A prospective study of soluble receptor for advanced glycation end products and adipokines in association with pancreatic cancer in postmenopausal women

Donna L. White, Ron C. Hoogeveen, Liang Chen, Peter Richardson, Milan Ravishankar, Preksha Shah, Lesley Tinker, Thomas Rohan, Eric A. Whitsel, Hashem B. El-Serag, Li Jiao

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

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 (aORQ4 vs. Q1= 0.70, 95% CI: 0.50–0.99). High MCP1 (aOR Q4 vs. Q1= 2.55, 95% CI: 1.41–4.61) and the higher CBS including MCP1, PAI1, and leptin (aORQ4 vs. Q1= 1.82, 95% CI = 1.04–3.18) were also associated with increased pancreatic cancer risk among women with BMI <25 kg/m2 (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.

Original languageEnglish (US)
Pages (from-to)2180-2191
Number of pages12
JournalCancer Medicine
Volume7
Issue number5
DOIs
StatePublished - May 2018

Keywords

  • Biomarker
  • CCL2
  • body weight
  • composite biomarker
  • pancreatic cancer
  • prospective
  • sRAGE

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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    White, D. L., Hoogeveen, R. C., Chen, L., Richardson, P., Ravishankar, M., Shah, P., Tinker, L., Rohan, T., Whitsel, E. A., El-Serag, H. B., & Jiao, L. (2018). A prospective study of soluble receptor for advanced glycation end products and adipokines in association with pancreatic cancer in postmenopausal women. Cancer Medicine, 7(5), 2180-2191. https://doi.org/10.1002/cam4.1426