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The Association between Glyceraldehyde-Derived Advanced Glycation End-Products and Colorectal Cancer Risk

Kong SY 1 , Takeuchi M 2 , Hyogo H 3 , McKeown-Eyssen G 4 , Yamagishi S 5 , Chayama K 3 Show all authors , O'Brien PJ 6 , Ferrari P 1 , Overvad K 7 , Olsen A 8 , Tjønneland A 8 , Boutron-Ruault MC 9 , Bastide N 9 , Carbonnel F 10 , Kühn T 11 , Kaaks R 11 , Boeing H 12 , Aleksandrova K 12 , Trichopoulou A 13 , Lagiou P 14 , Vasilopoulou E 15 , Masala G 16 , Pala V 17 , Santucci De Magistris M 18 , Tumino R 19 , Naccarati A 20 , Bueno-de-Mesquita HB 21 , Peeters PH 22 , Weiderpass E 23 , Quirós JR 24 , Jakszyn P 25 , Sánchez MJ 26 , Dorronsoro M 27 , Gavrila D 28 , Ardanaz E 29 , Rutegård M 30 , Nyström H 30 , Wareham NJ 31 , Khaw KT 32 , Bradbury KE 33 , Romieu I 1 , Freisling H 1 , Stavropoulou F 1 , Gunter MJ 34 , Cross AJ 34 , Riboli E 34 , Jenab M 35 , Bruce WR 36

Affiliations 

  • 1 Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon, France
  • 2 Department of Advanced Medicine, Medical Research Institute, Kanazawa Medical University, Kanazawa, Japan
  • 3 Department of Gastroenterology and Metabolism, Hiroshima University Hospital, Hiroshima, Japan
  • 4 Dalla Lana School of Public Health, University of Toronto, Toronto, Canada
  • 5 Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan
  • 6 Department of Pharmacology, University of Toronto, Toronto, Canada
  • 7 Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark
  • 8 Diet, Genes, and Environment, Danish Cancer Society Research Center, Copenhagen, Denmark
  • 9 Lifestyle, Genes, and Health: Trans-generational Integrated Epidemiology, EMT, Institute Gustave Roussy, Villejuif, France
  • 10 Lifestyle, Genes, and Health: Trans-generational Integrated Epidemiology, EMT, Institute Gustave Roussy, Villejuif, France. Service d'hépato-gastroentérologie, Hôpital Bicetre, Le Kremlin-Bicêtre Cedex, France
  • 11 Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
  • 12 Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany
  • 13 Hellenic Health Foundation, Athens, Greece. Department of Hygiene, Epidemiology, and Medical Statistics, University of Athens Medical School, Athens, Greece. Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece
  • 14 Department of Hygiene, Epidemiology, and Medical Statistics, University of Athens Medical School, Athens, Greece. Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece. Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts
  • 15 Department of Hygiene, Epidemiology, and Medical Statistics, University of Athens Medical School, Athens, Greece
  • 16 Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute - ISPO, Florence, Italy
  • 17 Epidemiology and Prevention Unit, IRCCS Foundation, National Cancer Institute, Milan, Italy
  • 18 Azienda Ospedaliera Universitaria (AOU) Federico II, Naples, Italy
  • 19 Cancer Registry and Histopathology Unit, "Civic - MP Arezzo" Hospital, Ragusa, Italy
  • 20 Human Genetics Foundation, Torino Molecular and Genetic Epidemiology Unit, Torino, Italy
  • 21 Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and Environment (RIVM), Bilthoven, the Netherlands. Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, the Netherlands. Department of Epidemiology and Biostatistics, The School of Public Health, Imperil College London, London, United Kingdom. Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
  • 22 Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands. MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatics, School of Public Health, Imperial College, London, United Kingdom
  • 23 Department of Community Medicine, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø, Norway. Cancer Registry of Norway, Oslo, Norway. Department of Medical Epidemiology and Biostatistics, Karolinska Instituet, Stockholm, Sweden. Department of Genetic Epidemiology, Folkhälsan Research Center, Helsinki, Finland
  • 24 Public Health Directorate, Asturias, Spain
  • 25 Unit of Nutrition, Environment, and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology, Barcelona, Spain
  • 26 CIBER Epidemiology and Public Health (CIBERESP), Spain. Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria ibs. GRANADA, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain
  • 27 Public Health Direction and CIBERESP-Biodonostia Research Institute, Basque Regional Health Department, San Sebastian, Spain
  • 28 CIBER Epidemiology and Public Health (CIBERESP), Spain. Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain
  • 29 CIBER Epidemiology and Public Health (CIBERESP), Spain. Navarre Public Health Institute, Pamplona, Spain
  • 30 Department of Surgery, Department of Surgical and Perioperative Sciences, Umeå University, Sweden
  • 31 MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, United Kingdom
  • 32 Clinical Gerontology Unit, Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge, United Kingdom
  • 33 Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom
  • 34 Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom
  • 35 Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon, France. jenabm@iarc.fr wrbruce@utoronto.ca
  • 36 Department of Nutritional Sciences, University of Toronto, Toronto, Canada. jenabm@iarc.fr wrbruce@utoronto.ca
Cancer Epidemiol Biomarkers Prev, 2015 Dec;24(12):1855-63.
PMID: 26404963 DOI: 10.1158/1055-9965.EPI-15-0422

Abstract

BACKGROUND: A large proportion of colorectal cancers are thought to be associated with unhealthy dietary and lifestyle exposures, particularly energy excess, obesity, hyperinsulinemia, and hyperglycemia. It has been suggested that these processes stimulate the production of toxic reactive carbonyls from sugars such as glyceraldehyde. Glyceraldehyde contributes to the production of a group of compounds known as glyceraldehyde-derived advanced glycation end-products (glycer-AGEs), which may promote colorectal cancer through their proinflammatory and pro-oxidative properties. The objective of this study nested within a prospective cohort was to explore the association of circulating glycer-AGEs with risk of colorectal cancer.

METHODS: A total of 1,055 colorectal cancer cases (colon n = 659; rectal n = 396) were matchced (1:1) to control subjects. Circulating glycer-AGEs were measured by a competitive ELISA. Multivariable conditional logistic regression models were used to calculate ORs and 95% confidence intervals (95% CI), adjusting for potential confounding factors, including smoking, alcohol, physical activity, body mass index, and diabetes status.

RESULTS: Elevated glycer-AGEs levels were not associated with colorectal cancer risk (highest vs. lowest quartile, 1.10; 95% CI, 0.82-1.49). Subgroup analyses showed possible divergence by anatomical subsites (OR for colon cancer, 0.83; 95% CI, 0.57-1.22; OR for rectal cancer, 1.90; 95% CI, 1.14-3.19; Pheterogeneity = 0.14).

CONCLUSIONS: In this prospective study, circulating glycer-AGEs were not associated with risk of colon cancer, but showed a positive association with the risk of rectal cancer.

IMPACT: Further research is needed to clarify the role of toxic products of carbohydrate metabolism and energy excess in colorectal cancer development.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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