Skip to Main Content

An official website of the United States government

About this Publication
Circulating adipokine concentrations and risk of five obesity-related cancers: A Mendelian randomization study.
Pubmed ID
33038280 (View this publication on the PubMed website)
Digital Object Identifier
Int J Cancer. 2021 Apr 1; Volume 148 (Issue 7): Pages 1625-1636
Dimou NL, Papadimitriou N, Mariosa D, Johansson M, Brennan P, Peters U, Chanock SJ, Purdue M, Bishop DT, Gago-Dominquez M, Giles GG, Moreno V, Platz EA, Tangen CM, Wolk A, Zheng W, Wu X, Campbell PT, Giovannucci E, Lin Y, more CCFR, Endometrial Cancer Association Consortium, Gunter MJ, Murphy N
  • Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France.
  • Section of Genetics, International Agency for Research on Cancer, Lyon, France.
  • Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
  • Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
  • Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK.
  • Fundación Gallega de Medicina Genómica, Grupo de Genéticadel Cáncer, Instituto de Investigación Sanitaria de Santiago IDIS, Complejo Hospitalario Univ. Santiago-CHUS, SERGAS, Santiago de Compostela, Spain.
  • Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.
  • Oncology Data Analytics Program, Catalan Institute of Oncology-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.
  • Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
  • SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA. more
  • Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
  • Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, Tennessee, USA.
  • Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
  • Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, Georgia, USA.
  • Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts, USA.
  • Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.

Obesity is considered a chronic inflammatory state characterized by continued secretion of adipokines and cytokines. Experimental and epidemiological evidence indicates that circulating adipokines may be associated with the development of obesity-related cancers, but it is unclear if these associations are causal or confounded. We examined potential causal associations of specific adipokines (adiponectin, leptin, soluble leptin receptor [sOB-R] and plasminogen activator inhibitor-1 [PAI-1]) with five obesity-related cancers (colorectal, pancreatic, renal cell carcinoma [RCC], ovarian and endometrial) using Mendelian randomization (MR) methods. We used summary-level data from large genetic consortia for 114 530 cancer cases and 245 284 controls. We constructed genetic instruments using 18 genetic variants for adiponectin, 2 for leptin and 4 for both sOB-R and PAI-1 (P value for inclusion<5 × 10-8 ). Causal estimates were obtained using two-sample MR methods. In the inverse-variance weighted models, we found an inverse association between adiponectin and risk of colorectal cancer (odds ratio per 1 μg/mL increment in adiponectin concentration: 0.90 [95% confidence interval = 0.84-0.97]; P = .01); but, evidence of horizontal pleiotropy was detected and the association was not present when this was taken into consideration. No association was found for adiponectin and risks of pancreatic cancer, RCC, ovarian cancer and endometrial cancer. Leptin, sOB-R and PAI-1 were also similarly unrelated to risk of obesity-related cancers. Despite the large sample size, our MR analyses do not support causal effects of circulating adiponectin, leptin, sOB-R and PAI-1 concentrations on the development of five obesity-related cancers.

Related CDAS Studies
Related CDAS Projects