Abstract
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.
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References
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
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
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
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
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
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
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
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
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
National Institutes of Health (2012) Overweight and obesity statistics. http://win.niddk.nih.gov/publications/PDFs/stat904z.pdf. Accessed 19 March 2015
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
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
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
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
Centers for Disease Control and Prevention (2015) Adult obesity facts. http://www.cdc.gov/obesity/data/adult.html. Accessed 24 July 2015
Word Health Oganization (2015) Obesity and overweight. http://www.who.int/mediacentre/factsheets/fs311/en/. Accessed 23 July 2015
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
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
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
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
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
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
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
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
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
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:10.1007/978–1-4614-2403-1
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:10.1007/978–1-4614-2403-1
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
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
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
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
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
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:10.1007/978–1-4614-6819-6
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
National Cancer Institute (2012) Obesity and Cancer risk. http://www.cancer.gov/cancertopics/causes-prevention/risk/weight-activity/obesity-fact-sheet. Accessed 19 March 2015
Cleary MP, Grossmann ME (2009) Minireview: Obesity and breast cancer: The estrogen connection. Endocrinology 150(6):2537–2542. doi:10.1210/en.2009-0070
World Cancer Research Fund / American Institute for Cancer Research (2007) Food, nutrition, physical activity, and the prevention of cancer: a global perspective. AICR, Washington DC
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
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
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
Travis RC, Key TJ (2003) Oestrogen exposure and breast cancer risk. Breast Cancer research : BCR 5(5):239–247. doi:10.1186/bcr628
Yager JD, Davidson NE (2006) Estrogen carcinogenesis in breast cancer. N Engl J Med 354(3):270–282. doi:10.1056/NEJMra050776
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
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):1218–1226
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
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):28–34
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
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
Pollak MN, Schernhammer ES, Hankinson SE (2004) Insulin-like growth factors and neoplasia. Nat Rev Cancer 4(7):505–518. doi:10.1038/nrc1387
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):42–51
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
Giovannucci E (1995) Insulin and colon cancer. Cancer Causes Control 6(2):164–179
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):687–695
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
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
Lueprasitsakul P, Latour D, Longcope C (1990) Aromatase activity in human adipose tissue stromal cells: effect of growth factors. Steroids 55(12):540–544
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
Hofbauer KG (2002) Molecular pathways to obesity. Int J Obes Relat Metab Disord 26(Suppl 2):S18–S27. doi:10.1038/sj.ijo.0802124
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
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
Tilg H, Moschen AR (2006) Adipocytokines: mediators linking adipose tissue, inflammation and immunity. Nat Rev Immunol 6(10):772–783. doi:10.1038/nri1937
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Garrett WS (2015) Cancer and the microbiota. Science 348(6230):80–86. doi:10.1126/science.aaa4972
Balkwill F, Mantovani A (2001) Inflammation and cancer: back to Virchow? Lancet 357(9255):539–545. doi:10.1016/S0140-6736(00)04046-0
Coussens LM, Werb Z (2002) Inflammation and cancer. Nature 420(6917):860–867. doi:10.1038/nature01322
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):2277–2286
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
Olefsky JM, Glass CK (2010) Macrophages, inflammation, and insulin resistance. Annu Rev Physiol 72:219–246. doi:10.1146/annurev-physiol-021909-135846
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
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
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
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
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
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
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
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
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
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
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
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):203–210
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
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
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
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
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
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
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
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
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2014 Conquer Cancer Foundation of ASCO LIFe Award (to Daniel F. Argolo).
Breast Cancer Research Foundation (to Clifford A. Hudis and Neil M. Iyengar).
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Argolo, D.F., Iyengar, N.M. & Hudis, C.A. Obesity and Cancer: Concepts and Challenges. Indian J Surg Oncol 6, 390–398 (2015). https://doi.org/10.1007/s13193-015-0483-z
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DOI: https://doi.org/10.1007/s13193-015-0483-z