Abstract
Abstract Background: Receptor for advanced glycation end-products (RAGE) plays an important role in promoting chronic inflammation. Soluble form of RAGE (sRAGE) represents a naturally occurring competitive inhibitor of RAGE-mediated events. We previously found that sRAGE was inversely associated with risk of colorectal cancer in a prospective study among male smokers. However, the relationship between sRAGE and colorectal polyps has not been examined. Methods: In this hospital-based case-control study, we examined the association of plasma levels of sRAGE, along with four soluble receptors of inflammatory cytokines including tumor necrosis factor-α receptor I and II (TNF-αRI and TNF-αRII) and interleukin-6 receptor (IL-6R), with risk of colorectal polyps in general and colon adenoma specifically. During 2008- 2010, we identified men with pathologically confirmed colorectal polyp as cases and those with no polyps as controls among prospectively enrolled men who underwent screening colonoscopy. We excluded men with clinical confirmed type 2 diabetes and serum creatinine > 1.2 mg/dl. A total of 73 cases (50 with adenoma) and 62 controls were included in the present analysis. Cases and controls were frequency-matched according to age and race. Plasma samples were obtained at time of colonoscopy and exposure information was collected using interviewer-administered questionnaire. We used multiplex-ELISA to determine plasma level of serological biomarkers. Multivariate logistic regression model adjusting for age, race, smoking status and body mass index was used to estimate odds ratio (OR) and its 95% confidence interval (CI). Results: The median age was 61.0 years for both groups. sRAGE had no correlation with TNF-RI, TNF-RII, and sIL-6R levels among controls. Cases had significantly lower levels of sRAGE than controls (P value for rank sum test = 0.01). When highest compared with lowest tertile of sRAGE, the OR (95% CI) was 0.28 (0.11-0.73) (P trend = 0.004) for colorectal polyps and 0.22 (0.06-0.85) (P trend =0.001) for adenoma. sIL-6R had statistically non-significant positive association with risk of colorectal polyps (OR = 1.65, 95% CI = 0.63-4.32, P trend = 0.30) and adenoma (OR = 2.49, 95% CI = 0.81 -7.60, P trend = 0.09) respectively. Plasma levels of TNF-RI and TNF-RII had no association with risk of colorectal polyps. Conclusion: This study suggests a protective role of sRAGE, an anti-inflammatory factor, for precursor lesions of colorectal cancer in men. Our finding is in line with the previous study that showed an inverse association between sRAGE and colorectal cancer. As a modifiable target, the role of sRAGE in colorectal carcinogenesis deserves further investigation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4638. doi:10.1158/1538-7445.AM2011-4638
Published Version
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