1. Circulating adipokine concentrations and risk of five obesity-related cancers: A Mendelian randomization study.
- Author
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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, Gunter MJ, and Murphy N
- Subjects
- Adiponectin blood, Adiponectin genetics, Body Mass Index, Carcinoma, Renal Cell complications, Colorectal Neoplasms complications, Correlation of Data, Endometrial Neoplasms complications, Female, Genome-Wide Association Study, Humans, Leptin blood, Leptin genetics, Mendelian Randomization Analysis, Ovarian Neoplasms complications, Pancreatic Neoplasms complications, Plasminogen Activator Inhibitor 1 blood, Plasminogen Activator Inhibitor 1 genetics, Principal Component Analysis, Receptors, Leptin blood, Receptors, Leptin genetics, Risk Factors, Adipokines blood, Adipokines genetics, Carcinoma, Renal Cell genetics, Colorectal Neoplasms genetics, Endometrial Neoplasms genetics, Obesity complications, Ovarian Neoplasms genetics, Pancreatic Neoplasms genetics
- Abstract
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., (© 2020 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of Union for International Cancer Control.)- Published
- 2021
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