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Circulating adipokine concentrations and risk of five obesity-related cancers: A Mendelian randomization study.
- Source :
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International journal of cancer [Int J Cancer] 2021 Apr 01; Vol. 148 (7), pp. 1625-1636. Date of Electronic Publication: 2020 Oct 26. - Publication Year :
- 2021
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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 <superscript>-8</superscript> ). 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.<br /> (© 2020 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of Union for International Cancer Control.)
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 1097-0215
- Volume :
- 148
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- International journal of cancer
- Publication Type :
- Academic Journal
- Accession number :
- 33038280
- Full Text :
- https://doi.org/10.1002/ijc.33338