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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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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Colorectal Neoplasms
Prospective Studies
Confidence Intervals
Adipokines
Women's Health
Proportional Hazards Models
Adipocytes
Advanced Glycosylation End Product-Specific Receptor
Cohort Studies
Obesity
Biomarkers
Enzyme-Linked Immunosorbent Assay
N(6)-carboxymethyllysine
Ligands
Inflammation

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

A prospective study of soluble receptor for advanced glycation end-products and colorectal cancer risk in postmenopausal women. / Chen, Liang; Duan, Zhigang; Tinker, Lesley; Sangi-Haghpeykar, Haleh; Strickler, Howard; Ho, Gloria Y F; Gunter, Marc J.; Rohan, Thomas E.; Logsdon, Craig; White, Donna L.; Royse, Kathryn; El-Serag, Hashem B.; Jiao, Li.

In: Cancer Epidemiology, Vol. 42, 01.06.2016, p. 115-123.

Research output: Contribution to journalArticle

Chen, L, Duan, Z, Tinker, L, Sangi-Haghpeykar, H, Strickler, H, Ho, GYF, Gunter, MJ, Rohan, TE, Logsdon, C, White, DL, Royse, K, El-Serag, HB & Jiao, L 2016, 'A prospective study of soluble receptor for advanced glycation end-products and colorectal cancer risk in postmenopausal women', Cancer Epidemiology, vol. 42, pp. 115-123. https://doi.org/10.1016/j.canep.2016.04.004
Chen, Liang ; Duan, Zhigang ; Tinker, Lesley ; Sangi-Haghpeykar, Haleh ; Strickler, Howard ; Ho, Gloria Y F ; Gunter, Marc J. ; Rohan, Thomas E. ; Logsdon, Craig ; White, Donna L. ; Royse, Kathryn ; El-Serag, Hashem B. ; Jiao, Li. / A prospective study of soluble receptor for advanced glycation end-products and colorectal cancer risk in postmenopausal women. In: Cancer Epidemiology. 2016 ; Vol. 42. pp. 115-123.
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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.",
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AU - Chen, Liang

AU - Duan, Zhigang

AU - Tinker, Lesley

AU - Sangi-Haghpeykar, Haleh

AU - Strickler, Howard

AU - Ho, Gloria Y F

AU - Gunter, Marc J.

AU - Rohan, Thomas E.

AU - Logsdon, Craig

AU - White, Donna L.

AU - Royse, Kathryn

AU - El-Serag, Hashem B.

AU - Jiao, Li

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