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

ABSTRACT: Receptor for advanced glycation end products (RAGE) expressed on adipocytes and immune cells can bind to ligand N(?)-(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).In 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.Average 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/m(2), 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/m(2) (P value for interaction=0.01).Among postmenopausal women, the RAGE pathway may be involved in obesity-related CRC.

SUBMITTER: Chen L

PROVIDER: S-EPMC4899266 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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

Chen Liang L Duan Zhigang Z Tinker Lesley L Sangi-Haghpeykar Haleh H Strickler Howard H Ho Gloria Y F GY Gunter Marc J MJ Rohan Thomas T Logsdon Craig C White Donna L DL Royse Kathryn K El-Serag Hashem B HB Jiao Li L

Cancer epidemiology 20160418

<h4>Objectives</h4>Receptor 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).<h4>Methods</h4>In a case-cohort study of the Women's Health Initiative Study, blood levels of CML-AG ...[more]

PMID: 27100837

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Project description:BackgroundSoluble receptor for advanced glycation end products (sRAGE) is a proposed emphysema and airflow obstruction biomarker; however, previous publications have shown inconsistent associations and only one study has investigate the association between sRAGE and emphysema. No cohorts have examined the association between sRAGE and progressive decline of lung function. There have also been no evaluation of assay compatibility, receiver operating characteristics, and little examination of the effect of genetic variability in non-white population. This manuscript addresses these deficiencies and introduces novel data from Pittsburgh COPD SCCOR and as well as novel work on airflow obstruction. A meta-analysis is used to quantify sRAGE associations with clinical phenotypes.MethodssRAGE was measured in four independent longitudinal cohorts on different analytic assays: COPDGene (n = 1443); SPIROMICS (n = 1623); ECLIPSE (n = 2349); Pittsburgh COPD SCCOR (n = 399). We constructed adjusted linear mixed models to determine associations of sRAGE with baseline and follow up forced expiratory volume at one second (FEV1) and emphysema by quantitative high-resolution CT lung density at the 15th percentile (adjusted for total lung capacity).ResultsLower plasma or serum sRAGE values were associated with a COPD diagnosis (P < 0.001), reduced FEV1 (P < 0.001), and emphysema severity (P < 0.001). In an inverse-variance weighted meta-analysis, one SD lower log10-transformed sRAGE was associated with 105 ± 22 mL lower FEV1 and 4.14 ± 0.55 g/L lower adjusted lung density. After adjusting for covariates, lower sRAGE at baseline was associated with greater FEV1 decline and emphysema progression only in the ECLIPSE cohort. Non-Hispanic white subjects carrying the rs2070600 minor allele (A) and non-Hispanic African Americans carrying the rs2071288 minor allele (A) had lower sRAGE measurements compare to those with the major allele, but their emphysema-sRAGE regression slopes were similar.ConclusionsLower blood sRAGE is associated with more severe airflow obstruction and emphysema, but associations with progression are inconsistent in the cohorts analyzed. In these cohorts, genotype influenced sRAGE measurements and strengthened variance modelling. Thus, genotype should be included in sRAGE evaluations.

Dataset Information

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

Publications

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

Similar Datasets

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