Obesity and cancer pathogenesis

Annals of the New York Academy of Sciences

Volumn 1311, Issue 1, 2014, Pages 57-76

  Berger, Nathan A ^a  

^a CASE WESTERN RESERVE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Cancer and obesity; Cholesterol; Diabetes; Dietary fats; Intestinal microbiome; Murine models; Pancreatic cancer

Indexed keywords

CHOLESTEROL;

ARTICLE; FAT INTAKE; HUMAN; INTESTINE FLORA; NEOPLASM; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OBESITY; PANCREAS CANCER; PATHOGENESIS; TUMOR PROMOTION;

CANCER AND OBESITY; CHOLESTEROL; DIABETES; DIETARY FATS; INTESTINAL MICROBIOME; MURINE MODELS; PANCREATIC CANCER;

ANIMALS; BODY MASS INDEX; DIABETES MELLITUS, TYPE 2; DIETARY FATS; DISEASE MODELS, ANIMAL; HUMANS; MICE; OBESITY; PANCREATIC NEOPLASMS; RISK FACTORS;

EID: 84898453962     PISSN: 00778923     EISSN: 17496632     Source Type: Book Series    
DOI: 10.1111/nyas.12416     Document Type: Article

References (213)

1. Popkin, B.M. 2006. Global nutrition dynamics: the world is shifting rapidly toward a diet linked with noncommunicable diseases. Am. J. Clin. Nutr. 84: 289-298.
2. Popkin, B.M. & M.M. Slining. 2013. New dynamics in global obesity facing low- and middle-income countries. Obes. Rev. 14(Suppl. 2): 11-20.
3. Wang, G.-R., L. Li, Y.-H. Pan, et al. 2013. Prevalence of metabolic syndrome among urban community residents in China. BMC Public Health 13: 599.
4. Ogden, C.L., M.D. Carroll, B.K. Kit & K.M. Flegal. 2012. Prevalence of obesity in the United States, 2009-2010. NCHS data brief, no 82: 1-8. National Center for Health Statistics 2012, Hyattsville, MD.
5. Ogden, C.L., M.D. Carroll, B.K. Kit & K.M. Flegal. 2013. Prevalence of obesity among adults: United States, 2011-2012. NCHS data brief, no 131: 1-8. National Center for Health Statistics 2013, Hyattsville, MD.
6. Flegal, K.M., M.D. Carroll, B.K. Kit & C.L. Ogden. 2012. Prevalence of obesity and trends in the distribution of body mass index among US adults, 1999-2010. JAMA 307: 491-497.
7. Flegal, K.M. & M.D. Carroll. 2010. Prevalence and trends in obesity among US adults, 1999-2008. JAMA 303: 235-241.
8. Finkelstein, E.A., O.A. Khavjou, H. Thompson, et al. 2012. Obesity and severe obesity forecasts through 2030. Am. J. Prev. Med. 42: 563-570.
9. Ballard-Barbash, R., D. Berrigan, N. Potischman & E. Doling. 2010. Obesity and cancer epidemiology. In Cancer and Energy Balance: Epidemiology and Overview, Vol. 1, N.A. Berger, Ed.: 1-45. Springer: New York.
10. Nock, N.L. & N.A. Berger. 2010. Obesity and cancer: overview of mechanisms. In Cancer and Energy Balance: Epidemiology and Overview, Vol. 1, N.A. Berger, Ed.: 129-179. Springer: New York.
11. Nock, N.L. 2012. Obesity and Gastrointestinal Cancers: Epidemiology. S.D. Markowitz & N.A. Berger, Eds.: 1-22. New York: Springer.
12. Handelsman, Y., D. Leroith, Z.T. Bloomgarden, et al. 2013. Diabetes and cancer-an AACE/ACE consensus statement. Endocr. Pract. 19: 675-693.
13. Ma, Y., Y. Yang, F. Wang, et al. 2013. Obesity and risk of colorectal cancer: a systematic review of prospective studies. PloS One 8: e53916.
14. Teras, L.R. & A. Patel. 2012. The epidemiology of obesity and hematologic malignancies. In Energy Balance and Hematologic Malignancies, Vol. 5, S.D. Mittelman & N.A. Berger, Eds.: 1-30. Springer: New York.
15. Iyengar, N., A. Kochhar, P. Morris, et al. 2014. Impact of obesity on survival of patients in early stage squamous cell carcinoma of the oral tongue. Cancer. 120: 983-991.
16. Berger, N.A. 2014. Cancer: obesity-associated gastrointestinal tract cancer, from beginning to end. Cancer. 120: 935-939.
17. Calle, E.E., C. Rodriguez, K. Walker-Thurmond & M.J. Thun. 2003. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N. Engl. J. Med. 348: 1625-1638.
18. Lyman, G.H. & A. Sparreboom. 2013. Chemotherapy dosing in overweight and obese patients with cancer. Nat. Rev. Clin. Oncol. 10: 451-459.
19. Hourdequin, K.C., W.L. Schpero, D.R. McKenna, et al. 2013. Toxic effect of chemotherapy dosing using actual body weight in obese versus normal-weight patients: a systematic review and meta-analysis. Ann. Oncol. 24: 2952-2962.
20. Griggs, J.J., M.E.S. Sorbero & G.H. Lyman. 2005. Undertreatment of obese women receiving breast cancer chemotherapy. Arch. Intern. Med. 165: 1267-1273.
21. Griggs, J.J., P.B. Mangu, S. Temin & G.H. Lyman. 2012. Appropriate chemotherapy dosing for obese adult patients with cancer: American Society of Clinical Oncology clinical practice guideline. J. Oncol. Pract. 8: e59-e61.
22. Weiss, B.M., D.T. Vogl, N.A. Berger, et al. 2013. Trimming the fat: obesity and hematopoietic cell transplantation. Bone Marrow Transplant. 48: 1152-1160.
23. Tao, W. & J. Lagergren. 2013. Clinical management of obese patients with cancer. Nat. Rev. Clin. Oncol. 10: 519-533.
24. Calle, E.E. & R. Kaaks. 2004. Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Nat. Rev. Cancer 4: 579-591.
25. Sjöström, L., K. Narbro, D. Sjöström, et al. 2007. Effects of bariatric surgery on mortality in Swedish obese subjects. N. Engl. J. Med. 357: 741-752.
26. Sjöström, L., A. Gummesson, C.D. Sjöström, 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.
27. Adams, T.D., R.E. Gress, S.C. Smith, et al. 2007. Long-term mortality after gastric bypass surgery. N. Engl. J. Med. 357: 753-761.
28. Nock, N.L., C.L. Thompson, T.C. Tucker, et al. 2008. Associations between obesity and changes in adult BMI over time and colon cancer risk. Obesity 16: 1099-1104.
29. Genkinger, J.M., D. Spiegelman, K.E. Anderson, et al. 2011. A pooled analysis of 14 cohort studies of anthropometric factors and pancreatic cancer risk. Int. J. Cancer 129: 1708-1717.
30. Yuan, C., Y. Bao, C. Wu, et al. 2013. Prediagnostic body mass index and pancreatic cancer survival. J. Clin. Oncol. 31: 4229-4234.
31. Berger, N.A., P. Savvides, S.M. Koroukian, et al. 2006. Cancer in the elderly. Trans. Am. Clin. Climatol. Assoc. 117: 147-155.
32. Wang, Y.C., G.A. Colditz & K.M. Kuntz. 2007. Forecasting the obesity epidemic in the aging US population. Obesity 15: 2855-2865.
33. Kushi, L.H., T. Byers, C. Doyle, et al.; The American Cancer Society, N., and Physical Activity Guidelines Advisory, C., 2012. American Cancer Society Guidelines on nutrition and physical activity for cancer prevention: reducing the risk of cancer with healthy food choices and physical activity. CA Cancer J. Clin. 12: 30-67.
34. Hursting, S.D., J. Digiovanni, A.J. Dannenberg, et al. 2012. Obesity, energy balance, and cancer: new opportunities for prevention. Cancer Prev. Res. 5: 1260-1272.
35. Alfano, C.M., A. Molfino & M. Muscaritoli. 2013. Interventions to promote energy balance and cancer survivorship: priorities for research and care. Cancer 119(Suppl): 2143-2150.
36. Calle, E.E., M.J. Thun, J.M. Petrelli, et al. 1999. Body-mass index and mortality in a prospective cohort of U.S. adults. N. Engl. J. Med. 341: 1097-1105.
37. Hursting, S.D. & N.A. Berger. 2010. Energy balance, host-related factors, and cancer progression. J. Clin. Oncol. 28: 4058-4065.
38. Hursting, S.D. 2014. Advances in nutrition and cancer: a mechanistic perspective. In Cancer Treatment and Research. Vol. 159: 21-33. Berlin, Heidelberg: Springer Berlin Heidelberg.
39. Sharma, D. & N.E. Davidson. 2013. Obesity and breast cancer: a multipartite connection. J. Mammary Gland Biol. Neoplasia 18: 253-255.
40. Ligibel, J.A. & H.D. Strickler. 2013. Obesity and its impact on breast cancer: tumor incidence, recurrence, survival, and possible interventions. Am. Soc. Clin. Oncol. Educ. Book 33: 52-59.
41. Vona-Davis, L. & D.P. Rose. 2013. The obesity-inflammation-eicosanoid axis in breast cancer. J. Mammary Gland Biol. Neoplasia 18: 291-307.
42. Strong, A.L., T.A. Strong, L.V. Rhodes, et al. 2013. Obesity associated alterations in the biology of adipose stem cells mediate enhanced tumorigenesis by estrogen dependent pathways. Breast Cancer Res. 15: R102.
43. Iyengar, N.M., C.A. Hudis & A. Gucalp. 2013. Omega-3 fatty acids for the prevention of breast cancer: an update and state of the science. Curr. Breast Cancer Rep. 5: 247-254.
44. Iyengar, N.M., C.A. Hudis & A.J. Dannenberg. 2013. Obesity and inflammation: new insights into breast cancer development and progression. Am. Soc. Clin. Oncol. Educ. Book 33: 46-51.
45. Ford, N.A., K.L. Devlin, L.M. Lashinger & S.D. Hursting. 2013. Deconvoluting the obesity and breast cancer link: secretome, soil and seed interactions. J. Mammary Gland Biol. Neoplasia 18: 267-275.
46. Belardi, V., E.J. Gallagher, R. Novosyadlyy & D. LeRoith. 2013. Insulin and IGFs in obesity-related breast cancer. J. Mammary Gland Biol. Neoplasia 18: 277-289.
47. Sundaram, S., A.R. Johnson & L. Makowski. 2013. Obesity, metabolism and the microenvironment: links to cancer. J. Carcinog. 12: 19.
48. Yehuda-Shnaidman, E. & B. Schwartz. 2012. Mechanisms linking obesity, inflammation and altered metabolism to colon carcinogenesis. Obes. Rev. 13: 1083-1095.
49. Ning, Y., L. Wang & E.L. Giovannucci. 2010. A quantitative analysis of body mass index and colorectal cancer: findings from 56 observational studies. Obes. Rev. 11: 19-30.
50. Giovannucci, E. 2007. Metabolic syndrome, hyperinsulinemia, and colon cancer: a review. Am. J. Clin. Nutr. 86: s836-s842.
51. Gunter, M.J. & M.F. Leitzmann. 2006. Obesity and colorectal cancer: epidemiology, mechanisms and candidate genes. J. Nutr. Biochem. 17: 145-156.
52. Bardou, M., A.N. Barkun & M. Martel. 2013. Obesity and colorectal cancer. Gut 62: 933-947.
53. Jain, D., N.C. Nayak, V. Kumaran & S. Saigal. 2013. Steatohepatitic hepatocellular carcinoma, a morphologic indicator of associated metabolic risk factors: a study from India. Arch. Pathol. Lab. Med. 137: 961-966.
54. Zhao, J. & M.W. Lawless. 2013. Stop feeding cancer: pro-inflammatory role of visceral adiposity in liver cancer. Cytokine 64: 626-637.
55. Alkhouri, N., L.J. Dixon & A.E. Feldstein. 2009. Lipotoxicity in nonalcoholic fatty liver disease: not all lipids are created equal. Expert Rev. Gastroenterol. Hepatol. 3: 445-451.
56. Wree, A., A. Kahraman, G. Gerken & A. Canbay, 2011. Obesity affects the liver-the link between adipocytes and hepatocytes. Digestion 83: 124-133.
57. Cohen, J.C., J.D. Horton & H.H. Hobbs. 2011. Human fatty liver disease: old questions and new insights. Science 332: 1519-1523.
58. Campbell, P.T., C.C. Newton, A.V. Patel, et al. 2012. Diabetes and cause-specific mortality in a prospective cohort of one million U.S. adults. Diabetes Care 35: 1835-1844.
59. Gallagher, E.J. & D. LeRoith. 2013. Diabetes, antihyperglycemic medications and cancer risk: smoke or fire? Curr. Opin. Endocrinol. Diabetes Obes. 20: 485-494.
60. Gallagher, E.J. & D. LeRoith. 2013. Epidemiology and molecular mechanisms tying obesity, diabetes, and the metabolic syndrome with cancer. Diabetes Care 36(Suppl 2): S233-S239.
61. Sciacca, L., R. Vigneri, A. Tumminia, et al. 2013. Clinical and molecular mechanisms favoring cancer initiation and progression in diabetic patients. Nutr. Metab. Cardiovasc. Dis. 23: 808-815.
62. Kaaks, R., P. Toniolo, A. Akhmedkhanov, et al. 2000. Serum C-peptide, insulin-like growth factor (IGF)-I, IGF-binding proteins, and colorectal cancer risk in women. J. Natl. Cancer Inst. 92: 1592-1600.
63. Medpagetoday. 2014. SABCS: Diabetes, Obesity Ups Risk of Breast Cancer. http://www.medpagetoday.com/MeetingCoverage/SABCS/30059. Accessed 1/25/2014.
64. Currie, C.J., C.D. Poole, S. Jenkins-Jones, et al. 2012. Mortality after incident cancer in people with and without type 2 diabetes: impact of metformin on survival. Diabetes Care 35: 299-304.
65. Phipps, A.I., R.T. Chlebowski, R. Prentice, et al. 2011. Body size, physical activity, and risk of triple-negative and estrogen receptor-positive breast cancer. Cancer Epidemiol. Biomarkers Prev. 20: 454-463.
66. Lopez, R., P. Agullo & R. Lakshmanaswamy. 2013. Links between obesity, diabetes and ethnic disparities in breast cancer among Hispanic populations. Obes. Rev. 14: 679-691.
67. CDC-Centers for Disease Control and Prevention. 2014. CDC-Diagnosed Diabetes Data & Trends- Diabetes DDT. http://www.cdc.gov/diabetes/statistics/prevalence_national.htm. Accessed 2/25/2014
68. Siegel, R., C. Naishadham & A. Jemal. 2012. Cancer statistics, 2012. CA Cancer J. Clin. 62: 10-29.
69. Kasper, J.S. & E. Giovannucci. 2006. A meta-analysis of diabetes mellitus and the risk of prostate cancer. Cancer Epidemiol. Biomarkers Prev. 15: 2056-2062.
70. Barrett-Conner, E., K.T. Khaw & S.S. Yen. 1990. Endogenous sex hormone levels in older adult men with diabetes mellitus. Am. J. Epidemiol. 132: 895-901.
71. Frasca, F., G. Pandini, P. Scalia, et al. 1999. Insulin receptor isoform A, a newly recognized, high-affinity insulin-like growth factor II receptor in fetal and cancer cells. Mol. Cell Bio. 19: 3278-3288.
72. Harrington, S.C., S.J. Weroha, C. Reynolds, et al. 2012. Quantifying insulin receptor isoform expression in FFPE breast tumors. Growth Horm. IGF Res. 22: 108-115.
73. Heni, M., J. Hennenlotter, M. Scharpf, et al. 2012. Insulin receptor isoforms A and B as well as insulin receptor substrates-1 and -2 are differentially expressed in prostate cancer. PloS One 7: e50953.
74. Andres, S.F., J.G. Simmons, A.T. Mah, et al. 2013. Insulin receptor isoform switching in intestinal stem cells, progenitors, differentiated lineages and tumors: evidence that IR-B limits proliferation. J. Cell Sci. 126(Pt 24): 5645-5656.
75. Del Giudice, M.E., I.G. Fantus, S. Ezzat, et al. 1998. Insulin and related factors in premenopausal breast cancer risk. Breast Cancer Res. Treat. 47: 111-120.
76. Thissen, J.-P., J.-M. Ketelslegers & L.E. Underwood. 1994. Nutritional regulation of the insulin-like growth factors. Endocr. Rev. 15: 80-101.
77. Taniguchi, C.M., B. Emanuelli & C.R. Kahn. 2006. Critical nodes in signalling pathways: insights into insulin action. Nat. Rev. Mol. Cell Biol. 7: 85-96.
78. Taniguchi, C.M. & C.R. Kahn. 2011. Insulin/IGF-1 Signaling Nodes and Their Role. In Insulin Resistance and Cancer, Vol. 2, I.G. Fantus & N.A. Berger, Eds.: 53-76. Springer: New York.
79. Babichev, Y., S. Khalid & I.G. Fantus. 2011. Potential Mechanisms Linking Insulin to Cancer. In Insulin Resistance and Cancer, Vol. 2, I.G. Fantus & N.A. Berger, Eds.: 159-180. Springer: New York.
80. Othman, E.M., A. Leyh & H. Stopper. 2013. Insulin mediated DNA damage in mammalian colon cells and human lymphocytes in vitro. Mutat. Res. 745-746: 34-39.
81. Pollak, M.N. 2012. Investigating metformin for cancer prevention and treatment: the end of the beginning. Cancer Discov. 2: 778-790.
82. Chlebowski, R.T., A. McTiernan, J. Wactawski-Wende, et al. 2012. Diabetes, metformin, and breast cancer in postmenopausal women. J. Clin. Oncol. 30: 2844-2852.
83. Jiralerspong, S., S.L. Palla, S.H. Giordano, et al. 2009. Metformin and pathologic complete responses to neoadjuvant chemotherapy in diabetic patients with breast cancer. J. Clin. Oncol. 27: 3297-3302.
84. Ben Sahra, I., Y. Le Marchand-Brustel, J.-F. Tanti & F. Bost. 2010. Metformin in cancer therapy: a new perspective for an old antidiabetic drug? Mol. Cancer Ther. 9: 1092-1099.
85. Niraula, S., R.J.O. Dowling, M. Ennis, et al. 2012. Metformin in early breast cancer: a prospective window of opportunity neoadjuvant study. Breast Cancer Res. Treat. 135: 821-830.
86. Goodwin, P.J., V. Stambolic, J. Lemieux, et al. 2011. Evaluation of metformin in early breast cancer: a modification of the traditional paradigm for clinical testing of anti-cancer agents. Breast Cancer Res. Treat. 126: 215-220.
87. Sandulache, V.C., J.S. Hamblin, H.D. Skinner, et al. 2013. Metformin use is associated with improved survival in patients with laryngeal squamous cell carcinoma. Head Neck. doi: 10.1002/hed.23409. Epub ahead of print.
88. Ahmadian, M., J.M. Suh, N. Hah, et al. 2013. PPARγ signaling and metabolism: the good, the bad and the future. Nat. Med. 19: 557-566.
89. Niho, N., M. Takahashi, Y. Shoji, et al. 2003. Dose-dependent suppression of hyperlipidemia and intestinal polyp formation in Min mice by pioglitazone, a PPAR gamma ligand. Cancer Sci. 94: 960-964.
90. Ueno, T., N. Teraoka, S. Takasu, et al. 2012. Suppressive effect of pioglitazone, a PPAR gamma ligand, on azoxymethane-induced colon aberrant crypt foci in KK-Ay mice. Asian Pac. J. Cancer Prev. 13: 4067-4073.
91. Warburg, O. 1956. On respiratory impairment in cancer cells. Science 123: 309-314.
92. Kim, J.-W. & C.V. Dang. 2006. Cancer's molecular sweet tooth and the Warburg effect. Cancer Res. 66: 8927-8930.
93. Büsing, K.A., S.O. Schönberg, J. Brade & K. Wasser. 2013. Impact of blood glucose, diabetes, insulin, and obesity on standardized uptake values in tumors and healthy organs on 18F-FDG PET/CT. Nucl. Med. Biol. 40: 206-213.
94. Meyerhardt, J.A., D. Niedzwiecki, D. Hollis, et al. 2007. Association of dietary patterns with cancer recurrence and survival in patients with stage III colon cancer. JAMA 298: 754-764.
95. Meyerhardt, J.A., K. Sato, D. Niedzwiecki, et al. 2012. Dietary glycemic load and cancer recurrence and survival in patients with stage III colon cancer: findings from CALGB 89803. J. Natl. Cancer Inst. 104: 1702-1711.
96. Jeon, J.Y., D.H. Jeong, M.G. Park, et al. 2013. Impact of diabetes on oncologic outcome of colorectal cancer patients: colon vs. rectal cancer. PloS One 8: e55196.
97. Huffman, D.M., L.H. Augenlicht, X. Zhang, et al. 2013. Abdominal obesity, independent from caloric intake, accounts for the development of intestinal tumors in Apc(1638N/+) female mice. Cancer Prev. Res. 6: 177-187.
98. Ignatenko, N.A. & E.W. Gerner. 2013. Get the fat out! Cancer Prev. Res. 6: 161-164.
99. Tee, M.C., Y. Cao, G.L. Warnock, et al. 2013. Effect of bariatric surgery on oncologic outcomes: a systematic review and meta-analysis. Surg. Endos. 27: 4449-4456.
100. Doerner, S.K. & N.A. Berger. 2013. Dietary Fats as Mediators of Obesity, Inflammation and Cancer. In Obesity, Inflammation and Cancer, Vol. 7, A.J. Dannenberg & N.A. Berger, Eds.: 99-132. Springer: New York.
101. Su, L.K., K.W. Kinzler & B. Vogelstein. 1992. Multiple intestinal neoplasia caused by a mutation in the murine homolog of the APC gene. Science 256: 668-670.
102. Moser, A.R., H.C. Pitot & W.F. Dove. 1990. A dominant mutation that predisposes to multiple intestinal neoplasia in the mouse. Science 247: 322-324.
103. Fodde, R. 2002. The APC gene in colorectal cancer. Eur. J. Cancer 38: 867-871.
104. Lefebvre, A.M., I. Chen, P. Desreumaux, et al. 1998. Activation of the peroxisome proliferator-activated receptor γ promotes the development of colon tumors in C57BL/6J-APCMin/+ mice. Nat. Med. 4: 1053-1057.
105. Doerner, S.K., E.S. Leung, J.S. Ko, et al. 2013. Differential effects of specific dietary fat sources on inflammation and intestinal tumorigenesis. [abstract no. 2859]. In Proceedings of the 104th Annual Meeting of the American Association for Cancer Research, Apr 6-10, Washington, DC. (Philadelphia (PA): Cancer Res. 73(Suppl).
106. Ferraris, R.P. & R.R. Vinnakota. 1995. Intestinal nutrient transport in genetically obese mice. Am. J. Clin. Nutr. 62: 540-546.
107. Ealey, K.N., S. Lu & M.C. Archer. 2008. Development of aberrant crypt foci in the colons of ob/ob and db/db mice: evidence that leptin is not a promoter. Mol. Carcinog. 47: 667-677.
108. Hirose, Y., K. Hata, T. Kuno, et al. 2004. Enhancement of development of azoxymethane-induced colonic premalignant lesions in C57BL/KsJ-db/db mice. Carcinogenesis 25: 821-825.
109. Zheng, Q., S.M. Dunlap, J. Zhu, et al. 2011. Leptin deficiency suppresses MMTV-Wnt-1 mammary tumor growth in obese mice and abrogates tumor initiating cell survival. Endocr. Relat. Cancer 18: 491-503.
110. Warwick, B.P. & D.R. Romsos. 1988. Energy balance in adrenalectomized ob/ob mice: effects of dietary starch and glucose. Am. J. Physiol. 255(1 Pt 2): R141-R148.
111. Tuominen, I., L. Al-Rabadi, D. Stavrakis, et al. 2013. Diet-induced obesity promotes colon tumor development in azoxymethane-treated mice. PloS One 8: e60939.
112. Newmark, H.L., K. Yang & M. Lipkin. 2001. A Western-style diet induces benign and malignant neoplasms in the colon of normal C57Bl/6 mice. Carcinogenesis 22: 1871-1875.
113. Hill-Baskin, A.E., M.M. Markiewski, D.A. Buchner, et al. 2009. Diet-induced hepatocellular carcinoma in genetically predisposed mice. Hum. Mol. Genet. 18: 2975-2988.
114. Nishida, T., K. Tsuneyama, M. Fujimoto, et al. 2013. Spontaneous onset of nonalcoholic steatohepatitis and hepatocellular carcinoma in a mouse model of metabolic syndrome. Lab. Invest. 93: 230-241.
115. Qian, S.S., J. Gao, J.X. Wang, et al. 1987. Establishment of a mouse forestomach carcinoma cell line (MFC) with spontaneous hematogenous metastasis and preliminary study of its biological characteristics. Zhonghua Zhong Liu Za Zhi 9: 261-264.
116. Li, H.-J., X.-M. Che, W. Zhao, et al. 2012. Diet-induced obesity potentiates the growth of gastric cancer in mice. Exp. Ther. Med. 4: 615-620.
117. Li, H.-J., X.-M. Che, W. Zhao, et al. 2013. Diet-induced obesity promotes murine gastric cancer growth through a nampt/sirt1/c-myc positive feedback loop. Oncol. Rep. 30: 2153-2160.
118. Dahl, T.B., S. Holm, P. Aukrust & B. Halvorsen. 2012. Visfatin/NAMPT: a multifaceted molecule with diverse roles in physiology and pathophysiology. Annu. Rev. Nutr. 32: 229-243.
119. Soucek, L., J. Whitfield, C.P. Martins, et al. 2008. Modelling Myc inhibition as a cancer therapy. Nature 455: 679-683.
120. Menssen, A., P. Hydbring, K. Kapelle, et al. 2012. The c-MYC oncoprotein, the NAMPT enzyme, the SIRT1-inhibitor DBC1, and the SIRT1 deacetylase form a positive feedback loop. Proc. Natl. Acad. Sci. USA 109: E187-E196.
121. Friedman, J.M. 2010. A tale of two hormones. Nat. Med. 16: 1100-1106.
122. Jung, C.H. & M.-S. Kim. 2013. Molecular mechanisms of central leptin resistance in obesity. Arch. Pharm. Res. 36: 201-207.
123. Uddin, S., A.R. Hussain, O.S. Khan & K.S. Al-Kuraya. 2014. Role of dysregulated expression of leptin and leptin receptors in colorectal carcinogenesis. Tumour Biol. 35: 871-879.
124. Zhang, Y., R. Proenca, M. Maffei, et al. 1994. Positional cloning of the mouse obese gene and its human homologue. Nature 372: 425-432.
125. Barone, I., S. Catalano, L. Gelsomino, et al. 2012. Leptin mediates tumor-stromal interactions that promote the invasive growth of breast cancer cells. Cancer Res. 72: 1416-1427.
126. Saxena, N.K., D. Sharma, X. Ding, et al. 2007. Concomitant activation of the JAK/STAT, PI3K/AKT, and ERK signaling is involved in leptin-mediated promotion of invasion and migration of hepatocellular carcinoma cells. Cancer Res. 67: 2497-2507.
127. Wang, D., J. Chen, H. Chen, et al. 2011. Leptin regulates proliferation and apoptosis of colorectal carcinoma through PI3K/Akt/mTOR signalling pathway. J. Biosci. 37: 91-101.
128. Zheng, Q., L. Banaszak, S. Fracci, et al. 2013. Leptin receptor maintains cancer stem-like properties in triple negative breast cancer cells. Endocr. Relat. Cancer 20: 797-808.
129. Newman, G. & R.R. Gonzalez-Perez. 2014. Leptin-cytokine crosstalk in breast cancer. Mol. Cell. Endocrinol. 382: 570-582.
130. Zhou, J., J. Wulfkuhle, H. Zhang, et al. 2007. Activation of the PTEN/mTOR/STAT3 pathway in breast cancer stem-like cells is required for viability and maintenance. Proc. Natl. Acad. Sci. USA 104: 16158-16163.
131. Beccari, S., I. Kovalszky, J.D. Wade, et al. 2013. Designer peptide antagonist of the leptin receptor with peripheral antineoplastic activity. Peptides 44: 127-134.
132. Bitton-Worms, K., R. Rostoker, S. Braun, et al. 2013. The effect of leptin administration on mammary tumor growth in diabetic mice. Horm. Metab. Res. 45: 655-659.
133. Vykhovanets, E.V., E. Shankar, O.V. Vykhovanets, et al. 2011. High-fat diet increases NF-κB signaling in the prostate of reporter mice. Prostate 71: 147-156.
134. Llaverias, G., C. Danilo, Y. Wang, et al. 2010. A Western-type diet accelerates tumor progression in an autochthonous mouse model of prostate cancer. Am. J. Pathol. 177: 3180-3191.
135. Greenberg, N.M., F. DeMayo, M.J. Finegold, et al. 1995. Prostate cancer in a transgenic mouse. Proc. Natl. Acad. Sci. USA 92: 3439-3443.
136. Cunhaii, G.R., A.A. Donjacourii, R.J. Matusik & J.M. Rosen. 1995. Prostate cancer in a transgenic mouse neoplasim epithelial. Proc. Natl. Acad. Sci. USA 92: 3439-3443.
137. Huffman, D.M., M.S. Johnson, A. Watts, et al. 2007. Cancer progression in the transgenic adenocarcinoma of mouse prostate mouse is related to energy balance, body mass, and body composition, but not food intake. Cancer Res. 67: 417-424.
138. Bonorden, M.J.L., M.E. Grossmann, S.A. Ewing, et al. 2012. Growth and progression of TRAMP prostate tumors in relationship to diet and obesity. Prostate Cancer 2012: 543970.
139. Grossmann, M.E., N.K. Mizuno, M.J.L. Bonorden, et al. 2009. Role of the adiponectin leptin ratio in prostate cancer. Oncol. Res. 18: 269-277.
140. Miyazaki, T., J.D. Bub & Y. Iwamoto. 2008. c-Jun NH-terminal kinase mediates leptin-stimulated androgen-independent prostate cancer cell proliferation via signal transducer and activator of transcription 3 and Akt. Biochim. Biophys. Acta 1782: 593-604.
141. Saw, C.L.L., T.-Y. Wu, X. Paredes-Gonzalez, et al. 2011. Pharmacodynamics of fish oil: protective effects against prostate cancer in TRAMP mice fed with a high fat western diet. Asian Pac. J. Cancer Prev. 12: 3331-3334.
142. Davis, P.A., V.T. Vasu, K. Gohil, et al. 2012. A high-fat diet containing whole walnuts (Juglans regia) reduces tumour size and growth along with plasma insulin-like growth factor 1 in the transgenic adenocarcinoma of the mouse prostate model. Br. J. Nutr. 108: 1764-1772.
143. Liu, K., M. Jiang, Y. Lu, et al. 2013. Sox2 cooperates with inflammation-mediated Stat3 activation in the malignant transformation of foregut basal progenitor cells. Cell Stem Cell 12: 304-315.
144. Fang, Y., X. Chen, M. Bajpai, et al. 2013. Cellular origins and molecular mechanisms of Barrett's esophagus and esophageal adenocarcinoma. Ann. N. Y. Acad. Sci. 1300: 187-199.
145. Duggan, C., L. Onstad, S. Hardikar, et al. 2013. Association between markers of obesity and progression from Barrett's esophagus to esophageal adenocarcinoma. Clin. Gastroenterol. Hepatol. 11: 934-943.
146. Michaud, D.S. & E. Giovannucci. 2001. Physical activity, obesity, height, and the risk of pancreatic cancer. JAMA 286: 921-929.
147. Michaud, D.S. 2013. Role of bacterial infections in pancreatic cancer. Carcinogenesis 34: 2193-2197.
148. Bracci, P.M. 2012. Obesity and pancreatic cancer: overview of epidemiologic evidence and biologic mechanisms. Mol. Carcinog. 51: 53-63.
149. Klein, A.P., S. Lindström, J.B. Mendelsohn, et al. 2013. An absolute risk model to identify individuals at elevated risk for pancreatic cancer in the general population. PloS One 8: e72311.
150. Tang, H., P. Wei, E.J. Duell, et al. 2013. Genes-environment interactions in obesity- and diabetes-associated pancreatic cancer: a GWAS data analysis. Cancer Epidemiol. Biomarkers Prev. 23: 98-106.
151. Papamichael, K.-X. 2009. Helicobacter pylori infection and endocrine disorders: is there a link? World J. Gastroenterol. 15: 2701-2707.
152. Aguirre, A.J., N. Bardeesy, M. Sinha, et al. 2003. Activated Kras and Ink4a/Arf deficiency cooperate to produce metastatic pancreatic ductal adenocarcinoma. Genes Dev. 17: 3112-3126.
153. Hingorani, S.R., E.F. Petricoin, A. Maitra, et al. 2003. Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse. Cancer Cell 4: 437-450.
154. Murtaugh, L.C. 2014. Pathogenesis of pancreatic cancer: lessons from animal models. Toxicol. Pathol. 42: 217-228.
155. Rhim, A.D., E.T. Mirek, N.M. Aiello, et al. 2012. EMT and dissemination precede pancreatic tumor formation. Cell 148: 349-361.
156. Daniluk, J., Y. Liu, D. Deng, et al. 2012. An NF- κ B pathway-mediated positive feedback loop amplifies Ras activity to pathological levels in mice. J. Clin. Invest. 122: 1519-1528.
157. Schneider, M.B., H. Matsuzaki, J. Haorah, et al. 2001. Prevention of pancreatic cancer induction in hamsters by metformin. Gastroenterology 120: 1263-1270.
158. Li, D. 2012. Diabetes and pancreatic cancer. Mol. Carcinog. 51: 64-74.
159. Gukovsky, I., N. Li, J. Todoric, et al. 2013. Inflammation, autophagy, and obesity: common features in the pathogenesis of pancreatitis and pancreatic cancer. Gastroenterology 144: 1199-1209.e4.
160. Dawson, D.W., K. Hertzer, A. Moro, et al. 2013. High-fat, high-calorie diet promotes early pancreatic neoplasia in the conditional KrasG12D mouse model. Cancer Prev. Res. 6: 1064-1073.
161. Lashinger, L.M., L.M. Harrison, A.J. Rasmussen, et al. 2013. Dietary energy balance modulation of Kras- and Ink4a/Arf+/-driven pancreatic cancer: the role of insulin-like growth factor-I. Cancer Prev. Res. 6: 1046-1055.
162. Kim, E.J., M.-R. Choi, H. Park, et al. 2011. Dietary fat increases solid tumor growth and metastasis of 4T1 murine mammary carcinoma cells and mortality in obesity-resistant BALB/c mice. Breast Cancer Res. 13: R78-R78.
163. Pelucchi, C., C. Bosetti, E. Negri, et al. 2011. Olive oil and cancer risk: an update of epidemiological findings through 2010. Curr. Pharm. Des. 17: 805-812.
164. D'Archivio, M., B. Scazzocchio, S. Giammarioli, et al. 2013. ω3-PUFAs exert anti-inflammatory activity in visceral adipocytes from colorectal cancer patients. PloS One 8: e77432.
165. Braun, D.A., M. Fribourg & S.C. Sealfon. 2013. Cytokine response is determined by duration of receptor and signal transducers and activators of transcription 3 (STAT3) activation. J. Biol. Chem. 288: 2986-2993.
166. Turk, H.F., J.M. Monk & T.Y. Hou. 2013. Omega-3 fatty acids in cancer prevention and control. In Obesity, Inflammation and Cancer, Vol. 7, A.J. Dannenberg & N.A. Berger, Eds.: 305-339. Springer: New York.
167. Bao, Y., F.B. Hu, E.L. Giovannucci, et al. 2013. Nut consumption and risk of pancreatic cancer in women. Br. J. Cancer 109: 2911-2916.
168. Bao, Y., J. Han, F.B. Hu, et al. 2013. Association of nut consumption with total and cause-specific mortality. N. Engl. J. Med. 369: 2001-2011.
169. Jaceldo-Siegl, K., E. Haddad, K. Oda, et al. 2014. Tree nuts are inversely associated with metabolic syndrome and obesity: the adventist health study-2. PloS One 9: e85133.
170. Bjørge, T., A. Engeland, A. Tverdal & G.D. Smith. 2008. Body mass index in adolescence in relation to cause-specific mortality: a follow-up of 230, 000 Norwegian adolescents. Am. J. Epidemiol. 168: 30-37.
171. Levi, Z., J.D. Kark, M. Barchana, et al. 2011. Measured body mass index in adolescence and the incidence of colorectal cancer in a cohort of 1.1 million males. Cancer Epidemiol. Biomarkers Prev. 20: 2524-2531.
172. Aso, Y., S. Wakabayashi, R. Yamamoto, et al. 2005. Hypercholesterolemia is strongly and impairment of fibrinolysis in patients with type 2 diabetes. Diabetes Care 28: 2211-2216.
173. Ford, E.S. 2005. Prevalence of the metabolic syndrome defined by the international diabetes. Diabetes Care 28: 2745-2749.
174. Kitahara, C.M., A. Berrington de González, N.D. Freedman, et al. 2011. Total cholesterol and cancer risk in a large prospective study in Korea. J. Clin. Oncol. 29: 1592-1598.
175. Poynter, J.N., S.B. Gruber, P.D. Higgins, et al. 2005. Statins and the risk of colorectal cancer. N. Engl. J. Med. 352: 2184-2192.
176. Nielsen, S.F., B.G. Nordestgaard & S.E. Bojesen. 2012. Statin use and reduced cancer-related mortality. N. Engl. J. Med. 367: 1792-1802.
177. Ahern, T.P., L. Pedersen, M. Tarp, et al. 2011. Statin prescriptions and breast cancer recurrence risk: a Danish nationwide prospective cohort study. J. Natl. Cancer Inst. 103: 1461-1468.
178. Graaf, M.R., A.B. Beiderbeck, A.C.G. Egberts. 2004. The risk of cancer in users of statins. J. Clin. Oncol. 22: 2388-2394.
179. Wu, Q., T. Ishikawa, R. Sirianni, et al. 2013. 27-Hydroxycholesterol promotes cell-autonomous, ER-positive breast cancer growth. Cell Rep. 5: 637-645.
180. Nelson, E.R., S.E. Wardell, J.S. Jasper, et al. 2013. 27-Hydroxycholesterol links hypercholesterolemia and breast cancer pathophysiology. Science 342: 1094-1098.
181. Kaiser, J. 2013. Cancer. Cholesterol forges link between obesity and breast cancer. Science 342: 1028-1028.
182. Tilg, H. & A. Kaser. 2011. Gut microbiome, obesity, and metabolic dysfunction. J. Clin. Invest. 121: 2126-2132.
183. Turnbaugh, P.J., F. Bäckhed, L. Fulton & J.I. Gordon 2008. Diet-induced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome. Cell Host Microbe 3: 213-223.
184. Bäckhed, F., R.E. Ley, J.L. Sonnenburg, et al. 2005. Host-bacterial mutualism in the human intestine. Science 307: 1915-1920.
185. Plottel, C.S. & M.J. Blaser. 2011. Microbiome and malignancy. Cell Host Microbe 10: 324-335.
186. Bäckhed, F., H. Ding, T. Wang, et al. 2004. The gut microbiota as an environmental factor that regulates fat storage. Proc. Natl. Acad. Sci. USA 101: 15718-15723.
187. Russell, W.R., S.H. Duncan & H.J. Flint. 2013. The gut microbial metabolome: modulation of cancer risk in obese individuals. Proc. Nutr. Soc. 72: 178-188.
188. Andersson, A.F., M. Lindberg, H. Jakobsson, et al. 2008. Comparative analysis of human gut microbiota by barcoded pyrosequencing. PloS One 3: e2836.
189. Carvalho, B.M. & M.J.A. Saad 2013. Influence of gut microbiota on subclinical inflammation and insulin resistance. Mediators Inflamm. 2013: 986734.
190. Ley, R.E., F. Bäckhed, P. Turnbaugh, et al. 2005. Obesity alters gut microbial ecology. Proc. Natl. Acad. Sci. USA 102: 11070-11075.
191. Hildebrandt, M.A., C. Hoffmann, S.A. Sherrill-Mix, et al. 2009. High-fat diet determines the composition of the murine gut microbiome independently of obesity. Gastroenterology 137: 1716-1724.e1-2.
192. Mujico, J.R., G.C. Baccan, A. Gheorghe, et al. 2013. Changes in gut microbiota due to supplemented fatty acids in diet-induced obese mice. Br. J. Nutr. 110: 711-720.
193. Turnbaugh, P.J., R.E. Ley, M.A. Mahowald, et al. 2006. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444: 1027-1031.
194. Zhang, H., J.K. DiBaise, A. Zuccolo, et al. 2009. Human gut microbiota in obesity and after gastric bypass. Proc. Natl. Acad. Sci. USA 106: 2365-2370.
195. Ridaura, V.K., J.J. Faith, F.E. Rey, et al. 2013. Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science 341: 1241214-1-1241214-10.
196. Ziebarth, D., B. Spiegelhalder & H. Bartsch. 1997. N-nitrosation of medicinal drugs catalysed by bacteria from human saliva and gastro-intestinal tract, including Helicobacter pylori. Carcinogenesis 18: 383-389.
197. Membrez, M., F. Blancher, M. Jaquet, et al. 2008. Gut microbiota modulation with norfloxacin and ampicillin enhances glucose tolerance in mice. FASEB J. 22: 2416-2426.
198. Polk, D.B. & R.M. Peek. 2010. Helicobacter pylori: gastric cancer and beyond. Nat. Rev. Cancer 10: 403-414.
199. Bessède, E., C. Staedel, L.A. Acuña Amador, et al. 2013. Helicobacter pylori generates cells with cancer stem cell properties via epithelial-mesenchymal transition-like changes. Oncogene 33: 1-9.
200. Hatakeyama, M. 2009. Helicobacter pylori and gastric carcinogenesis. J. Gastroenterol. 44: 239-248.
201. Coussens, L.M. & Z. Werb. 2002. Inflammation and cancer. Nature 420: 860-867.
202. Reddy, B.S., K. Watanabe, J.H. Weisburger & E.L. Wynder. 1977.Promoting effect of bile acids in colon carcinogenesis in germ-free and conventional F344 rats. Cancer Res. 37: 3238-3242.
203. Goodson, J.M., D. Groppo, S. Halem & E. Carpino. 2009. Is obesity an oral bacterial disease? J. Dent. Res. 88: 519-523.
204. McCoy, A.N., F. Araújo-Pérez, A. Azcárate-Peril, et al. 2013. Fusobacterium is associated with colorectal adenomas. PloS One 8: e53653.
205. Kostic, A.D., E. Chun, L. Robertson, et al. 2013. Fusobacterium nucleatum potentiates intestinal tumorigenesis and modulates the tumor-immune microenvironment. Cell Host Microbe 14: 207-215.
206. Rubinstein, M.R., X. Wang, W. Liu, et al. 2013. Fusobacterium nucleatum promotes colorectal carcinogenesis by modulating E-cadherin/β-catenin signaling via its FadA adhesin. Cell Host Microbe 14: 195-206.
207. Yoshimoto, S., T.M. Loo, K. Atarashi, et al. 2013. Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome. Nature 499: 97-101.
208. Coppé, J.-P., C.K. Patil, F. Rodier, et al. 2008. Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. PLoS Biol. 6: 2853-2868.
209. Reddy, B.S. & B. Reddy. 1981. Dietary fat and its relationship to large bowel cancer. Cancer Res. 41: 3700-3705.
210. Qiao, D., S.V. Gaitonde, W. Qi & J.D. Martinez. 2001. Deoxycholic acid suppresses p53 by stimulating proteasome-mediated p53 protein degradation. Carcinogenesis 22: 957-964.
211. Devkota, S. & P.J. Turnbaugh, 2013. Cancer: an acidic link. Nature 499: 4-5.
212. Devkota, S., Y. Wang, M.W. Musch, et al. 2012. Dietary-fat-induced taurocholic acid promotes pathobiont expansion and colitis in Il10-/- mice. Nature 487: 104-108.
213. Clapper, M.L., H.S. Cooper & W.-C.L. Chang. 2007. Dextran sulfate sodium-induced colitis-associated neoplasia: a promising model for the development of chemopreventive interventions. Acta Pharmacol. Sin. 28: 1450-1459.