TY - JOUR
T1 - Circulating adipokine concentrations and risk of five obesity-related cancers
T2 - A Mendelian randomization study
AU - CCFR, Endometrial Cancer Association Consortium
AU - Dimou, Niki L.
AU - Papadimitriou, Nikos
AU - Mariosa, Daniela
AU - Johansson, Mattias
AU - Brennan, Paul
AU - Peters, Ulrike
AU - Chanock, Stephen J.
AU - Purdue, Mark
AU - Bishop, D. Timothy
AU - Gago-Dominquez, Manuela
AU - Giles, Graham G.
AU - Moreno, Victor
AU - Platz, Elizabeth A.
AU - Tangen, Catherine M.
AU - Wolk, Alicja
AU - Zheng, Wei
AU - Wu, Xifeng
AU - Campbell, Peter T.
AU - Giovannucci, Edward
AU - Lin, Yi
AU - Gunter, Marc J.
AU - Murphy, Neil
N1 - Publisher Copyright:
© 2020 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of Union for International Cancer Control.
PY - 2021/4/1
Y1 - 2021/4/1
N2 - 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.
AB - 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.
KW - Mendelian randomization
KW - adiponectin
KW - cancer
KW - leptin
KW - plasminogen activator inhibitor
KW - soluble leptin receptor
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U2 - 10.1002/ijc.33338
DO - 10.1002/ijc.33338
M3 - Article
C2 - 33038280
AN - SCOPUS:85093957171
SN - 0020-7136
VL - 148
SP - 1625
EP - 1636
JO - International Journal of Cancer
JF - International Journal of Cancer
IS - 7
ER -