Obesity as a tumour development triggering factor
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Radiotherapy Department, St. John’s Cancer Centre, Lublin, Poland
Neurosurgery and Paediatric Neurosurgery Department, Medical University, Lublin, Poland
Pneumology, Oncology and Allergology Department, Medical University, Lublin, Poland
Oncology Department, St. John’s Cancer Centre, Lublin, Poland
Clinical Immunology and Immunotherapy Department, Medical University, Lublin, Poland
Human Anatomy Department, Medical University, Lublin, Poland
The overweight and obesity epidemic represents a rapidly growing threat to the health of populations in an increasing number of countries. Nearly one-third of the world’s population has excess adipose tissue. Nowadays, obesity occurrence is so common that it is replacing more traditional problems, such as an undernutrition and infectious diseases, as the most significant causes of ill health. If the current trend continues, almost half of the world’s adult population will be overweight or obese by 2030.

The aim of this study is to show the connection between recent trends in body mass index, and the globally changing cancer profile.

State of knowledge:
A range of clinical and epidemiological studies have shown the relationship between excess body fat and the most frequently occurring malignancies. Obesity is associated with many cancers, such as: breast, colorectal, liver, lung, kidney, oesophageal, pancreatic, endometrium, ovarian, prostate, thyroid, and gallbladder cancer.

In the light of this information, the study supports the claimed statement that obesity is one of the major health problems of the 21st century. Considering the increase in the number of obese people worldwide, it is necessary to develop a strategy allowing to prevent it. Fighting against unhealthy lifestyle in order to reduce overweight and obesity in society may have an essential impact on decreasing the number of incidences of cancer.

Agnieszka Budny   
Radiotherapy Department, St. John’s Cancer Center, Lublin, Poland
1. Koh JC, Loo WM, Goh KL, Sugano K, Chan WK, Chiu WY, et al. Asian consensus on the relationship between obesity and gastrointestinal and liver diseases. J Gastroenterol Hepatol. 2016; 31: 1405–13.
2. World Health Organization. Obesity: preventing and managing the global epidemic: report of a WHO consultation. World Health Organ Tech Rep Ser. 2000; 894: 1–253.
3. Ogden CL, Yanovski SZ, Carroll MD, Flegal KM. The epidemiology of obesity. Gastroenterology. 2007; 132: 2087–102.
4. NCD Risk Factor Collaboration (NCD-RisC). Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 population-based measurement studies with 19·2 million participants. Lancet. 2016; 387: 1377–96.
5. Ogden CL, Carroll MD, Curtin LR, McDowell MA, Tabak CJ, Flegal KM. Prevalence of overweight and obesity in the United States, 1999–2004. JAMA. 2006; 295: 1549–55.
6. Ng M, Fleming T, Robinson M, Thomson B, Graetz N, Margono C, et al. Global, regional, and national prevalence of overweight and obesity in children and adults during 1980–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2014; 384: 766–81.
7. Klimek-Piotrowska W, Koziej M, Hołda MK, et al. Anthropometry and body composition of adolescents in Cracow, Poland. PLoS One. 2015; 10(3): e0122274.
8. Smith KB, Smith MS. Obesity Statistics. Prim Care. 2016; 43: 121–35.
9. Kopelman P. Obesity as a medical problem. Nature. 2000; 404: 635–43.
10. Dixon JB. The effect of obesity on health outcomes. Mol Cell Endocrinol. 2010; 316: 104–8.
11. Vucenik I, Stains JP. Obesity and cancer risk: Evidence, mechanisms, and recommendations. Ann N Y Acad Sci. 2012; 1271: 37–43.
12. Arnold M, Pandeya N, Byrnes G, Renehan PAG, Stevens GA, Ezzati PM, et al. Global burden of cancer attributable to high body-mass index in 2012: a population-based study. Lancet Oncol. 2015; 16: 36–46.
13. Bergstrom A, Pisani P, Tenet V, Wolk A, Adami HO. Overweight as an avoidable cause of cancer in Europe. Int J Cancer. 2001; 91: 421–30.
14. Carroll K. Obesity as a risk factor for certain types of cancer. Lipids. 1998;33:1055–9.
15. Lauby-Secretan B, Scoccianti C, Loomis D, Grosse Y, Bianchini F, Straif K, et al. Body Fatness and Cancer--Viewpoint of the IARC Working Group. N Engl J Med. 2016; 375: 794–8.
16. Oh SW, Yoon YS, Shin SA. 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. 2005; 23: 4742–4754.
17. Adami HO, Trichopoulos D. Obesity and mortality from cancer. New Engl J Med. 2003; 348: 1623–4.
18. Sciacca L, Vigneri R, Tumminia A, Frasca F, Squatrito S, Frittitta L, et al. Clinical and molecular mechanisms favoring cancer initiation and progression in diabetic patients Nutr Metab Cardiovasc Dis. 2013; 23: 808–15.
19. Vigneri P, Frasca F, Sciacca L, Frittitta L, Vigneri R. Obesity and cancer nutrition. Nutr Metab Cardiovasc Dis. 2006; 16: 1–7.
20. Chang SC, Yang WCV. Hyperglycemia,tumorigenesis,and chronic inflammation. Crit Rev Oncol Hematol. 2016;108:146–53.
21. Arnold M, Leitzmann M, Freisling H, Bray F, Romieu I, Renehan A, et al. Obesity and cancer: an update of the global impact. Cancer Epidemiol. 2016;41:8–15.
22. Kuriyama S, Tsubono Y, Hozawa A, Shimazu T, Suzuki Y, Koizumi Y, et al. Obesity and risk of cancer in Japan. Int J Cancer. 2005; 113: 148–57.
23. Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med. 2003; 348: 1625–38.
24. Batty GD, Shipley MJ, Jarrett RJ, Breeze E, Marmot MG, Smith GD. Obesity and overweight in relation to organ-specific cancer mortality in London (UK): findings from the original Whitehall study. Int J Obes (Lond). 2005; 29: 1267–74.
25. Calle EE, Kaaks R. Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Nat Rev Cancer. 2004; 4: 579–91.
26. Pietrzyk L, Torres A, Maciejewski R, Torres K. Obesity and Obese-related Chronic Low-grade Inflammation in Promotion of Colorectal Cancer Development. Asian Pac J Cancer Prev. 2015; 16: 4161–8.
27. Renehan AG, Zwahlen M, Egger M. Adiposity and cancer risk: new mechanistic insights from epidemiology. Nat Rev Cancer. 2015; 15: 484–98.
28. Kruk J. Lifestyle components and primary breast cancer prevention. Asian Pac J Cancer Prev. 2014; 15: 10543–55.
29. Wąsowski M, Marcinowska-Suchowierska E. The link between obesity and cancer. Post Nauk Med. 2013; 4: 316–25.
30. Barone I, Catalano S, Gelsomino L, Marsico S, Giordano C, Panza S, et al. Leptin mediates tumor-stromal interactions that promote the invasive groth of breast cancer cells. Cancer Res. 2012; 72: 1416–27.
31. Vigneri R, Goldfine ID , Frittitta L. Insulin, insulin receptors, and cancer. J Endocrinol Invest. 2016; 39: 1365–1376.
32. Kahn BB, Flier JS. Obesity and insulin resistance. J Clin Invest. 2000; 106: 473–81.
33. Kaaks R, Lukanova A, Kurzer MS. Obesity, endogenous hormones, and endometrial cancer risk: a synthetic review. Cancer Epidemiol Biomarkers Prev. 2002; 11: 1531–43.
34. Geer EB, Shen W. Gender differences in insulin resistance, body composition, and energy balance. Gend Med. 2009; 356: 60–75.
35. Cohen DH, LeRoith D. Obesity, type 2 diabetes, and cancer: the insulin and IGF connection. Endocr Relat Cancer. 2012; 19: F27-F45.
36. Gallagher EJ, LeRoith D. Obesity and diabetes: The increased risk of cancer and cancer-related mortality. Physiol Rev. 2015; 95: 727–48.
37. Randi G, Franceschi S, La Vecchia C. Gallbladder cancer worldwide: geographical distribution and risk factors. Int J Cancer. 2006; 118: 1591–1602.
38. Bishayee A. The role of inflammation and liver cancer. Adv Exp Med Biol. 2014; 816: 401–35.
39. Beavis AL, Smith AJB, Fader AN. Lifestyle changes and the risk of developing endometrial and ovarian cancers: opportunities for prevention and management. Int J Womens Health. 2016; 8: 151–67.
40. Zhang Y, Liu H, Yang S, Zhang J, Qian L, Chen X. Overweight, obesity and endometrial cancer risk: results from a systematic review and meta-analysis. Int J Biol Markers. 2014; 29: e21–9.
41. Setiawan VW, Yang HP, Pike MC, McCann SE, Yu H, Xiang YB, et al. Type I and II endometrial cancers: have they different risk factors? J Clin Oncol. 2013; 31: 2607–18.
42. Bhaskaran K, Douglas I, Forbes H, dos-Santos-Silva I, Leon DA, Smeeth L. Body-mass index and risk of 22 specific cancers: a population-based cohort study of 5·24 million UK adults. Lancet. 2014; 384: 755–65.
43. Renehan AG, Tyson M, Egger M, Heller RF, Zwahlen M. Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet. 2008; 371: 569–78.
44. Crosbie EJ, Zwahlen M, Kitchener HC, Egger M, Renehan AG. Body mass index, hormone replacement therapy, and endometrial cancer risk: a meta-analysis. Cancer Epidemiol Biomarkers Prev. 2010; 19: 3119–30.
45. Aune D, Navarro Rosenblatt DA, Chan DS, Vingeliene S, Abar L, Vieira L, et al. Anthropometric factors and endometrial cancer risk: a systematic review and dose-response meta-analysis of prospective studies. Ann Oncol. 2015; 26: 1635–48.
46. Collaborative Group on Epidemiological Studies of Ovarian Cancer. Ovarian cancer and body size: individual participant meta-analysis including 25,157 women with ovarian cancer from 47 epidemiological studies. PLoS Med. 2012; 9: e1001200.
47. Purdie DM, Bain CJ, Webb PM, Whiteman DC, Pirozzo S, Green AC. Body size and ovarian cancer: case-control study and systematic review (Australia). Cancer Causes Control. 2001; 12: 855–63.
48. Aune D, Navarro Rosenblatt DA, Chan DS, Abar L, Vingeliene S, Vieira AR, et al. Anthropometric factors and ovarian cancer risk: a systematic review and nonlinear dose-response meta-analysis of prospective studies. Int J Cancer. 2015; 136: 1888–98.
49. Dixon SC, Nagle CM, Thrift AP, Pharoah PD, Pearce CL, Zheng W, et al. Adult body mass index and risk of ovarian cancer by subtype: a Mendelian randomization study. Int J Epidemiol. 2016; 45: 884–95.
50. El-Serag HB. Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology. 2012; 142: 1264–73.
51. Scalera A, Tarantino G. Could metabolic syndrome lead to hepatocarcinoma via non-alcoholic fatty liver disease? World J Gastroenterol. 2014; 20: 9217–28.
52. Hung CH, Wang JH, Hu TH, Chen CH, Chang KC, Yen YH, et al. Insulin resistance is associated with hepatocellular carcinoma in chronic hepatitis C infection. World J Gastroenterol. 2010; 16: 2265–71.
53. Seyda Seydel G, Kucukoglu O, Altinbasv A, Demir OO, Yilmaz S, Akkiz H, et al. Economic growth leads to increase of obesity and associated hepatocellular carcinoma in developing countries. Ann Hepatol. 2016; 15: 662–72.
54. Larsson SC, Wolk A. Overweight, obesity and risk of liver cancer: a meta-analysis of cohort studies. Br J Cancer. 2007; 97: 1005–8.
55. Nair S, Mason A, Eason J, Loss G, Perrillo RP. Is obesity an independent risk factor for hepatocellular carcinoma in cirrhosis? Hepatology. 2002; 36: 150–5.
56. Chen Y, Wang X, Wang J, Yan Z, Luo J. Excess body weight and the risk of primary liver cancer: an updated meta-analysis of prospective studies. Eur J Cancer. 2012; 48: 2137–45.
57. Wang Y, Wang B, Shen F, Fan J, Cao H. Body mass index and risk of primary liver cancer: a meta-analysis of prospective studies. Oncologist. 2012; 17: 1461–8.
58. Donadon V, Balbi M, Zanette G. Hyperinsulinemia and risk for hepato-cellular carcinoma in patients with chronic liver diseases and Type 2 diabetes mellitus. Expert Rev Gastroenterol Hepatol. 2009; 3: 465–7.
59. N’Kontchou G, Paries J, Htar MTT, Ganne-Carrie N, Costentin L, Grando-Lemaire V, et al. Risk Factors for Hepatocellular Carcinoma in Patients With Alcoholic or Viral C Cirrhosis. Clin Gastroenterol Hepatol. 2006; 8: 1062–8.
60. Streba LA, Vere CC, Rogoveanu I, Streba CT. Nonalcoholic fatty liver disease, metabolic risk factors, and hepatocellular carcinoma: an open question. World J Gastroenterol. 2015; 21: 4103–10.
61. Tanaka K, Tsuji I, Tamakoshi A, Matsuo K, Ito H, Wakai K, et al. Obesity and liver cancer risk: an evaluation based on a systematic review of epidemiologic evidence among the Japanese population. Jpn J Clin Oncol. 2012; 42: 212–21.
62. Samanic C, Chow WH, Gridley G, Jarvholm B, Fraumeni JF Jr. Relation of body mass index to cancer risk in 362,552 Swedish men. Cancer Causes Control. 2006; 17: 901–9.
63. Baffy G, Brunt EM, Caldwell SH. Hepatocellular carcinoma in non-alcoholic fatty liver disease: an emerging menace. J Hepatol. 2012; 56: 1384–91.
64. Wolk A, Gridley G, Svensson M, Nyrén O, McLaughlin JK, Fraumeni JF, et al. A prospective study of obesity and cancer risk (Sweden). Cancer Causes Control. 2001; 12: 13–21.
65. Sergentanis TN, Tsivgoulis G, Perlepe C, Ntanasis-Stathopoulos I, Tzanninis IG, Sergentanis TN, et al. Obesity and Risk for Brain/CNS Tumors, Gliomas and Meningiomas: A Meta-Analysis. PLoS ONE. 2015; 10: e0136974.
66. Shao C, Bai L-P, Qi Z-Y, Hui G-Z, Wang Z. Overweight, Obesity and Meningioma Risk: A Meta-Analysis. PLoS ONE. 2014; 9: e90167.
67. Niedermaier T, Behrens G, Schmid D, Schlecht I, Fischer B, Leitzmann MF. Body mass index, physical activity, and risk of adult meningioma and glioma. Neurology. 2015; 85: 1342–50.
68. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015; 136: E359–86.
69. Matthews SB, Thompson HJ. The Obesity-Breast Cancer Conundrum: An Analysis of the Issues. Int J Mol Sci. 2016; 17: 989.
70. Petrelli JM, Calle EE, Rodriguez C, Thun MJ. Body mass index, height, and postmenopausal breast cancer mortality in a prospective cohort of US women. Cancer Causes Control. 2002; 13: 325–32.
71. Maehle BO, Tretli S, Thorsen T . The associations of obesity, lymph node status and prognosis in breast cancer patients: dependence on estrogen and progesterone receptor status. APMIS. 2004; 112: 349–57.
72. Baer HJ, Colditz GA, Rosner B, Michels KB, Rich-Edwards JW, Hunter DJ, et al. Body fatness during childhood and adolescence and incidence of breast cancer in premenopausal women: a prospective cohort study. Breast Cancer Res. 2005; 356: R314–25.
73. Baer HJ, Tworoger SS, Hankinson SE, Willett WC. Body fatness at young ages and risk of breast cancer throughout life. Am J Epidemiol. 2010; 356: 1183–94.
74. Berstad P, Coates RJ, Bernstein L, Folger SG, Malone KE, Marchbanks PA, et al. A case-control study of body mass index and breast cancer risk in white and African-American women. Cancer Epidemiol Biomarkers Prev. 2010; 19: 1532–44.
75. Cheraghi Z, Poorolajal J, Hashem T, Esmailnasab N, Irani AD. Effect of Body Mass Index on Breast Cancer during Premenopausal and Postmenopausal Periods: A Meta-Analysis. PLoS ONE. 2012; 7: 989.
76. Munsell MF, Sprague BL, Berry DA, Chisholm G, Trentham-Dietz A. Body mass index and breast cancer risk according to postmenopausal estrogen-progestin use and hormone receptor status. Epidemiol Rev. 2014; 36: 114–36.
77. Suzuki R, Orsini N, Saji S, Key TJ, Wolk A. Body weight and incidence of breast cancer defined by estrogen and progesterone receptor status—A meta-analysis. Int J Cancer. 2009; 124: 698–712.
78. Pierobon M, Frankenfeld CL. Obesity as a risk factor for triple-negative breast cancers: a systematic review and meta-analysis. Breast Cancer Res Treat. 2013; 137: 307–14.
79. Renehan AG, Zwahlen M, Minder C, O’Dwyer ST, Shalet SM, Egger M. Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis. Lancet. 2014; 356: 1346–53.
80. Divella R, De Luca R, Abbate I, Naglieri E, Daniele A. Obesity and cancer: the role of adipose tissue and adipo-cytokines-induced chronic inflammation. J Cancer. 2016; 7: 2346–2359.
81. Rinaldi S, Key TJ, Peeters PHM, Lahmann PH, Lukanova A, Dossus L, et al. Anthropometric measures, endogenous sex steroids and breast cancer risk in postmenopausal women: A study within the EPIC cohort. Int J Cancer. 2006; 118: 2832–39.
82. Emaus MJ, van Gils CH, Bakker MF, Bishchop CN, Monninkhof EM, Bueno-de-Mesquita HB, et al. Weight change in middle adulthood and breast cancer risk in the EPIC-PANACEA study. Int J Cancer. 2014; 135: 2887–99.
83. Mahoney MC, Bevers T, Linos E, Willett WC. Opportunities and strategies for breast cancer prevention through risk reduction. CA Cancer J Clin. 2008; 58: 347–71.
84. Kyrgiou M, Kalliala I, Markozannes G, Gunter MJ, Paraskevaidis E, Gabra H, et al. Adiposity and cancer at major anatomical sites: umbrella review of the literature. BMJ. 2017; 356: j477.
85. Lahmann PH, Hoffmann K , Allen N, van Gils CH, Khaw KT, Tehard B, et al. Body size and breast cancer risk: findings from the European Prospective Investigation into Cancer And Nutrition (EPIC). Int J Cancer. 2004; 111: 762–71.
86. Ritte R, Lukanova A, Berrino F, Dossus L, Tjønneland A, Olsen A, et al. Adiposity, hormone replacement therapy use and breast cancer risk by age and hormone receptor status: a large prospective cohort study. Breast Cancer Res. 2012; 14: R76.
87. Manders P, Pijpe A, Hooning MJ, Kluiijt I, Vasen HF, Hoogerbrugge N, et al. Body weight and risk of breast cancer in BRCA1/2 mutation. Breast Cancer Res Treat. 2011; 126: 193–202.
88. Kotsopoulos J, Olopado OI, Ghadirian P, Lubinski L, Lynch HT, Isaacs C, et al. Changes in body weight and the risk of breast cancer in BRCA1and BRCA2 mutation carriers. Breast Cancer Res. 2005; 7: R833–43.
89. Amadou A, Ferrari P, Muwonge R, Moskal A, Biessy C, Romieu I, et al. Overweight, obesity and risk of premenopausal breast cancer according to ethnicity: a systematic review and dose-response meta-analysis. Obes Rev. 2013; 14: 665–78.
90. Suzuki S, Kojima M, Tokudome S, Mori M, Sakauchi F, Wakai K, et al. Obesity/weight gain and breast cancer risk: findings from the Japan collaborative cohort study for the evaluation of cancer risk. J Epidemiol. 2013; 23: 139–45.
91. Keum N, Greenwood DC, Lee DH, Kim R, Aune D, Ju W, et al. Adult weight gain and adiposity-related cancers: a dose-response meta-analysis of prospective observational studies. J Natl Cancer Inst. 2015; 107: pii:djv088.
92. Pacholczak R, Klimek-Piotrowska W, Kuszmiersz P. Associations of anthropometric measures on breast cancer risk in pre- and postmeno-pausal women--a case-control study. J Physiol Anthropol. 2016; 35: 7.
93. Connolly BS, Barnett C, Vogt KN, Li T, Stone J, Boyd NF. A meta-analysis of published literature on waist-to-hip ratio and risk of breast cancer. Nutr Cancer. 2002; 44: 127–38.
94. Harvie M, Hooper L, Howell AH. Central obesity and breast cancer risk: a systematic review. Obes Rev. 2003; 4: 157–73.
95. Lahmann PH, Lissner L, Gullberg B, Olsson H, Berglund G. A prospective study of adiposity and postmenopausal breast cancer risk: The Malmö diet and cancer study. Int J Cancer. 2003; 103: 246–52.
96. Dal Maso L, Zucchetto A, Talamini R, Serraino D, Stocco CF, Vercelli M, et al. Effect of obesity and other lifestyle factors on mortality in women with breast cancer. Int J Cancer. 2008; 123: 2188–94.
97. Kruk J. Overweight, Obesity, Oxidative Stress and the Risk of Breast Cancer. Asian Pac J Cancer Prev. 2014; 15: 9579–86.
98. Anderson GL, Neuhouser ML. Obesity and the Risk for Premenopausal and Postmenopausal Breast Cancer. Cancer Prev Res. 2012; 5: 515–21.
99. Wang F, Xu Y. Body mass index and risk of renal cell cancer: a dose-response meta-analysis of published cohort studies. Int J Cancer. 2014; 135: 1673–86.
100. Dobbins M, Decorby K, Choi BCK. The Association between Obesity and Cancer Risk: A Meta-Analysis of Observational Studies from 1985 to 2011. ISRN Prev Med. 2013; 680536.
101. Sanfilippo KM , McTigue KM, Fidler CJ, Neaton JD, Chang Y, Fried LF, et al. Hypertension and obesity and the risk of kidney cancer in 2 large cohorts of US men and women. Hypertension. 2014; 63: 934–41.
102. Li L, Gan Y, Li W, Wu C, Lu Z. Overweight, obesity and the risk of gallbladder and extrahepatic bile duct cancers: A meta-analysis of observational studiem. Obesity (Silver Sprong). 2016; 24: 1786–802.
103. Larsson SC, Wolk A. Obesity and the risk of gallbladder cancer: a meta-analysis. Br J Cancer. 2007; 96: 1457–61.
104. Liu H, Zhang Y, Ai M, Wang J, Jin B, Teng Z, et al. Body Mass Index Can Increase the Risk of Gallbladder Cancer: A Meta-Analysis of 14 Cohort Studies. Med Sci Monit Basic Res. 2016; 22: 146–55.
105. Kitahara CM, McCullough ML, Franceschi S, Rinaldi S, Wolk A, Neta G, et al. Anthropometric factors and thyroid cancer risk by histological subtype: Pooled analysis of 22 prospective studies. Thyroid. 2016; 26: 306–18.
106. Ma J, Huang M, Wang L, Ye W, Tong Y, Wang H. Obesity and Risk of Thyroid Cancer: Evidence from a Meta-Analysis of 21 Observational Studies. Med Sci Monit. 2015; 21: 283–91.
107. Xu L, Port M, Landi S, Gemignani F, Cipollini M, Elisei R, et al. Obesity and the risk of papillary thyroid cancer: a pooled analysis of three case – control studies. Thyroid. 2014; 24: 966–974.
108. Kaaks R, Toniolo P, Akhmedkhanov A, Lukanova A, Biessy C, Dechaud H, et al. Serum C-peptide, insulin-like growth factor (IGF)-I, IGF-binding proteins, and colorectal cancer risk in women. J Natl Cancer Inst. 2000;92:1592–600.
109. Yoon YS, Keum N, Zhang X, Cho E, Giovannucci EL. Hyperinsulinemia, insulin resistance and colorectal adenomas: A meta-analysis. Metabolism. 2015;64:1324–33.
110. Schoen RE, Tangen CM, Kuller LH, Burke GL, Cushman M, Tracy RP, et al. Increased blood glucose and insulin, body size, and incident colorectal cancer. J Natl Cancer Inst. 1999; 91: 1147–54.
111. Ma Y, Yang Y, Wang F, Zhang P, Shi C, Zou Y, et al. Obesity and risk of colorectal cancer: a systematic review of prospective studies. PLoS One. 2013; 8: e53916.
112. Moghaddam AA, Woodward M, Huxley R. Obesity and risk of colorectal cancer: a meta-analysis of 31 studies with 70,000 events. Cancer Epidemiol Biomarkers Prev. 2007; 16: 2533–47.
113. Schlesinger S, Lieb W, Koch M, Fedirko V, Dahm CC, Pischon T, et al. Body weight gain and risk of colorectal cancer: a systematic review and meta-analysis of observational studies. Obes Rev. 2015; 16: 607–19.
114. Harriss DJ, Atkinson G, George K, Cable NT, Reilly T, Haboubi N, et al. Lifestyle factors and colorectal cancer risk (1): systematic review and meta-analysis of associations with body mass index. Colorectal Dis. 2009; 11: 547–63.
115. Robsahm TE, Aagnes B, Hjartåker A, Langseth H, Bray FI, Larsen IK. Body mass index, physical activity, and colorectal cancer by anatomical subsites: a systematic review and meta-analysis of cohort studies. Eur J Cancer Prev. 2013; 22: 492–505.
116. Matsuo K, Mizoue T, Tanaka K, Tsuji I, Sugawara Y, Sasazuki S, et al. Association between body mass index and the colorectal cancer risk in Japan: pooled analysis of population-based cohort studies in Japan. Ann Oncol. 2012; 23: 479–90.
117. Parr CL, Batty GD, Lam TH, Barzi F, Fang X, Ho SC, et al. Body-mass index and cancer mortality in the Asia-Pacific Cohort Studies Collaboration: pooled analyses of 424 519 participants. Lancet Oncol. 2010; 11: 741–52.
118. Larsson SC, Wolk A. Obesity and colon and rectal cancer risk: a meta-analysis of prospective studies. Am J Clin Nutr. 2007; 86: 556–65.
119. Jeong TG, Kim JW, Lee SY, Park HS, Han HS, Hwang DY. Inverse Correlation between Cancer Size and Abdominal Obesity in Colorectal Cancer Cases. Asian Pac J Cancer Prev. 2016; 17: 4025–30.
120. Raimondi S, Maisonneuve P, Lowenfels AB. Epidemiology of pancreatic cancer: an overwier. Nat Rev Gastroenterol Hepatol. 2009; 6: 699–708.
121. Aune D, Greenwood DC, Chan DSM, Vieira AR, Navarro Rosenblatt DA, Cade JE, et al. Body mass index, abdominal fatness and pancreatic cancer risk: a systematic review and non-linear dose–response meta-analysis of prospective studies. Ann Oncol. 2012; 23: 843–52.
122. Wörmann SM, Algül H. Risk factors and therapeutic targets in pancreatic cancer. Front Oncol. 2013; 3: 282.
123. Genkinger JM, Spiegelman D, Anderson KE, Bernstein L, van den Brandt PA, Calle EE, et al. A pooled analysis of 14 cohort studies of anthropometric factors and pancreatic cancer risk. Int J Cancer. 2011; 129: 1708–17.
124. Jiao L, de Gonzalez AB, Hartge P, Pfeiffer RM, Park Y, Freedman DM, et al. Body mass index, effect modifiers, and risk of pancreatic cancer: a pooled study of seven prospective cohorts. Cancer Causes Control. 2010: 21: 1305–14.
125. Silverman DT, Swanson CA, Gridley G, Wacholder S, Greenberg RS, Brown LM, et al. Dietary and nutritional factors and pancreatic cancer: a case-control study based on direct interviews. J Natl Cancer Inst, 1998; 90: 1710–9.
126. Arslan AA, Helzlsouer KJ, Kooperberg C, Shu XO, Steplowski E, Bueno-de-Mesquita HB, et al. Anthropometric Measures, Body MassIndex and Pancreatic Cancer: a Pooled Analysis from the Pancreatic Cancer Cohort Consortium (PanScan). Arch Intern Med. 2010; 170: 791–802.
127. Jee S, Yun J, Park E, Cho ER, Park IS, Sull JW, et al. Body mass index and cancer risk in Korean men and women. Int J Cancer. 2008; 123: 1892–6.
128. Gapstur SM, Gann PH, Lowe W, Liu K, Colangelo L, Dyer A. Abnormal glucose metabolism and pancreatic cancer mortality. JAMA. 2000; 283: 2552–8.
129. Lin Y, Kikuchi S, Tamakoshi A, Yagyu K, Obata Y, Inaba Y, et al. Obesity, physical activity and the risk of pancreatic cancer in a large Japanese cohort. Int J Cancer. 2007; 120: 2665–71.
130. Michaud DS, Giovannucci E, Willett WC, Colditz G, Stampfer M, Fuchs CS. Physical activity, obesity, height, and the risk of pancreatic cancer. JAMA. 2001; 286: 921–9.
131. Larsson SC, Orsini N, Wolk A. Body mass index and pancreatic cancer risk: A meta-analysis of prospective studies. Int J Cancer. 2007; 120: 1993–8.
132. Huxley R, Ansary-Moghaddam A, Berrington de González A, Barzi F, Woodward M. Type-II diabetes and pancreatic cancer: a meta-analysis of 36 studies. Br J Cancer. 2005; 92: 2076–83.
133. Singh S, Sharma A, Murad M, Buttar NS, El-Serag HB, Katzka DA, et al. Central adiposity is associated with increased risk of esophageal inflammation, metaplasia, and adenocarcinoma: a systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2013; 11: 1399–412.
134. Chow W-H, Blot WJ, Vaughan TL, Risch HA, Gammon MD, Stanford JL, et al. Body mass index and risk of adenocarcinomas of the esophagus and gastric cardia. J Natl Cancer Inst. 1998; 90: 150–5.
135. Vaughan TL, Davis S, Kristal A, Thomas DB. Obesity, alcohol, and tobacco as risk factors for cancers of the esophagus and gastric cardia: adenocarcinoma versus squamous cell carcinoma. Cancer Epidemiol Biomarkers Prev. 1995; 4: 85–92.
136. Freedman ND, Abnet CC, Leitzmann MF, Mouw T, Subar AF, Hollenbeck AR, et al. A prospective study of tobacco, alcohol, and the risk of esophageal and gastric cancer subtypes. Am J Epidemiol. 2007; 165: 1424–33.
137. Hoyo C, Cook MB, Kamangar F, Freedman ND, Whiteman DC, Bernstein L, et al. Body mass index in relation to oesophageal and oesophagogastric junction adenocarcinomas: a pooled analysis from the International BEACON Consortium. Int J Epidemiol. 2012; 41: 1706–18.
138. Turati F, Tramacere I, La Vecchia C, Negri E. A meta-analysis of body mass index and esophageal and gastric cardia adenocarcinoma. Ann Oncol. 2013; 24: 609–17.
139. Parikesit D, Mochtar CA, Umbas R, Hamid AR. The impact of obesity towards prostate diseases. Prostate Int. 2016; 4: 1–6.
140. Kolonel LN. Nutrition and prostate cancer. Cancer Causes Control. 1996; 7: 83–94.
141. Giovannucci E, Rimm EB, Stampfer MJ, Colditz GA, Willett WC. Height, body weight, and risk of prostate cancer. Cancer Epidemiol Biomarkers Prev. 1997; 6: 557–63.
142. Ma J, Li H, Giovannucci E, Mucci L, Qiu W, Nguyen PL, et al. A long-term survival analysis of prediagnostic body mass index, plasma C-peptide concentration, and prostate cancer-specific mortality among men with prostate cancer. Lancet oncol. 2008; 11: 1039–47.
143. Frasca F, Pandini G, Sciacca L, Pezzino V, Squatrito S, Belfiore A, et al. The role of insulin receptors and IGF-I receptors in cancer and other diseases. Arch Physiol Biochem. 2008; 114: 23–37.
144. Andersson SO, Wolk A, Bergstrom R, Adami HO, Engholm G, Englund A, et al. Body size and prostate cancer: a 20-year follow-up study among 135006 Swedish construction workers. J Natl Cancer Inst. 1997; 89: 385–9.
145. Rodriguez C, Patel AV, Calle EE, Jacobs EJ, Chao A, Thun MJ. Body mass index, height, and prostate cancer mortality in two large cohorts of adult men in the United States. Cancer Epidemiol Biomarkers Prev. 2001; 10: 345–53.
146. MacInnis RJ, English DR. Body size and composition and prostate cancer risk: systematic review and meta-regression analysis. Cancer Causes Control. 2006; 17: 989–1003.
147. Discacciati A, Orsini N, Wolk A. Body mass index and incidence of localized and advanced prostate cancer--a dose-response meta-analysis of prospective studies. Ann Oncol. 2012; 23: 1665–71.
148. Zhang X, Zhou G, Sun B, Zhao G, Liu D, Sun J, et al. Impact of obesity upon prostate cancer-associated mortality: A meta-analysis of 17 cohort studies. Oncol Lett. 2015; 9: 1307–12.
149. Cao Y, Ma J. Body-mass index, prostate cancer-specific mortality and biochemical recurrence: A systematic review and meta-analysis. Cancer Prev Res. 2011; 4: 486–501.
150. Vidal AC, Freedland SJ. Obesity and Prostate Cancer: A Focused Update on Active Surveillance, Race, and Molecular Subtyping. Eur Urol. 2017; 72: 78–83.
151. Barrington WE, Schenk JM, Etzioni R, Arnold KB, Neuhouser ML, Thompson IM Jr, et al. Difference in Association of Obesity With Prostate Cancer Risk Between US African American and Non-Hispanic White Men in the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA Oncol. 2015; 1: 342–9.
152. Yang Y, Dong J, Sun K, Zhao L, Zhao F, Wang L, et al. Obesity and incidence of lung cancer: a meta-analysis. Int J Cancer. 2013; 132: 1162–1169.