Excess body weight and obesity-the link with gastrointestinal and hepatobiliary cancer

Nature Reviews Gastroenterology and Hepatology

Volumn 8, Issue 4, 2011, Pages 224-238

  Kant, Prashant ^a   Hull, Mark A ^a  

^a UNIVERSITY OF LEEDS   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ADIPONECTIN; BEVACIZUMAB; FLUOROURACIL; INSULIN; LEPTIN; SOMATOMEDIN;

ADJUVANT THERAPY; BARIATRIC SURGERY; BARRETT ESOPHAGUS; BEHAVIOR CHANGE; BILE DUCT CARCINOMA; CALORIC RESTRICTION; CANCER INCIDENCE; CANCER RISK; CANCER SURVIVAL; CARCINOGENESIS; CHRONIC INFLAMMATION; COLORECTAL ADENOMA; COLORECTAL CANCER; DIGESTIVE SYSTEM CANCER; DISEASE ASSOCIATION; ESOPHAGEAL ADENOCARCINOMA; GALLBLADDER CANCER; HEPATOBILIARY SYSTEM CANCER; HUMAN; INTESTINE FLORA; LIVER CELL CARCINOMA; MOLECULAR PATHOLOGY; NONALCOHOLIC FATTY LIVER; NONHUMAN; OBESITY; PANCREAS CANCER; PHYSICAL ACTIVITY; PRIORITY JOURNAL; PROGNOSIS; REVIEW; RISK ASSESSMENT; RISK FACTOR; SIGNAL TRANSDUCTION; STOMACH CANCER; WEIGHT REDUCTION;

BILIARY TRACT NEOPLASMS; BODY WEIGHT; GASTROINTESTINAL NEOPLASMS; HUMANS; LIVER NEOPLASMS; OBESITY; PROGNOSIS; RISK FACTORS;

EID: 79953710531     PISSN: 17595045     EISSN: 17595053     Source Type: Journal    
DOI: 10.1038/nrgastro.2011.23     Document Type: Review

References (201)

1. Moghaddam, A. A., Woodward, M. & Huxley, R. Obesity and risk of colorectal cancer: a meta-analysis of 31 studies with 70,000 events. Cancer Epidemiol. Biomarkers Prev. 16, 2533-2547 (2007). (Pubitemid 351196307)
2. Renehan, A. G., Tyson, M., Egger, M., Heller, R. F. & Zwahlen, M. Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet 371, 569-578 (2008). (Pubitemid 351232031)
3. WHO. Obesity and overweight. Fact Sheet No 311. World Health Organization [online], http://www.who.int/mediacentre/factsheets/fs311/en/index.html (2006).
4. nd edn (American Institute for Cancer Research, Washington, 2007).
5. Vainoio, H. & Bianchinin, F. (Eds) International Agency for Research in Cancer. Weight control and physical activity. (IARC Press, Lyon, 2002).
6. Renehan, A. G. et al. Incident cancer burden attributable to excess body mass index in 30 European countries. Int. J. Cancer 126, 692-702 (2010).
7. Wolk, A. et al. A prospective study of obesity and cancer risk (Sweden). Cancer Causes Control 12, 13-21 (2001). (Pubitemid 32125897)
8. Siddiqui, A. et al. Obesity is associated with an increased prevalence of advanced adenomatous colon polyps in a male veteran population. Dig. Dis. Sci. 54, 1560-1564 (2009).
9. Jacobson, B. C., Chan, A. T., Giovannucci, E. L. & Fuchs, C S. Body mass index and Barrett's oesophagus in women. Gut 58, 1460-1466 (2009).
10. Sato, Y., Nozaki, R., Yamada, K., Takano, M. & Haruma, K. Relation between obesity and adenomatous polyps of the large bowel. Dig. Endosc 21, 154-157 (2009).
11. Cook, M. B., Greenwood, D. C., Hardie, L J., Wild, C R. & Forman, D. A systematic review and meta-analysis of the risk of increasing adiposity on Barrett's esophagus. Am. J. Gastroenterol. 103, 292-300 (2008). (Pubitemid 351248722)
12. Thygesen, L. C et al. Prospective weight change and colon cancer risk in male US health professionals. Int. J. Cancer 123, 1160-1165 (2008).
13. National Institutes for Health. Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults. The evidence report. (NHLBI, 1998).
14. Larsson, S. C & Wolk, A. Obesity and colon and rectal cancer risk: a meta-analysis of prospective studies. Am. J. Clin. Nutr. 86, 556-565 (2007). (Pubitemid 47435820)
15. Dai, Z., Xu, Y C & Niu, L. Obesity and colorectal cancer risk: a meta-analysis of cohort studies. World J. Gastroenterol. 13, 4199-4206 (2007). (Pubitemid 47377159)
16. Moore, L. L. et al. BMI and waist circumference as predictors of lifetime colon cancer risk in Framingham Study adults. Int. J. Obes. 28, 559-567 (2004). (Pubitemid 38491147)
17. Wise, L. A., Rosenberg, L., Palmer, J. R. & Adams-Campbell, L L. Anthropometric risk factors for colorectal polyps in African-American women. Obesity 16, 859-868 (2008). (Pubitemid 351465644)
18. Sedjo, R. L. et al. Change in body size and the risk of colorectal adenomas. Cancer Epidemiol. Biomarkers Prev. 16, 526-531 (2007). (Pubitemid 46548656)
19. Larsen, I. K., Grotmol, T., Almendingen, K. & Hoff, G. Lifestyle as a predictor for colonic neoplasia in asymptomatic individuals. BMC Gastroenterol. 6, 5 (2006).
20. Neugut, A. I. et al. Obesity and colorectal adenomatous polyps. J. Natl Cancer Inst. 83, 359-361 (1991).
21. Morois, S., Mesrine, S., Josset, M., Clavel-Chapelon, F & Boutron-Ruault, M.-C. Anthropometric factors in adulthood and risk of colorectal adenomas. Am. J. Epidemiol. 172, 1166-1180 (2010).
22. Giovannucci, E. et al. Physical activity, obesity and risk for colon cancer and adenoma in men. Ann. Intern. Med. 122, 327-334 (1995).
23. Giovannucci, E., Colditz, G. A., Stampfer, M. J. & Willett, W. C Physical activity obesity and risk of colorectal adenoma in women (United States). Cancer Causes Control 7, 253-263 (1996). (Pubitemid 26155463)
24. Yamaji, Y et al. The effect of body weight reduction on the incidence of colorectal adenoma. Am. J. Gastroenterol. 103, 2061-2067 (2008).
25. Lieberman, D. A., Prindiville, S., Weiss, D. G. & Willett, W. Risk factors for advanced colonic neoplasia and hyperplastic polyps in asymptomatic individuals. JAMA 290, 2959-2967 (2003). (Pubitemid 37505528)
26. Anderson, J. C et al. Body mass index: a marker for significant colorectal neoplasia in a screening population. J. Clin. Gastroenterol. 41, 285-290 (2007). (Pubitemid 46340751)
27. Omata, F et al. Modifiable risk factors for colorectal neoplasms and hyperplastic polyps. Intern. Med. 48, 123-128 (2009).
28. Kim, Y & Lee, S. An association between colonic adenoma and abdominal obesity: a cross-sectional study. BMC Gastroenterol. 9, 4 (2009).
29. Betes, M. et al. Use of colonoscopy as a primary screening test for colorectal cancer in average risk people. Am. J. Gastroenterol. 98, 2648-2654 (2003). (Pubitemid 38020103)
30. Bird, C L., Frankl, H. D., Lee, E. R. & Haile, R. W. Obesity, weight gain, large weight changes, and adenomatous polyps of the left colon and rectum. Am. J. Epidemiol. 147, 670-680 (1998). (Pubitemid 28180310)
31. Kono, S., Shinchi, K. & Imanishi, K. Body mass index and adenomas of the sigmoid colon in Japanese men. Eur. J. Epidemiol. 12, 425-426 (1996).
32. Boutron-Ruault, M.-C., Senesse, P, Méance, S., Belghiti, C & Faivre, J. Energy intake, body mass index, physical activity, and the colorectal adenoma-carcinoma sequence. Nutr. Cancer 39, 50-57 (2001). (Pubitemid 32880948)
33. Wallace, K. et al. The association of physical activity and body mass index with the risk of large bowel polyps. Cancer Epidemiol. Biomarkers Prev. 14, 2082-2086 (2005). (Pubitemid 41603249)
34. Terry, M. B. et al. Risk factors for advanced colorectal adenomas: a pooled analysis. Cancer Epidemiol. Biomarkers Prev. 11, 622-629 (2002). (Pubitemid 34760820)
35. Wolf, L. A., Terry, P D., Potter, J. D. & Bostick, R. M. Do factors related to endogenous and exogenous estrogens modify the relationship between obesity and risk of colorectal adenomas in women? Cancer Epidemiol. Biomarkers Prev. 16, 676-683 (2007). (Pubitemid 46650568)
36. Almendingen, K., Hofstad, B. & Vatn, M. H. Does high body fatness increase the risk of presence and growth of colorectal adenomas followed up in situ for 3 years? Am. J. Gastroenterol. 96, 2238-2246 (2001). (Pubitemid 32660924)
37. Bayerdörffer, E. et al. Increased risk of 'high-risk' colorectal adenomas in overweight men. Gastroenterology 104, 137-144 (1993). (Pubitemid 23040016)
38. Kang, H. W. et al. Visceral obesity and insulin resistance as risk factors for colorectal adenoma: a cross-sectional, case-control study. Am. J. Gastroenterol. 105, 178-187 (2010).
39. Kim, J. H. et al. Is metabolic syndrome a risk factor for colorectal adenoma? Cancer Epidemiol. Biomarkers Prev. 16, 1543-1546 (2007).
40. Kim, K. S. et al. The frequency and risk factors of colorectal adenoma in health-check-up subjects in South Korea: relationship to abdominal obesity and age. Gut Liver 4, 36-42 (2010).
41. Jacobs, E. T et al. Association between body mass index and colorectal neoplasia at follow-up colonoscopy: a pooling study. Am. J. Epidemiol. 169, 657-666 (2009).
42. Sainsbury, A. et al. Increased colorectal epithelial cell proliferation and crypt fission associated with obesity and roux-en-Y gastric bypass. Cancer Epidemiol. Biomarkers Prev. 17, 1401-1410 (2008).
43. Ferrante, J. M. et al. Colorectal cancer screening among obese versus non-obese patients in primary care practices. Cancer Detect. Prev. 30, 459-465 (2006). (Pubitemid 44750410)
44. Rosen, A. B. & Schneider, E. C Colorectal cancer screening disparities related to obesity and gender. J. Gen. Intern. Med. 19, 332-338 (2004). (Pubitemid 38530504)
45. Borg, B. B., Gupta, N. K., Zuckerman, G. R., Banerjee, B. & Gyawali, C P. Impact of obesity on bowel preparation for colonoscopy. Clin. Gastroenterol. Hepatol. 7, 670-675 (2009).
46. Pera, M., Manterola, C., Vidal, O. & Grande, L Epidemiology of esophageal adenocarcinoma. J. Surg. Onc 92, 151-159 (2005). (Pubitemid 41779297)
47. Lagergren, J., Bergstrom, R., Lindgren, A. & Nyren, O. Symptomatic gastroesophageal reflux as a risk factor for esophageal adenocarcinoma. N. Engl. J. Med. 340, 825-831 (1999). (Pubitemid 29142625)
48. Hampel, H., Abraham, N. S. & El-Serag, H. B. Meta-analysis: obesity and the risk for gastroesophageal reflux disease and its complications. Ann. Intern. Med. 143, 199-211 (2005). (Pubitemid 41076753)
49. Corley, D. A. & Kubo, A. Body mass index and gastroesophageal reflux disease: a systematic review and meta-analysis. Am. J. Gastroenterol. 101, 2619-2628 (2006). (Pubitemid 44665262)
50. Corley, D. A., Kubo, A. & Zhao, W. Abdominal obesity, ethnicity and gastro-oesophageal reflux symptoms. Gut 56, 756-762 (2007). (Pubitemid 46854187)
51. Whiteman, D. et al. The role of obesity gastroesophageal reflux and smoking in adenocarcinomas of the esophagus and esophago-gastric junction [abstract]. Gastroenterology 132, A418 (2007).
52. Yousef, F. et al. The incidence of esophageal cancer and high-grade dysplasia in Barrett's esophagus: a systematic review and meta-analysis. Am. J. Epidemiol. 168, 237-249 (2008). (Pubitemid 352019777)
53. Kamat, P, Wen, S. J., Morris, J. & Anandasabapathy, S. Exploring the association between elevated body mass index and Barrett's esophagus: a systematic review and meta-analysis. Ann. Thorac Surg. 87, 655-662 (2009).
54. Edelstein, Z. R., Farrow, D. C., Bronner, M. P, Rosen, S. N. & Vaughan, T L. Central adiposity and risk of Barrett's esophagus. Gastroenterology 133, 403-411 (2007). (Pubitemid 47187351)
55. Corley, D. A. et al. Abdominal obesity and body mass index as risk factors for Barrett's esophagus. Gastroenterology 133, 34-41 (2007). (Pubitemid 47031134)
56. Oberg, S., Wenner, J., Johansson, J., Walther, B. & Willen, R. Barrett esophagus: risk factors for progression to dysplasia and adenocarcinoma. Ann. Surg. 242, 49-54 (2005). (Pubitemid 40917967)
57. Arslan, A. A. et al. Anthropometric measures, body mass index, and pancreatic cancer: a pooled analysis from the Pancreatic Cancer Cohort Consortium (PanScan). Arch. Intern. Med. 170, 791-802 (2010).
58. Larsson, S. C., Orsini, N. & Wolk, A. Body mass index and pancreatic cancer risk: a meta-analysis of prospective studies. Int. J. Cancer 120, 1993-1998 (2007). (Pubitemid 46418379)
59. Li, D. et al. Body mass index and risk, age of onset, and survival in patients with pancreatic cancer. JAMA 301, 2553-2562 (2009).
60. Huxley, R., Ansary-Moghaddam, A., de Gonzalez, A. B., Barzi, F. & Woodward, M. Type-II diabetes and pancreatic cancer: a meta-analysis of 36 studies. Br. J. Cancer 92, 2076-2083 (2005). (Pubitemid 40897433)
61. Permert, J. et al. Is profound peripheral insulin resistance in patients with pancreatic cancer caused by a tumor-associated factor? Am. J. Surg. 165, 61-66 (1993).
62. Lowenfels, A. B. et al. Pancreatitis and the risk of pancreatic cancer. N. Engl. J. Med. 328, 1433-1437 (1993). (Pubitemid 23143844)
63. Yang, P et al. Overweight, obesity and gastric cancer risk: results from a meta-analysis of cohort studies. Eur. J. Cancer 45, 2867-2873 (2009).
64. Leung, W. K. et al. Screening for gastric cancer in Asia: current evidence and practice. Lancet Oncol. 9, 279-287 (2008). (Pubitemid 351722947)
65. Goldblum, J. R. et al. Helicobacter pylori infection, not gastroesophageal reflux, is the major cause of inflammation and intestinal metaplasia of gastric cardiac mucosa. Am. J. Gastroenterol. 97, 302-311 (2002). (Pubitemid 34160754)
66. Kelley, J. R. & Duggan, J. M. Gastric cancer epidemiology and risk factors. J. Clin. Epidemiol. 56, 1-9 (2003). (Pubitemid 36183309)
67. Wistuba, I. I. & Gazdar, A. F. Gallbladder cancer: Lessons from a rare tumour. Nat Rev. Cancer 4, 695-706 (2004). (Pubitemid 39215068)
68. Engeland, A., Tretli, S., Austad, G. & Bjorge, T Height and body mass index in relation to colorectal and gallbladder cancer in two million Norwegian men and women. Cancer Causes Control 16, 987-996 (2005). (Pubitemid 41191423)
69. Hsing, A. W. et al. Body size and the risk of biliary tract cancer: a population-based study in China. Br. J. Cancer 99, 811-815 (2008).
70. Stampfer, M. J., Maclure, K. M., Colditz, G. A., Manson, J. E. & Willett, W. C Risk of symptomatic gallstones in women with severe obesity Am. J. Clin. Nutr. 55, 652-658 (1992).
71. Lazcano-Ponce, E. C et al. Epidemiology and molecular pathology of gallbladder cancer. CA Cancer J. 51, 349-364 (2001). (Pubitemid 34232782)
72. Warren, B. L. & Marais, A. W. Carcinoma of the gallbladder: a possible regional predisposition in the western Cape and the northern Cape. S. Afr. J. Surg. 33, 161-164 (1995). (Pubitemid 27374562)
73. Shrikhande, S. V., Barreto, S. G., Singh, S., Udwadia, T. E. & Agarwal, A. K. Cholelithiasis in gallbladder cancer: coincidence, cofactor, or cause! Eur. J. Surg. Oncol. 36, 514-519 (2010).
74. Randi, G., Franceschi, S. & La Vecchia, C Gallbladder cancer worldwide: geographical distribution and risk factors. Int. J. Cancer 118, 1591-1602 (2006). (Pubitemid 43376420)
75. Mohandas, K. M. & Patil, P S. Cholecystectomy for asymptomatic gallstones can reduce gal bladder cancer mortality in northern Indian women. Ind. J. Gastroenterol. 25, 147-151 (2006). (Pubitemid 44326054)
76. Duarte, I., Llanos, O., Domke, H., Harz, C & Valdivieso, V Metaplasia and precursor lesions of gallbladder carcinoma. Frequency distribution, and probability of detection in routine histologic samples. Cancer 72, 1878-1884 (1993). (Pubitemid 23262115)
77. Lim, S. H. et al. Is metabolic syndrome one of the risk factors for gallbladder polyps Found by ultrasonography during health screening? Gut Liver 1, 138-144 (2007).
78. Segawa, K. et al. Prevalence of gallbladder polyps among apparently healthy Japanese: ultrasonographic study. Am. J. Gastroenterol. 87, 630-633 (1992).
79. Liew, P L. et al. Gallbladder disease among obese patients in Taiwan. Obes. Surg. 17, 383-390 (2007).
80. Patel, T Worldwide trends in mortality from biliary tract malignancies. BMC Cancer 2, 10 (2002).
81. Grainge, M. J., West, J., Solaymani-Dodaran, M., Aithal, G. P. & Card, T R. The antecedents of biliary cancer: a primary care case-control study in the United Kingdom. Br. J. Cancer 100, 178-180 (2008).
82. Welzel, T M. et al. Risk factors for intrahepatic and extrahepatic cholangiocarcinoma in the United States: a population-based case-control study. Clin. Gastroenterol. Hepatol. 5, 1221-1228 (2007). (Pubitemid 47496233)
83. Welzel, T M. et al. Risk factors for intrahepatic cholangiocarcinoma in a low-risk population: a nationwide case-control study. Int. J. Cancer 120, 638-641 (2007). (Pubitemid 46001359)
84. Starley, B. Q., Calcagno, C J. & Harrison, S. A. Nonalcoholic fatty liver disease and hepatocellular carcinoma: a weighty connection. Hepatology 51, 1820-1832 (2010).
85. Liu, B., Balkwill, A., Reeves, G. & Beral, V Body mass index and risk of liver cirrhosis in middle aged UK women: prospective study BMJ 340, c912 (2010).
86. Omagari, K. et al. Fatty liver in non-alcoholic non-overweight Japanese adults: incidence and clinical characteristics. J. Gastroenterol. Hepatol. 17, 1098-1105 (2002). (Pubitemid 35013966)
87. Browning, J. D. et al. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology 40, 1387-1395 (2004). (Pubitemid 39657013)
88. Machado, M., Marques-Vidal, P & Cortez-Pinto, H. Hepatic histology in obese patients undergoing bariatric surgery J. Hepatol. 45, 600-606 (2006). (Pubitemid 44307393)
89. Saunders D., Seidel, D., Allison, M. & Lyratzopoulos, G. Systematic review: the association between obesity and hepatocellular carcinoma\ epidemiological evidence. Aliment. Pharmacol. Ther. 31. 1051-1063 (2010).
90. Larsson, S. C & Wolk, A. Overweight, obesity and risk of liver cancer: a meta-analysis of cohort studies. Br. J. Cancer 97, 1005-1008 (2007). (Pubitemid 47519294)
91. Oh, S. W., Yoon, Y S. & Shin, S. A. Effects of excess weight on cancer incidences depending on cancer sites and histologic findings among men: Korea National Health Insurance Corporation Study J. Clin. Oncol. 23, 4742-4754 (2005). (Pubitemid 46224078)
92. Nair, S., Mason, A., Eason, J., Loss, G. & Perrillo, R. P Is obesity an independent risk factor for hepatocellular carcinoma in cirrhosis? Hepatology 36, 150-155 (2002). (Pubitemid 34700772)
93. Ohki, T et al. Obesity is an independent risk factor for hepatocellular carcinoma development in chronic hepatitis C patients. Clin. Gastroenterol. Hepatol. 6, 459-464 (2008). (Pubitemid 351443115)
94. Park, E. J. et al. Dietary and genetic obesity promote liver inflammation and tumorigenesis by enhancing IL-6 and TNF expression. Cell 140, 197-208 (2010).
95. Ichikawa, T et al. Two cases of non-alcoholic steatohepatitis with development of hepatocellular carcinoma without cirrhosis. J. Gastroenterol. Hepatol. 21, 1865-1866 (2006). (Pubitemid 44657016)
96. Kawada, N. et al. Hepatocellular carcinoma arising from non-cirrhotic nonalcoholic steatohepatitis. J. Gastroenterol. 44, 1190-1194 (2009).
97. Wellen, K. E. & Hotamisligil, G. S. Inflammation, stress, and diabetes. J. Clin. Invest 115, 1111-1119 (2005).
98. Roberts, D. L., Dive, C & Renehan, A. G. Biological mechanisms linking obesity and cancer risk: new perspectives. Ann. Rev. Med. 61, 301-316 (2010).
99. Lin, J. H. & Giovannucci, E. Sex hormones and colorectal cancer: what have we learned so far? J. Natl Cancer Inst 102, 1746-1747 (2010).
100. Ley, R. E., Turnbaugh, P J., Klein, S. & Gordon, J. I. Microbial ecology: human gut microbes associated with obesity. Nature 444, 1022-1023 (2006). (Pubitemid 46018512)
101. Caesar, R., Fåk, F & Bäckhed, F Effects of gut microbiota on obesity and atherosclerosis via modulation of inflammation and lipid metabolism. J. Int Med. 268, 320-328 (2010).
102. Cowey, S. & Hardy, R. W. The metabolic syndrome: a high-risk state for cancer? Am. J. Pathol. 169, 1505-1522 (2006). (Pubitemid 351181984)
103. Donohoe, C L., Pidgeon, G. P, Lysaght, J. & Reynolds, J. V Obesity and gastrointestinal cancer. Br. J. Surg. 97, 628-642 (2010).
104. Renehan, A. G., Frystyk, J. & Flyvbjerg, A. Obesity and cancer risk: the role of the insulin-IGF axis. Trends Endocrinol. Metab. 17, 328-336 (2006). (Pubitemid 44397568)
105. Larsson, S. C., Giovannucci, E. & Wolk, A. Diabetes and colorectal cancer incidence in the cohort of Swedish men. Diabetes Care 28, 1805-1807 (2005). (Pubitemid 40923101)
106. Clayton, P E., Banerjee, I., Murray, P G. & Renehan, A. G. Growth hormone, the insulin-like growth factor axis, insulin and cancer risk. Nat Rev. Endocrinol. 7, 11-24 (2011).
107. Giovannucci, E. Insulin, insulin-like growth factors and colon cancer: a review of the evidence. J. Nutr. 131, 3109S-3120S (2001). (Pubitemid 33070788)
108. Corpet, D. E., Jacquinet, C., Peiffer, G. & Tache, S. Insulin injections promote the growth of aberrant crypt foci in the colon of rats. Nutr. Cancer 27, 316-320 (1997). (Pubitemid 27161531)
109. Samani, A. A., Yakar, S., LeRoith, D. & Brodt, P. The role of the IGF system in cancer growth and metastasis: overview and recent insights. Endocr. Rev. 28, 20-47 (2007). (Pubitemid 46220849)
110. Sears, R. et al. Multiple Ras-dependent phosphorylation pathways regulate Myc protein stability. Genes Dev. 14, 2501-2514 (2000).
111. Hursting, S. D. et al. Reducing the weight of cancer: mechanistic targets for breaking the obesity-carcinogenesis link. Best Pract Res. Clin. Endocrinol. Metab. 22, 659-669 (2008).
112. Hosono, K. et al. Metformin suppresses colorectal aberrant crypt foci in a short-term clinical trial. Cancer Prev. Res. 3, 1077-1083 (2010).
113. Tomimoto, A. et al. Metformin suppresses intestinal polyp growth in ApcMin/+ mice. Cancer Sci. 99, 2136-2141 (2008).
114. Renehan, A. G. et al. Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis. Lancet 363, 1346-1353 (2004). (Pubitemid 38529873)
115. Schoen, R. E. et al. Insulin-like growth factor-I and insulin are associated with the presence and advancement of adenomatous polyps. Gastroenterology 129, 464-475 (2005). (Pubitemid 41096634)
116. Renehan, A. G. et al. High-risk colorectal adenomas and serum insulin-like growth factors. Br. J. Surg. 88, 107-113 (2001). (Pubitemid 32066068)
117. Flood, A. et al. Serum concentrations of insulin-ike growth factor and insulin-like growth factor binding protein 3 and recurrent colorectal adenomas. Cancer Epidemiol. Biomarkers Prev. 17, 1493-1498 (2008).
118. Wolpin, B. M. et al. Circulating insulin-like growth factor binding protein-1 and the risk of pancreatic cancer. Cancer Res. 67, 7923-7928 (2007). (Pubitemid 47281389)
119. Bergmann, U., Funatomi, H., Yokoyama, M., Beger, H. G. & Korc, M. Insulin-like growth factor overexpression in human pancreatic cancer: evidence for autocrine and paracrine roles. Cancer Res. 55, 2007-2011 (1995).
120. Zhao, R., Macdonald, K. & Casson, A. G. Insulin-ike growth factor type I receptor gene expression and obesity in esophageal adenocarcinoma. Mol. Carcinog. 48, 982-988 (2009).
121. Hoyo, C et al. IGF2R polymorphisms and risk of esophageal and gastric adenocarcinomas. Int. J. Cancer 125, 2673-2678 (2009).
122. McElholm, A. R. et al. A population-based study of IGF axis polymorphisms and the esophageal inflammation, metaplasia, adenocarcinoma sequence. Gastroenterology 139, 204-212.e3 (2010).
123. Park, H. S., Park, J. Y & Yu, R. Relationship of obesity and visceral adiposity with serum concentrations of CRP, TNF-[alpha] and IL-6. Diab. Res. Clin. Pract 69, 29-35 (2005). (Pubitemid 40813409)
124. Nishimura, S. et al. CD8+ effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity. Nat Med. 15, 914-920 (2009).
125. Feuerer, M. et al. Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters. Nat Med. 15, 930-939 (2009).
126. Balistreri, C R., Caruso, C & Candore, G. The role of adipose tissue and adipokines in obesity-related inflammatory diseases. Mediators Inflamm. 2010, 802078 (2010).
127. Song, M. J., Kim, K. H., Yoon, J. M. & Kim, J. B. Activation of Toll-like receptor 4 is associated with insulin resistance in adipocytes. Biochem. Biophys. Res. Commun. 346, 739-745 (2006).
128. Balkwill, F, Charles, K. A. & Mantovani, A. Smoldering and polarized inflammation in the initiation and promotion of malignant disease. Cancer Cell 7, 211-217 (2005). (Pubitemid 40568680)
129. Poullis, A. bowel inflammation as measured by faecal calprotectin: a link between lifestyle factors and colorectal cancer risk. Cancer Epidemiol. Biomarkers Prev. 13, 279-284 (2004). (Pubitemid 38222561)
130. Pendyala, S., Neff, L. M., Suárez-Fariñas, M. & Holt, P R. Diet-induced weight loss reduces colorectal inflammation: implications for colorectal carcinogenesis. Am. J. Clin. Nutr. 93, 234-242 (2011).
131. Martínez, M. E. et al. Physical activity, body mass index, and prostaglandin E2 levels in rectal mucosa. J. Natl Cancer Inst 91, 950-953 (1999). (Pubitemid 29272521)
132. Hotamisligil, G. S. Inflammation and metabolic disorders. Nature 444, 860-867 (2006). (Pubitemid 46024993)
133. Tsilidis, K. K. et al. C-reactive protein and colorectal cancer risk: a systematic review of prospective studies. Int J. Cancer 123, 1133-1140 (2008).
134. Tsilidis, K. K. et al. C-reactive protein and colorectal adenoma in the CLUE II cohort. Cancer Causes Control 19, 559-567 (2008).
135. Kim, S. et al. Circulating levels of inflammatory cytokines and risk of colorectal adenomas. Cancer Res. 68, 323-328 (2008). (Pubitemid 351380135)
136. Considine, R. V et al. Serum immunoreactive leptin concentrations in normal-weight and obese humans. N. Engl. J. Med. 334, 292-295 (1996). (Pubitemid 26033933)
137. Aloulou, N. et al. Involvement of the leptin receptor in the immune response in intestinal cancer. Cancer Res. 68, 9413-9422 (2008).
138. Liu, Z. H., Uesaka, T., Watanabe, H. & Kato, N. High fat diet enhances colonic cell proliferation and carcinogenesis in rats by elevating serum leptin. Int J. Oncol. 19, 1009-1014 (2001).
139. Rouet-Benzineb, P et al. Leptin counteracts sodium butyrate-induced apoptosis in human colon cancer HT-29 cells via NF-kappaB signaling. J. Biol. Chem. 279, 16495-16502 (2004). (Pubitemid 38509348)
140. Hirose, Y et al. Enhancement of development of azoxymethane-induced colonic premalignant lesions in C57BL/KsJ-db/db mice. Carcinogenesis 25, 821-825 (2004). (Pubitemid 38618536)
141. Ogunwobi, O., Mutungi, G. & Beales, I. L P. 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 147, 4505-4516 (2006). (Pubitemid 44268402)
142. Chia, V M. et al. Leptin concentrations, leptin receptor polymorphisms, and colorectal adenoma risk. Cancer Epidemiol. Biomarkers Prev. 16, 2697-2703 (2007). (Pubitemid 351196326)
143. Stattin, P et al. Plasma leptin and colorectal cancer risk: a prospective study in Northern Sweden. Oncol. Rep. 10, 2015-2021 (2003).
144. Stattin, P et al. Obesity and colon cancer: does leptin provide a link? Int J. Cancer 109, 149-152 (2004). (Pubitemid 38160676)
145. Kendall, B. J. et al. Leptin and the risk of Barrett's oesophagus. Gut 57, 448-454 (2008). (Pubitemid 351442525)
146. Wang, S. N., Lee, K. T & Ker, C G. Leptin in hepatocellular carcinoma. World J. Gastroenterol. 16, 5801-5809 (2010).
147. Arita, Y et al. Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem. Biophys. Res. Commun. 257, 79-83 (1999). (Pubitemid 29299050)
148. Sugiyama, M. et al. Adiponectin inhibits colorectal cancer cell growth through the AMPK/mTOR pathway. Int J. Oncol. 34, 339-344 (2009).
149. Otani, K. et al. Adiponectin suppresses tumorigenesis in Apc(Min/+) mice. Cancer Lett 288, 177-182 (2010).
150. Takahashi, H. et al. Association of visceral fat accumulation and plasma adiponectin with rectal dysplastic aberrant crypt foci in a clinical population. Cancer Sci. 100, 29-32 (2009).
151. Wei, E. K., Giovannucci, E., Fuchs, C S., Willett, W. C & Mantzoros, C S. Low plasma adiponectin levels and risk of colorectal cancer in men: A prospective study. J. Natl Cancer Inst 97, 1688-1694 (2005). (Pubitemid 41672235)
152. Nakajima, T E. et al. Adipocytokines as new promising markers of colorectal tumors: adiponectin for colorectal adenoma, and resistin and visfatin for colorectal cancer. Cancer Sci. 101, 1286-1291 (2010).
153. Yamaji, T., Iwasaki, M., Sasazuki, S. & Tsugane, S. Interaction between adiponectin and leptin Influences the risk of colorectal adenoma. Cancer Res. 70, 5430-5437 (2010).
154. Otake, S. et al. Decreased levels of plasma adiponectin associated with increased risk of colorectal cancer. World J. Gastroenterol. 16, 1252-1257 (2010).
155. Ishikawa, M. et al. Plasma adiponectin and gastric cancer. Clin. Cancer Res. 11, 466-472 (2005). (Pubitemid 40116868)
156. Otani, K. et al. Adiponectin receptors are downregulated in human gastric cancer. J. Gastroenterol. 45, 918-927 (2010).
157. Konturek, P C., Burnat, G., Rau, T., Hahn, E. G. & Konturek, S. Effect of adiponectin and ghrelin on apoptosis of barrett adenocarcinoma cell line. Dig. Dis. Sci. 53, 597-605 (2008). (Pubitemid 351317076)
158. Sharma, D. et al. Adiponectin antagonizes the oncogenic actions of leptin in hepatocellular carcinogenesis. Hepatology 52, 1713-1722 (2010).
159. Backhed, F et al. The gut microbiota as an environmental factor that regulates fat storage. Proc. Natl Acad. Sci. USA 101, 15718-15723 (2004). (Pubitemid 39473554)
160. Backhed, F, Manchester, J. K., Semenkovich, C F. & Gordon, J. I. Mechanisms underlying the resistance to diet-induced obesity in germ-free mice. Proc. Natl Acad. Sci. USA 104, 979-984 (2007). (Pubitemid 46154722)
161. Furet, J. P et al. Differential adaptation of human gut microbiota to bariatric surgery-induced weight loss: links with metabolic and low-grade inflammation markers. Diabetes 59, 3049-3057 (2010).
162. Shen, X. J. et al. Molecular characterization of mucosal adherent bacteria and associations with colorectal adenomas. Gut Microbes 1, 138-147 (2010).
163. Vannucci, L. et al. Colorectal carcinogenesis in germ-free and conventionally reared rats: different intestinal environments affect the systemic immunity. Int J. Oncol. 32, 609-617 (2008). (Pubitemid 351330467)
164. Martin, H. M. et al. Enhanced Escherichia coli adherence and invasion in Crohn's disease and colon cancer. Gastroenterology 127, 80-93 (2004). (Pubitemid 38962277)
165. Swidsinski, A. et al. Association between intraepithelial Escherichia coli and colorectal cancer. Gastroenterology 115, 281-286 (1998). (Pubitemid 28363420)
166. Cani, P D. et al. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes 56, 1761-1772 (2007). (Pubitemid 47025442)
167. Parker, E. D. & Folsom, A. R. Intentional weight loss and incidence of obesity-related cancers: the Iowa Women's Health Study. Int. J. Obes. Relat Metab. Disord. 27, 1447-1452 (2003). (Pubitemid 38019155)
168. Rapp, K. et al. Weight change and cancer risk in a cohort of more than 65 000 adults in Austria. Ann. Oncol. 19, 641-648 (2008). (Pubitemid 351461032)
169. St. George, A. et al. Effect of a lifestyle intervention in patients with abnormal liver enzymes and metabolic risk factors. J. Gastroenterol. Hepatol. 24, 399-407 (2009).
170. Stewart, L. K. et al. The influence of exercise training on inflammatory cytokines and C-reactive protein. Med. Sci. Sports Exerc. 39, 1714-1719 (2007). (Pubitemid 47511477)
171. Rankin, J. W. & Turpyn, A. D. Low carbohydrate, high fat diet increases C-reactive protein during weight loss. J. Am. Coll. Nutr. 26, 163-169 (2007). (Pubitemid 46911260)
172. Tammariello, A. E. & Milner, J. A. Mouse models for unraveling the importance of diet in colon cancer prevention. J. Nutr. Biochem. 21, 77-88 (2010).
173. Johnson, N. A. et al. Aerobic exercise training reduces hepatic and visceral lipids in obese individuals without weight loss. Hepatology 50, 1105-1112 (2009).
174. Kirkegaard, H. et al. Association of adherence to ifestyle recommendations and risk of colorectal cancer: a prospective Danish cohort study. BMJ 341, c5504 (2010).
175. Sjöström, L. et al. 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 (2009).
176. Adams, T. D. et al. Cancer incidence and mortality after gastric bypass surgery. Obesity 17, 796-802 (2009).
177. Christou, N. V., Lieberman, M., Sampalis, F. & Sampalis, J. S. Bariatric surgery reduces cancer risk in morbidly obese patients. Surg. Obes. Relat Dis. 4, 691-695 (2008).
178. Plecka-Ostlund, M. Risk of obesity-related cancer after obesity surgery in a population-based cohort study. Ann. Surg. 252, 972-976 (2010).
179. Prizment, A. E., Flood, A., Anderson, K. E. & Folsom, A. R. Survival of women with colon cancer in relation to precancer anthropometric characteristics: the Iowa Women's Health Study. Cancer Epidemiol. Biomarkers Prev. 19, 2229-2237 (2010).
180. Haydon, A. M. M., MacInnis, R. J., English, D. R. & Giles, G. G. Effect of physical activity and body size on survival after diagnosis with colorectal cancer. Gut 55, 62-67 (2006). (Pubitemid 41820637)
181. Wu, Y. J. et al. Insulin-like growth factor-I regulates the liver microenvironment in obese mice and promotes liver metastasis. Cancer Res. 70, 57-67 (2010).
182. Earl, T. M. et al. Silencing of TLR4 decreases iver tumor burden in a murine model of colorectal metastasis and hepatic steatosis. Ann. Surg. Oncol. 16, 1043-1050 (2009).
183. Benoist, S., Panis, Y., Alves, A. & Valleur, P. mpact of obesity on surgical outcomes after colorectal resection. Am. J. Surg. 179, 275-281 (2000). (Pubitemid 30394688)
184. Meyerhardt, J. A. et al. Impact of body mass index on outcomes and treatment-related toxicity in patients with stage II and III rectal cancer: findings from intergroup trial 0114. J. Clin. Oncol. 22, 648-657 (2004). (Pubitemid 41095068)
185. Moon, H. G. et al. Visceral obesity may affect oncologic outcome in patients with colorectal cancer. Ann. Surg. Oncol. 15, 1918-1922 (2008).
186. Meyerhardt, J. A. et al. Influence of body mass index on outcomes and treatment-related toxicity in patients with colon carcinoma. Cancer 98, 484-495 (2003). (Pubitemid 36885987)
187. Dignam, J. J. et al. Body mass index and outcomes in patients who receive adjuvant chemotherapy for colon cancer. J. Natl Cancer Inst 98, 1647-1654 (2006). (Pubitemid 44811647)
188. Guiu, B. et al. Visceral fat area is an independent predictive biomarker of outcome after first-line bevacizumab-based treatment in metastatic colorectal cancer. Gut 59, 341-347 (2010).
189. Grotenhuis, B. A. et al. Prognostic value of body mass index on short-term and long-term outcome after resection of esophageal cancer. World J. Surg. 34, 2621-2627 (2010).
190. Healy, L A. et al. Impact of obesity on outcomes in the management of localized adenocarcinoma of the esophagus and esophagogastric junction. J. Thorac Cardiovasc Surg. 134, 1284-1291 (2007). (Pubitemid 47633649)
191. Scipione, C N., Chang, A. C., Pickens, A., Lau, C L & Orringer, M. B. Transhiatal esophagectomy in the profoundly obese: mplications and experience. Ann. Thorac Surg. 84, 376-383 (2007). (Pubitemid 47069150)
192. Melis, M. et al. An elevated body mass index does not reduce survival after esophagectomy for cancer. Ann. Surg. Oncol. doi:10.1245/s10434-010-1336-1.
193. Oh, S. J. et al. Effect of being overweight on postoperative morbidity and long-term surgical outcomes in proximal gastric carcinoma. J. Gastroenterol. Hepatol. 24, 475-479 (2009).
194. Tokunaga, M. et al. Better 5-year survival rate following curative gastrectomy in overweight patients. Ann. Surg. Oncol. 16, 3245-3251 (2009).
195. Zyromski, N. J. et al. Obesity potentiates the growth and dissemination of pancreatic cancer. Surgery 146, 258-263 (2009).
196. Noun, R. et al. The impact of obesity on surgical outcome after pancreaticoduodenectomy. JOP 9, 468-476 (2008).
197. Rosso, E. et al. The role of "fatty pancreas" and of BMI in the occurrence of pancreatic fistula after pancreaticoduodenectomy. J. Gastrointest Surg. 13, 1845-1851 (2009).
198. Lermite, E. et al. Risk factors of pancreatic fistula and delayed gastric emptying after pancreaticoduodenectomy with pancreaticogastrostomy. J. Am. Coll. Surg. 204, 588-596 (2007). (Pubitemid 46428570)
199. Fleming, J. B. et al. Influence of obesity on cancer-related outcomes after pancreatectomy to treat pancreatic adenocarcinoma. Arch. Surg. 144, 216-221 (2009).
200. Tsai, S. et al. Impact of obesity on perioperative outcomes and survival following pancreaticoduodenectomy for pancreatic cancer: a large single-institution study. J. Gastrointest Surg. 14, 1143-1150 (2010).
201. de Vries, E. et al. Lifestyle changes and reduction of colon cancer incidence in Europe: a scenario study of physical activity promotion and weight reduction. Eur. J. Cancer 46, 2605-2616 (2010).