Skip to content
Licensed Unlicensed Requires Authentication Published by De Gruyter March 14, 2015

Body fatness, related biomarkers and cancer risk: an epidemiological perspective

  • Katharina Nimptsch EMAIL logo and Tobias Pischon

Abstract

Higher body fatness is not only associated with a higher risk of hypertension, type 2 diabetes, and coronary heart disease but also with certain types of cancer. The scope of this review is to summarize the epidemiological evidence for an association between body fatness and specific types of cancer and to outline the mediating role of obesity-related biomarkers in this context. Epidemiological studies have gathered convincing evidence that greater body fatness is associated with a higher risk of colorectal cancer, postmenopausal breast cancer, endometrial cancer, esophageal adenocarcinoma, renal cell carcinoma, and pancreatic cancer. Further, evidence for an association between higher body fatness and higher risk of ovarian cancer, advanced prostate cancer, and hepatocellular carcinoma is growing. Abdominal obesity is an independent risk factor for colorectal cancer beyond general obesity, whereas an independent role is less clear for other obesity-related cancer types. Epidemiological biomarker studies have shown that the positive association between body fatness and risk of cancer may be partly explained by hyperinsulinemia and altered concentrations in adipokines and sex-steroid hormones. In addition, obesity-associated low-grade inflammation plays a role in colorectal carcinogenesis. While epidemiology has contributed substantially to the understanding of the role of higher body fatness and related metabolic alterations in the development of cancer, further epidemiological biomarker studies are necessary to elucidate the complex interrelations between mediating pathways as well as to study novel pathways. Knowledge resulting from this research may help identify an obesity phenotype that is particularly strongly associated with cancer risk and thus pave the way for targeted prevention of cancer morbidity and mortality.


Corresponding author: Dr. Katharina Nimptsch, Molecular Epidemiology Research Group, Max Delbrück Center for Molecular Medicine (MDC), Robert-Rössle-Straße 10, 13125 Berlin, Germany, Phone: +49-30- 9406-4573, Fax: +49-30-9406-4576, E-mail:

References

1. World Health Organization. Obesity: preventing and managing the global epidemic. Report of a WHO consultation. World Health Organ Tech Rep Ser 2000;894:1–253.Search in Google Scholar

2. Finucane MM, Stevens GA, Cowan MJ, Danaei G, Lin JK, Paciorek CJ, Singh GM, Gutierrez HR, Lu Y, Bahalim AN, Farzadfar F, Riley LM, Ezzati M, Global Burden of Metabolic Risk Factors of Chronic Diseases Collaborating Group. 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 2011;377:557–67.10.1016/S0140-6736(10)62037-5Search in Google Scholar

3. World Health Organization. Global health risks: mortality and burden of disease attributable to selected major risks. Geneva: World Health Organization, 2009.Search in Google Scholar

4. IARC Working Group on the Evaluation of Cancer-Preventive Strategies. Weight control and physical activity. Lyon: IARC Press, 2002.Search in Google Scholar

5. World Cancer Research Fund/American Institute for Cancer Research. Food, nutrition, physical activity, and the prevention of cancer: a global perspective. Washington, DC, 2007.Search in Google Scholar

6. World Cancer Research Fund/American Institute for Cancer Research. Continuous Update Project Report. Food, nutrition, physical activity, and the prevention of ovarian cancer. Washington, DC, 2014.Search in Google Scholar

7. World Cancer Research Fund/American Institute for Cancer Research. Continuous Update Project Report. Food, nutrition, physical activity, and the prevention of prostate cancer. Washington, DC, 2014.Search in Google Scholar

8. Vazzana N, Riondino S, Toto V, Guadagni F, Roselli M, Davi G, Ferroni P. Obesity-driven inflammation and colorectal cancer. Curr Med Chem 2012;19:5837–53.10.2174/092986712804143349Search in Google Scholar PubMed

9. Calle EE, Kaaks R. Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Nat Rev Cancer 2004;4:579–91.10.1038/nrc1408Search in Google Scholar PubMed

10. Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults: executive summary. Expert Panel on the Identification, Evaluation, and Treatment of Overweight in Adults. Am J Clin Nutr 1998;68:899–917.10.1093/ajcn/68.4.899Search in Google Scholar PubMed

11. Okorodudu DO, Jumean MF, Montori VM, Romero-Corral A, Somers VK, Erwin PJ, Lopez-Jimenez F. Diagnostic performance of body mass index to identify obesity as defined by body adiposity: a systematic review and meta-analysis. Int J Obes (Lond) 2010;34:791–9.10.1038/ijo.2010.5Search in Google Scholar PubMed

12. Wajchenberg BL. Subcutaneous and visceral adipose tissue: their relation to the metabolic syndrome. Endocr Rev 2000;21:697–738.10.1210/edrv.21.6.0415Search in Google Scholar PubMed

13. Huxley R, Mendis S, Zheleznyakov E, Reddy S, Chan J. Body mass index, waist circumference and waist:hip ratio as predictors of cardiovascular risk – a review of the literature. Eur J Clin Nutr 2010;64:16–22.10.1038/ejcn.2009.68Search in Google Scholar PubMed

14. Lee CM, Huxley RR, Wildman RP, Woodward M. Indices of abdominal obesity are better discriminators of cardiovascular risk factors than BMI: a meta-analysis. J Clin Epidemiol 2008;61:646–53.10.1016/j.jclinepi.2007.08.012Search in Google Scholar PubMed

15. Grundy SM, Brewer HB, Jr, Cleeman JI, Smith SC, Jr, Lenfant C, National Heart, Lung, Blood Institute/American Heart Association. Definition of metabolic syndrome: report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition. Arterioscler Thromb Vasc Biol 2004;24:e13–8.10.1161/01.ATV.0000111245.75752.C6Search in Google Scholar PubMed

16. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive summary of the third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). J Am Med Assoc 2001;285:2486–97.10.1001/jama.285.19.2486Search in Google Scholar PubMed

17. Pi-Sunyer FX. Obesity: criteria and classification. Proc Nutr Soc 2000;59:505–9.10.1017/S0029665100000732Search in Google Scholar

18. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010;127:2893–917.10.1002/ijc.25516Search in Google Scholar PubMed

19. Ning Y, Wang L, Giovannucci EL. A quantitative analysis of body mass index and colorectal cancer: findings from 56 observational studies. Obes Rev 2010;11:19–30.10.1111/j.1467-789X.2009.00613.xSearch in Google Scholar PubMed

20. Galic S, Oakhill JS, Steinberg GR. Adipose tissue as an endocrine organ. Mol Cell Endocrinol 2010;316:129–39.10.1016/j.mce.2009.08.018Search in Google Scholar PubMed

21. Pischon T, Lahmann PH, Boeing H, Friedenreich C, Norat T, Tjonneland A, Halkjaer J, Overvad K, Clavel-Chapelon F, Boutron-Ruault MC, Guernec G, Bergmann MM, Linseisen J, Becker N, Trichopoulou A, Trichopoulos D, Sieri S, Palli D, Tumino R, Vineis P, Panico S, Peeters PH, Bueno-de-Mesquita HB, Boshuizen HC, Van Guelpen B, Palmqvist R, Berglund G, Gonzalez CA, Dorronsoro M, Barricarte A, Navarro C, Martinez C, Quiros JR, Roddam A, Allen N, Bingham S, Khaw KT, Ferrari P, Kaaks R, Slimani N, Riboli E. Body size and risk of colon and rectal cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC). J Natl Cancer Inst 2006;98:920–31.10.1093/jnci/djj246Search in Google Scholar PubMed

22. Dai Z, Xu YC, Niu L. Obesity and colorectal cancer risk: a meta-analysis of cohort studies. World J Gastroenterol 2007;13:4199–206.10.3748/wjg.v13.i31.4199Search in Google Scholar PubMed PubMed Central

23. World Cancer Research Fund/American Institute for Cancer Research. Continuous Update Project Report. Food, nutrition, physical activity, and the prevention of colorectal cancer. Washington, DC, 2011.Search in Google Scholar

24. Cali AM, Caprio S. Obesity in children and adolescents. J Clin Endocrinol Metab 2008;93(Suppl 1):S31–6.10.1210/jc.2008-1363Search in Google Scholar PubMed PubMed Central

25. Uauy R, Solomons N. Diet, nutrition, and the life-course approach to cancer prevention. J Nutr 2005;135(Suppl):2934S–45S.10.1093/jn/135.12.2934SSearch in Google Scholar PubMed

26. Nimptsch K, Giovannucci E, Willett WC, Fuchs CS, Wei EK, Wu K. Body fatness during childhood and adolescence, adult height, and risk of colorectal adenoma in women. Cancer Prev Res (Phila) 2011;4:1710–8.10.1158/1940-6207.CAPR-11-0272Search in Google Scholar PubMed PubMed Central

27. Stunkard AJ, Sorensen T, Schulsinger F. Use of the Danish Adoption Register for the study of obesity and thinness. In: Kety SS, Rowland LP, Sidman SQ, Mathysee SW, editors. The genetics of neurological and psychiatric disorders. New York: Raven Press, 1983:115–20.Search in Google Scholar

28. Must A, Willett WC, Dietz WH. Remote recall of childhood height, weight, and body build by elderly subjects. Am J Epidemiol 1993;138:56–64.10.1093/oxfordjournals.aje.a116777Search in Google Scholar PubMed

29. World Health Organization. Breast cancer: prevention and control. Geneva: World Health Organization, 2012.Search in Google Scholar

30. Cheraghi Z, Poorolajal J, Hashem T, Esmailnasab N, Doosti Irani A. Effect of body mass index on breast cancer during premenopausal and postmenopausal periods: a meta-analysis. PLoS One 2012;7:e51446.10.1371/journal.pone.0051446Search in Google Scholar

31. Renehan AG, Tyson M, Egger M, Heller RF, Zwahlen M. Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet 2008;371:569–78.10.1016/S0140-6736(08)60269-XSearch in Google Scholar

32. Lahmann PH, Hoffmann K, Allen N, Van Gils CH, Khaw KT, Tehard B, Berrino F, Tjonneland A, Bigaard J, Olsen A, Overvad K, Clavel-Chapelon F, Nagel G, Boeing H, Trichopoulos D, Economou G, Bellos G, Palli D, Tumino R, Panico S, Sacerdote C, Krogh V, Peeters PH, Bueno-De-Mesquita HB, Lund E, Ardanaz E, Amiano P, Pera G, Quiros JR, Martinez C, Tormo MJ, Wirfalt E, Berglund G, Hallmans G, Key TJ, Reeves G, Bingham S, Norat T, Biessy C, Kaaks R, Riboli E. Body size and breast cancer risk: findings from the European Prospective Investigation into Cancer and Nutrition (EPIC). Int J Cancer 2004;111:762–71.10.1002/ijc.20315Search in Google Scholar PubMed

33. White KK, Park SY, Kolonel LN, Henderson BE, Wilkens LR. Body size and breast cancer risk: the Multiethnic Cohort. Int J Cancer 2012;131:E705–16.10.1002/ijc.27373Search in Google Scholar PubMed PubMed Central

34. Gaudet MM, Carter BD, Patel AV, Teras LR, Jacobs EJ, Gapstur SM. Waist circumference, body mass index, and postmenopausal breast cancer incidence in the Cancer Prevention Study-II Nutrition Cohort. Cancer Cause Control 2014;25:737–45.10.1007/s10552-014-0376-4Search in Google Scholar PubMed

35. World Cancer Research Fund/American Institute for Cancer Research. Continuous Update Project Report. Food, nutrition, physical activity, and the prevention of breast cancer. Washington, DC, 2010.Search in Google Scholar

36. World Cancer Research Fund/American Institute for Cancer Research. Continuous Update Project Report. Food, nutrition, physical activity, and the prevention of endometrial cancer. Washington, DC, 2013.Search in Google Scholar

37. Friedenreich C, Cust A, Lahmann PH, Steindorf K, Boutron-Ruault MC, Clavel-Chapelon F, Mesrine S, Linseisen J, Rohrmann S, Boeing H, Pischon T, Tjonneland A, Halkjaer J, Overvad K, Mendez M, Redondo ML, Garcia CM, Larranaga N, Tormo MJ, Gurrea AB, Bingham S, Khaw KT, Allen N, Key T, Trichopoulou A, Vasilopoulou E, Trichopoulos D, Pala V, Palli D, Tumino R, Mattiello A, Vineis P, Bueno-de-Mesquita HB, Peeters PH, Berglund G, Manjer J, Lundin E, Lukanova A, Slimani N, Jenab M, Kaaks R, Riboli E. Anthropometric factors and risk of endometrial cancer: the European Prospective Investigation into Cancer and Nutrition. Cancer Cause Control 2007;18:399–413.10.1007/s10552-006-0113-8Search in Google Scholar PubMed

38. Ryan AM, Duong M, Healy L, Ryan SA, Parekh N, Reynolds JV, Power DG. Obesity, metabolic syndrome and esophageal adenocarcinoma: epidemiology, etiology and new targets. Cancer Epidemiol 2011;35:309–19.10.1016/j.canep.2011.03.001Search in Google Scholar PubMed

39. Pera M, Manterola C, Vidal O, Grande L. Epidemiology of esophageal adenocarcinoma. J Surg Oncol 2005;92:151–9.10.1002/jso.20357Search in Google Scholar PubMed

40. Adami HO, Hunter D, Trichopoulos D. Textbook of cancer epidemiology. Oxford: Oxford University Press, 2008.10.1093/acprof:oso/9780195311174.001.0001Search in Google Scholar

41. O’Doherty MG, Freedman ND, Hollenbeck AR, Schatzkin A, Abnet CC. A prospective cohort study of obesity and risk of oesophageal and gastric adenocarcinoma in the NIH-AARP Diet and Health Study. Gut 2012;61:1261–8.10.1136/gutjnl-2011-300551Search in Google Scholar PubMed PubMed Central

42. Ljungberg B, Campbell SC, Choi HY, Jacqmin D, Lee JE, Weikert S, Kiemeney LA. The epidemiology of renal cell carcinoma. Eur Urol 2011;60:615–21.10.1016/j.eururo.2011.06.049Search in Google Scholar PubMed

43. Weikert S, Boeing H, Pischon T, Weikert C, Olsen A, Tjonneland A, Overvad K, Becker N, Linseisen J, Trichopoulou A, Mountokalakis T, Trichopoulos D, Sieri S, Palli D, Vineis P, Panico S, Peeters PH, Bueno-de-Mesquita HB, Verschuren WM, Ljungberg B, Hallmans G, Berglund G, Gonzalez CA, Dorronsoro M, Barricarte A, Tormo MJ, Allen N, Roddam A, Bingham S, Khaw KT, Rinaldi S, Ferrari P, Norat T, Riboli E. Blood pressure and risk of renal cell carcinoma in the European Prospective Investigation into Cancer and Nutrition. Am J Epidemiol 2008;167:438–46.10.1093/aje/kwm321Search in Google Scholar PubMed

44. Pischon T, Lahmann PH, Boeing H, Tjonneland A, Halkjaer J, Overvad K, Klipstein-Grobusch K, Linseisen J, Becker N, Trichopoulou A, Benetou V, Trichopoulos D, Sieri S, Palli D, Tumino R, Vineis P, Panico S, Monninkhof E, Peeters PH, Bueno-de-Mesquita HB, Buchner FL, Ljungberg B, Hallmans G, Berglund G, Gonzalez CA, Dorronsoro M, Gurrea AB, Navarro C, Martinez C, Quiros JR, Roddam A, Allen N, Bingham S, Khaw KT, Kaaks R, Norat T, Slimani N, Riboli E. Body size and risk of renal cell carcinoma in the European Prospective Investigation into Cancer and Nutrition (EPIC). Int J Cancer 2006;118:728–38.10.1002/ijc.21398Search in Google Scholar PubMed

45. Adams KF, Leitzmann MF, Albanes D, Kipnis V, Moore SC, Schatzkin A, Chow WH. Body size and renal cell cancer incidence in a large US cohort study. Am J Epidemiol 2008;168:268–77.10.1093/aje/kwn122Search in Google Scholar PubMed PubMed Central

46. Flaherty KT, Fuchs CS, Colditz GA, Stampfer MJ, Speizer FE, Willett WC, Curhan GC. A prospective study of body mass index, hypertension, and smoking and the risk of renal cell carcinoma (United States). Cancer Cause Control 2005;16:1099–106.10.1007/s10552-005-0349-8Search in Google Scholar PubMed

47. IARC. World Cancer Report 2008. In: Boyle P, Levin B, editors. Lyon: World Health Organization, International Agency for Research on Cancer, 2008.Search in Google Scholar

48. Larsson SC, Orsini N, Wolk A. Body mass index and pancreatic cancer risk: a meta-analysis of prospective studies. Int J Cancer 2007;120:1993–8.10.1002/ijc.22535Search in Google Scholar PubMed

49. World Cancer Research Fund/American Institute for Cancer Research. Continuous Update Project Report. Food, nutrition, physical activity, and the prevention of pancreatic cancer. Washington, DC, 2012.Search in Google Scholar

50. Trichopoulos D, Bamia C, Lagiou P, Fedirko V, Trepo E, Jenab M, Pischon T, Nothlings U, Overved K, Tjonneland A, Outzen M, Clavel-Chapelon F, Kaaks R, Lukanova A, Boeing H, Aleksandrova K, Benetou V, Zylis D, Palli D, Pala V, Panico S, Tumino R, Sacerdote C, Bueno-De-Mesquita HB, Van Kranen HJ, Peeters PH, Lund E, Quiros JR, Gonzalez CA, Sanchez Perez MJ, Navarro C, Dorronsoro M, Barricarte A, Lindkvist B, Regner S, Werner M, Hallmans G, Khaw KT, Wareham N, Key T, Romieu I, Chuang SC, Murphy N, Boffetta P, Trichopoulou A, Riboli E. Hepatocellular carcinoma risk factors and disease burden in a European cohort: a nested case-control study. J Natl Cancer Inst 2011;103:1686–95.10.1093/jnci/djr395Search in Google Scholar PubMed PubMed Central

51. Roberts DL, Dive C, Renehan AG. Biological mechanisms linking obesity and cancer risk: new perspectives. Annu Rev Med 2010;61:301–16.10.1146/annurev.med.080708.082713Search in Google Scholar PubMed

52. Kaaks R, Lukanova A. Energy balance and cancer: the role of insulin and insulin-like growth factor-I. Proc Nutr Soc 2001;60:91–106.10.1079/PNS200070Search in Google Scholar PubMed

53. Giovannucci E. Insulin, insulin-like growth factors and colon cancer: a review of the evidence. J Nutr 2001;131(Suppl):3109S–20S.10.1093/jn/131.11.3109SSearch in Google Scholar PubMed

54. Pollak M, Beamer W, Zhang JC. Insulin-like growth factors and prostate cancer. Cancer Metastas Rev 1998;17:383–90.10.1023/A:1006154108619Search in Google Scholar

55. Renehan AG, Frystyk J, Flyvbjerg A. Obesity and cancer risk: the role of the insulin-IGF axis. Trends Endocrinol Metab 2006;17:328–36.10.1016/j.tem.2006.08.006Search in Google Scholar PubMed

56. Pollak M. Insulin and insulin-like growth factor signalling in neoplasia. Nat Rev Cancer 2008;8:915–28.10.1038/nrc2536Search in Google Scholar PubMed

57. Larsson SC, Orsini N, Wolk A. Diabetes mellitus and risk of colorectal cancer: a meta-analysis. J Natl Cancer Inst 2005;97:1679–87.10.1093/jnci/dji375Search in Google Scholar PubMed

58. Kaaks R, Toniolo P, Akhmedkhanov A, Lukanova A, Biessy C, Dechaud H, Rinaldi S, Zeleniuch-Jacquotte A, Shore RE, Riboli E. Serum C-peptide, insulin-like growth factor (IGF)-I, IGF-binding proteins, and colorectal cancer risk in women. J Natl Cancer Inst 2000;92:1592–600.10.1093/jnci/92.19.1592Search in Google Scholar PubMed

59. Ma J, Giovannucci E, Pollak M, Leavitt A, Tao Y, Gaziano JM, Stampfer MJ. A prospective study of plasma C-peptide and colorectal cancer risk in men. J Natl Cancer Inst 2004;96:546–53.10.1093/jnci/djh082Search in Google Scholar PubMed

60. Palmqvist R, Hallmans G, Rinaldi S, Biessy C, Stenling R, Riboli E, Kaaks R. Plasma insulin-like growth factor 1, insulin-like growth factor binding protein 3, and risk of colorectal cancer: a prospective study in northern Sweden. Gut 2002;50:642–6.10.1136/gut.50.5.642Search in Google Scholar PubMed PubMed Central

61. 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. 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 2007;121:368–76.10.1002/ijc.22697Search in Google Scholar PubMed

62. Pisani P. Hyper-insulinaemia and cancer, meta-analyses of epidemiological studies. Arch Physiol Biochem 2008;114:63–70.10.1080/13813450801954451Search in Google Scholar PubMed

63. 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. 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 2010;126:1702–15.10.1002/ijc.24927Search in Google Scholar PubMed

64. Giovannucci E, Michaud D. The role of obesity and related metabolic disturbances in cancers of the colon, prostate, and pancreas. Gastroenterology 2007;132:2208–25.10.1053/j.gastro.2007.03.050Search in Google Scholar PubMed

65. Stolzenberg-Solomon RZ, Graubard BI, Chari S, Limburg P, Taylor PR, Virtamo J, Albanes D. Insulin, glucose, insulin resistance, and pancreatic cancer in male smokers. J Am Med Assoc 2005;294:2872–8.10.1001/jama.294.22.2872Search in Google Scholar PubMed

66. Bell L, Considine R, editors. Leptin and obesity. New York: Springer, 2006 (Chapter 3).Search in Google Scholar

67. Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature 1994;372:425–32.10.1038/372425a0Search in Google Scholar PubMed

68. Garofalo C, Surmacz E. Leptin and cancer. J Cell Physiol 2006;207:12–22.10.1002/jcp.20472Search in Google Scholar PubMed

69. Slattery ML, Wolff RK. Leptin and colorectal cancer: an undefined link. Nat Clin Pract Gastroenterol Hepatol 2007;4:118–9.10.1038/ncpgasthep0743Search in Google Scholar PubMed

70. Stattin P, Lukanova A, Biessy C, Soderberg S, Palmqvist R, Kaaks R, Olsson T, Jellum E. Obesity and colon cancer: does leptin provide a link? Int J Cancer 2004;109:149–52.10.1002/ijc.11668Search in Google Scholar PubMed

71. Stattin P, Palmqvist R, Soderberg S, Biessy C, Ardnor B, Hallmans G, Kaaks R, Olsson T. Plasma leptin and colorectal cancer risk: a prospective study in Northern Sweden. Oncol Rep 2003;10:2015–21.10.3892/or.10.6.2015Search in Google Scholar

72. 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. Leptin is associated with an increased female colorectal cancer risk: a nested case-control study in Japan. Oncology 2005;68:454–61.10.1159/000086988Search in Google Scholar PubMed

73. 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. Adipokines linking obesity with colorectal cancer risk in postmenopausal women. Cancer Res 2012;72:3029–37.10.1158/0008-5472.CAN-11-2771Search in Google Scholar PubMed PubMed Central

74. 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. Leptin and soluble leptin receptor in risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition Cohort. Cancer Res 2012;72:5328–37.10.1158/0008-5472.CAN-12-0465Search in Google Scholar PubMed

75. Chandran M, Phillips SA, Ciaraldi T, Henry RR. Adiponectin: more than just another fat cell hormone? Diabetes Care 2003;26:2442–50.10.2337/diacare.26.8.2442Search in Google Scholar PubMed

76. 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. Adiponectin represses colon cancer cell proliferation via AdipoR1- and -R2-mediated AMPK activation. Mol Endocrinol 2010;24:1441–52.10.1210/me.2009-0498Search in Google Scholar PubMed PubMed Central

77. Wei EK, Giovannucci E, Fuchs CS, Willett WC, Mantzoros CS. Low plasma adiponectin levels and risk of colorectal cancer in men: a prospective study. J Natl Cancer Inst 2005;97:1688–94.10.1093/jnci/dji376Search in Google Scholar PubMed

78. 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. Total and high-molecular weight adiponectin and risk of colorectal cancer: the European Prospective Investigation into Cancer and Nutrition Study. Carcinogenesis 2012;33:1–8.10.1093/carcin/bgs133Search in Google Scholar PubMed PubMed Central

79. 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. Inflammatory and metabolic biomarkers and risk of liver and biliary tract cancer. Hepatology 2014;60:858–71.10.1002/hep.27016Search in Google Scholar PubMed PubMed Central

80. Key TJ, Allen NE, Verkasalo PK, Banks E. Energy balance and cancer: the role of sex hormones. Proc Nutr Soc 2001;60:81–9.10.1079/PNS200068Search in Google Scholar

81. 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. Postmenopausal serum androgens, oestrogens and breast cancer risk: the European Prospective Investigation into Cancer and Nutrition. Endocr Relat Cancer 2005;12:1071–82.10.1677/erc.1.01038Search in Google Scholar PubMed

82. Key T, Appleby P, Barnes I, Reeves G. Endogenous sex hormones and breast cancer in postmenopausal women: reanalysis of nine prospective studies. J Natl Cancer Inst 2002;94:606–16.10.1093/jnci/94.8.606Search in Google Scholar PubMed

83. Kaaks R, Lukanova A, Kurzer MS. Obesity, endogenous hormones, and endometrial cancer risk: a synthetic review. Cancer Epidemiol Biomarkers Prevent 2002;11:1531–43.Search in Google Scholar

84. 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. Circulating levels of sex steroid hormones and risk of endometrial cancer in postmenopausal women. Int J Cancer 2004;108:425–32.10.1002/ijc.11529Search in Google Scholar PubMed

85. Lashinger LM, Ford NA, Hursting SD. Interacting inflammatory and growth factor signals underlie the obesity-cancer link. J Nutr 2014;144:109–13.10.3945/jn.113.178533Search in Google Scholar PubMed PubMed Central

86. Kim CS, Park HS, Kawada T, Kim JH, Lim D, Hubbard NE, Kwon BS, Erickson KL, Yu R. Circulating levels of MCP-1 and IL-8 are elevated in human obese subjects and associated with obesity-related parameters. Int J Obes (Lond) 2006;30:1347–55.10.1038/sj.ijo.0803259Search in Google Scholar

87. Fain JN. Release of interleukins and other inflammatory cytokines by human adipose tissue is enhanced in obesity and primarily due to the nonfat cells. Vitam Horm 2006;74:443–77.10.1016/S0083-6729(06)74018-3Search in Google Scholar

88. Pendyala S, Neff LM, Suarez-Farinas M, Holt PR. Diet-induced weight loss reduces colorectal inflammation: implications for colorectal carcinogenesis. Am J Clin Nutr 2011;93:234–42.10.3945/ajcn.110.002683Search in Google Scholar PubMed PubMed Central

89. Coussens LM, Werb Z. Inflammation and cancer. Nature 2002;420:860–7.10.1038/nature01322Search in Google Scholar PubMed PubMed Central

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. 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 2010;172:407–18.10.1093/aje/kwq135Search in Google Scholar PubMed

91. Nimptsch K, Aleksandrova K, Boeing H, Janke J, Lee YA, Jenab M, Bueno-De-Mesquita BH, Jansen EH, Tsilidis KK, Trichopoulou A, Weiderpass E, Wu C, Overvad K, Tj Nneland 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, VanGuelpen B, Khaw KT, Wareham N, Peeters PH, Quiros JR, Garcia AV, Molina-Montes E, Dorronsoro M, Chirlaque MD, Gurrea AB, Key TJ, Duarte-Salles T, Stepien M, Gunter MJ, Riboli E, Pischon T. Association of CRP genetic variants with blood concentrations of C-reactive protein and colorectal cancer risk. Int J Cancer 2015;136:1181–92.10.1002/ijc.29086Search in Google Scholar PubMed PubMed Central

92. Paz-Filho G, Lim EL, Wong ML, Licinio J. Associations between adipokines and obesity-related cancer. Front Biosci 2011;16:1634–50.10.2741/3810Search in Google Scholar PubMed

93. Gago-Dominguez M, Castelao JE. Lipid peroxidation and renal cell carcinoma: further supportive evidence and new mechanistic insights. Free Radic Biol Med 2006;40:721–33.10.1016/j.freeradbiomed.2005.09.026Search in Google Scholar PubMed

Received: 2014-12-22
Accepted: 2015-2-16
Published Online: 2015-3-14
Published in Print: 2015-5-1

©2015 by De Gruyter

Downloaded on 19.4.2024 from https://www.degruyter.com/document/doi/10.1515/hmbci-2014-0043/html
Scroll to top button