@article{3154113, title = "Leptin and Soluble Leptin Receptor in Risk of Colorectal Cancer in the European Prospective Investigation into Cancer and Nutrition Cohort", author = "Aleksandrova, Krasimira and Boeing, Heiner and Jenab, Mazda and and Bueno-de-Mesquita, H. Bas and Jansen, Eugene and van Duijnhoven, Franzel and J. B. and Rinaldi, Sabina and Fedirko, Veronika and Romieu, Isabelle and and Riboli, Elio and Gunter, Marc J. and Westphal, Sabine and Overvad, Kim and and Tjonneland, Anne and Halkjaer, Jytte and Racine, Antoine and and Boutron-Ruault, Marie-Christine and Clavel-Chapelon, Francoise and and Kaaks, Rudolf and Lukanova, Annekatrin and Trichopoulou, Antonia and and Lagiou, Pagona and Trichopoulos, Dimitrios and Mattiello, Amalia and and Pala, Valeria and Palli, Domenico and Tumino, Rosario and Vineis, Paolo and and Buckland, Genevieve and Sanchez, Maria-Jose and Amiano, Pilar and and Maria Huerta, Jose and Barricarte, Aurelio and Menendez, Virginia and and Peeters, Petra H. and Soderberg, Stefan and Palmqvist, Richard and and Allen, Naomi E. and Crowe, Francesca L. and Khaw, Kay-Tee and Wareham, and Nickolas and Pischon, Tobias", journal = "Current Cancer Research", year = "2012", volume = "72", number = "20", pages = "5328-5337", publisher = "AMER ASSOC CANCER RESEARCH", doi = "10.1158/0008-5472.CAN-12-0465", 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 physiologic functions; however its relation to CRC risk is unknown. This study explored the association of leptin and sOB-R with risk of CRC in a prospective nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. A total of 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 (RR) and 95% confidence intervals (CI). After multivariable adjustment including body mass index (BMI), waist circumference, and baseline leptin concentrations, sOB-R was strongly inversely associated with CRC (RR comparing the highest quintile vs. the lowest, 0.55; 95% CI, 0.40-0.76; P-trend = 0.0004) and colon cancer (RR, 0.42; 95% CI, 0.28-0.63, P-trend = 0.0001); whereas no association was seen for rectal cancer (RR adjusted for BMI and waist circumference, 0.83; 95% CI, 0.48-1.44, P-trend = 0.38). In contrast, leptin was not associated with risk of CRC (RR adjusted for BMI and waist circumference, 0.85; 95% CI, 0.56-1.29, P-trend = 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. Cancer Res; 72(20); 5328-37. (C) 2012 AACR." }