title: Circulating adiponectin levels and expression of adiponectin receptors in relation to lung cancer: two case-control studies.
abstract: BACKGROUND
  Decreased circulating levels of adiponectin, an adipocyte-secreted hormone and endogenous insulin sensitizer, have been associated with several obesity-related malignancies. Thiazolidinedione administration, which increases adiponectin levels, decreases risk for lung cancer. Whether circulating adiponectin levels are associated with lung cancer and/or whether adiponectin receptors are expressed in lung cancer remains unknown.
  
  
  METHODS
  We conducted a case-control study of 85 patients with incidental, histologically confirmed lung cancer and 170 healthy controls matched by gender and age. In a separate study, archival lung specimens from 134 cancerous and 8 noncancerous tissues were examined for relative expression of adiponectin receptors AdipoR1 and AdipoR2 using immunohistochemistry.
  
  
  RESULTS
  Tobacco smoking, heavy alcohol intake and education were all associated with lung cancer risk, whereas serum adiponectin levels were not significantly different between cases and controls (multiple logistic regression, odds ratio per SD of adiponectin among controls: 1.13, 95% confidence interval: 0.64-2.02). Adiponectin levels were significantly lower (odds ratio: 0.25, 95% confidence interval: 0.10-0.78) among patients with advanced compared to those with limited disease stage. Expression of adiponectin receptors was apparent only in the cancerous lung tissue (64.2% AdipoR1 and 61.9% AdipoR2 in cancerous vs. 0% among noncancerous tissue). Specifically, AdipoR1 was expressed in all disease types, but no difference was noted with disease stage, whereas AdipoR2 was mainly expressed in the non-small cell carcinomas and more prominently in the advanced disease stage (80%).
  
  
  CONCLUSIONS
  Circulating adiponectin levels are not different in cases of this malignancy - which seems to be unrelated to obesity and insulin resistance - compared to their healthy controls, though hormonal levels were significantly lower in advanced versus limited lung cancer. Both adiponectin receptors were expressed in cancerous lung tissue, but not in normal control tissue and there was a differential expression by disease stage. These findings should be further explored, especially in the context of the recently reported protective effect of thiazolidinediones in diabetic patients with lung cancer.
authors.affiliation: Department of Hygiene and Epidemiology, University of Athens Medical School, Athens, Greece. epetrid@med.uoa.gr
authors.forename: Eleni T
authors.initials: ET
authors.lastname: Petridou
authors.forename: Nicholas
authors.initials: N
authors.lastname: Mitsiades
authors.forename: Spyros
authors.initials: S
authors.lastname: Gialamas
authors.forename: Miltiadis
authors.initials: M
authors.lastname: Angelopoulos
authors.forename: Alkistis
authors.initials: A
authors.lastname: Skalkidou
authors.forename: Nick
authors.initials: N
authors.lastname: Dessypris
authors.forename: Alex
authors.initials: A
authors.lastname: Hsi
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Lazaris
authors.forename: Aristidis
authors.initials: A
authors.lastname: Polyzos
authors.forename: Constantinos
authors.initials: C
authors.lastname: Syrigos
authors.forename: Aoife M
authors.initials: AM
authors.lastname: Brennan
authors.forename: Sofia
authors.initials: S
authors.lastname: Tseleni-Balafouta
authors.forename: Christos S
authors.initials: CS
authors.lastname: Mantzoros
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000453:epidemiology; D052242:Adiponectin / Q000097:blood*; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D015992:Body Mass Index; D018288:Carcinoma, Small Cell / Q000097:blood / Q000453:epidemiology; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007333:Insulin Resistance; D008168:Lung / Q000378:metabolism*; D008175:Lung Neoplasms / Q000097:blood* / Q000453:epidemiology; D008297:Male; D008654:Mesothelioma / Q000097:blood / Q000453:epidemiology; D008875:Middle Aged; D009765:Obesity; D054419:Receptors, Adiponectin / Q000097:blood*; D012307:Risk Factors
chemical_list: C475420:ADIPOR2 protein, human; D052242:Adiponectin; D014408:Biomarkers, Tumor; D054419:Receptors, Adiponectin