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White DL, Hoogeveen RC, Chen L, Richardson P, Ravishankar M, Shah P, Tinker L, Rohan T, Whitsel EA, El-Serag HB, Jiao L. A prospective study of soluble receptor for advanced glycation end products and adipokines in association with pancreatic cancer in postmenopausal women. Cancer medicine. 2018 May 1; 7(5):2180-2191.
Advanced glycation end products (AGEs) dysregulate adipokines and induce inflammation by binding to their adipocyte receptor (RAGE). Soluble RAGE (sRAGE) prevents AGEs/RAGE signaling. We performed a nested case-control study of the association between sRAGE, adipokines, and incident pancreatic cancer risk in the prospective Women's Health Initiative Study. We individually matched controls (n = 802) to cases (n = 472) on age, race, and blood draw date. We evaluated serum concentrations of sRAGE, adiponectin, leptin, monocyte chemotactic protein 1 (MCP1), and plasminogen activator inhibitor-1 (PAI1) using immunoassay. We used conditional logistic regression model to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for pancreatic cancer over biomarker quartiles (Q1-Q4). We used principal component analysis to create two composite biomarkers and performed a confirmatory factor analysis to examine the association between composite biomarker scores (CBS) and pancreatic cancer risk. Baseline serum sRAGE concentrations were inversely associated with pancreatic cancer risk (aOR = 0.70, 95% CI: 0.50-0.99). High MCP1 (aOR = 2.55, 95% CI: 1.41-4.61) and the higher CBS including MCP1, PAI1, and leptin (aOR = 1.82, 95% CI = 1.04-3.18) were also associated with increased pancreatic cancer risk among women with BMI < 25 kg/m (P values for interaction < 0.05). We found an inverse association between prediagnostic sRAGE concentrations and risk of incident pancreatic cancer in postmenopausal women. A proinflammatory CBS was associated with increased risk only in women with normal BMI. MCP1 was not modulated by sRAGE.