title: Circulating adiponectin is inversely associated with risk of thyroid cancer: in vivo and in vitro studies.
abstract: BACKGROUND
  Circulating adiponectin has been inversely associated with risk for several malignancies. Its association with thyroid cancer has not yet been evaluated.
  
  
  OBJECTIVE
  We measured circulating adiponectin levels in 175 thyroid carcinoma patients and 107 controls. We also examined the expression of adiponectin receptors (AdipoR1 and AdipoR2) using immunohistochemistry in 82 thyroid carcinoma tissues and using RT-qPCR in 40 human thyroid carcinoma tissues (32 papillary, six follicular/Hurthle, one anaplastic, one medullary), four normal human thyroid tissue specimens, and the BHP7 and SW579 thyroid cancer cell lines. We then utilized these thyroid cancer cell lines to investigate whether adiponectin could directly regulate cell cycle or apoptosis.
  
  
  RESULTS
  Thyroid cancer patients had lower circulating adiponectin levels than controls (17.00 ± 6.32 vs. 19.26 ± 6.28 μg/ml; P < 0.001). Subjects in the highest tertile of circulating adiponectin concentrations had significantly lower odds of developing any type of thyroid carcinoma (odds ratio = 0.29; 95% confidence interval, 0.16-0.55), or papillary thyroid carcinoma (odds ratio = 0.27; 95% confidence interval, 0.14-0.55), before and after adjustment for potential confounders. Both thyroid carcinoma cell lines and tissues expressed AdipoR1 and AdipoR2. Recombinant adiponectin did not exert a clinically significant direct effect on cell cycle, proliferation, or apoptosis in thyroid cancer cell lines in vitro.
  
  
  CONCLUSIONS
  Circulating adiponectin is independently and inversely associated with the risk of thyroid cancer. Human thyroid carcinomas and cell lines express adiponectin receptors. However, in the absence of a major direct effect of adiponectin on thyroid cancer cell lines in vitro, the negative association observed herein may be attributed to the metabolic effects of adiponectin.
authors.affiliation: Department of Internal Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Mitsiades
authors.forename: Kalliopi
authors.initials: K
authors.lastname: Pazaitou-Panayiotou
authors.forename: Konstantinos N
authors.initials: KN
authors.lastname: Aronis
authors.forename: Hyun-Seuk
authors.initials: HS
authors.lastname: Moon
authors.forename: John P
authors.initials: JP
authors.lastname: Chamberland
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Liu
authors.forename: Kalliope N
authors.initials: KN
authors.lastname: Diakopoulos
authors.forename: Vasileios
authors.initials: V
authors.lastname: Kyttaris
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Panagiotou
authors.forename: Geetha
authors.initials: G
authors.lastname: Mylvaganam
authors.forename: Sofia
authors.initials: S
authors.lastname: Tseleni-Balafouta
authors.forename: Christos S
authors.initials: CS
authors.lastname: Mantzoros
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000378:metabolism*; D000231:Adenocarcinoma, Papillary / Q000378:metabolism*; D052242:Adiponectin / Q000097:blood*; D000328:Adult; D005260:Female; D006801:Humans; D008297:Male; D054419:Receptors, Adiponectin / Q000378:metabolism; D012307:Risk Factors; D013961:Thyroid Gland / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000378:metabolism*
chemical_list: D052242:Adiponectin; D054419:Receptors, Adiponectin