Plasma concentrations of advanced glycation end-products and colorectal cancer risk in the EPIC study

A new study by scientists from the International Agency for Research on Cancer (IARC), Maastricht University, and partner institutions examined the relationship between blood levels of advanced glycation end-products (AGEs) and risk of colorectal cancer. The results have been published in the journal Carcinogenesis.

The research, led by Dr Elom Aglago and Dr Mazda Jenab of the Nutrition and Metabolism Branch at IARC, was a case–control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The study was performed in close collaboration with the laboratory of Professor Casper Schalkwijk at the CARIM School for Cardiovascular Diseases at Maastricht University Medical Center, The Netherlands. The researchers used the gold standard method, ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS), to measure blood levels of three AGEs: N^ε-(carboxy-methyl)lysine (CML), N^ε-(carboxy-ethyl)lysine (CEL), and N^δ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1). The three AGEs measured are among the most abundant in the body, and the researchers specifically measured the protein-bound fraction, because this form of AGEs is known to promote inflammation in colon tissues.

The researchers found that the levels of CML and MG-H1, but not of CEL, were inversely associated with the risk of colorectal cancer. When the chemical origins of the specific AGEs were considered, the ratio of AGEs derived from methylglyoxal (CEL and MG-H1) to those derived from glyoxal (CML) was positively associated with the risk of colorectal cancer.

The study is important to increase the scientific knowledge on specific AGEs and how their levels are associated with risk of colorectal cancer. AGEs are a class of molecules that are generally considered to be harmful compounds. AGEs can be ingested (through the diet) and are also produced endogenously; endogenous AGE formation is increased in individuals with diabetes. This study is among the few to show that specific AGEs may have different associations with diseases depending on their chemical origins. The authors note that additional evidence is needed on the chemical origin of AGEs, as well as on other types such as the free (non-protein-bound) form of AGEs, and their roles in the development of colorectal cancer.

The study was made possible with the generous financial support of World Cancer Research Fund International (WCRF).

Aglago EK, Schalkwijk CG, Freisling H, Fedirko V, Hughes DJ, Jiao L, et al.
Plasma concentrations of advanced glycation end-products and colorectal cancer risk in the EPIC study
Carcinogenesis, Published online 29 March 2021;
https://doi.org/10.1093/carcin/bgab026

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