A prospective study of soluble receptor for advanced glycation end-products and colorectal cancer risk in postmenopausal women.
Receptor for advanced glycation end products (RAGE) expressed on adipocytes and immune cells can bind to ligand N(ε)-(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).



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.



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≥25kg/m(2), those with highest levels of sRAGE had significantly lower risk for CRC as compared to women with lowest levels of sRAGE (HRQ4versusQ1: 0.39; 95% CI: 0.17-0.91). This inverse association was not observed among women with BMI <25kg/m(2) (P value for interaction=0.01).



Among postmenopausal women, the RAGE pathway may be involved in obesity-related CRC.
Department of Medicine, Baylor College of Medicine, Houston, TX, USA; Center for Innovations in Quality, Effectiveness and Safety (IQuESt), Michael. E DeBakey VA Medical Center, Houston, TX, USA; Center for Translational Research on Inflammatory Diseases (CTRID), Michael E. DeBakey VA Medical Center, Houston, TX, USA.
Liang
L
Chen
Department of Medicine, Baylor College of Medicine, Houston, TX, USA; Center for Innovations in Quality, Effectiveness and Safety (IQuESt), Michael. E DeBakey VA Medical Center, Houston, TX, USA; Michael E. DeBakey VA Medical Center, Houston, TX, USA.
Zhigang
Z
Duan
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Lesley
L
Tinker
Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX, USA.
Haleh
H
Sangi-Haghpeykar
Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA.
Howard
H
Strickler
Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA.
Gloria Y F
GY
Ho
Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
Marc J
MJ
Gunter
Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA.
Thomas
T
Rohan
Department of Cancer Biology, Department of GI Medical Oncology, University of Texas, M. D. Anderson Cancer Center, Houston, TX, USA.
Craig
C
Logsdon
Department of Medicine, Baylor College of Medicine, Houston, TX, USA; Center for Innovations in Quality, Effectiveness and Safety (IQuESt), Michael. E DeBakey VA Medical Center, Houston, TX, USA; Texas Medical Center Digestive Disease Center, Houston, TX, USA; Dan L. Duncan Cancer Center at Baylor College of Medicine, Houston, TX, USA; Center for Translational Research on Inflammatory Diseases (CTRID), Michael E. DeBakey VA Medical Center, Houston, TX, USA; Michael E. DeBakey VA Medical Center, Houston, TX, USA.
Donna L
DL
White
Department of Medicine, Baylor College of Medicine, Houston, TX, USA; Center for Innovations in Quality, Effectiveness and Safety (IQuESt), Michael. E DeBakey VA Medical Center, Houston, TX, USA; Center for Translational Research on Inflammatory Diseases (CTRID), Michael E. DeBakey VA Medical Center, Houston, TX, USA.
Kathryn
K
Royse
Department of Medicine, Baylor College of Medicine, Houston, TX, USA; Center for Innovations in Quality, Effectiveness and Safety (IQuESt), Michael. E DeBakey VA Medical Center, Houston, TX, USA; Texas Medical Center Digestive Disease Center, Houston, TX, USA; Dan L. Duncan Cancer Center at Baylor College of Medicine, Houston, TX, USA; Michael E. DeBakey VA Medical Center, Houston, TX, USA.
Hashem B
HB
El-Serag
Department of Medicine, Baylor College of Medicine, Houston, TX, USA; Center for Innovations in Quality, Effectiveness and Safety (IQuESt), Michael. E DeBakey VA Medical Center, Houston, TX, USA; Texas Medical Center Digestive Disease Center, Houston, TX, USA; Dan L. Duncan Cancer Center at Baylor College of Medicine, Houston, TX, USA; Center for Translational Research on Inflammatory Diseases (CTRID), Michael E. DeBakey VA Medical Center, Houston, TX, USA; Michael E. DeBakey VA Medical Center, Houston, TX, USA. Electronic address: jiao@bcm.edu.
Li
L
Jiao
D000328:Adult; D000368:Aged; D015179:Colorectal Neoplasms / Q000209:etiology*; D005260:Female; D006801:Humans; D008875:Middle Aged; D017698:Postmenopause; D011446:Prospective Studies; D000067759:Receptor for Advanced Glycation End Products / Q000378:metabolism*; D012307:Risk Factors
D000067759:Receptor for Advanced Glycation End Products
Advanced glycation end-products; Body weight; Colorectal cancer; Epidemiology; N(ε)-(carboxymethyl)-lysine; Obesity; Pattern recognition receptors; Receptor for advanced glycosylation end-products; sRAGE