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Obesity Biomarkers, Metabolism and Risk of Cancer: An Epidemiological Perspective

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Obesity and Cancer

Part of the book series: Recent Results in Cancer Research ((RECENTCANCER,volume 208))

Abstract

Obesity is associated with metabolic alterations that may pose a biological link between body fatness and risk of cancer. Elucidating the role of obesity-related biomarkers in cancer development is essential for developing targeted strategies aiming at obesity-associated cancer prevention. Molecular epidemiological studies of the past decades have provided evidence that major hormonal pathways linking obesity and cancer risk include the insulin and insulin-like growth factor-1 (IGF-1) axis, sex-steroid hormones, adipokines and chronic low-grade inflammation. These pathways are interrelated with each other, and their importance varies by obesity-related cancer type. The insulin/IGF-1 axis has been implicated to play an important mediating role in the association between obesity and risk of pancreatic, colorectal and prostate cancer. Endogenous sex-steroid hormone concentrations, in particular obesity-associated pre-diagnostic elevations of estrogens and androgens, play an important role in postmenopausal breast cancer and endometrial cancer development. The adipokines adiponectin and leptin and adipocyte-mediated chronic low-grade inflammation represented by the acute-phase C-reactive protein may explain a substantial part of the association between obesity and risk of colorectal cancer. There is less evidence on whether these hormonal pathways play a mediating role in other obesity-associated types of cancer. In this chapter, the molecular epidemiologic evidence from prospective studies relating circulating obesity-related biomarkers to cancer risk is summarized, taking into account available evidence from Mendelian Randomization investigations aiming at improving causal inference.

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References

  1. Britton KA, Massaro JM, Murabito JM, Kreger BE, Hoffmann U, Fox CS (2013) Body fat distribution, incident cardiovascular disease, cancer, and all-cause mortality. J Am Coll Cardiol 62(10):921–925. doi:10.1016/j.jacc.2013.06.027

    Article  PubMed  PubMed Central  Google Scholar 

  2. Despres JP (2012) Body fat distribution and risk of cardiovascular disease: an update. Circulation 126(10):1301–1313. doi:10.1161/CIRCULATIONAHA.111.067264

    Article  PubMed  Google Scholar 

  3. Calle EE, Kaaks R (2004) Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Nat Rev 4(8):579–591. doi:10.1038/nrc1408

    Article  CAS  Google Scholar 

  4. Roberts DL, Dive C, Renehan AG (2010) Biological mechanisms linking obesity and cancer risk: new perspectives. Annu Rev Med 61:301–316. doi:10.1146/annurev.med.080708.082713

    Article  CAS  PubMed  Google Scholar 

  5. Davey Smith G, Ebrahim S (2003) ‘Mendelian randomization’: can genetic epidemiology contribute to understanding environmental determinants of disease? Int J Epidemiol 32(1):1–22

    Google Scholar 

  6. Reaven GM (2011) Insulin resistance: the link between obesity and cardiovascular disease. Med Clin N Am 95(5):875–892. doi:10.1016/j.mcna.2011.06.002

    Article  CAS  PubMed  Google Scholar 

  7. Kaaks R, Lukanova A (2001) Energy balance and cancer: the role of insulin and insulin-like growth factor-I. Proc Nutr Soc 60(1):91–106

    Article  CAS  PubMed  Google Scholar 

  8. Tilg H, Moschen AR (2006) Adipocytokines: mediators linking adipose tissue, inflammation and immunity. Nat Rev Immunol 6(10):772–783. doi:10.1038/nri1937

    Article  CAS  PubMed  Google Scholar 

  9. Pollak M (2008) Insulin and insulin-like growth factor signalling in neoplasia. Nat Rev 8(12):915–928

    Article  CAS  Google Scholar 

  10. Giovannucci E (2001) Insulin, insulin-like growth factors and colon cancer: a review of the evidence. J Nutr 131(11 Suppl):3109S–3120S

    CAS  PubMed  Google Scholar 

  11. Renehan AG, Frystyk J, Flyvbjerg A (2006) Obesity and cancer risk: the role of the insulin-IGF axis. Trends Endocrinol Metab (TEM) 17(8):328–336. doi:10.1016/j.tem.2006.08.006

    Article  CAS  Google Scholar 

  12. Giovannucci E (2003) Nutrition, insulin, insulin-like growth factors and cancer. Horm Metab Res = Hormon- und Stoffwechselforschung = Hormones et metabolisme 35(11–12):694–704. doi:10.1055/s-2004-814147

  13. Key TJ, Appleby PN, Reeves GK, Roddam AW (2010) Insulin-like growth factor 1 (IGF1), IGF binding protein 3 (IGFBP3), and breast cancer risk: pooled individual data analysis of 17 prospective studies. Lancet Oncol 11(6):530–542. doi:10.1016/S1470-2045(10)70095-4

    Article  PubMed  Google Scholar 

  14. Fowke JH, Matthews CE, Yu H, Cai Q, Cohen S, Buchowski MS, Zheng W, Blot WJ (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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Vigneri P, Frasca F, Sciacca L, Pandini G, Vigneri R (2009) Diabetes and cancer. Endocr Relat Cancer 16(4):1103–1123. doi:10.1677/ERC-09-0087

    Article  CAS  PubMed  Google Scholar 

  16. Ohmura E, Okada M, Onoda N, Kamiya Y, Murakami H, Tsushima T, Shizume K (1990) Insulin-like growth factor I and transforming growth factor alpha as autocrine growth factors in human pancreatic cancer cell growth. Cancer Res 50(1):103–107

    CAS  PubMed  Google Scholar 

  17. Trajkovic-Arsic M, Kalideris E, Siveke JT (2013) The role of insulin and IGF system in pancreatic cancer. J Mol Endocrinol 50(3):R67–R74. doi:10.1530/JME-12-0259

    Article  CAS  PubMed  Google Scholar 

  18. Stolzenberg-Solomon RZ, Graubard BI, Chari S, Limburg P, Taylor PR, Virtamo J, Albanes D (2005) Insulin, glucose, insulin resistance, and pancreatic cancer in male smokers. JAMA 294(22):2872–2878. doi:10.1001/jama.294.22.2872

    Article  CAS  PubMed  Google Scholar 

  19. Wolpin BM, Bao Y, Qian ZR, Wu C, Kraft P, Ogino S, Stampfer MJ, Sato K, Ma J, Buring JE, Sesso HD, Lee IM, Gaziano JM, McTiernan A, Phillips LS, Cochrane BB, Pollak MN, Manson JE, Giovannucci EL, Fuchs CS (2013) Hyperglycemia, insulin resistance, impaired pancreatic beta-cell function, and risk of pancreatic cancer. J Natl Cancer Inst 105(14):1027–1035. doi:10.1093/jnci/djt123

    Google Scholar 

  20. Douglas JB, Silverman DT, Pollak MN, Tao Y, Soliman AS, Stolzenberg-Solomon RZ (2010) Serum IGF-I, IGF-II, IGFBP-3, and IGF-I/IGFBP-3 molar ratio and risk of pancreatic cancer in the prostate, lung, colorectal, and ovarian cancer screening trial. Cancer Epidemiol Biomark Prev 19(9):2298–2306. doi:10.1158/1055-9965.EPI-10-0400

    Article  CAS  Google Scholar 

  21. Lin Y, Tamakoshi A, Kikuchi S, Yagyu K, Obata Y, Ishibashi T, Kawamura T, Inaba Y, Kurosawa M, Motohashi Y, Ohno Y (2004) Serum insulin-like growth factor-I, insulin-like growth factor binding protein-3, and the risk of pancreatic cancer death. Int J Cancer 110(4):584–588. doi:10.1002/ijc.20147

    Article  CAS  PubMed  Google Scholar 

  22. Rohrmann S, Grote VA, Becker S, Rinaldi S, Tjonneland A, Roswall N, Gronbaek H, Overvad K, Boutron-Ruault MC, Clavel-Chapelon F, Racine A, Teucher B, Boeing H, Drogan D, Dilis V, Lagiou P, Trichopoulou A, Palli D, Tagliabue G, Tumino R, Vineis P, Mattiello A, Rodriguez L, Duell EJ, Molina-Montes E, Dorronsoro M, Huerta JM, Ardanaz E, Jeurnink S, Peeters PH, Lindkvist B, Johansen D, Sund M, Ye W, Khaw KT, Wareham NJ, Allen NE, Crowe FL, Fedirko V, Jenab M, Michaud DS, Norat T, Riboli E, Bueno-de-Mesquita HB, Kaaks R (2012) Concentrations of IGF-I and IGFBP-3 and pancreatic cancer risk in the European prospective investigation into cancer and nutrition. Br J Cancer 106(5):1004–1010. doi:10.1038/bjc.2012.19

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Wolpin BM, Michaud DS, Giovannucci EL, Schernhammer ES, Stampfer MJ, Manson JE, Cochrane BB, Rohan TE, Ma J, Pollak MN, Fuchs CS (2007) Circulating insulin-like growth factor axis and the risk of pancreatic cancer in four prospective cohorts. Br J Cancer 97(1):98–104. doi:10.1038/sj.bjc.6603826

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Jenab M, Riboli E, Cleveland RJ, Norat T, Rinaldi S, Nieters A, Biessy C, Tjonneland A, Olsen A, Overvad K, Gronbaek H, Clavel-Chapelon F, Boutron-Ruault MC, Linseisen J, Boeing H, Pischon T, Trichopoulos D, Oikonomou E, Trichopoulou A, Panico S, Vineis P, Berrino F, Tumino R, Masala G, Peters PH, van Gils CH, Bueno-de-Mesquita HB, Ocke MC, Lund E, Mendez MA, Tormo MJ, Barricarte A, Martinez-Garcia C, Dorronsoro M, Quiros JR, Hallmans G, Palmqvist R, Berglund G, Manjer J, Key T, Allen NE, Bingham S, Khaw KT, Cust A, Kaaks R (2007) Serum C-peptide, IGFBP-1 and IGFBP-2 and risk of colon and rectal cancers in the European prospective investigation into cancer and nutrition. Int J Cancer 121(2):368–376. doi:10.1002/ijc.22697

    Article  CAS  PubMed  Google Scholar 

  25. Pisani P (2008) Hyper-insulinaemia and cancer, meta-analyses of epidemiological studies. Arch Physiol Biochem 114(1):63–70

    Article  CAS  PubMed  Google Scholar 

  26. Rinaldi S, Cleveland R, Norat T, Biessy C, Rohrmann S, Linseisen J, Boeing H, Pischon T, Panico S, Agnoli C, Palli D, Tumino R, Vineis P, Peeters PH, van Gils CH, Bueno-de-Mesquita BH, Vrieling A, Allen NE, Roddam A, Bingham S, Khaw KT, Manjer J, Borgquist S, Dumeaux V, Torhild Gram I, Lund E, Trichopoulou A, Makrygiannis G, Benetou V, Molina E, Donate Suarez I, Barricarte Gurrea A, Gonzalez CA, Tormo MJ, Altzibar JM, Olsen A, Tjonneland A, Gronbaek H, Overvad K, Clavel-Chapelon F, Boutron-Ruault MC, Morois S, Slimani N, Boffetta P, Jenab M, Riboli E, Kaaks R (2010) Serum levels of IGF-I, IGFBP-3 and colorectal cancer risk: results from the EPIC cohort, plus a meta-analysis of prospective studies. Int J Cancer 126(7):1702–1715

    CAS  PubMed  Google Scholar 

  27. Ahern TP, Hankinson SE, Willett WC, Pollak MN, Eliassen AH, Tamimi RM (2013) Plasma C-peptide, mammographic breast density, and risk of invasive breast cancer. Cancer Epidemiol Biomark Prev 22(10):1786–1796. doi:10.1158/1055-9965.EPI-13-0375

    Article  CAS  Google Scholar 

  28. Gunter MJ, Hoover DR, Yu H, Wassertheil-Smoller S, Rohan TE, Manson JE, Li J, Ho GY, Xue X, Anderson GL, Kaplan RC, Harris TG, Howard BV, Wylie-Rosett J, Burk RD, Strickler HD (2009) Insulin, insulin-like growth factor-I, and risk of breast cancer in postmenopausal women. J Natl Cancer Inst 101(1):48–60. doi:10.1093/jnci/djn415

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Kabat GC, Kim MY, Strickler HD, Shikany JM, Lane D, Luo J, Ning Y, Gunter MJ, Rohan TE (2012) A longitudinal study of serum insulin and glucose levels in relation to colorectal cancer risk among postmenopausal women. Br J Cancer 106(1):227–232. doi:10.1038/bjc.2011.512

    Article  CAS  PubMed  Google Scholar 

  30. Keinan-Boker L, Bueno De Mesquita HB, Kaaks R, Van Gils CH, Van Noord PA, Rinaldi S, Riboli E, Seidell JC, Grobbee DE, Peeters PH (2003) Circulating levels of insulin-like growth factor I, its binding proteins -1,-2, -3, C-peptide and risk of postmenopausal breast cancer. Int J Cancer 106(1):90–95. doi:10.1002/ijc.11193

    Article  CAS  PubMed  Google Scholar 

  31. Gunter MJ, Hoover DR, Yu H, Wassertheil-Smoller S, Manson JE, Li J, Harris TG, Rohan TE, Xue X, Ho GY, Einstein MH, Kaplan RC, Burk RD, Wylie-Rosett J, Pollak MN, Anderson G, Howard BV, Strickler HD (2008) A prospective evaluation of insulin and insulin-like growth factor-I as risk factors for endometrial cancer. Cancer Epidemiol Biomark Prev 17(4):921–929. doi:10.1158/1055-9965.EPI-07-2686

    Article  CAS  Google Scholar 

  32. Wang Q, Bian CE, Peng H, He L, Zhao X (2015) Association of circulating insulin-like growth factor 1 and insulin-like growth factor binding protein 3 with the risk of ovarian cancer: a systematic review and meta-analysis. Mol Clin Oncol 3(3):623–628. doi:10.3892/mco.2015.516

    PubMed  PubMed Central  Google Scholar 

  33. Albanes D, Weinstein SJ, Wright ME, Mannisto S, Limburg PJ, Snyder K, Virtamo J (2009) Serum insulin, glucose, indices of insulin resistance, and risk of prostate cancer. J Natl Cancer Inst 101(18):1272–1279

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Borugian MJ, Spinelli JJ, Sun Z, Kolonel LN, Oakley-Girvan I, Pollak MD, Whittemore AS, Wu AH, Gallagher RP (2008) Prostate cancer risk in relation to insulin-like growth factor (IGF)-I and IGF-binding protein-3: a prospective multiethnic study. Cancer Epidemiol Biomark Prev 17(1):252–254

    Article  CAS  Google Scholar 

  35. Chen C, Lewis SK, Voigt L, Fitzpatrick A, Plymate SR, Weiss NS (2005) Prostate carcinoma incidence in relation to prediagnostic circulating levels of insulin-like growth factor I, insulin-like growth factor binding protein 3, and insulin. Cancer 103(1):76–84

    Article  CAS  PubMed  Google Scholar 

  36. Hubbard JS, Rohrmann S, Landis PK, Metter EJ, Muller DC, Andres R, Carter HB, Platz EA (2004) Association of prostate cancer risk with insulin, glucose, and anthropometry in the Baltimore longitudinal study of aging. Urology 63(2):253–258

    Article  PubMed  Google Scholar 

  37. Stattin P, Bylund A, Rinaldi S, Biessy C, Dechaud H, Stenman UH, Egevad L, Riboli E, Hallmans G, Kaaks R (2000) Plasma insulin-like growth factor-I, insulin-like growth factor-binding proteins, and prostate cancer risk: a prospective study. J Natl Cancer Inst 92(23):1910–1917

    Article  CAS  PubMed  Google Scholar 

  38. Stocks T, Lukanova A, Rinaldi S, Biessy C, Dossus L, Lindahl B, Hallmans G, Kaaks R, Stattin P (2007) Insulin resistance is inversely related to prostate cancer: a prospective study in Northern Sweden. Int J Cancer 120(12):2678–2686

    Article  CAS  PubMed  Google Scholar 

  39. Lai GY, Giovannucci EL, Pollak MN, Peskoe SB, Stampfer MJ, Willett WC, Platz EA (2014) Association of C-peptide and leptin with prostate cancer incidence in the health professionals follow-up study. Cancer Causes Control 25(5):625–632. doi:10.1007/s10552-014-0369-3

    Article  PubMed  PubMed Central  Google Scholar 

  40. Roddam AW, Allen NE, Appleby P, Key TJ, Ferrucci L, Carter HB, Metter EJ, Chen C, Weiss NS, Fitzpatrick A, Hsing AW, Lacey JV Jr, Helzlsouer K, Rinaldi S, Riboli E, Kaaks R, Janssen JA, Wildhagen MF, Schroder FH, Platz EA, Pollak M, Giovannucci E, Schaefer C, Quesenberry CP Jr, Vogelman JH, Severi G, English DR, Giles GG, Stattin P, Hallmans G, Johansson M, Chan JM, Gann P, Oliver SE, Holly JM, Donovan J, Meyer F, Bairati I, Galan P (2008) Insulin-like growth factors, their binding proteins, and prostate cancer risk: analysis of individual patient data from 12 prospective studies. Ann Intern Med 149(7):461–471, W483–W468

    Google Scholar 

  41. Aleksandrova K, Boeing H, Nothlings U, Jenab M, Fedirko V, Kaaks R, Lukanova A, Trichopoulou A, Trichopoulos D, Boffetta P, Trepo E, Westhpal S, Duarte-Salles T, Stepien M, Overvad K, Tjonneland A, Halkjaer J, Boutron-Ruault MC, Dossus L, Racine A, Lagiou P, Bamia C, Benetou V, Agnoli C, Palli D, Panico S, Tumino R, Vineis P, Bueno-de-Mesquita B, Peeters PH, Gram IT, Lund E, Weiderpass E, Quiros JR, Agudo A, Sanchez MJ, Gavrila D, Barricarte A, Dorronsoro M, Ohlsson B, Lindkvist B, Johansson A, Sund M, Khaw KT, Wareham N, Travis RC, Riboli E, Pischon T (2014) Inflammatory and metabolic biomarkers and risk of liver and biliary tract cancer. Hepatology 60(3):858–871. doi:10.1002/hep.27016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Nead KT, Sharp SJ, Thompson DJ, Painter JN, Savage DB, Semple RK, Barker A, Perry JR, Attia J, Dunning AM, Easton DF, Holliday E, Lotta LA, O’Mara T, McEvoy M, Pharoah PD, Scott RJ, Spurdle AB, Langenberg C, Wareham NJ, Scott RA (2015) Evidence of a causal association between insulinemia and endometrial cancer: a mendelian randomization analysis. J Natl Cancer Inst 107(9). doi:10.1093/jnci/djv178

  43. Lukanova A, Lundin E, Micheli A, Arslan A, Ferrari P, Rinaldi S, Krogh V, Lenner P, Shore RE, Biessy C, Muti P, Riboli E, Koenig KL, Levitz M, Stattin P, Berrino F, Hallmans G, Kaaks R, Toniolo P, Zeleniuch-Jacquotte A (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

    Article  CAS  PubMed  Google Scholar 

  44. Kaaks R, Rinaldi S, Key TJ, Berrino F, Peeters PH, Biessy C, Dossus L, Lukanova A, Bingham S, Khaw KT, Allen NE, Bueno-de-Mesquita HB, van Gils CH, Grobbee D, Boeing H, Lahmann PH, Nagel G, Chang-Claude J, Clavel-Chapelon F, Fournier A, Thiebaut A, Gonzalez CA, Quiros JR, Tormo MJ, Ardanaz E, Amiano P, Krogh V, Palli D, Panico S, Tumino R, Vineis P, Trichopoulou A, Kalapothaki V, Trichopoulos D, Ferrari P, Norat T, Saracci R, Riboli E (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

    Article  CAS  PubMed  Google Scholar 

  45. Key T, Appleby P, Barnes I, Reeves G (2002) Endogenous sex hormones and breast cancer in postmenopausal women: reanalysis of nine prospective studies. J Natl Cancer Inst 94(8):606–616

    Article  CAS  PubMed  Google Scholar 

  46. Kleinman D, Karas M, Danilenko M, Arbell A, Roberts CT, LeRoith D, Levy J, Sharoni Y (1996) Stimulation of endometrial cancer cell growth by tamoxifen is associated with increased insulin-like growth factor (IGF)-I induced tyrosine phosphorylation and reduction in IGF binding proteins. Endocrinology 137(3):1089–1095. doi:10.1210/endo.137.3.8603578

    CAS  PubMed  Google Scholar 

  47. Kaaks R, Lukanova A, Kurzer MS (2002) Obesity, endogenous hormones, and endometrial cancer risk: a synthetic review. Cancer Epidemiol Biomark Prev 11(12):1531–1543

    CAS  Google Scholar 

  48. Wild S, Pierpoint T, Jacobs H, McKeigue P (2000) Long-term consequences of polycystic ovary syndrome: results of a 31 year follow-up study. Hum Fertil (Camb) 3(2):101–105

    Article  Google Scholar 

  49. Roddam AW, Allen NE, Appleby P, Key TJ (2008) Endogenous sex hormones and prostate cancer: a collaborative analysis of 18 prospective studies. J Natl Cancer Inst 100(3):170–183

    Article  CAS  PubMed  Google Scholar 

  50. Rinaldi S, Dossus L, Lukanova A, Peeters PH, Allen NE, Key T, Bingham S, Khaw KT, Trichopoulos D, Trichopoulou A, Oikonomou E, Pera G, Larranaga N, Martinez-Garcia C, Ardanaz E, Quiros JR, Tormo MJ, Tjonneland A, Olsen A, Overvad K, Chang-Claude J, Linseisen J, Schulz M, Boeing H, van Gils CH, Bueno-de-Mesquita BH, Pala V, Palli D, Panico S, Tumino R, Vineis P, Clavel-Chapelon F, Mesrine S, Boutron-Ruault MC, Lundin E, Agren A, Berglund G, Manjer J, Kumle M, Lund E, Slimani N, Saracci R, Riboli E, Kaaks R (2007) Endogenous androgens and risk of epithelial ovarian cancer: results from the European prospective investigation into cancer and nutrition (EPIC). Cancer Epidemiol Biomark Prev 16(1):23–29. doi:10.1158/1055-9965.EPI-06-0755

    Article  CAS  Google Scholar 

  51. Lukanova A, Lundin E, Akhmedkhanov A, Micheli A, Rinaldi S, Zeleniuch-Jacquotte A, Lenner P, Muti P, Biessy C, Krogh V, Berrino F, Hallmans G, Riboli E, Kaaks R, Toniolo P (2003) Circulating levels of sex steroid hormones and risk of ovarian cancer. Int J Cancer 104(5):636–642. doi:10.1002/ijc.10990

    Article  CAS  PubMed  Google Scholar 

  52. Chandran M, Phillips SA, Ciaraldi T, Henry RR (2003) Adiponectin: more than just another fat cell hormone? Diabetes Care 26(8):2442–2450

    Google Scholar 

  53. Stefan N, Vozarova B, Funahashi T, Matsuzawa Y, Weyer C, Lindsay RS, Youngren JF, Havel PJ, Pratley RE, Bogardus C, Tataranni PA (2002) Plasma adiponectin concentration is associated with skeletal muscle insulin receptor tyrosine phosphorylation, and low plasma concentration precedes a decrease in whole-body insulin sensitivity in humans. Diabetes 51(6):1884–1888

    Article  CAS  PubMed  Google Scholar 

  54. Kim AY, Lee YS, Kim KH, Lee JH, Lee HK, Jang SH, Kim SE, Lee GY, Lee JW, Jung SA, Chung HY, Jeong S, Kim JB (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

    Article  CAS  PubMed  Google Scholar 

  55. Aleksandrova K, Boeing H, Jenab M, Bueno-de-Mesquita HB, Jansen E, van Duijnhoven FJ, Fedirko V, Rinaldi S, Romieu I, Riboli E, Romaguera D, Westphal S, Overvad K, Tjonneland A, Boutron-Ruault MC, Clavel-Chapelon F, Kaaks R, Lukanova A, Trichopoulou A, Lagiou P, Trichopoulos D, Agnoli C, Mattiello A, Saieva C, Vineis P, Tumino R, Peeters PH, Arguelles M, Bonet C, Sanchez MJ, Dorronsoro M, Huerta JM, Barricarte A, Palmqvist R, Hallmans G, Khaw KT, Wareham N, Allen NE, Crowe FL, Pischon T (2012) Total and high-molecular weight adiponectin and risk of colorectal cancer: the European prospective investigation into cancer and nutrition study. Carcinogenesis 33(6):1–8. doi:10.1093/carcin/bgs133

    Article  CAS  Google Scholar 

  56. Song M, Zhang X, Wu K, Ogino S, Fuchs CS, Giovannucci EL, Chan AT (2013) Plasma adiponectin and soluble leptin receptor and risk of colorectal cancer: a prospective study. Cancer Prev Res 6(9):875–885. doi:10.1158/1940-6207.CAPR-13-0169

    Google Scholar 

  57. Xu XT, Xu Q, Tong JL, Zhu MM, Huang ML, Ran ZH, Xiao SD (2011) Meta-analysis: circulating adiponectin levels and risk of colorectal cancer and adenoma. J Dig Dis 12(4):234–244. doi:10.1111/j.1751-2980.2011.00504.x

    Article  CAS  PubMed  Google Scholar 

  58. Yang X, Li J, Cai W, Yang Q, Lu Z, Yu J, Yu H, Zhang N, Sun D, Qu Y, Guo H, Wen F, Ji Y (2015) Adiponectin gene polymorphisms are associated with increased risk of colorectal cancer. Med Sci Monit Int Med J Exp Clin Res 21:2595–2606. doi:10.12659/MSM.893472

    Article  Google Scholar 

  59. Song M, Gong J, Giovannucci EL, Berndt SI, Brenner H, Chang-Claude J, Curtis KR, Harrison TA, Hoffmeister M, Hsu L, Jiao S, Le Marchand L, Potter JD, Schoen RE, Seminara D, Slattery ML, White E, Wu K, Ogino S, Fuchs CS, Hunter DJ, Tworoger SS, Hu FB, Rimm E, Jensen M, Peters U, Chan AT (2014) Genetic variants of adiponectin and risk of colorectal cancer. Int J Cancer. doi:10.1002/ijc.29360

    Google Scholar 

  60. Gunter MJ, Wang T, Cushman M, Xue X, Wassertheil-Smoller S, Strickler HD, Rohan TE, Manson JE, McTiernan A, Kaplan RC, Scherer PE, Chlebowski RT, Snetselaar L, Wang D, Ho GY (2015) Circulating adipokines and inflammatory markers and postmenopausal breast cancer risk. J Natl Cancer Inst 107(9). doi:10.1093/jnci/djv169

  61. Liao LM, Weinstein SJ, Pollak M, Li Z, Virtamo J, Albanes D, Chow WH, Purdue MP (2013) Prediagnostic circulating adipokine concentrations and risk of renal cell carcinoma in male smokers. Carcinogenesis 34(1):109–112. doi:10.1093/carcin/bgs322

    Article  PubMed  Google Scholar 

  62. Soliman PT, Cui X, Zhang Q, Hankinson SE, Lu KH (2011) Circulating adiponectin levels and risk of endometrial cancer: the prospective Nurses’ Health Study. Am J Obstet Gynecol 204(2):167 e161–165. doi:10.1016/j.ajog.2010.08.045

    Google Scholar 

  63. Aleksandrova K, Boeing H, Nothlings U, Jenab M, Fedirko V, Kaaks R, Lukanova A, Trichopoulou A, Trichopoulos D, Boffetta P, Trepo E, Westhpal S, Duarte-Salles T, Stepien M, Overvad K, Tjonneland A, Halkjaer J, Boutron-Ruault MC, Dossus L, Racine A, Lagiou P, Bamia C, Benetou V, Agnoli C, Palli D, Panico S, Tumino R, Vineis P, Bueno-de-Mesquita B, Peeters PH, Gram IT, Lund E, Weiderpass E, Quiros JR, Agudo A, Sanchez MJ, Gavrila D, Barricarte A, Dorronsoro M, Ohlsson B, Lindkvist B, Johansson A, Sund M, Khaw KT, Wareham N, Travis RC, Riboli E, Pischon T (2014) Inflammatory and metabolic biomarkers and risk of liver and bilary tract cancer. Hepatology. doi:10.1002/hep.27016

    PubMed Central  Google Scholar 

  64. Michikawa T, Inoue M, Sawada N, Sasazuki S, Tanaka Y, Iwasaki M, Shimazu T, Yamaji T, Mizokami M, Tsugane S (2013) Plasma levels of adiponectin and primary liver cancer risk in middle-aged Japanese adults with hepatitis virus infection: a nested case-control study. Cancer Epidemiol Biomark Prev 22(12):2250–2257. doi:10.1158/1055-9965.EPI-13-0363

    Article  CAS  Google Scholar 

  65. Nkontchou G, Bastard JP, Ziol M, Aout M, Cosson E, Ganne-Carrie N, Grando-Lemaire V, Roulot D, Capeau J, Trinchet JC, Vicaut E, Beaugrand M (2010) Insulin resistance, serum leptin, and adiponectin levels and outcomes of viral hepatitis C cirrhosis. J Hepatol 53(5):827–833. doi:10.1016/j.jhep.2010.04.035

    Article  CAS  PubMed  Google Scholar 

  66. Bell L, Considine R (eds) (2006) Chapter 3: leptin and obesity. Leptin. Springer, New York

    Google Scholar 

  67. Slattery ML, Wolff RK (2007) Leptin and colorectal cancer: an undefined link. Nat Clin Pract Gastroenterol Hepatol 4(3):118–119. doi:10.1038/ncpgasthep0743

    Article  PubMed  Google Scholar 

  68. Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM (1994) Positional cloning of the mouse obese gene and its human homologue. Nature 372(6505):425–432

    Article  CAS  PubMed  Google Scholar 

  69. Garofalo C, Surmacz E (2006) Leptin and cancer. J Cell Physiol 207(1):12–22. doi:10.1002/jcp.20472

    Article  CAS  PubMed  Google Scholar 

  70. Hardwick JC, Van Den Brink GR, Offerhaus GJ, Van Deventer SJ, Peppelenbosch MP (2001) Leptin is a growth factor for colonic epithelial cells. Gastroenterology 121(1):79–90

    Article  CAS  PubMed  Google Scholar 

  71. Stattin P, Palmqvist R, Soderberg S, Biessy C, Ardnor B, Hallmans G, Kaaks R, Olsson T (2003) Plasma leptin and colorectal cancer risk: a prospective study in Northern Sweden. Oncol Rep 10(6):2015–2021

    PubMed  Google Scholar 

  72. Aleksandrova K, Boeing H, Jenab M, Bueno-de-Mesquita HB, Jansen E, van Duijnhoven FJ, Rinaldi S, Fedirko V, Romieu I, Riboli E, Gunter MJ, Westphal S, Overvad K, Tjonneland A, Halkjaer J, Racine A, Boutron-Ruault MC, Clavel-Chapelon F, Kaaks R, Lukanova A, Trichopoulou A, Lagiou P, Trichopoulos D, Mattiello A, Pala V, Palli D, Tumino R, Vineis P, Buckland G, Sanchez MJ, Amiano P, Huerta JM, Barricarte A, Menendez V, Peeters PH, Soderberg S, Palmqvist R, Allen NE, Crowe FL, Khaw KT, Wareham N, Pischon T (2012) Leptin and soluble leptin receptor in risk of colorectal cancer in the European prospective investigation into cancer and nutrition cohort. Cancer Res. doi:10.1158/0008-5472.CAN-12-0465

    PubMed  Google Scholar 

  73. Stattin P, Lukanova A, Biessy C, Soderberg S, Palmqvist R, Kaaks R, Olsson T, Jellum E (2004) Obesity and colon cancer: does leptin provide a link? Int J Cancer 109(1):149–152. doi:10.1002/ijc.11668

    Google Scholar 

  74. Tamakoshi K, Toyoshima H, Wakai K, Kojima M, Suzuki K, Watanabe Y, Hayakawa N, Yatsuya H, Kondo T, Tokudome S, Hashimoto S, Suzuki S, Kawado M, Ozasa K, Ito Y, Tamakoshi A (2005) Leptin is associated with an increased female colorectal cancer risk: a nested case-control study in Japan. Oncology 68(4–6):454–461

    Article  CAS  PubMed  Google Scholar 

  75. Ho GY, Wang T, Gunter MJ, Strickler HD, Cushman M, Kaplan RC, Wassertheil-Smoller S, Xue X, Rajpathak SN, Chlebowski RT, Vitolins MZ, Scherer PE, Rohan TE (2012) Adipokines linking obesity with colorectal cancer risk in postmenopausal women. Cancer Res 72(12):3029–3037. doi:10.1158/0008-5472.CAN-11-2771

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Joshi RK, Kim WJ, Lee SA (2014) Association between obesity-related adipokines and colorectal cancer: a case-control study and meta-analysis. World J Gastroenterol (WJG) 20(24):7941–7949. doi:10.3748/wjg.v20.i24.7941

    Article  Google Scholar 

  77. Partida-Perez M, de la Luz Ayala-Madrigal M, Peregrina-Sandoval J, Macias-Gomez N, Moreno-Ortiz J, Leal-Ugarte E, Cardenas-Meza M, Centeno-Flores M, Maciel-Gutierrez V, Cabrales E, Cervantes-Ortiz S, Gutierrez-Angulo M (2010) Association of LEP and ADIPOQ common variants with colorectal cancer in Mexican patients. Cancer Biomark (section A of Disease markers) 7(3):117–121. doi:10.3233/CBM-2010-0154

    Google Scholar 

  78. Balkwill F, Mantovani A (2001) Inflammation and cancer: back to Virchow? Lancet 357(9255):539–545. doi:10.1016/S0140-6736(00)04046-0

    Google Scholar 

  79. Jess T, Rungoe C, Peyrin-Biroulet L (2012) Risk of colorectal cancer in patients with ulcerative colitis: a meta-analysis of population-based cohort studies. Clin Gastroenterol Hepatol (The Official Clinical Practice Journal of the American Gastroenterological Association) 10(6):639–645. doi:10.1016/j.cgh.2012.01.010

    Article  Google Scholar 

  80. Laukoetter MG, Mennigen R, Hannig CM, Osada N, Rijcken E, Vowinkel T, Krieglstein CF, Senninger N, Anthoni C, Bruewer M (2011) Intestinal cancer risk in Crohn’s disease: a meta-analysis. J Gastrointest Surg (Official Journal of the Society for Surgery of the Alimentary Tract) 15(4):576–583. doi:10.1007/s11605-010-1402-9

    Article  Google Scholar 

  81. Chan AT, Giovannucci EL, Meyerhardt JA, Schernhammer ES, Curhan GC, Fuchs CS (2005) Long-term use of aspirin and nonsteroidal anti-inflammatory drugs and risk of colorectal cancer. JAMA 294(8):914–923. doi:10.1001/jama.294.8.914

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Chan AT, Giovannucci EL, Meyerhardt JA, Schernhammer ES, Wu K, Fuchs CS (2008) Aspirin dose and duration of use and risk of colorectal cancer in men. Gastroenterology 134(1):21–28. doi:10.1053/j.gastro.2007.09.035

    Article  CAS  PubMed  Google Scholar 

  83. Chan AT, Ogino S, Fuchs CS (2007) Aspirin and the risk of colorectal cancer in relation to the expression of COX-2. N Engl J Med 356(21):2131–2142. doi:10.1056/NEJMoa067208

    Article  CAS  PubMed  Google Scholar 

  84. Cole BF, Logan RF, Halabi S, Benamouzig R, Sandler RS, Grainge MJ, Chaussade S, Baron JA (2009) Aspirin for the chemoprevention of colorectal adenomas: meta-analysis of the randomized trials. J Natl Cancer Inst 101(4):256–266. doi:10.1093/jnci/djn485

    Article  CAS  PubMed  Google Scholar 

  85. Coussens LM, Werb Z (2002) Inflammation and cancer. Nature 420(6917):860–867. doi:10.1038/nature01322

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Pendyala S, Neff LM, Suarez-Farinas M, Holt PR (2011) Diet-induced weight loss reduces colorectal inflammation: implications for colorectal carcinogenesis. Am J Clin Nutr 93(2):234–242. doi:10.3945/ajcn.110.002683

    Article  CAS  PubMed  Google Scholar 

  87. Toriola AT, Cheng TY, Neuhouser ML, Wener MH, Zheng Y, Brown E, Miller JW, Song X, Beresford SA, Gunter MJ, Caudill MA, Ulrich CM (2012) Biomarkers of inflammation are associated with colorectal cancer risk in women but are not suitable as early detection markers. Int J Cancer. doi:10.1002/ijc.27942

    PubMed  PubMed Central  Google Scholar 

  88. Toriola AT, Ulrich CM (2011) Is there a potential use for C-reactive protein as a diagnostic and prognostic marker for colorectal cancer? Future Oncol 7(10):1125–1128. doi:10.2217/fon.11.92

    Google Scholar 

  89. Tsilidis KK, Branchini C, Guallar E, Helzlsouer KJ, Erlinger TP, Platz EA (2008) C-reactive protein and colorectal cancer risk: a systematic review of prospective studies. Int J Cancer 123(5):1133–1140. doi:10.1002/ijc.23606

    Article  CAS  PubMed  Google Scholar 

  90. Aleksandrova K, Jenab M, Boeing H, Jansen E, Bueno-de-Mesquita HB, Rinaldi S, Riboli E, Overvad K, Dahm CC, Olsen A, Tjonneland A, Boutron-Ruault MC, Clavel-Chapelon F, Morois S, Palli D, Krogh V, Tumino R, Vineis P, Panico S, Kaaks R, Rohrmann S, Trichopoulou A, Lagiou P, Trichopoulos D, van Duijnhoven FJ, Leufkens AM, Peeters PH, Rodriguez L, Bonet C, Sanchez MJ, Dorronsoro M, Navarro C, Barricarte A, Palmqvist R, Hallmans G, Khaw KT, Wareham N, Allen NE, Spencer E, Romaguera D, Norat T, Pischon T (2010) Circulating C-reactive protein concentrations and risks of colon and rectal cancer: a nested case-control study within the European prospective investigation into cancer and nutrition. Am J Epidemiol 172(4):407–418. doi:10.1093/aje/kwq135

    Article  PubMed  Google Scholar 

  91. Nimptsch K, Aleksandrova K, Boeing H, Janke J, Lee YA, Jenab M, Bueno-de-Mesquita HB, Jansen EH, Tsilidis KK, Trichopoulou A, Weiderpass E, Wu C, Overvad K, Tjonneland A, Boutron-Ruault MC, Dossus L, Racine A, Kaaks R, Canzian F, Lagiou P, Trichopoulos D, Palli D, Agnoli C, Tumino R, Vineis P, Panico S, Johansson A, Van Guelpen B, Khaw KT, Wareham N, Peeters PH, Quiros JR, Vencesla Garcia A, Molina-Montes E, Dorronsoro M, Chirlaque MD, Barricarte Gurrea A, Key TJ, Duarte-Salles T, Stepien M, Gunter MJ, Riboli E, Pischon T (2015) Association of CRP genetic variants with blood concentrations of C-reactive protein and colorectal cancer risk. Int J Cancer 136(5):1181–1192. doi:10.1002/ijc.29086

    Article  CAS  PubMed  Google Scholar 

  92. Prizment AE, Folsom AR, Dreyfus J, Anderson KE, Visvanathan K, Joshu CE, Platz EA, Pankow JS (2013) Plasma C-reactive protein, genetic risk score, and risk of common cancers in the atherosclerosis risk in communities study. Cancer Causes Control 24(12):2077–2087. doi:10.1007/s10552-013-0285-y

    Article  PubMed  Google Scholar 

  93. Allin KH, Nordestgaard BG, Zacho J, Tybjaerg-Hansen A, Bojesen SE (2010) C-reactive protein and the risk of cancer: a mendelian randomization study. J Natl Cancer Inst 102(3):202–206. doi:10.1093/jnci/djp459

    Article  CAS  PubMed  Google Scholar 

  94. Kakourou A, Koutsioumpa C, Lopez DS, Hoffman-Bolton J, Bradwin G, Rifai N, Helzlsouer KJ, Platz EA, Tsilidis KK (2015) Interleukin-6 and risk of colorectal cancer: results from the CLUE II cohort and a meta-analysis of prospective studies. Cancer Causes Control 26(10):1449–1460. doi:10.1007/s10552-015-0641-1

    Article  PubMed  PubMed Central  Google Scholar 

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  1. Molecular Epidemiology Research Group, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Robert-Rössle-Straße 10, 13125, Berlin, Germany

    Katharina Nimptsch & Tobias Pischon

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    Tobias Pischon

  2. Molecular Epidemiology Research Group, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Robert-Rössle-Straße, Berlin, Germany

    Katharina Nimptsch

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Nimptsch, K., Pischon, T. (2016). Obesity Biomarkers, Metabolism and Risk of Cancer: An Epidemiological Perspective. In: Pischon, T., Nimptsch, K. (eds) Obesity and Cancer. Recent Results in Cancer Research, vol 208. Springer, Cham. https://doi.org/10.1007/978-3-319-42542-9_11

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