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Leptin and soluble leptin receptor in risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition Cohort

Item Type:Article
Title:Leptin and soluble leptin receptor in risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition Cohort
Creators Name:Aleksandrova, K. and Boeing, H. and Jenab, M. and Bueno-de-Mesquita, H.B. and Jansen, E. and van Duijnhoven, F.J.B. and Rinaldi, S. and Fedirko, V. and Romieu, I. and Riboli, E. and Gunter, M.J. and Westphal, S. and Overvad, K. and Tjonneland, A. and Halkjaer, J. and Racine, A. and Boutron-Ruault, M.C. and Clavel-Chapelon, F. and Kaaks, R. and Lukanova, A. and Trichopoulou, A. and Lagiou, P. and Trichopoulos, D. and Mattiello, A. and Pala, V. and Palli, D. and Tumino, R. and Vineis, P. and Buckland, G. and Sanchez, M.J. and Amiano, P. and Huerta, J.M. and Barricarte, A. and Menendez, V. and Peeters, P.H. and Soederberg, S. and Palmqvist, R. and Allen, N.E. and Crowe, F.L. and Khaw, K.T. and Wareham, N. and Pischon, T.
Abstract:Leptin, a peptide hormone produced primarily by the adipocytes, is hypothesized to play a role in the pathogenesis of colorectal cancer (CRC). Soluble leptin receptor (sOB-R) may regulate leptin's physiological functions; however its relation to CRC risk is unknown. This study explored the association of leptin and sOB-R with risk of colorectal cancer in a prospective nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. 1,129 incident CRC cases (713 colon, 416 rectal) were matched within risk sets to 1,129 controls. Conditional logistic regression was used to calculate relative risks (RRs) and 95% confidence intervals (95% CIs). After multivariable adjustment including body mass index, waist circumference and baseline leptin concentrations, sOB-R was strongly inversely associated with CRC (RR comparing the highest quintile versus the lowest,0.55; 95% CI, 0.40-0.76; Ptrend = 0.0004) and colon cancer (RR, 0.42; 95% CI,0.28-0.63, Ptrend = 0.0001); whereas no association was seen for rectal cancer (RR adjusted for body mass index and waist circumference, 0.83; 95% CI, 0.48-1.44, Ptrend = 0.38). In contrast, leptin was not associated with risk of CRC (RR adjusted for body mass index and waist circumference, 0.85; 95% CI, 0.56-1.29, Ptrend = 0.23). Additional adjustments for circulating metabolic biomarkers did not attenuate these results. These novel findings suggest a strong inverse association between circulating sOB-R and CRC risk, independent of obesity measures, leptin concentrations and other metabolic biomarkers. Further research is needed to confirm the potentially important role of sOB-R in CRC pathogenesis.
Keywords:Obesity, Adipokines, Leptin, Soluble Leptin Receptor, Colorectal Cancer
Source:Cancer Research
ISSN:0008-5472
Publisher:American Association for Cancer Research
Volume:72
Number:20
Page Range:5328-5337
Date:15 October 2012
Official Publication:https://doi.org/10.1158/0008-5472.CAN-12-0465
PubMed:View item in PubMed

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