Control, vol. 6, no. 2, pp. 164–179, 1995. View at Publisher · View at Google Scholar · View at Scopus
  51. J. Ma, M. N. Pollak, E. Giovannucci et al., “Prospective study of colorectal cancer risk in men and plasma levels of insulin-like growth factor (IGF)-I and IGF-binding protein-3,” Journal of the National Cancer Institute, vol. 91, no. 7, pp. 620–625, 1999. View at Scopus
  52. J. Ma, E. Giovannucci, M. Pollak et al., “A prospective study of plasma C-peptide and colorectal cancer risk in men,” Journal of the National Cancer Institute, vol. 96, no. 7, pp. 546–553, 2004. View at Scopus
  53. D. Ennishi, K. Shitara, H. Ito, et al., “Association between insulin-like growth factor-1 polymorphisms and stomach cancer risk in a Japanese population,” Cancer Science, vol. 102, no. 12, pp. 2231–2235, 2011.
  54. K. Shitara, S. Ito, K. Misawa, et al., “Genetic polymorphism of IGF-1 predicts recurrence in patients with gastric cancer who have undergone curative gastrectomy,” Annals of Oncology, vol. 23, no. 3, pp. 659–664, 2012.
  55. M. B. Schneider, H. Matsuzaki, J. Haorah et al., “Prevention of pancreatic cancer induction in hamsters by metformin,” Gastroenterology, vol. 120, no. 5, pp. 1263–1270, 2001. View at Scopus
  56. K. Kato, J. Gong, and H. Iwama, “The antidiabetic drug metformin inhibits gastric cancer cell proliferation in vitro and in vivo,” Molecular Cancer Therapeutics, vol. 11, no. 3, pp. 549–560, 2012.
  57. H. Tilg and A. R. Moschen, “Adipocytokines: mediators linking adipose tissue, inflammation and immunity,” Nature Reviews Immunology, vol. 6, no. 10, pp. 772–783, 2006. View at Publisher · View at Google Scholar · View at Scopus
  58. T. Kadowaki and T. Yamauchi, “Adiponectin and adiponectin receptors,” Endocrine Reviews, vol. 26, no. 3, pp. 439–451, 2005. View at Publisher · View at Google Scholar · View at Scopus
  59. D. P. Rose, D. Komninou, and G. D. Stephenson, “Obesity, adipocytokines, and insulin resistance in breast cancer,” Obesity Reviews, vol. 5, no. 3, pp. 153–165, 2004. View at Publisher · View at Google Scholar · View at Scopus
  60. M. Ishikawa, J. Kitayama, S. Kazama, T. Hiramatsu, K. Hatano, and H. Nagawa, “Plasma adiponectin and gastric cancer,” Clinical Cancer Research, vol. 11, no. 2 I, pp. 466–472, 2005. View at Scopus
  61. N. K. Saxena, P. P. Fu, A. Nagalingam et al., “Adiponectin modulates C-Jun N-terminal kinase and mammalian target of rapamycin and inhibits hepatocellular carcinoma,” Gastroenterology, vol. 139, no. 5, pp. 1762–1773, 2010. View at Publisher · View at Google Scholar · View at Scopus
  62. M. Mutoh, N. Teraoka, S. Takasu et al., “Loss of adiponectin promotes intestinal carcinogenesis in min and wild-type mice,” Gastroenterology, vol. 140, no. 7, pp. 2000–2008, 2011. View at Publisher · View at Google Scholar · View at Scopus
  63. T. Kadowaki, T. Yamauchi, N. Kubota, K. Hara, K. Ueki, and K. Tobe, “Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome,” Journal of Clinical Investigation, vol. 116, no. 7, pp. 1784–1792, 2006. View at Publisher · View at Google Scholar · View at Scopus
  64. A. Y. Kim, Y. S. Lee, K. H. Kim et al., “Adiponectin represses colon cancer cell proliferation via AdipoR1- and -R2-mediated AMPK activation,” Molecular Endocrinology, vol. 24, no. 7, pp. 1441–1452, 2010. View at Publisher · View at Google Scholar · View at Scopus
  65. D. Barb, C. J. Williams, A. K. Neuwirth, and C. S. Mantzoros, “Adiponectin in relation to malignancies: a review of existing basic research and clinical evidence,” The American Journal of Clinical Nutrition, vol. 86, no. 3, pp. s858–866, 2007. View at Scopus
  66. K. Yoneda, A. Tomimoto, H. Endo et al., “Expression of adiponectin receptors, AdipoR1 and AdipoR2, in normal colon epithelium and colon cancer tissue,” Oncology Reports, vol. 20, no. 3, pp. 479–483, 2008. View at Publisher · View at Google Scholar · View at Scopus
  67. D. E. Cummings and K. E. Foster, “Ghrelin-Leptin tango in body-weight regulation,” Gastroenterology, vol. 124, no. 5, pp. 1532–1535, 2003. View at Publisher · View at Google Scholar · View at Scopus
  68. P. Stattin, R. Palmqvist, S. Söderberg et al., “Plasma leptin and colorectal cancer risk: a prospective study in Northern Sweden,” Oncology Reports, vol. 10, no. 6, pp. 2015–2021, 2003. View at Scopus
  69. P. Stattin, A. Lukanova, C. Biessy et al., “Obesity and colon cancer: does leptin provide a link?” International Journal of Cancer, vol. 109, no. 1, pp. 149–152, 2004. View at Publisher · View at Google Scholar · View at Scopus
  70. H. Endo, K. Hosono, T. Uchiyama et al., “Leptin acts as a growth factor for colorectal tumours at stages subsequent to tumour initiation in murine colon carcinogenesis,” Gut, vol. 60, no. 10, pp. 1363–1371, 2011. View at Publisher · View at Google Scholar · View at Scopus
  71. P. Somasundar, D. W. McFadden, S. M. Hileman, and L. Vona-Davis, “Leptin is a growth factor in cancer,” Journal of Surgical Research, vol. 116, no. 2, pp. 337–349, 2004. View at Publisher · View at Google Scholar · View at Scopus
  72. U. Meier and A. M. Gressner, “Endocrine regulation of energy metabolism: review of pathobiochemical and clinical chemical aspects of leptin, ghrelin, adiponectin, and resistin,” Clinical Chemistry, vol. 50, no. 9, pp. 1511–1525, 2004. View at Publisher · View at Google Scholar · View at Scopus
  73. C. M. Kusminski, P. G. McTernan, and S. Kumar, “Role of resistin in obesity, insulin resistance and Type II diabetes,” Clinical Science, vol. 109, no. 3, pp. 243–256, 2005. View at Publisher · View at Google Scholar · View at Scopus
  74. S. E. Wozniak, L. L. Gee, M. S. Wachtel, and E. E. Frezza, “Adipose tissue: the new endocrine organ? a review article,” Digestive Diseases and Sciences, vol. 54, no. 9, pp. 1847–1856, 2009. View at Publisher · View at Google Scholar · View at Scopus
  75. C. M. Steppan and M. A. Lazar, “The current biology of resistin,” Journal of Internal Medicine, vol. 255, no. 4, pp. 439–447, 2004. View at Publisher · View at Google Scholar · View at Scopus
  76. G. Gonullu, H. Kahraman, A. Bedir, A. Bektas, and I. Yücel, “Association between adiponectin, resistin, insulin resistance, and colorectal tumors,” International Journal of Colorectal Disease, vol. 25, no. 2, pp. 205–212, 2010. View at Publisher · View at Google Scholar · View at Scopus
  77. U. N. Das, “Is obesity an inflammatory condition?” Nutrition, vol. 17, no. 11-12, pp. 953–966, 2001. View at Publisher · View at Google Scholar · View at Scopus
  78. A. Schäffler, U. Müller-Ladner, J. Schölmerich, and C. Büchler, “Role of adipose tissue as an inflammatory organ in human diseases,” Endocrine Reviews, vol. 27, no. 5, pp. 449–467, 2006. View at Publisher · View at Google Scholar · View at Scopus
  79. H. Xu, G. T. Barnes, Q. Yang et al., “Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance,” Journal of Clinical Investigation, vol. 112, no. 12, pp. 1821–1830, 2003. View at Publisher · View at Google Scholar · View at Scopus
  80. S. P. Weisberg, D. McCann, M. Desai, M. Rosenbaum, R. L. Leibel, and A. W. Ferrante, “Obesity is associated with macrophage accumulation in adipose tissue,” Journal of Clinical Investigation, vol. 112, no. 12, pp. 1796–1808, 2003. View at Publisher · View at Google Scholar · View at Scopus
  81. J. G. Neels and J. M. Olefsky, “Inflamed fat: what starts the fire?” Journal of Clinical Investigation, vol. 116, no. 1, pp. 33–35, 2006. View at Publisher · View at Google Scholar · View at Scopus
  82. F. Balkwill, “Cancer and the chemokine network,” Nature Reviews Cancer, vol. 4, no. 7, pp. 540–550, 2004. View at Scopus
  83. D. A. Corley and A. Kubo, “Body mass index and gastroesophageal reflux disease: a systematic review and meta-analysis,” American Journal of Gastroenterology, vol. 101, no. 11, pp. 2619–2628, 2006. View at Publisher · View at Google Scholar · View at Scopus
  84. H. Hampel, N. S. Abraham, and H. B. El-Serag, “Meta-analysis: obesity and the risk for gastroesophageal reflux disease and its complications,” Annals of Internal Medicine, vol. 143, no. 3, pp. 199–211, 2005. View at Scopus
  85. C. C. Abnet, N. D. Freedman, A. R. Hollenbeck, J. F. Fraumeni, M. Leitzmann, and A. Schatzkin, “A prospective study of BMI and risk of oesophageal and gastric adenocarcinoma,” European Journal of Cancer, vol. 44, no. 3, pp. 465–471, 2008. View at Publisher · View at Google Scholar · View at Scopus
  86. A. Kubo and D. A. Corley, “Body mass index and adenocarcinomas of the esophagus or gastric cardia: a systematic review and meta-analysis,” Cancer Epidemiology Biomarkers and Prevention, vol. 15, no. 5, pp. 872–878, 2006. View at Publisher · View at Google Scholar · View at Scopus
  87. B. J. John, S. Irukulla, A. M. Abulafi, D. Kumar, and M. A. Mendall, “Systematic review: adipose tissue, obesity and gastrointestinal diseases,” Alimentary Pharmacology and Therapeutics, vol. 23, no. 11, pp. 1511–1523, 2006. View at Publisher · View at Google Scholar · View at Scopus
  88. R. V. Considine, M. K. Sinha, M. L. Heiman et al., “Serum immunoreactive-leptin concentrations in normal-weight and obese humans,” New England Journal of Medicine, vol. 334, no. 5, pp. 292–295, 1996. View at Publisher · View at Google Scholar · View at Scopus
  89. O. Ogunwobi, G. Mutungi, and I. L. P. Beales, “Leptin stimulates proliferation and inhibits apoptosis in Barrett's esophageal adenocarcinoma cells by cyclooxygenase-2-dependent, prostaglandin-E2-mediated transactivation of the epidermal growth factor receptor and c-Jun NH2-terminal kinase activation,” Endocrinology, vol. 147, no. 9, pp. 4505–4516, 2006. View at Publisher · View at Google Scholar · View at Scopus
  90. J. M. Howard, P. Beddy, D. Ennis, M. Keogan, G. P. Pidgeon, and J. V. Reynolds, “Associations between leptin and adiponectin receptor upregulation, visceral obesity and tumour stage in oesophageal and junctional adenocarcinoma,” British Journal of Surgery, vol. 97, no. 7, pp. 1020–1027, 2010. View at Publisher · View at Google Scholar · View at Scopus
  91. A. M. Ryan, M. Duong, L. Healy et al., “Obesity, metabolic syndrome and esophageal adenocarcinoma: epidemiology, etiology and new targets,” Cancer Epidemiology, vol. 35, no. 4, pp. 309–319, 2011. View at Publisher · View at Google Scholar · View at Scopus
  92. K. B. Greer, C. L. Thompson, L. Brenner, et al., “Association of insulin and insulin-like growth factors with Barrett's oesophagus,” Gut, vol. 61, no. 5, pp. 665–672, 2012.
  93. P. Yang, Y. Zhou, B. Chen et al., “Overweight, obesity and gastric cancer risk: results from a meta-analysis of cohort studies,” European Journal of Cancer, vol. 45, no. 16, pp. 2867–2873, 2009. View at Publisher · View at Google Scholar · View at Scopus
  94. J. Kulig, M. Sierzega, P. Kolodziejczyk et al., “Implications of overweight in gastric cancer: a multicenter study in a Western patient population,” European Journal of Surgical Oncology, vol. 36, no. 10, pp. 969–976, 2010. View at Publisher · View at Google Scholar · View at Scopus
  95. T. Mizoue, M. Inoue, K. Wakai et al., “Alcohol drinking and colorectal cancer in Japanese: a pooled analysis of results from five cohort studies,” American Journal of Epidemiology, vol. 167, no. 12, pp. 1397–1406, 2008. View at Scopus
  96. L. Harnack, D. R. Jacobs Jr., K. Nicodemus, D. Lazovich, K. Anderson, and A. R. Folsom, “Relationship of folate, vitamin B-6, vitamin B-12, and methionine intake to incidence of colorectal cancers,” Nutrition and Cancer, vol. 43, no. 2, pp. 152–158, 2002. View at Scopus
  97. E. Giovannucci, E. B. Rimm, A. Ascherio, M. J. Stampfer, G. A. Colditz, and W. C. Willett, “Alcohol, low-methionine-low-folate diets, and risk of colon cancer in men,” Journal of the National Cancer Institute, vol. 87, no. 4, pp. 265–273, 1995. View at Scopus
  98. E. E. Calle, “Obesity and cancer,” British Medical Journal, vol. 335, no. 7630, pp. 1107–1108, 2007. View at Publisher · View at Google Scholar · View at Scopus
  99. D. S. M. Chan, R. Lau, D. Aune et al., “Red and processed meat and colorectal cancer incidence: meta-analysis of prospective studies,” PLoS ONE, vol. 6, no. 6, Article ID e20456, 2011. View at Publisher · View at Google Scholar · View at Scopus
  100. T. Norat, S. Bingham, P. Ferrari, et al., “Meat, fish, and colorectal cancer risk. The European prospective investigation into cancer and nutrition,” Journal of the National Cancer Institute, vol. 97, no. 23, pp. 1787–1789, 2005. View at Publisher · View at Google Scholar · View at Scopus
  101. H. M. Chiu, J. T. Lin, C. T. Shun et al., “Association of Metabolic Syndrome With Proximal and Synchronous Colorectal Neoplasm,” Clinical Gastroenterology and Hepatology, vol. 5, no. 2, pp. 221–229, 2007. View at Publisher · View at Google Scholar · View at Scopus
  102. K. Bowers, D. Albanes, P. Limburg et al., “A prospective study of anthropometric and clinical measurements associated with insulin resistance syndrome and colorectal cancer in male smokers,” American Journal of Epidemiology, vol. 164, no. 7, pp. 652–664, 2006. View at Publisher · View at Google Scholar · View at Scopus
  103. B. C. Kim, A. Shin, and C. W. Hong, “Association of colorectal adenoma with components of metabolic syndrome,” Cancer Causes & Control, vol. 23, no. 5, pp. 727–735, 2012.
  104. H. B. El-Serag, T. Tran, and J. E. Everhart, “Diabetes increases the risk of chronic liver disease and hepatocellular carcinoma,” Gastroenterology, vol. 126, no. 2, pp. 460–468, 2004. View at Publisher · View at Google Scholar · View at Scopus
  105. S. H. Jee, H. Ohrr, J. W. Sull, et al., “Fasting serum glucose level and cancer risk in Korean men and women,” Journal of the American Medical Association, vol. 293, no. 2, pp. 194–202, 2005. View at Publisher · View at Google Scholar · View at Scopus
  106. C. Wang, X. Wang, G. Gong et al., “Increased risk of hepatocellular carcinoma in patients with diabetes mellitus: a systematic review and meta-analysis of cohort studies,” International Journal of Cancer, vol. 130, no. 6, pp. 1639–1648, 2011. View at Publisher · View at Google Scholar · View at Scopus
  107. E. Bugianesi, N. Leone, E. Vanni et al., “Expanding the natural history of nonalcoholic steatohepatitis: from cryptogenic cirrhosis to hepatocellular carcinoma,” Gastroenterology, vol. 123, no. 1, pp. 134–140, 2002. View at Publisher · View at Google Scholar · View at Scopus
  108. A. B. Siegel and A. X. Zhu, “Metabolic syndrome and hepatocellular carcinoma: two growing epidemics with a potential link,” Cancer, vol. 115, no. 24, pp. 5651–5661, 2009. View at Publisher · View at Google Scholar · View at Scopus
  109. N. F. Peng, L. Q. Li, X. Qin et al., “Evaluation of risk factors and clinicopathologic features for intrahepatic cholangiocarcinoma in Southern China: a possible role of Hepatitis B virus,” Annals of Surgical Oncology, vol. 18, no. 5, pp. 1258–1266, 2011. View at Publisher · View at Google Scholar · View at Scopus
  110. W. Jing, G. Jin, and X. Zhou, “Diabetes mellitus and increased risk of cholangiocarcinoma: a meta-analysis,” European Journal of Cancer Prevention, vol. 21, no. 1, pp. 24–31, 2012.
  111. E. J. Duell, E. A. Holly, P. M. Bracci, M. Liu, J. K. Wiencke, and K. T. Kelsey, “A population-based, case-control study of polymorphisms in carcinogen-metabolizing genes, smoking, and pancreatic adenocarcinoma risk,” Journal of the National Cancer Institute, vol. 94, no. 4, pp. 297–306, 2002. View at Scopus
  112. C. S. Fuchs, G. A. Colditz, M. J. Stampfer et al., “A prospective study of cigarette smoking and the risk of pancreatic cancer,” Archives of Internal Medicine, vol. 156, no. 19, pp. 2255–2260, 1996. View at Publisher · View at Google Scholar · View at Scopus
  113. D. S. Michaud, E. Giovannucci, W. C. Willett, G. A. Colditz, M. J. Stampfer, and C. S. Fuchs, “Physical activity, obesity, height, and the risk of pancreatic cancer,” Journal of the American Medical Association, vol. 286, no. 8, pp. 921–929, 2001. View at Scopus
  114. R. Z. Stolzenberg-Solomon, K. Adams, M. Leitzmann et al., “Adiposity, physical activity, and pancreatic cancer in the National Institutes of Health-AARP diet and health cohort,” American Journal of Epidemiology, vol. 167, no. 5, pp. 586–597, 2008. View at Publisher · View at Google Scholar · View at Scopus
  115. J. Luo, K. L. Margolis, H. O. Adami, A. LaCroix, and W. Ye, “Obesity and risk of pancreatic cancer among postmenopausal women: the Women's Health Initiative (United States),” British Journal of Cancer, vol. 99, no. 3, pp. 527–531, 2008. View at Publisher · View at Google Scholar · View at Scopus
  116. D. Li, J. S. Morris, J. Liu et al., “Body mass index and risk, age of onset, and survival in patients with pancreatic cancer,” Journal of the American Medical Association, vol. 301, no. 24, pp. 2553–2562, 2009. View at Publisher · View at Google Scholar · View at Scopus
  117. M. A. O'Rorke, M. M. Cantwell, C. R. Cardwell, H. G. Mulholland, and L. J. Murray, “Can physical activity modulate pancreatic cancer risk? A systematic review and meta-analysis,” International Journal of Cancer, vol. 126, no. 12, pp. 2957–2968, 2010. View at Publisher · View at Google Scholar · View at Scopus
  118. R. R. McWilliams, M. E. Matsumoto, P. A. Burch et al., “Obesity adversely affects survival in pancreatic cancer patients,” Cancer, vol. 116, no. 21, pp. 5054–5062, 2010. View at Publisher · View at Google Scholar · View at Scopus
  119. E. D. Parker and A. R. Folsom, “Intentional weight loss and incidence of obesity-related cancers: the Iowa Women's Health Study,” International Journal of Obesity, vol. 27, no. 12, pp. 1447–1452, 2003. View at Publisher · View at Google Scholar · View at Scopus