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Pancreatic cancer expresses adiponectin receptors and is associated with hypoleptinemia and hyperadiponectinemia: a case–control study

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Abstract

Obesity and insulin resistance have been implicated in the etiology of pancreatic cancer (PC). Whether adiponectin and/or leptin, two adipocyte-secreted hormones important in metabolic regulation, are associated with PC pathogenesis and whether adiponectin receptors are expressed in PC remains unknown. In a hospital-based case–control study, we studied 81 cases with incident, histologically confirmed PC and 81 controls matched on gender and age between 2000 and 2007 to investigate the role of adiponectin and leptin adjusting for risk factors linked to PC. In a separate study, we also studied for the first time whether adiponectin receptors 1 and 2 are expressed in PC by studying 16 PC tumor tissue samples which were analyzed using immunohistochemistry. When subjects were divided into control-defined quartiles of adiponectin and leptin, lower leptin but higher adiponectin levels were associated with PC (p = 0.001 and p = 0.05 respectively) before and after controlling for age, gender, BMI, smoking status, alcohol consumption, history of diabetes, and family history of pancreatic cancer. Of the PC tumor tissue samples analyzed, 87.5% had positive or strong positive expression of AdipoR1 and 93.7% had positive or strong positive expression of AdipoR2. Further prospective studies are needed to determine whether the elevated adiponectin and low leptin levels reported in this study reflect compensatory changes during PC progression and thus can be used as markers for PC or whether they are causally implicated in PC.

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References

  1. Jemal A, Tiwari RC, Murray T et al (2004) Cancer statistics, 2004. CA Cancer J Clin 54:8–29

    Article  PubMed  Google Scholar 

  2. Warshaw AL, Fernandez-del CC (1992) Pancreatic carcinoma. N Engl J Med 326:455–465

    PubMed  CAS  Google Scholar 

  3. Schima W, Ba-Ssalamah A, Kolblinger C, Kulinna-Cosentini C, Puespoek A, Gotzinger P (2007) Pancreatic adenocarcinoma. Eur Radiol 17:638–649. doi:10.1007/s00330-006-0435-7

    Article  PubMed  Google Scholar 

  4. Freelove R, Walling AD (2006) Pancreatic cancer: diagnosis and management. Am Fam Physician 73:485–492

    PubMed  Google Scholar 

  5. Fuchs CS, Colditz GA, Stampfer MJ et al (1996) A prospective study of cigarette smoking and the risk of pancreatic cancer. Arch Intern Med 156:2255–2260. doi:10.1001/archinte.156.19.2255

    Article  PubMed  CAS  Google Scholar 

  6. Kalapothaki V, Tzonou A, Hsieh CC, Toupadaki N, Karakatsani A, Trichopoulos D (1993) Tobacco, ethanol, coffee, pancreatitis, diabetes mellitus, and cholelithiasis as risk factors for pancreatic carcinoma. Cancer Causes Control 4:375–382. doi:10.1007/BF00051341

    Article  PubMed  CAS  Google Scholar 

  7. Everhart J, Wright D (1995) Diabetes mellitus as a risk factor for pancreatic cancer. A meta-analysis. JAMA 273:1605–1609. doi:10.1001/jama.273.20.1605

    Article  PubMed  CAS  Google Scholar 

  8. Berrington de Gonzalez A, Sweetland S, Spencer E (2003) A meta-analysis of obesity and the risk of pancreatic cancer. Br J Cancer 89:519–523. doi:10.1038/sj.bjc.6601140

    Article  PubMed  CAS  Google Scholar 

  9. Larsson SC, Orsini N, Wolk A (2007) Body mass index and pancreatic cancer risk: a meta-analysis of prospective studies. Int J Cancer 120:1993–1998. doi:10.1002/ijc.22535

    Article  PubMed  CAS  Google Scholar 

  10. Hanley AJ, Johnson KC, Villeneuve PJ, Mao Y (2001) Physical activity, anthropometric factors and risk of pancreatic cancer: results from the Canadian enhanced cancer surveillance system. Int J Cancer 94:140–147. doi:10.1002/ijc.1446

    Article  PubMed  CAS  Google Scholar 

  11. Stolzenberg-Solomon RZ, Graubard BI et al (2005) Insulin, glucose, insulin resistance, and pancreatic cancer in male smokers. JAMA 294:2872–2878. doi:10.1001/jama.294.22.2872

    Article  PubMed  CAS  Google Scholar 

  12. Tersmette AC, Petersen GM, Offerhaus GJ et al (2001) Increased risk of incident pancreatic cancer among first-degree relatives of patients with familial pancreatic cancer. Clin Cancer Res 7:738–744

    PubMed  CAS  Google Scholar 

  13. Lowenfels AB, Maisonneuve P, DiMagno EP et al (1997) Hereditary pancreatitis and the risk of pancreatic cancer. International Hereditary Pancreatitis Study Group. J Natl Cancer Inst 89:442–446. doi:10.1093/jnci/89.6.442

    Article  PubMed  CAS  Google Scholar 

  14. Matarese G, Mantzoros C, La Cava A (2007) Leptin and adipocytokines: bridging the gap between immunity and atherosclerosis. Curr Pharm Des 13:3676–3680. doi:10.2174/138161207783018635

    Article  PubMed  CAS  Google Scholar 

  15. Kershaw EE, Flier JS (2004) Adipose tissue as an endocrine organ. J Clin Endocrinol Metab 89:2548–2556. doi:10.1210/jc.2004-0395

    Article  PubMed  CAS  Google Scholar 

  16. Brennan AM, Mantzoros CS (2006) Drug Insight: the role of leptin in human physiology and pathophysiology–emerging clinical applications. Nat Clin Pract Endocrinol Metab 2:318–327. doi:10.1038/ncpendmet0196

    Article  PubMed  CAS  Google Scholar 

  17. Barb D, Williams CJ, Neuwirth AK, Mantzoros CS (2007) Adiponectin in relation to malignancies: a review of existing basic research and clinical evidence. Am J Clin Nutr 86:s858–s866

    PubMed  Google Scholar 

  18. Mantzoros C, Petridou E, Dessypris N et al (2004) Adiponectin and breast cancer risk. J Clin Endocrinol Metab 89:1102–1107. doi:10.1210/jc.2003-031804

    Article  PubMed  CAS  Google Scholar 

  19. Dal Maso L, Augustin LS, Karalis A et al (2004) Circulating adiponectin and endometrial cancer risk. J Clin Endocrinol Metab 89:1160–1163. doi:10.1210/jc.2003-031716

    Article  PubMed  CAS  Google Scholar 

  20. Goktas S, Yilmaz MI, Caglar K, Sonmez A, Kilic S, Bedir S (2005) Prostate cancer and adiponectin. Urology 65:1168–1172. doi:10.1016/j.urology.2004.12.053

    Article  PubMed  Google Scholar 

  21. Ishikawa M, Kitayama J, Kazama S, Hiramatsu T, Hatano K, Nagawa H (2005) Plasma adiponectin and gastric cancer. Clin Cancer Res 11:466–472. doi:10.1158/1078-0432.CCR-04-1453

    Article  PubMed  CAS  Google Scholar 

  22. Spyridopoulos TN, Petridou ET, Skalkidou A, Dessypris N, Chrousos GP, Mantzoros CS (2007) Low adiponectin levels are associated with renal cell carcinoma: a case-control study. Int J Cancer 120:1573–1578. doi:10.1002/ijc.22526

    Article  PubMed  CAS  Google Scholar 

  23. Wei EK, Giovannucci E, Fuchs CS, Willett WC, Mantzoros CS (2005) Low plasma adiponectin levels and risk of colorectal cancer in men: a prospective study. J Natl Cancer Inst 97:1688–1694

    Article  PubMed  CAS  Google Scholar 

  24. Mantzoros CS, Trakatelli M, Gogas H et al (2007) Circulating adiponectin levels in relation to melanoma: a case-control study. Eur J Cancer 43:1430–1436. doi:10.1016/j.ejca.2007.03.026

    Article  PubMed  CAS  Google Scholar 

  25. Petridou E, Mantzoros CS, Dessypris N, Dikalioti SK, Trichopoulos D (2006) Adiponectin in relation to childhood myeloblastic leukaemia. Br J Cancer 94:156–160. doi:10.1038/sj.bjc.6602896

    Article  PubMed  CAS  Google Scholar 

  26. Dalamaga M, Nikolaidou A, Karmaniolas K et al (2007) Circulating adiponectin and leptin in relation to myelodysplastic syndrome: a case-control study. Oncology 73(1–2):26–32. doi:10.1159/000120995

    Article  PubMed  Google Scholar 

  27. Chang MC, Chang YT, Su TC et al (2007) Adiponectin as a potential differential marker to distinguish pancreatic cancer and chronic pancreatitis. Pancreas 35:16–21. doi:10.1097/MPA.0b013e3180547709

    Article  PubMed  CAS  Google Scholar 

  28. Greene FL, American Joint Committee on Cancer ACS (2002) AJCC cancer staging manual, 6th edn. Springer, New York, pp 157–165

    Google Scholar 

  29. Stolzenberg-Solomon RZ, Weinstein S, Pollak M et al (2008) Prediagnostic adiponectin concentrations and pancreatic cancer risk in male smokers. Am J Epidemiol (in press)

  30. Stolzenberg-Solomon RZ, Pietinen P, Taylor PR, Virtamo J, Albanes D (2002) A prospective study of medical conditions, anthropometry, physical activity, and pancreatic cancer in male smokers (Finland). Cancer Causes Control 13:417–426. doi:10.1023/A:1015729615148

    Article  PubMed  Google Scholar 

  31. Costacou T, Zgibor JC, Evans RW et al (2005) The prospective association between adiponectin and coronary artery disease among individuals with type 1 diabetes. The Pittsburgh epidemiology of diabetes complications study. Diabetologia 48:41–48. doi:10.1007/s00125-004-1597-y

    Article  PubMed  CAS  Google Scholar 

  32. Fryzek JP, Schenk M, Kinnard M, Greenson JK, Garabrant DH (2005) The association of body mass index and pancreatic cancer in residents of southeastern Michigan, 1996–1999. Am J Epidemiol 162:222–228. doi:10.1093/aje/kwi183

    Article  PubMed  Google Scholar 

  33. Michaud DS, Wolpin B, Giovannucci E et al (2007) Prediagnostic plasma C-peptide and pancreatic cancer risk in men and women. Cancer Epidemiol Biomarkers Prev 16:2101–2109. doi:10.1158/1055-9965.EPI-07-0182

    Article  PubMed  CAS  Google Scholar 

  34. Lin Y, Tamakoshi A, Kikuchi S et al (2004) Serum insulin-like growth factor-I, insulin-like growth factor binding protein-3, and the risk of pancreatic cancer death. Int J Cancer 110:584–588. doi:10.1002/ijc.20147

    Article  PubMed  CAS  Google Scholar 

  35. Pilz S, Mangge H, Wellnitz B et al (2006) Adiponectin and mortality in patients undergoing coronary angiography. J Clin Endocrinol Metab 91:4277–4286. doi:10.1210/jc.2006-0836

    Article  PubMed  CAS  Google Scholar 

  36. Kistorp C, Faber J, Galatius S et al (2005) Plasma adiponectin, body mass index, and mortality in patients with chronic heart failure. Circulation 112:1756–1762. doi:10.1161/CIRCULATIONAHA.104.530972

    Article  PubMed  CAS  Google Scholar 

  37. Menon V, Li L, Wang X et al (2006) Adiponectin and mortality in patients with chronic kidney disease. J Am Soc Nephrol 17:2599–2606. doi:10.1681/ASN.2006040331

    Article  PubMed  CAS  Google Scholar 

  38. Wolf I, Sadetzki S, Kanety H et al (2006) Adiponectin, ghrelin, and leptin in cancer cachexia in breast and colon cancer patients. Cancer 106:966–973. doi:10.1002/cncr.21690

    Article  PubMed  CAS  Google Scholar 

  39. Brichard SM, Delporte ML, Lambert M (2003) Adipocytokines in anorexia nervosa: a review focusing on leptin and adiponectin. Horm Metab Res 35:337–342. doi:10.1055/s-2003-41353

    Article  PubMed  CAS  Google Scholar 

  40. Barber MD, McMillan DC, Wallace AM, Ross JA, Preston T, Fearon KC (2004) The response of leptin, interleukin-6 and fat oxidation to feeding in weight-losing patients with pancreatic cancer. Br J Cancer 90:1129–1132. doi:10.1038/sj.bjc.6601712

    Article  PubMed  CAS  Google Scholar 

  41. Brown DR, Berkowitz DE, Breslow MJ (2001) Weight loss is not associated with hyperleptinemia in humans with pancreatic cancer. J Clin Endocrinol Metab 86:162–166. doi:10.1210/jc.86.1.162

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

Financial support: Grants DK081913, DK79929, and DK 58785 from the NIH.

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Correspondence to Christos S. Mantzoros.

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Dalamaga, M., Migdalis, I., Fargnoli, J.L. et al. Pancreatic cancer expresses adiponectin receptors and is associated with hypoleptinemia and hyperadiponectinemia: a case–control study. Cancer Causes Control 20, 625–633 (2009). https://doi.org/10.1007/s10552-008-9273-z

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  • DOI: https://doi.org/10.1007/s10552-008-9273-z

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