TY - JOUR TI - Leptin and Soluble Leptin Receptor in Risk of Colorectal Cancer in the European Prospective Investigation into Cancer and Nutrition Cohort AU - Aleksandrova, Krasimira AU - Boeing, Heiner AU - Jenab, Mazda and AU - Bueno-de-Mesquita, H. Bas AU - Jansen, Eugene AU - van Duijnhoven, Franzel AU - J. B. AU - Rinaldi, Sabina AU - Fedirko, Veronika AU - Romieu, Isabelle and AU - Riboli, Elio AU - Gunter, Marc J. AU - Westphal, Sabine AU - Overvad, Kim AU - and Tjonneland, Anne AU - Halkjaer, Jytte AU - Racine, Antoine and AU - Boutron-Ruault, Marie-Christine AU - Clavel-Chapelon, Francoise and AU - Kaaks, Rudolf AU - Lukanova, Annekatrin AU - Trichopoulou, Antonia and AU - Lagiou, Pagona AU - Trichopoulos, Dimitrios AU - Mattiello, Amalia and AU - Pala, Valeria AU - Palli, Domenico AU - Tumino, Rosario AU - Vineis, Paolo AU - and Buckland, Genevieve AU - Sanchez, Maria-Jose AU - Amiano, Pilar and AU - Maria Huerta, Jose AU - Barricarte, Aurelio AU - Menendez, Virginia and AU - Peeters, Petra H. AU - Soderberg, Stefan AU - Palmqvist, Richard and AU - Allen, Naomi E. AU - Crowe, Francesca L. AU - Khaw, Kay-Tee AU - Wareham, AU - Nickolas AU - Pischon, Tobias JO - Current Cancer Research PY - 2012 VL - 72 TODO - 20 SP - 5328-5337 PB - AMER ASSOC CANCER RESEARCH SN - null TODO - 10.1158/0008-5472.CAN-12-0465 TODO - null TODO - 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. ER -