Dietary Advanced Glycation End-Products and Colorectal Cancer Risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study

Abstract

Dietary advanced glycation end-products (dAGEs) have been hypothesized to be associated with a higher risk of colorectal cancer (CRC) by promoting inflammation, metabolic dysfunction, and oxidative stress in the colonic epithelium. However, evidence from prospective cohort studies is scarce and inconclusive. We evaluated CRC risk associated with the intake of dAGEs in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Dietary intakes of three major dAGEs: Nε-carboxy-methyllysine (CML), Nε-carboxyethyllysine (CEL), and Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) were estimated in 450,111 participants (median follow-up = 13 years, with 6162 CRC cases) by matching to a detailed published European food composition database. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of dAGEs with CRC were computed using multivariable-adjusted Cox regression models. Inverse CRC risk associations were observed for CML (HR comparing extreme quintiles: HRQ5vs.Q1 = 0.92, 95% CI = 0.85–1.00) and MG-H1 (HRQ5vs.Q1 = 0.92, 95% CI = 0.85–1.00), but not for CEL (HRQ5vs.Q1 = 0.97, 95% CI = 0.89–1.05). The associations did not differ by sex or anatomical location of the tumor. Contrary to the initial hypothesis, our findings suggest an inverse association between dAGEs and CRC risk. More research is required to verify these findings and better differentiate the role of dAGEs from that of endogenously produced AGEs and their precursor compounds in CRC development.

Dietary advanced glycation end products and cancer risk in Japan: From the Takayama study

“…Another cohort study has suggested an inverse association between dietary CML and colorectal cancer risk. 18 …”

“…They observed that dietary CML was inversely associated with the risks of colorectal cancer and hepatocellular carcinoma, and positively associated with gallbladder cancer. 18 , 19 …”

“…By contrast, the European Prospective Investigation into Cancer and Nutrition (EPIC) study estimated dietary CML and other two AGEs, N ε ‐(1‐carboxyethyl)‐lysine and N δ ‐(5‐hydro‐5‐methyl‐4‐imidazolon‐2‐yl)‐ornithine, using databases based on UPLC–MS/MS. They observed that dietary CML was inversely associated with the risks of colorectal cancer and hepatocellular carcinoma, and positively associated with gallbladder cancer 18,19 …”

Dietary Intake of Advanced Glycation End Products (AGEs) and Mortality among Individuals with Colorectal Cancer

“…The major strengths of this study include the prospective study design, large sample size, comprehensive collection and assessment of multiple potential confounding/effect modifying factors, and multiple sensitivity analyses. In addition, our study used a state-ofthe-art quantitative instrumental mass-spectrometry-based method to assess three different types of AGEs in foods [35], and we followed the recent "quality control" recommendations for studies on AGEs, i.e., the study of several specific AGEs and the use of a validated food composition database to estimate individual dietary AGE exposures [50].…”

“…Dietary AGEs were estimated using a reference dietary AGE food composition database, which is based on the CML, CEL, and MG-H1 concentrations (in mg/100 g of food) obtained from 190 food items commonly consumed in Europe using ultra-performance liquid chromatography tandem mass-spectrometry analysis [10]. Foods from the reference database were matched to those included in the DQs by name and descriptors, particularly those pertaining to preparation and processing whenever applicable [35]. Generic or multi-ingredient DQ foods were decomposed into more specific foods or ingredients based on country-specific recipes obtained from previous EPIC projects [34,36].…”