Novel Association Between Omentin And Risk Of Colorectal Cancer: Data From The EPIC-Potsdam Cohort

Krasimira ALEKSANDROVA, German Institute of Human Nutrition Potsdam-Rehbrücke, Germany
DI GIUSEPPE R. 2,3,4 , ISERMANN B. 5 , BIEMANN R. 5 , SCHULZE M. 3,6 , WITTENBECHER C. 3,6 , FRITSCHE A. 6,7 , LEHMANN R. 6,7 , MENZEL J. 2,3,8 , WEIKERT C. 2,8 , PISCHON T. 9 , BOEING H. 10

1 Nutrition, Immunity and Metabolism Start-up Lab, Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany
2 Research group cardiovascular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany
3 Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany
4 Institute of Epidemiology, Christian-Albrechts University of Kiel, Kiel, Germany
5 Department for Clinical Chemistry and Pathobiochemistry, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany
6 German Center of Diabetes Research (DZD), Germany
7 Department of Internal Medicine, Division of Endocrinology, Diabetology, Nephrology, Vascular Disease and Clinical Chemistry, University of Tübingen, Tübingen, Germany
8 Institute for Social Medicine, Epidemiology and Health Economics, Charité University Medical Center, Berlin, Germany
9 Molecular Epidemiology Group, Max Delbrueck Center for Molecular Medicine (MDC), Berlin-Buch, Germany
10 Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany

Background
Omentin - also known as intelectin-1 or intestinal lactoferrin receptor - is a novel biomarker described to exert metabolic, inflammatory and immune-related properties. Higher omentin concentrations have been particularly associated to inflammatory bowel disease, immune responses, and infection as potentially predisposing factors for the development of colorectal cancer [CRC]. However, population-based studies to evaluate the association of omentin with CRC risk are currently lacking. 
Methods
We investigated the association between circulating plasma omentin concentrations and risk of CRC in a case-cohort study comprising 251 incident CRC cases diagnosed over a mean follow-up time of 10.4 years and 2295 cancer-free individuals in the European Prospective Investigation into Cancer and Nutrition (EPIC) - Potsdam. Multivariable-adjusted hazard ratios as a measure of relative risks (RR-s) and 95% confidence intervals (CI-s) were computed using a Prentice modified Cox regression analysis.
Results
In a model adjusted for age, sex, education, dietary and lifestyle factors, body mass index (BMI) and waist circumference, higher omentin concentrations were associated with a higher CRC risk (RR for highest quartile versus the lowest = 2.31, 95% CI: 1.48 – 3.58; Ptrend <0.0001). The association was not altered after additional adjustment for inflammatory and metabolic biomarkers. Furthermore, addition of omentin to the multivariable-adjusted model statistically significantly improved risk assessment of CRC beyond established and suspected risk factors. When the analysis was stratified according to body mass index (BMI) status, the association was retained in participants with a BMI < 30 (RRcontinuously per doubling of omentin concentrations= 2.26; 95% CI: 1.57-3.27), but not in those with BMI ≥ 30  (RRcontinuously per doubling of omentin concentrations= 1.07; 95% CI: 0.63-1.83; Pinteraction= 0.005).  
Conclusions
In this prospective cohort study, higher circulating concentrations of omentin were associated with a higher CRC risk, independent of CRC risk factors, adiposity and metabolic biomarkers.