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

Liang Chen, Zhigang Duan, Lesley Tinker, Haleh Sangi-Haghpeykar, Howard Strickler, Gloria Y F Ho, Marc J. Gunter, Thomas E. Rohan, Craig Logsdon, Donna L. White, Kathryn Royse, Hashem B. El-Serag, Li Jiao

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4 Scopus citations

Abstract

Objectives: Receptor for advanced glycation end products (RAGE) expressed on adipocytes and immune cells can bind to ligand Nε-(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). Methods: 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. Results: 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 ≥ 25 kg/m2, those with highest levels of sRAGE had significantly lower risk for CRC as compared to women with lowest levels of sRAGE (HRQ4 versus Q1: 0.39; 95% CI: 0.17-0.91). This inverse association was not observed among women with BMI 2 (P value for interaction = 0.01). Conclusions: Among postmenopausal women, the RAGE pathway may be involved in obesity-related CRC.

Original languageEnglish (US)
Pages (from-to)115-123
Number of pages9
JournalCancer Epidemiology
Volume42
DOIs
StatePublished - Jun 1 2016

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Keywords

  • Advanced glycation end-products
  • Body weight
  • Colorectal cancer
  • Epidemiology
  • N-(carboxymethyl)-lysine
  • Obesity
  • Pattern recognition receptors
  • Receptor for advanced glycosylation end-products
  • SRAGE

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Epidemiology

Cite this

Chen, L., Duan, Z., Tinker, L., Sangi-Haghpeykar, H., Strickler, H., Ho, G. Y. F., Gunter, M. J., Rohan, T. E., Logsdon, C., White, D. L., Royse, K., El-Serag, H. B., & Jiao, L. (2016). A prospective study of soluble receptor for advanced glycation end-products and colorectal cancer risk in postmenopausal women. Cancer Epidemiology, 42, 115-123. https://doi.org/10.1016/j.canep.2016.04.004