Indian Journal of Surgical Oncology

, Volume 6, Issue 4, pp 390–398 | Cite as

Obesity and Cancer: Concepts and Challenges

  • Daniel F. ArgoloEmail author
  • Neil M. Iyengar
  • Clifford A. Hudis
Review Article


The rates of overweight and obesity are increasing worldwide in both developed and developing countries. Obesity is a major public health problem as it is associated with many diseases, including diabetes, hypertension, dyslipidemia, atherosclerosis, and some types of cancer. Breast cancer is a malignancy in which both the risk of development and the prognosis are negatively impacted by the obese state. The precise mechanisms pathophysiologically linking obesity and cancer are still under investigation. The biological basis for these associations includes both systemic and local tissue effects and white adipose tissue inflammation appears to be a critical component. A comprehensive understanding of the mechanisms linking obesity, inflammation and cancer may provide an opportunity for the development of strategies to attenuate the negative impact of obesity.


Obesity Cancer Breast cancer Risk factors Adipose tissue Inflammation 


Compliance with Ethical Standards

Conflict of Interest

All authors declare that they have no conflict of interest.

Funding/Grant Support

2014 Conquer Cancer Foundation of ASCO LIFe Award (to Daniel F. Argolo).

Breast Cancer Research Foundation (to Clifford A. Hudis and Neil M. Iyengar).


  1. 1.
    Popkin BM, Adair LS, Ng SW (2012) Global nutrition transition and the pandemic of obesity in developing countries. Nutr Rev 70(1):3–21. doi: 10.1111/j.1753-4887.2011.00456.x CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Swinburn BA, Sacks G, Hall KD, McPherson K, Finegood DT, Moodie ML, Gortmaker SL (2011) The global obesity pandemic: shaped by global drivers and local environments. Lancet 378(9793):804–814. doi: 10.1016/S0140-6736(11)60813-1 CrossRefPubMedGoogle Scholar
  3. 3.
    Roth J, Qiang X, Marban SL, Redelt H, Lowell BC (2004) The obesity pandemic: where have we been and where are we going? Obes Res 12(Suppl 2):88S–101S. doi: 10.1038/oby.2004.273 CrossRefPubMedGoogle Scholar
  4. 4.
    Shah NR, Braverman ER (2012) Measuring adiposity in patients: the utility of body mass index (bmi), percent body fat, and leptin. PLoS One 7(4):e33308. doi: 10.1371/journal.pone.0033308 CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Lim SS, Vos T, Flaxman AD, Danaei G, Shibuya K, Adair-Rohani H, Memish ZA, et al. (2012) A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990–2010: A systematic analysis for the global burden of disease study 2010. Lancet 380(9859):2224–2260. doi: 10.1016/S0140-6736(12)61766-8 CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Finucane MM, Stevens GA, Cowan MJ, Danaei G, Lin JK, Paciorek CJ, Global burden of metabolic risk factors of chronic diseases collaborating G, et al. (2011) national, regional, and global trends in body-mass index since 1980: systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9.1 million participants. Lancet 377(9765):557–567. doi: 10.1016/S0140-6736(10)62037-5 CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Ng M, Fleming T, Robinson M, Thomson B, Graetz N, Margono C, Gakidou E, et al. (2014) 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 384(9945):766–781. doi: 10.1016/S0140-6736(14)60460-8 CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Stevens GA, Singh GM, Lu Y, Danaei G, Lin JK, Finucane MM, Global Burden Of Metabolic Risk Factors Of Chronic Diseases Collaborating G, et al. (2012) National, regional, and global trends in adult overweight and obesity prevalences. Popul Health Metrics 10(1):22. doi: 10.1186/1478-7954-10-22 CrossRefGoogle Scholar
  9. 9.
    Ogden CL, Carroll MD, Kit BK, Flegal KM (2014) Prevalence of childhood and adult obesity in the United States, 2011–2012. JAMA 311(8):806–814. doi: 10.1001/jama.2014.732 CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    National Institutes of Health (2012) Overweight and obesity statistics. Accessed 19 March 2015
  11. 11.
    Flegal KM, Graubard BI, Williamson DF, Gail MH (2005) Excess deaths associated with underweight, overweight, and obesity. JAMA 293(15):1861–1867. doi: 10.1001/jama.293.15.1861 CrossRefPubMedGoogle Scholar
  12. 12.
    Olshansky SJ, Passaro DJ, Hershow RC, Layden J, Carnes BA, Brody J, Ludwig DS, et al. (2005) A potential decline in life expectancy in the United States in the 21st century. N Engl J Med 352(11):1138–1145. doi: 10.1056/NEJMsr043743 CrossRefPubMedGoogle Scholar
  13. 13.
    Finkelstein EA, Trogdon JG, Cohen JW, Dietz W (2009) Annual medical spending attributable to obesity: payer-and service-specific estimates. Health Aff 28(5):w822–w831. doi: 10.1377/hlthaff.28.5.w822 CrossRefGoogle Scholar
  14. 14.
    Wang YC, McPherson K, Marsh T, Gortmaker SL, Brown M (2011) Health and economic burden of the projected obesity trends in the USA and the UK. Lancet 378(9793):815–825. doi: 10.1016/S0140-6736(11)60814-3 CrossRefPubMedGoogle Scholar
  15. 15.
    Centers for Disease Control and Prevention (2015) Adult obesity facts. Accessed 24 July 2015
  16. 16.
    Word Health Oganization (2015) Obesity and overweight. Accessed 23 July 2015
  17. 17.
    Wang Y, Chen HJ, Shaikh S, Mathur P (2009) Is obesity becoming a public health problem in India? Examine the shift from under- to overnutrition problems over time. Obesity Reviews : an Official Journal of the International Association for the Study of Obesity 10(4):456–474. doi: 10.1111/j.1467-789X.2009.00568.x CrossRefGoogle Scholar
  18. 18.
    Khandelwal S, Reddy KS (2013) Eliciting a policy response for the rising epidemic of overweight-obesity in India. Obesity Reviews : An Official Journal of the International Association for the Study of Obesity 14(Suppl 2):114–125. doi: 10.1111/obr.12097 CrossRefGoogle Scholar
  19. 19.
    Jayawardena R, Ranasinghe P, Byrne NM, Soares MJ, Katulanda P, Hills AP (2012) Prevalence and trends of the diabetes epidemic in South Asia: a systematic review and meta-analysis. BMC Public Health 12:380. doi: 10.1186/1471-2458-12-380 CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Siddiqui ST, Kandala NB, Stranges S (2015) Urbanisation and geographic variation of overweight and obesity in India: A cross-sectional analysis of the Indian demographic health survey 2005–2006. International Journal of Public Health. doi: 10.1007/s00038-015-0720-9 PubMedGoogle Scholar
  21. 21.
    Gupta R, Guptha S, Sharma KK, Gupta A, Deedwania P (2012) Regional variations in cardiovascular risk factors in India: India heart watch. World J Cardiol 4(4):112–120. doi: 10.4330/wjc.v4.i4.112 CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Devi P, Rao M, Sigamani A, Faruqui A, Jose M, Gupta R, Xavier D, et al. (2013) Prevalence, risk factors and awareness of hypertension in India: A systematic review. J Hum Hypertens 27(5):281–287. doi: 10.1038/jhh.2012.33 CrossRefPubMedGoogle Scholar
  23. 23.
    Calle EE, Kaaks R (2004) Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Nat Rev Cancer 4(8):579–591. doi: 10.1038/nrc1408 CrossRefPubMedGoogle Scholar
  24. 24.
    van Kruijsdijk RC, van der Wall E, Visseren FL (2009) Obesity and cancer: The role of dysfunctional adipose tissue. Cancer epidemiology, biomarkers & prevention : A publication of the American association for cancer research, cosponsored by the American society of preventive oncology 18 (10):2569–2578. doi: 10.1158/1055-9965.EPI-09-0372
  25. 25.
    Renehan AG, Tyson M, Egger M, Heller RF, Zwahlen M (2008) Body-mass index and incidence of cancer: A systematic review and meta-analysis of prospective observational studies. Lancet 371(9612):569–578. doi: 10.1016/S0140-6736(08)60269-X CrossRefPubMedGoogle Scholar
  26. 26.
    Beason T, Colditz G (2012) Obesity and multiple myeloma. In: Mittelman SD, Berger NA (eds) Energy balance and hematologic malignancies. Energy balance and cancer, vol 5, 1st edn. Springer US, pp 71–95. doi:10.1007/978–1-4614-2403-1Google Scholar
  27. 27.
    Terras LR, Patel AV (2012) The epidemiology of obesity and hematologic malignancies. In: Mittelman SD, Berger NA (eds) Energy balance and hematologic malignancies. Energy balance and cancer, vol 5, 1st edn. Springer US, pp 1–30. doi:10.1007/978–1-4614-2403-1Google Scholar
  28. 28.
    Li CI, Daling JR, Porter PL, Tang MT, Malone KE (2009) Relationship between potentially modifiable lifestyle factors and risk of second primary contralateral breast cancer among women diagnosed with estrogen receptor-positive invasive breast cancer. J Clin Oncol Off J Am Soc Clin Oncol 27(32):5312–5318. doi: 10.1200/JCO.2009.23.1597 CrossRefGoogle Scholar
  29. 29.
    Li D, Morris JS, Liu J, Hassan MM, Day RS, Bondy ML, Abbruzzese JL (2009) Body mass index and risk, age of onset, and survival in patients with pancreatic cancer. JAMA 301(24):2553–2562. doi: 10.1001/jama.2009.886 CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Park JS, Choi GS, Jang YS, Jun SH, Kang H (2010) Influence of obesity on the serum carcinoembryonic antigen value in patients with colorectal cancer. Cancer Epidemiology, Biomarkers & Prevention : A Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology 19(10):2461–2468. doi: 10.1158/1055-9965.EPI-10-0569 CrossRefGoogle Scholar
  31. 31.
    Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ (2003) Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med 348(17):1625–1638. doi: 10.1056/NEJMoa021423 CrossRefPubMedGoogle Scholar
  32. 32.
    Iyengar NM, Hudis CA, Dannenberg AJ (2013) Obesity and inflammation: new insights into breast cancer development and progression. American Society of Clinical Oncology educational book/ASCO American Society of Clinical Oncology Meeting:46–51. doi: 10.1200/EdBook_AM.2013.33.46
  33. 33.
    Iyengar NM, Morris PG, Hudis CA, Dannenberg AJ (2013) Obesity, inflammation, and breast cancer. In: Dannenberg AJ, Berger NA (eds) Obesity, Inflammation and cancer. Energy balance and cancer, vol 7, 1st edn. Springer-Verlag New York, pp 181–217. doi:10.1007/978–1-4614-6819-6Google Scholar
  34. 34.
    Yoon HH, Lewis MA, Shi Q, Khan M, Cassivi SD, Diasio RB, Sinicrope FA (2011) Prognostic impact of body mass index stratified by smoking status in patients with esophageal adenocarcinoma. J Clin Oncol Off J Am Soc Clin Oncol 29(34):4561–4567. doi: 10.1200/JCO.2011.37.1260 CrossRefGoogle Scholar
  35. 35.
    National Cancer Institute (2012) Obesity and Cancer risk. Accessed 19 March 2015
  36. 36.
    Cleary MP, Grossmann ME (2009) Minireview: Obesity and breast cancer: The estrogen connection. Endocrinology 150(6):2537–2542. doi: 10.1210/en.2009-0070 CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    World Cancer Research Fund / American Institute for Cancer Research (2007) Food, nutrition, physical activity, and the prevention of cancer: a global perspective. AICR, Washington DCGoogle Scholar
  38. 38.
    Suzuki R, Orsini N, Saji S, Key TJ, Wolk A (2009) Body weight and incidence of breast cancer defined by estrogen and progesterone receptor status–a meta-analysis. International Journal of Cancer Journal International du Cancer 124(3):698–712. doi: 10.1002/ijc.23943 CrossRefPubMedGoogle Scholar
  39. 39.
    Singh P, Kapil U, Shukla N, Deo S, Dwivedi S (2011) Association of overweight and obesity with breast cancer in India. Indian Journal of Community Medicine : Official Publication of Indian Association of Preventive & Social Medicine 36(4):259–262. doi: 10.4103/0970-0218.91326 CrossRefGoogle Scholar
  40. 40.
    Pierobon M, Frankenfeld CL (2013) Obesity as a risk factor for triple-negative breast cancers: a systematic review and meta-analysis. Breast Cancer Res Treat 137(1):307–314. doi: 10.1007/s10549-012-2339-3 CrossRefPubMedGoogle Scholar
  41. 41.
    Travis RC, Key TJ (2003) Oestrogen exposure and breast cancer risk. Breast Cancer research : BCR 5(5):239–247. doi: 10.1186/bcr628 CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Yager JD, Davidson NE (2006) Estrogen carcinogenesis in breast cancer. N Engl J Med 354(3):270–282. doi: 10.1056/NEJMra050776 CrossRefPubMedGoogle Scholar
  43. 43.
    Pequeux C, Raymond-Letron I, Blacher S, Boudou F, Adlanmerini M, Fouque MJ, Lenfant F, et al. (2012) Stromal estrogen receptor-alpha promotes tumor growth by normalizing an increased angiogenesis. Cancer Res 72(12):3010–3019. doi: 10.1158/0008-5472.CAN-11-3768 CrossRefPubMedGoogle Scholar
  44. 44.
    Key TJ, Appleby PN, Reeves GK, Roddam A, Dorgan JF, Longcope C, Endogenous Hormones Breast Cancer Collaborative G, et al. (2003) Body mass index, serum sex hormones, and breast cancer risk in postmenopausal women. J Natl Cancer Inst 95(16):1218–1226CrossRefPubMedGoogle Scholar
  45. 45.
    Kaaks R, Rinaldi S, Key TJ, Berrino F, Peeters PH, Biessy C, Riboli E, et al. (2005) Postmenopausal serum androgens, oestrogens and breast cancer risk: the European prospective investigation into cancer and nutrition. Endocr Relat Cancer 12(4):1071–1082. doi: 10.1677/erc.1.01038 CrossRefPubMedGoogle Scholar
  46. 46.
    Li CI, Daling JR, Malone KE (2003) Incidence of Invasive breast cancer by hormone receptor status from 1992 to 1998. J Clin Oncol Off J Am Soc Clin Oncol 21(1):28–34CrossRefGoogle Scholar
  47. 47.
    Subbaramaiah K, Howe LR, Bhardwaj P, Du B, Gravaghi C, Yantiss RK, Dannenberg AJ, et al. (2011) Obesity is associated with inflammation and elevated aromatase expression in the mouse mammary gland. Cancer Prevention Research 4(3):329–346. doi: 10.1158/1940-6207.CAPR-10-0381 CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Khandekar MJ, Cohen P, Spiegelman BM (2011) Molecular mechanisms of cancer development in obesity. Nat Rev Cancer 11(12):886–895. doi: 10.1038/nrc3174 CrossRefPubMedGoogle Scholar
  49. 49.
    Pollak MN, Schernhammer ES, Hankinson SE (2004) Insulin-like growth factors and neoplasia. Nat Rev Cancer 4(7):505–518. doi: 10.1038/nrc1387 CrossRefPubMedGoogle Scholar
  50. 50.
    Goodwin PJ, Ennis M, Pritchard KI, Trudeau ME, Koo J, Madarnas Y, Hood N, et al. (2002) Fasting insulin and outcome in early-stage breast cancer: results of a prospective cohort study. J Clin Oncol Off J Am Soc Clin Oncol 20(1):42–51CrossRefGoogle Scholar
  51. 51.
    Barone BB, Yeh HC, Snyder CF, Peairs KS, Stein KB, Derr RL, Brancati FL, et al. (2008) Long-term all-cause mortality in cancer patients with preexisting diabetes mellitus: a systematic review and meta-analysis. JAMA 300(23):2754–2764. doi: 10.1001/jama.2008.824 CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Giovannucci E (1995) Insulin and colon cancer. Cancer Causes Control 6(2):164–179CrossRefPubMedGoogle Scholar
  53. 53.
    McKeown-Eyssen G (1994) Epidemiology of colorectal cancer revisited: are serum triglycerides and/or plasma glucose associated with risk? Cancer Epidemiology, Biomarkers & Prevention : A Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology 3(8):687–695Google Scholar
  54. 54.
    Clayton PE, Banerjee I, Murray PG, Renehan AG (2011) Growth hormone, the insulin-like growth factor axis, insulin and cancer risk. Nat Rev Endocrinol 7(1):11–24. doi: 10.1038/nrendo.2010.171 CrossRefPubMedGoogle Scholar
  55. 55.
    Renehan AG, Zwahlen M, Minder C, O'Dwyer ST, Shalet SM, Egger M (2004) Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis. Lancet 363(9418):1346–1353. doi: 10.1016/S0140-6736(04)16044-3 CrossRefPubMedGoogle Scholar
  56. 56.
    Lueprasitsakul P, Latour D, Longcope C (1990) Aromatase activity in human adipose tissue stromal cells: effect of growth factors. Steroids 55(12):540–544CrossRefPubMedGoogle Scholar
  57. 57.
    Rosen ED, Spiegelman BM (2014) What we talk about when we talk about fat. Cell 156(1–2):20–44. doi: 10.1016/j.cell.2013.12.012 CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Hofbauer KG (2002) Molecular pathways to obesity. Int J Obes Relat Metab Disord 26(Suppl 2):S18–S27. doi: 10.1038/sj.ijo.0802124 CrossRefPubMedGoogle Scholar
  59. 59.
    Robertson JF, Ferrero JM, Bourgeois H, Kennecke H, de Boer RH, Jacot W, Kaufman PA, et al. (2013) Ganitumab with either exemestane or fulvestrant for postmenopausal women with advanced, hormone-receptor-positive breast cancer: a randomised, controlled, double-blind, phase 2 trial. The Lancet Oncology 14(3):228–235. doi: 10.1016/S1470-2045(13)70026-3 CrossRefPubMedGoogle Scholar
  60. 60.
    Fischer-Posovszky P, Wabitsch M, Hochberg Z (2007) endocrinology of adipose tissue - an update. Horm Metab Res 39(5):314–321. doi: 10.1055/s-2007-976539 CrossRefPubMedGoogle Scholar
  61. 61.
    Tilg H, Moschen AR (2006) Adipocytokines: mediators linking adipose tissue, inflammation and immunity. Nat Rev Immunol 6(10):772–783. doi: 10.1038/nri1937 CrossRefPubMedGoogle Scholar
  62. 62.
    Hursting SD, Digiovanni J, Dannenberg AJ, Azrad M, Leroith D, Demark-Wahnefried W, Berger NA, et al. (2012) Obesity, energy balance, and cancer: new opportunities for prevention. Cancer Prevention Research 5(11):1260–1272. doi: 10.1158/1940-6207.CAPR-12-0140 CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Renehan AG, Zwahlen M, Egger M (2015) Adiposity and cancer risk: new mechanistic insights from epidemiology. Nat Rev Cancer 15(8):484–498. doi: 10.1038/nrc3967 CrossRefPubMedGoogle Scholar
  64. 64.
    Grossmann ME, Nkhata KJ, Mizuno NK, Ray A, Cleary MP (2008) Effects of adiponectin on breast cancer cell growth and signaling. Br J Cancer 98(2):370–379. doi: 10.1038/sj.bjc.6604166 CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Cong L, Gasser J, Zhao J, Yang B, Li F, Zhao AZ (2007) Human adiponectin inhibits cell growth and induces apoptosis in human endometrial carcinoma cells, HEC-1-A and RL95 2. Endocr Relat Cancer 14(3):713–720. doi: 10.1677/ERC-07-0065 CrossRefPubMedGoogle Scholar
  66. 66.
    Kim AY, Lee YS, Kim KH, Lee JH, Lee HK, Jang SH, Kim JB, et al. (2010) Adiponectin represses colon cancer cell proliferation via AdipoR1- and -R2-mediated AMPK activation. Mol Endocrinol 24(7):1441–1452. doi: 10.1210/me.2009-0498 CrossRefPubMedGoogle Scholar
  67. 67.
    Bub JD, Miyazaki T, Iwamoto Y (2006) Adiponectin as a growth inhibitor in prostate cancer cells. Biochem Biophys Res Commun 340(4):1158–1166. doi: 10.1016/j.bbrc.2005.12.103 CrossRefPubMedGoogle Scholar
  68. 68.
    Gialamas SP, Sergentanis TN, Antonopoulos CN, Dessypris N, Chrousos GP, Petridou ET (2013) Circulating leptin levels and risk of colorectal cancer and adenoma: a case-control study and meta-analysis. Cancer Causes Control 24(12):2129–2141. doi: 10.1007/s10552-013-0290-1 CrossRefPubMedGoogle Scholar
  69. 69.
    Renehan AG, Roberts DL, Dive C (2008) Obesity and cancer: pathophysiological and biological mechanisms. Arch Physiol Biochem 114(1):71–83. doi: 10.1080/13813450801954303 CrossRefPubMedGoogle Scholar
  70. 70.
    Iyengar NM, Hudis CA, Dannenberg AJ (2015) Obesity and cancer: local and systemic mechanisms. Annu Rev Med 66:297–309. doi: 10.1146/annurev-med-050913-022228 CrossRefPubMedGoogle Scholar
  71. 71.
    Bertolini F, Petit JY, Kolonin MG (2015) Stem cells from adipose tissue and breast cancer: hype, risks and hope. Br J Cancer 112(3):419–423. doi: 10.1038/bjc.2014.657 CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Kamada N, Seo SU, Chen GY, Nunez G (2013) Role of the gut microbiota in immunity and inflammatory disease. Nat Rev Immunol 13(5):321–335. doi: 10.1038/nri3430 CrossRefPubMedGoogle Scholar
  73. 73.
    Ley RE, Turnbaugh PJ, Klein S, Gordon JI (2006) Microbial ecology: human gut microbes associated with obesity. Nature 444(7122):1022–1023. doi: 10.1038/4441022a CrossRefPubMedGoogle Scholar
  74. 74.
    Ley RE, Backhed F, Turnbaugh P, Lozupone CA, Knight RD, Gordon JI (2005) Obesity alters gut microbial ecology. Proc Natl Acad Sci U S A 102(31):11070–11075. doi: 10.1073/pnas.0504978102 CrossRefPubMedPubMedCentralGoogle Scholar
  75. 75.
    Holmes E, Li JV, Marchesi JR, Nicholson JK (2012) Gut microbiota composition and activity in relation to host metabolic phenotype and disease risk. Cell Metab 16(5):559–564. doi: 10.1016/j.cmet.2012.10.007 CrossRefPubMedGoogle Scholar
  76. 76.
    Henao-Mejia J, Elinav E, Jin C, Hao L, Mehal WZ, Strowig T, Flavell RA, et al. (2012) Inflammasome-mediated dysbiosis regulates progression of nafld and obesity. Nature 482(7384):179–185. doi: 10.1038/nature10809 PubMedPubMedCentralGoogle Scholar
  77. 77.
    Koeth RA, Wang Z, Levison BS, Buffa JA, Org E, Sheehy BT, Hazen SL, et al. (2013) Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med 19(5):576–585. doi: 10.1038/nm.3145 CrossRefPubMedPubMedCentralGoogle Scholar
  78. 78.
    Yokote H, Miyake S, Croxford JL, Oki S, Mizusawa H, Yamamura T (2008) NKT cell-dependent amelioration of a mouse model of multiple sclerosis by altering gut flora. Am J Pathol 173(6):1714–1723. doi: 10.2353/ajpath.2008.080622 CrossRefPubMedPubMedCentralGoogle Scholar
  79. 79.
    Collins SM, Surette M, Bercik P (2012) The interplay between the intestinal microbiota and the brain. Nat Rev Microbiol 10(11):735–742. doi: 10.1038/nrmicro2876 CrossRefPubMedGoogle Scholar
  80. 80.
    Yoshimoto S, Loo TM, Atarashi K, Kanda H, Sato S, Oyadomari S, Ohtani N, et al. (2013) Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome. Nature 499(7456):97–101. doi: 10.1038/nature12347 CrossRefPubMedGoogle Scholar
  81. 81.
    Garrett WS (2015) Cancer and the microbiota. Science 348(6230):80–86. doi: 10.1126/science.aaa4972 CrossRefPubMedGoogle Scholar
  82. 82.
    Balkwill F, Mantovani A (2001) Inflammation and cancer: back to Virchow? Lancet 357(9255):539–545. doi: 10.1016/S0140-6736(00)04046-0 CrossRefPubMedGoogle Scholar
  83. 83.
    Coussens LM, Werb Z (2002) Inflammation and cancer. Nature 420(6917):860–867. doi: 10.1038/nature01322 CrossRefPubMedPubMedCentralGoogle Scholar
  84. 84.
    Cancello R, Henegar C, Viguerie N, Taleb S, Poitou C, Rouault C, Clement K, et al. (2005) Reduction of macrophage infiltration and chemoattractant gene expression changes in white adipose tissue of morbidly obese subjects after surgery-induced weight loss. Diabetes 54(8):2277–2286CrossRefPubMedGoogle Scholar
  85. 85.
    Cinti S, Mitchell G, Barbatelli G, Murano I, Ceresi E, Faloia E, Obin MS, et al. (2005) Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J Lipid Res 46(11):2347–2355. doi: 10.1194/jlr.M500294-JLR200 CrossRefPubMedGoogle Scholar
  86. 86.
    Olefsky JM, Glass CK (2010) Macrophages, inflammation, and insulin resistance. Annu Rev Physiol 72:219–246. doi: 10.1146/annurev-physiol-021909-135846 CrossRefPubMedGoogle Scholar
  87. 87.
    Balkwill F, Charles KA, Mantovani A (2005) Smoldering and polarized inflammation in the initiation and promotion of malignant disease. Cancer Cell 7(3):211–217. doi: 10.1016/j.ccr.2005.02.013 CrossRefPubMedGoogle Scholar
  88. 88.
    Morris PG, Zhou XK, Milne GL, Goldstein D, Hawks LC, Dang CT, Dannenberg AJ, et al. (2013) Increased levels of urinary pge-m, a biomarker of inflammation, occur in association with obesity, aging, and lung metastases in patients with breast cancer. Cancer Prevention Research 6(5):428–436. doi: 10.1158/1940-6207.CAPR-12-0431 CrossRefPubMedPubMedCentralGoogle Scholar
  89. 89.
    Amano SU, Cohen JL, Vangala P, Tencerova M, Nicoloro SM, Yawe JC, Aouadi M, et al. (2014) Local proliferation of macrophages contributes to obesity-associated adipose tissue inflammation. Cell Metab 19(1):162–171. doi: 10.1016/j.cmet.2013.11.017 CrossRefPubMedPubMedCentralGoogle Scholar
  90. 90.
    Murano I, Barbatelli G, Parisani V, Latini C, Muzzonigro G, Castellucci M, Cinti S (2008) Dead adipocytes, detected as crown-like structures, are prevalent in visceral fat depots of genetically obese mice. J Lipid Res 49(7):1562–1568. doi: 10.1194/jlr.M800019-JLR200 CrossRefPubMedGoogle Scholar
  91. 91.
    Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW, Jr. (2003) Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 112 (12):1796–1808. doi: 10.1172/JCI19246 CrossRefPubMedPubMedCentralGoogle Scholar
  92. 92.
    Morris PG, Hudis CA, Giri D, Morrow M, Falcone DJ, Zhou XK, Dannenberg AJ, et al. (2011) Inflammation and increased aromatase expression occur in the breast tissue of obese women with breast cancer. Cancer Prevention Research 4(7):1021–1029. doi: 10.1158/1940-6207.CAPR-11-0110 CrossRefPubMedPubMedCentralGoogle Scholar
  93. 93.
    Hardy DB, Janowski BA, Chen CC, Mendelson CR (2008) Progesterone receptor inhibits aromatase and inflammatory response pathways in breast cancer cells via ligand-dependent and ligand-independent mechanisms. Mol Endocrinol 22(8):1812–1824. doi: 10.1210/me.2007-0443 CrossRefPubMedPubMedCentralGoogle Scholar
  94. 94.
    Irahara N, Miyoshi Y, Taguchi T, Tamaki Y, Noguchi S (2006) Quantitative analysis of aromatase mRNA expression derived from various promoters (I.4, I.3, PII and I.7) and its association with expression of TNF-alpha, IL-6 and COX-2 mRNAs in human breast cancer. International Journal of Cancer Journal International du Cancer 118(8):1915–1921. doi: 10.1002/ijc.21562 CrossRefPubMedGoogle Scholar
  95. 95.
    Salama SA, Kamel MW, Diaz-Arrastia CR, Xu X, Veenstra TD, Salih S, Kumar R, et al. (2009) Effect of tumor necrosis factor-alpha on estrogen metabolism and endometrial cells: potential physiological and pathological relevance. The Journal of Clinical endocrinology and Metabolism 94(1):285–293. doi: 10.1210/jc.2008-1389 CrossRefPubMedPubMedCentralGoogle Scholar
  96. 96.
    Subbaramaiah K, Hudis C, Chang SH, Hla T, Dannenberg AJ (2008) EP2 and EP4 receptors regulate aromatase expression in human adipocytes and breast cancer cells. Evidence of a BRCA1 and p300 exchange. The Journal of Biological Chemistry 283(6):3433–3444. doi: 10.1074/jbc.M705409200 CrossRefPubMedGoogle Scholar
  97. 97.
    Zhao Y, Agarwal VR, Mendelson CR, Simpson ER (1996) Estrogen biosynthesis proximal to a breast tumor is stimulated by PGE2 via cyclic AMP, leading to activation of promoter II of the CYP19 (Aromatase) gene. Endocrinology 137(12):5739–5742. doi: 10.1210/endo.137.12.8940410 PubMedGoogle Scholar
  98. 98.
    Zhao Y, Agarwal VR, Mendelson CR, Simpson ER (1997) Transcriptional regulation of CYP19 gene (Aromatase) expression in adipose stromal cells in primary culture. The Journal of Steroid biochemistry and Molecular Biology 61(3–6):203–210CrossRefPubMedGoogle Scholar
  99. 99.
    Zhao Y, Nichols JE, Valdez R, Mendelson CR, Simpson ER (1996) Tumor necrosis factor-alpha stimulates aromatase gene expression in human adipose stromal cells through use of an activating protein-1 binding site upstream of promoter 1.4. Mol Endocrinol 10(11):1350–1357. doi: 10.1210/mend.10.11.8923461 PubMedGoogle Scholar
  100. 100.
    Iyengar NM, Morris PG, Zhou XK, Gucalp A, Giri D, Harbus MD, Dannenberg AJ, et al. (2015) Menopause is a determinant of breast adipose inflammation. Cancer Prevention research. doi: 10.1158/1940-6207.CAPR-14-0243 PubMedGoogle Scholar
  101. 101.
    Iyengar NM, Gucalp A, Zhou XK, Howe LR, Morris PG, Giri D, et al. Dannenberg AJ (2015) Abstract P4-04-12: Both metabolic syndrome and statin use are more common in women with breast inflammation. Cancer research 75 (9 Supplement):P4-04-12. doi: 10.1158/1538-7445.sabcs14-p4-04-12
  102. 102.
    Seo MH, Rhee EJ (2014) Metabolic and cardiovascular implications of a metabolically healthy obesity phenotype. Endocrinol Metab (Seoul) 29(4):427–434. doi: 10.3803/EnM.2014.29.4.427 CrossRefGoogle Scholar
  103. 103.
    Cook NR, Lee IM, Gaziano JM, Gordon D, Ridker PM, Manson JE, Buring JE, et al. (2005) Low-dose aspirin in the primary prevention of cancer: The women's health study: A randomized controlled trial. JAMA 294(1):47–55. doi: 10.1001/jama.294.1.47 CrossRefPubMedGoogle Scholar
  104. 104.
    Takkouche B, Regueira-Mendez C, Etminan M (2008) Breast cancer and use of nonsteroidal anti-inflammatory drugs: A meta-analysis. J Natl Cancer Inst 100(20):1439–1447. doi: 10.1093/jnci/djn324 CrossRefPubMedGoogle Scholar
  105. 105.
    Zhang X, Smith-Warner SA, Collins LC, Rosner B, Willett WC, Hankinson SE (2012) Use of aspirin, other nonsteroidal anti-inflammatory drugs, and acetaminophen and postmenopausal breast cancer incidence. J Clin Oncol Off J Am Soc Clin Oncol 30(28):3468–3477. doi: 10.1200/JCO.2012.42.2006 CrossRefGoogle Scholar
  106. 106.
    Ligibel JA, Alfano CM, Courneya KS, Demark-Wahnefried W, Burger RA, Chlebowski RT, Hudis CA, et al. (2014) American Society of clinical oncology position statement on obesity and cancer. J Clin Oncol Off J Am Soc Clin Oncol 32(31):3568–3574. doi: 10.1200/JCO.2014.58.4680 CrossRefGoogle Scholar

Copyright information

© Indian Association of Surgical Oncology 2015

Authors and Affiliations

  • Daniel F. Argolo
    • 1
    • 3
    Email author
  • Neil M. Iyengar
    • 1
    • 2
  • Clifford A. Hudis
    • 1
    • 2
  1. 1.Memorial Sloan Kettering Cancer CenterNew YorkUSA
  2. 2.Weill Cornell Medical CollegeNew YorkUSA
  3. 3.CLION – CAM GroupSalvadorBrazil

Personalised recommendations