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Cancer and Obesity: A Biological Perspective

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Richa Chauhan


The rising incidence and associated mortality of cancer on the worldwide scale has made cancer a global health problem. Although the cause of oncogenesis is multifactorial, certain well-established risk factors are known to play their part in cancer development. The risk for cancers can be reduced since these factors are manageable. For instance, tobacco and alcohol use can be avoided, and obesity can be controlled with the help of lifestyle modification. This review provides a brief insight into the postulated mechanisms on how obesity can lead to cancer initiation, progression, and even treatment resistance. Mediators and pathways with documented clinical evidence that connects obesity to cancer are also discussed. These mediators include various adipokines, free fatty acids, insulin and insulin-like growth factor-1, sex hormones, and products of chronic inflammation. The recent concept of obesity paradox has also been discussed. Exploring these biological mediators and pathways linking obesity to cancer will open new avenues for not only cancer treatment but also its prevention.


Cancer, Obesity, Adipokines, Insulin, Sex hormones

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Bray F, Ferlay J, Soerjomataram I, et al., 2018, Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin, 68(6):394–424. DOI: 10.3322/caac.21492.

Bray F, 2014, Transitions in human development and the global cancer burden. In: Stewart BW, Wild CP, editors. World Cancer Report 2014. Lyon: IARC Press. p42–55.

Maule M, Merletti F, 2012, Cancer Transition and Priorities for Cancer Control. Lancet Oncol, 13(8):745-6. DOI: 10.1016/s1470-2045(12)70268-1.

World Health Organization, 2016, Obesity and Overweight. World Health Organization, Geneva. Available from: https://

Most Obese Countries Population, 2019. Available from: [Last accessed on 2020 Jan 27].

Wolin KY, Carson K, Colditz GA, 2010, Obesity and Cancer. Oncologist, 15(6):556–65.

Blüher M, 2019, Obesity: Global Epidemiology and Pathogenesis. Nat Rev Endocrinol, 15(5):288–98.

De Pergola G, Silvestris F, 2013, Obesity as a Major Risk Factor for Cancer. J Obes, 2013:291546.

Lauby-Secretan B, Scoccianti C, Loomis D, et al., 2016, Body Fatness and Cancer-Viewpoint of the IARC Working Group. N Engl J Med, 375(8):794–8. DOI: 10.1056/ nejmsr1606602.

Booth A, Magnuson A, Fouts J, et al., 2015, Adipose Tissue, Obesity and Adipokines: Role in Cancer Promotion. Horm Mol Biol Clin Investig, 21(1):57–74. DOI: 10.1515/ hmbci-2014-0037.

Fletcher I, 2014, Defining an Epidemic: The Body Mass Index in British and US Obesity Research 1960-2000. Sociol Health Illn, 36(3):338–53. DOI: 10.1111/1467- 9566.12050.

Louie SM, Roberts LS, Nomura DK, 2013, Mechanisms Linking Obesity and Cancer. Biochim Biophys Acta, 1831(10):1499–508.

Nieman KM, Kenny HA, Penicka CV, et al., 2011, Adipocytes Promote Ovarian Cancer Metastasis and Provide Energy for Rapid Tumor Growth. Nat Med, 17(11):1498–503. DOI: 10.1038/nm.2492.

Divella R, De Luca R, Abbate I, et al., 2016, Obesity and Cancer: The Role of Adipose Tissue and Adipo-cytokines-induced Chronic Inflammation. J Cancer, 7(15):2346–59. DOI: 10.7150/jca.16884.

Lee MJ, Wu Y, Fried SK, 2010, Adipose Tissue Remodeling in Pathophysiology of Obesity. Curr Opin Clin Nutr Metab Care, 13(4):371–6.

Garofalo C, Surmacz E, 2006, Leptin and Cancer. J Cell Physiol, 207(1):12–22.

Dauer DJ, Ferraro B, Song L, et al., 2005, Stat3 Regulates Genes Common to Both Wound Healing and Cancer. Oncogene, 24(21):3397–408. DOI: 10.1038/ sj.onc.1208469.

Koda M, Sulkowska M, Kanczuga-Koda L, et al., 2007, Expression of Leptin and Its Receptor in Female Breast Cancer in Relation with Selected Apoptotic Markers. Folia Histochem Cytobiol, 45(1):S187–91. DOI: 10.2478/ v10042-009-0099-7.

Garcia-Robles MJ, Segura-Ortega JE, Fafutis-Morris M, 2013, The Biology of Leptin and Its Implications in Breast Cancer: A General View. J Interferon Cytokine Res, 33(12):717–27. DOI: 10.1089/jir.2012.0168.

Bartella V, Cascio S, Fiorio E, et al., 2008, Insulin-dependent Leptin Expression in Breast Cancer Cells. Cancer Res, 68(12):4919–27. DOI: 10.1158/0008-5472.can-08-0642.

Bain GH, Collie-Duguid E, Murray GI, et al., 2014. Tumour Expression of Leptin is Associated with Chemotherapy Resistance and Therapy-independent Prognosis in Gastro-oesophageal Adenocarcinomas. Br J Cancer, 110:1525–34. DOI: 10.1038/bjc.2014.45.

Koda M, Sulkowska M, Kanczuga-Koda L, et al., 2007, Overexpression of the Obesity Hormone Leptin in Human Colorectal Cancer. J Clin Pathol, 60(8):902–6. DOI: 10.1136/jcp.2006.041004.

Xiong Y, Zhang J, Liu M, et al., 2014, Human Leptin Protein Activates the Growth of HepG2 Cells by Inhibiting PERK-Mediated ER Stress and Apoptosis. Mol Med Rep, 10(3):1649–55. DOI: 10.3892/mmr.2014.2373.

Wang Y, Lam KS, Xu JY, et al., 2005, Adiponectin Inhibits Cell Proliferation by Interacting with Several Growth Factors in An Oligomerization-dependent Manner. J Biol Chem, 280(18):18341–7. DOI: 10.1074/jbc.m501149200.

Arita Y, Kihara S, Ouchi N, et al., 1999, Paradoxical Decrease of An Adipose-specific Protein, Adiponectin, in Obesity. Biochem Biophys Res Commun, 257(1):79–83.

Yamauchi N, Takazawa Y, Maeda D, et al., 2012, Expression Levels of Adiponectin Receptors are Decreased in Human Endometrial Adenocarcinoma Tissues. Int J Gynecol Pathol, 31(4):352–7. DOI: 10.1097/pgp.0b013e3182469583.

Gonullu G, Kahraman H, Bedir A, et al., 2010, Association Between Adiponectin, Resistin, Insulin Resistance, and Colorectal Tumors. Int J Colorectal Dis, 25(2):205–12. DOI: 10.1007/s00384-009-0828-6.

Berta J, Hoda MA, Laszlo V, et al., 2014, Apelin Promotes Lymphangiogenesis and Lymph Node Metastasis. Oncotarget, 5(12):4426–37.

Altinkaya SO, Nergiz S, Kucuk M, et al., 2015, Apelin Levels are Higher in Obese Patients with Endometrial Cancer. J Obstet Gynaecol Res, 41(2):294–300. DOI: 10.1111/jog.12503.

Van Gool F, Galli M, Gueydan C, et al., 2009, Intracellular NAD Levels Regulate Tumor Necrosis Factor Protein Synthesis in a Sirtuin-dependent Manner. Nat Med, 15(2):206–10. DOI: 10.1038/nm.1906.

Kollmar O, Rupertus K, Scheuer C, et al., 2007, Stromal Cell-derived Factor-1 Promotes Cell Migration, Tumor Growth of Colorectal Metastasis. Neoplasia, 9(10):862–70. DOI: 10.1593/neo.07559.

Buldak RJ, Buldak L, Polaniak R, et al., 2013, Visfatin Affects Redox Adaptative Responses and Proliferation in Me45 Human Malignant Melanoma Cells: An In vitro Study. Oncol Rep, 29(2):771–8. DOI: 10.3892/or.2012.2175.

Shackelford RE, Bui MM, Coppola D, et al., 2010, Over-expression of Nicotinamide Phosphoribosyltransferase in Ovarian Cancers. Int J Clin Exp Pathol, 3(5):522–7.

Kaser S, Kaser A, Sandhofer A, et al., 2003, Resistin Messenger-RNA Expression is Increased by Proinflammatory Cytokines In vitro. Biochem Biophys Res Commun, 309(2):286–90. DOI: 10.1016/j.bbrc.2003.07.003.

Silswal N, Singh AK, Aruna B, et al., 2005, Human Resistin Stimulates the Pro-inflammatory Cytokines TNF-alpha and IL-12 in Macrophages by NFkappaB-dependent Pathway. Biochem Biophys Res Commun, 334(4):1092–101. DOI: 10.1016/j.bbrc.2005.06.202.

Yoong KF, McNab G, Hubscher SG, et al., 1998, Vascular Adhesion Protein-1 and ICAM-1 Support the Adhesion of Tumor-infiltrating Lymphocytes to Tumor Endothelium in Human Hepatocellular Carcinoma. J Immunol, 160: 3978–88.

Ghaemmaghami S, Mohaddes SM, Hedayati M, et al., 2013, Resistin and Visfatin Expression in HCT-116 Colorectal Cancer Cell Line. Int J Mol Cell Med, 2(3):143–50.

Sun CA, Wu MH, Chu CH, et al., 2010, Adipocytokine Resistin and Breast Cancer Risk. Breast Cancer Res Treat, 123(3):869–76. DOI: 10.1007/s10549-010-0792-4.

Kim HJ, Lee YS, Won EH, et al., 2011, Expression of Resistin in the Prostate and its Stimulatory Effect on Prostate Cancer Cell Proliferation. BJU Int, 108(2):E77–83. DOI: 10.1111/j.1464-410x.2010.09813.x.

Yang CC, Chang SF, Chao JK, et al., 2014, Activation of AMP-activated Protein Kinase Attenuates Hepatocellular Carcinoma Cell Adhesion Stimulated by Adipokine Resistin. BMC Cancer, 14:112. DOI: 10.1186/1471-2407- 14-112.

Reaven GM, 2011, Insulin Resistance: The Link Between Obesity and Cardiovascular Disease. Med Clin North Am, 95(5):875–92.

Pollak M, 2008, Insulin and Insulin-like Growth Factor Signalling in Neoplasia. Nat Rev 8(12):915–928. DOI: 10.1038/nrc2536.

Fowke JH, Matthews CE, Yu H, et al., 2010, Racial Differences in the Association Between Body Mass Index and Serum IGF1, IGF2, and IGFBP3. Endocr Relat Cancer, 17(1):51–60. DOI: 10.1677/erc-09-0023.

Giovannucci E, 2001, Insulin, Insulin-like Growth Factors and Colon Cancer: A Review of the Evidence. J Nutr, 131(11):3109S–20S. DOI: 10.1093/jn/131.11.3109s.

Vigneri P, Frasca F, Sciacca L, et al., 2009, Diabetes and Cancer. Endocr Relat Cancer, 16(4):1103–23.

Lukanova A, Lundin E, Micheli A, et al., 2004, Circulating Levels of Sex Steroid Hormones and Risk of Endometrial Cancer in Postmenopausal Women. Int J Cancer, 108(3):425–432. DOI: 10.1002/ijc.11529.

Calle EE, Kaaks R, 2004, Overweight, Obesity and Cancer: Epidemiological Evidence and Proposed Mechanisms. Nat Rev, 4(8):579–91. DOI: 10.1038/nrc1408.

Morris PG, Hudis CA, Giri D, et al., 2011, Inflammation and Increased Aromatase Expression Occur in the Breast Tissue of Obese Women with Breast Cancer. Cancer Prev Res (Phila), 4(7):1021–9. DOI: 10.1158/1940-6207.capr- 11-0110.

Yager JD, Davidson NE, 2006, Estrogen Carcinogenesis in Breast Cancer. N Engl J Med, 354(3):270–82.

Bhardwaj P, Au CC, Benito-Martin A, et al., 2019, Estrogens and Breast Cancer: Mechanisms Involved in Obesity-related Development, Growth and Progression. J Steroid Biochem Mol Biol, 189:161–70. DOI: 10.1016/j.jsbmb.2019.03.002.

Felty Q, Xiong WC, Sun D, et al., 2005, Estrogen-induced Mitochondrial Reactive Oxygen Species as Signal Transducing Messengers. Biochemistry, 44(18):6900–9. DOI: 10.1021/bi047629p.

Schiff R, Massarweh SA, Shou J, et al., 2004, Cross-talk Between Estrogen Receptor and Growth Factor Pathways as a Molecular Target for Overcoming Endocrine Resistance. Clin Cancer Res, 10(1):331S–6S. DOI: 10.1158/1078- 0432.ccr-031212.

Chauhan R, Trivedi V, 2020, Inflammatory Markers in Cancer: Potential Resources. Front Biosci (Schol Ed), 12:1–24.

Weisberg SP, McCann D, Desai M, et al., 2003, Obesity is Associated with Macrophage Accumulation in Adipose Tissue. J Clin Invest, 112(12):1796–808. DOI: 10.1172/ jci200319246.

Mayi TH, Daoudi M, Derudas B, et al., 2012, Human Adipose Tissue Macrophages Display Activation of Cancer-related Pathways. J Biol Chem, 287(25):21904–13. DOI: 10.1074/jbc.m111.315200.

Murphy CA, Langrish CL, Chen Y, et al., 2003, Divergent Pro and Anti-inflammatory Roles for IL-23 and IL-12 in Joint Autoimmune Inflammation. J Exp Med, 198(12):1951– 7. DOI: 10.1084/jem.20030896.

Kulbe H, Thompson R, Wilson JL, et al., 2007, The Inflammatory Cytokine Tumor Necrosis Factor-α Generates an Autocrine Tumor-promoting Network in Epithelial Ovarian Cancer Cells. Cancer Res, 67(2):585–92. DOI: 10.1158/0008-5472.can-06-2941.

Naugler WE, Sakurai T, Kim S, et al., 2007, Gender Disparity in Liver Cancer Due to Sex Differences in MyD88-dependent IL-6 Production. Science, 317:121–4. DOI: 10.1126/science.1140485.

Lennon H, Sperrin M, Badrick E, et al., 2016, The Obesity Paradox in Cancer: A Review. Curr Oncol Rep, 18(9):56. DOI: 10.1007/s11912-016-0539-4.

Lee DH, Giovannucci EL, 2019, The Obesity Paradox in Cancer: Epidemiologic Insights and Perspectives. Curr Nutr Rep, 8(3):175–181. DOI: 10.1007/s13668-019-00280-6.

Bruggeman AR, Kamal AH, LeBlanc TW, et al., 2016, Cancer Cachexia: Beyond Weight Loss. J Oncol Pract, 12(11):1163–71.

Meyerhardt JA, Kroenke CH, Prado CM, et al., 2017, Association of Weight Change After Colorectal Cancer Diagnosis and Outcomes in the Kaiser Permanente Northern California Population. Cancer Epidemiol Biomarkers Prev, 26(1):30–7. DOI: 10.1158/1055-9965.epi-16-0145.

Roubenoff R, 2007, Physical Activity, Inflammation, and Muscle Loss. Nutr Rev, 65:S208–12.

Wellens RI, Roche AF, Khamis HJ, et al., 1996, Relationships Between the Body Mass Index and Body Composition. Obes Res, 4:35–44. DOI: 10.1002/j.1550- 8528.1996.tb00510.x.

Okorodudu DO, Jumean MF, Montori VM, et al., 2010, Diagnostic Performance of Body Mass Index to Identify Obesity as Defined by Body Adiposity: A Systematic Review and Meta-analysis. Int J Obes (Lond), 34(5):791–9. DOI: 10.1038/ijo.2010.5.

Je Y, Jeon JY, Giovannucci EL, et al., 2013, Association Between Physical Activity and Mortality in Colorectal Cancer: A Meta-analysis of Prospective Cohort Studies. Int J Cancer, 133(8):1905–13. DOI: 10.1002/ijc.28208.

Rothman KJ, 2008, BMI-related Errors in the Measurement of Obesity. Int J Obes (Lond), 32:S56–9. DOI: 10.1038/ ijo.2008.87.

Mullie P, Vansant G, Hulens M, et al., 2008, Evaluation of Body Fat Estimated from Body Mass Index and Impedance in Belgian Male Military Candidates: Comparing Two Methods for Estimating Body Composition. Mil Med, 173:266–70. DOI: 10.7205/milmed.173.3.266.

Duren DL, Sherwood RJ, Czerwinski SA, et al., 2008, Body Composition Methods: Comparisons and Interpretation. J Diabetes Sci Technol, 2(6):1139–46.



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