Cases (n = 50) were matched with two randomly selected controls (n = 100). Conditional logistic regression models were used to investigate the associations between pre-diagnostic levels of hs-CRP, adiponectin, leptin, soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular sellectchem adhesion molecule-1, E-selectin, monocyte chemoattractant protein-1 and colorectal cancer risk. Area under the receiver operating curves (AUC) and relative integrated discrimination improvement (RIDI) statistics were used to assess the discriminatory potential of the models. RESULTS: Plasma adiponectin level was associated with decreased colorectal cancer risk (P for linear trend = 0.03). Quartiles of sVCAM-1 were associated with increased colorectal cancer risk (P for linear trend = 0.02).
No association was observed with any of the other biomarkers. Compared to standard models with known risk factors, those including both adiponectin and sVCAM-1 had substantially improved performance for colorectal cancer risk prediction (P for AUC improvement = 0.01, RIDI = 26.5%). CONCLUSION: These results suggest that pre-diagnostic plasma adiponectin and sVCAM-1 levels are associated with decreased and increased colorectal cancer risk, respectively. These relationships must be confirmed in large validation studies. Keywords: Colorectal cancer, Adiponectin, Soluble vascular cell adhesion molecule-1, Nested case-control study, Prospective study INTRODUCTION Colorectal cancer is the third most frequently diagnosed cancer worldwide, accounting for more than one million cases and 600 000 deaths every year[1].
The identification of pre-diagnostic biomarkers associated with subsequent colorectal cancer risk is a key challenge. Markers of adiposity, endothelial adhesion, and inflammation may be suitable candidates[2-5]. Adipose tissue is an endocrine organ that produces adipokines and plays a critical role in the regulation of inflammatory processes[6]. Leptin reflects body fat storage and acts as a pro-inflammatory adipokine. Conversely, adiponectin production is decreased in obesity and generally has anti-inflammatory properties. Adhesion molecules such as E-selectin, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and the chemokine monocyte chemoattractant protein-1 (MCP-1) are important in cell-cell and cell-basement membrane interactions.
They are also intimately involved in inflammatory reactions[7]. C-reactive protein (CRP) is a widely used systemic biomarker for diagnosing acute and chronic inflammation[8]. Previous cross-sectional studies suggest the potential involvement of these biomarkers in colorectal carcinogenesis, with higher blood levels of CRP[9], leptin[10], soluble adhesion AV-951 molecules[11,12], and lower levels of adiponectin[10,13] observed in patients with colorectal cancer compared to controls.