A prospective study of soluble receptor for advanced glycation end-products and colorectal cancer risk in postmenopausal women

Publication date: June 2016
Source:Cancer Epidemiology, Volume 42
Author(s): Liang Chen, Zhigang Duan, Lesley Tinker, Haleh Sangi-Haghpeykar, Howard Strickler, Gloria Y.F. Ho, Marc J. Gunter, Thomas Rohan, Craig Logsdon, Donna L. White, Kathryn Royse, Hashem B. El-Serag, Li Jiao
ObjectivesReceptor for advanced glycation end products (RAGE) expressed on adipocytes and immune cells can bind to ligand N^ε-(carboxymethyl)-lysine (CML) and trigger dysregulation of adipokines and chronic inflammation. Soluble RAGE (sRAGE) mitigates the detrimental effect of RAGE. We examined the associations between circulating levels of CML-AGE and sRAGE and colorectal cancer (CRC).MethodsIn a case-cohort study of the Women's Health Initiative Study, blood levels of CML-AGE and sRAGE were measured using ELISA. We used multivariable Cox regression model to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of incident CRC in relation to quartiles (Q) of biomarker levels.ResultsAverage follow-up was 7.8 years for 444 cases and 805 subcohort members. In the subcohort, CML-AGE and sRAGE were inversely correlated with BMI (P values<0.0001). Levels of CML-AGE and sRAGE were not associated with CRC. In BMI-specific analysis, the association between sRAGE and CRC was observed. Among women with BMI≥25kg/m², those with highest levels of sRAGE had significantly lower risk for CRC as compared to women with lowest levels of sRAGE (HRQ4versusQ1: 0.39; 95% CI: 0.17–0.91). This inverse association was not observed among women with BMI <25kg/m² (P value for interaction=0.01).ConclusionsAmong postmenopausal women, the RAGE pathway may be involved in obesity-related CRC.



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