Circulating Levels of Inflammatory and Metabolic Biomarkers and Risk of Esophageal Adenocarcinoma and Barrett Esophagus: Systematic Review and Meta-analysis

Abstract

Associations between circulating levels of obesity-related biomarkers and risk of esophageal adenocarcinoma and Barrett esophagus have been reported, but the results are inconsistent. A literature search until October 2018 in MEDLINE and EMBASE was performed. Pooled ORs with 95% confidence intervals (CI) were estimated for associations between 13 obesity-related inflammatory and metabolic biomarkers and risk of esophageal adenocarcinoma or Barrett esophagus using random effect meta-analyses. Among 7,641 studies, 19 were eligible for inclusion (12 cross-sectional, two nested case-control, and five cohort studies). Comparing the highest versus lowest categories of circulating biomarker levels, the pooled ORs were increased for leptin (OR, 1.68; 95% CI, 0.95-2.97 for Barrett esophagus), glucose (OR, 1.12; 95% CI, 1.03-1.22 for esophageal adenocar-cinoma), insulin (OR, 1.47; 95% CI, 1.06-2.00 for Barrett esophagus), C-reactive protein (CRP; OR, 2.06; 95% CI, 1.28-3.31 for esophageal adenocarcinoma), IL6 (OR, 1.50; 95% CI, 1.03-2.19 for esophageal adenocarcinoma), and soluble TNF receptor 2 (sTNFR-2; OR, 3.16; 95% CI, 1.76-5.65 for esophageal adenocarcinoma). No associations were identified for adiponectin, ghrelin, insulin-like growth factor 1, insulin-like growth factor-binding protein 3, triglycerides, IL8, or TNFa. Higher circulating levels of leptin, glucose, insulin, CRP, IL6, and sTNFR-2 may be associated with an increased risk of esophageal adenocarcinoma or Barrett esophagus. More prospective studies are required to identify biomarkers that can help select high-risk individuals for targeted prevention and early detection.

Matrix Metalloproteinases and Arterial Hypertension: Role of Oxidative Stress and Nitric Oxide in Vascular Functional and Structural Alterations

“…Several studies correlate circulating MMP concentrations and hypertension [ 85 , 86 , 87 , 88 ]. The activation of MMPs, especially MMP-2 and MMP-9, is directly involved in the vascular remodeling observed in hypertension since they are responsible for the degradation of extracellular matrix proteins, including elastin and collagen, and promote migration and phenotypic alterations of VSMC in resistance and conductance arteries [ 84 ].…”

“…In fact, mechanical forces and vasoconstrictor agonists have synergistic effects on the expression and activity of MMPs in hypertension [ 95 ]. Increases in both the MMP-2 and MMP-9 concentrations and activity assessed in the vessels or in the plasma of hypertensive animals or humans are apparently not accompanied by corresponding increases in the activity of endogenous MMP inhibitors (the tissue inhibitors of matrix metalloproteinases), thus revealing imbalanced MMP activity in hypertension [ 77 , 85 , 86 , 88 ]. In addition to increasing the degradation of the extracellular matrix components, these alterations stimulate vascular smooth muscle cells to switch from contractile to synthetic phenotypes, thus facilitating cell growth or migration [ 96 ].…”

Ghrelin and its role in gastrointestinal tract tumors (Review)

“…Upregulated expression of GHSR in BE compared with normal esophageal mucosa has also been reported ( 122 ). However, no correlation between ghrelin levels and the risk of BE was found in a recent meta-analysis compared with other adipokines, but only two studies approaching this interaction were considered ( 123 ).…”

Obesity as a risk factor for diseases of the digestive system

“…Важно отметить, что абдоминальное ожирение часто ассоциировано с ИР и гиперинсулинемией, которые являются общеизвестными факторами риска различных неоплазий человека [2,3,18,34]. Помимо этого, абдоминальное ожирение тесно связано с изменениями уровня циркулирующих цитокинов и пептидов, ассоциированных с риском развития ПБ и формированием АКП [3,26,[34][35][36]. [36].…”

“…Помимо этого, абдоминальное ожирение тесно связано с изменениями уровня циркулирующих цитокинов и пептидов, ассоциированных с риском развития ПБ и формированием АКП [3,26,[34][35][36]. [36]. Ожирение является фактором риска моторных нарушений пищевода [16,23].…”