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Published in: Cancer Causes & Control 5/2009

01-07-2009 | Original Paper

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

Authors: Maria Dalamaga, Ilias Migdalis, Jessica L. Fargnoli, Evangelia Papadavid, Erica Bloom, Nicholas Mitsiades, Konstantinos Karmaniolas, Nicolaos Pelecanos, Sofia Tseleni-Balafouta, Amalia Dionyssiou-Asteriou, Christos S. Mantzoros

Published in: Cancer Causes & Control | Issue 5/2009

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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.
Literature
1.
2.
go back to reference Warshaw AL, Fernandez-del CC (1992) Pancreatic carcinoma. N Engl J Med 326:455–465PubMed Warshaw AL, Fernandez-del CC (1992) Pancreatic carcinoma. N Engl J Med 326:455–465PubMed
4.
go back to reference Freelove R, Walling AD (2006) Pancreatic cancer: diagnosis and management. Am Fam Physician 73:485–492PubMed Freelove R, Walling AD (2006) Pancreatic cancer: diagnosis and management. Am Fam Physician 73:485–492PubMed
6.
go back to reference 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 PubMedCrossRef 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 PubMedCrossRef
10.
go back to reference 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 PubMedCrossRef 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 PubMedCrossRef
12.
go back to reference 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 7:738–744PubMed 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 7:738–744PubMed
13.
16.
17.
go back to reference 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–s866PubMed 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–s866PubMed
22.
go back to reference 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 PubMedCrossRef 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 PubMedCrossRef
23.
go back to reference 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 97:1688–1694PubMedCrossRef 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 97:1688–1694PubMedCrossRef
26.
go back to reference 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 PubMedCrossRef 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 PubMedCrossRef
28.
go back to reference Greene FL, American Joint Committee on Cancer ACS (2002) AJCC cancer staging manual, 6th edn. Springer, New York, pp 157–165 Greene FL, American Joint Committee on Cancer ACS (2002) AJCC cancer staging manual, 6th edn. Springer, New York, pp 157–165
29.
go back to reference 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) 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.
go back to reference 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 PubMedCrossRef 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 PubMedCrossRef
31.
go back to reference 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 PubMedCrossRef 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 PubMedCrossRef
32.
go back to reference 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 PubMedCrossRef 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 PubMedCrossRef
34.
go back to reference 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 PubMedCrossRef 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 PubMedCrossRef
40.
go back to reference 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 PubMedCrossRef 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 PubMedCrossRef
Metadata
Title
Pancreatic cancer expresses adiponectin receptors and is associated with hypoleptinemia and hyperadiponectinemia: a case–control study
Authors
Maria Dalamaga
Ilias Migdalis
Jessica L. Fargnoli
Evangelia Papadavid
Erica Bloom
Nicholas Mitsiades
Konstantinos Karmaniolas
Nicolaos Pelecanos
Sofia Tseleni-Balafouta
Amalia Dionyssiou-Asteriou
Christos S. Mantzoros
Publication date
01-07-2009
Publisher
Springer Netherlands
Published in
Cancer Causes & Control / Issue 5/2009
Print ISSN: 0957-5243
Electronic ISSN: 1573-7225
DOI
https://doi.org/10.1007/s10552-008-9273-z

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