IJMEG Copyright © 2010-present. All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711
Int J Mol Epidemiol Genet 2012;3(4):294-304

Original Article
Plasma soluble receptor for advanced glycation end-products and risk of
colorectal adenoma

Li Jiao, Liang Chen, Abeer Alsarraj, David Ramsey, Zhigang Duan, Hashem B El-Serag

Houston VA Health Services Research Center of Excellence, Michael E. DeBakey VA Medical Center, Houston, TX,
USA; Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston,
TX, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, USA

Received August 31, 2012; Accepted October 22, 2012; Epub November 15, 2012; Published November 30, 2012

Abstract: Receptor for advanced glycation end products (RAGE) plays an important role in promoting chronic inflammation
with activation of NF-κB. Soluble form of RAGE (sRAGE) represents a naturally occurring competitive inhibitor
of RAGE-mediated events. In a colonoscopy-based case-control study, we examined the associations of plasma
levels of sRAGE, sTNF-αRI, sTNF-αRII, sIL-6R, EGF, IFNα2, G-CSF, MCP1, TNFβ, and VEGF with risk of colorectal
adenoma. We prospectively identified 158 cases with colorectal adenoma and 203 polyp-free controls who were
frequency-matched according to age, sex, race, and time of blood draw. Exposure information was collected using
a questionnaire and fasting plasma samples were obtained before the colonoscopy. We used Luminex bead-based
multiplex assays to determine level of biomarkers. Multivariate logistic regression model was used to estimate odds
ratio (OR) and its 95% confidence interval (CI). Cases had insignificant lower levels of sRAGE, and higher levels of
EGF and VEGF than controls. When the highest compared with the lowest category, the OR (95% CI) of colorectal
adenoma was 0.55 (0.31-0.96) (P trend = 0.03) for sRAGE and 1.75 (1.05-2.93) (P trend =0.04) for VEGF, adjusting
for age, smoking status, hypertension and type 2 diabetes. The inverse association between sRAGE and colorectal
adenoma was seen only among those without hypertension (P interaction = 0.02). An inverse association between
sRAGE and colorectal adenoma was in line with an inverse association between sRAGE and colorectal cancer previously
reported. This study supported the involvement of RAGE-NF-kB related inflammatory mechanism in the formation
of colorectal adenoma. (IJMEG1208004).

Keywords: Case-control, colorectal adenoma, risk, inflammation, sRAGE, VEGF, NF-kB

Address all correspondence to:
Dr. Li Jiao
Department of Medicine, Baylor College of Medicine
2002 Holcombe Blvd, 152, Houston, TX, 77030, USA.
Tel: +713-794-8631; Fax: +713-748-7359
E-mail: jiao@bcm.edu