| In patient samples (cancer/control) |
| Analysis of genetically modified circulating levels of AGEs in 1,051 patients with breast cancer by ELISA | Higher levels of AGEs and AGEs/sRAGE-ratio—correlated with increased breast cancer risk sRAGE levels—negative correlation with breast cancer risk AGEs—positive correlation with bad cancer prognosis
| [41] |
| Analysis of plasma AGEs in 1,378 patients with primary colorectal cancer by ultra-performance liquid chromatography-tandem mass spectrometry | Higher ratio of MG-derived AGEs versus those derived from glyoxal displayed a strong positive correlation with colorectal cancer risk CML, CEL and MG-H1—inverse correlation with colorectal cancer risk
| [23] |
| Analysis of dietary AGEs intake in 450,111 participants by European Prospective Investigation into Cancer and Nutrition (EPIC) study | CML and MG-H1—inverse correlation with colorectal cancer risk, but not for CEL AGEs analysed in this study may not be colorectal cancer-promotive
| [42] |
| Analysis of dietary AGEs intake—prospective observational study by Women’s Health Initiative (WHI, WHI-USA) in 2,073 women with invasive breast cancer | After a median 15.1 years of follow-up, 642 deaths were registered, including 198 breast cancer specific and 129 cardio-vascular specific deaths Higher consumption of dietary AGEs (CML-AGEs) after cancer diagnosis in post-menopausal women—correlated with enhanced risk of mortality from cancer as well as cardio-vascular diseases
| [43] |
| Analysis of dietary AGEs intake—Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial in cancer-free healthy women | After a median 11.5 years of follow-up, 1,592 women were diagnosed with breast cancer in the PLCO Highest CML-AGE intake—related to increased breast cancer risk (in situ and hormone receptor positive breast cancer) and mortality risk in healthy women Increased CML-AGE intake post-diagnosis coupled with lower intake of fruits and vegetables—associated with increased mortality rate in both hormone receptor positive and negative breast cancers
| [44] |
| Analysis of plasma AGEs—a 5-year follow-up cohort study by Shaanxi Provincial People’s Hospital, in 131 patients with stage II and III breast cancer, surgically treated | Incidence of metastasis significantly associated with serum AGE concentrations in the patients For the period of follow-up, metastasis interval was shorter in diabetic than non-diabetic subjects
| [45] |
| Analysis of plasma AGEs in peripheral blood mononuclear cells (PBMCs) from 20 adult survivors of paediatric Hodgkin’s lymphoma (HL) | Plasma AGEs (CML and MG-H1)—significantly higher in HL survivors than healthy subjects Higher levels of RAGE, NADPH oxidase, oxidative stress, NF-κB and IL-6 expression, along with weakened anti-oxidant defence Co-existence of AGEs, oxidative and inflammatory stress in HL survivors Potentially detrimental in initiating long-term complications in HL survivors
| [46] |
| Analysis of MG AGEs/adducts in blood-derived cultures (BDCs, liquid biopsy) of patients with cancer (18 localized and 20 advanced cases) | | [26] |
| Analysis of cutaneous AGEs by skin auto-fluorescence (SAF) in type-2 diabetic patients | SAF is indicative of pentosidine, an AGE prevalent in skin biopsies SAF values > 2.6 projected a 2.6 fold increased risk of cancer with significant association between AGEs and cancer incidence Diabetic patients who had cancer or went onto develop new cancers had considerably higher initial SAF values than those who did not have or develop cancer
| [47] |
| Analysis of histone-glycation adducts in SKBR3 breast cancer cells in vitro, MCF7 and CAMA-1 tumor xenografts in vivo and tumour samples from patients with metastasis or recurrence | Histones are basally glycated in breast cancer Histone glycation disrupts chromatin architecture, nucleosome assembly and stability Breast cancer cells, xenografts, as well as patients’ tumours showed high basal histone glycation levels and deglycase enzyme (DJ-1) overexpression Link between metabolic perturbation and epigenetic dysregulation in cancer
| [48] |
| In animal (mice) models—in vivo |
| Analysis of impact of dietary AGEs in pubertal FVB/n mice (model of breast cancer), fed a high AGE diet | High AGE-rich dietary consumption, especially in pubertal age, elicit breast cancer risk via substantial dysregulation in normal growth of mammary glands and promotion of hyperplastic lesions by adulthood AGEs leave a “metabolic imprint” in the normal mammary gland micro-milieu, with potential risk for breast cancer development
| [37] |
| Analysis of impact of dietary AGEs in wild type FVB/n and RAGE null (RAGE–/–) mice, fed persistent high AGE diet (chronic dietary-AGE model of breast cancer) | By influencing cellular matrix, AGEs perturb developmental programs during puberty and induce breast cancer growth AGE driven changes in tissue architecture and cell function led to 3-fold rise in neoplastic growth Both RAGE-dependent and independent mechanisms were involved in eliciting the same Dietary AGE activated RAGE-stimulated stroma resulting in pre-neoplastic lesions, continuing into adulthood
| [38] |
| Analysis of impact of dietary AGEs in FVB-RAGE+/+ and FVB-RAGE–/– xenograft mice (prostate cancer model), fed AGE-rich diet | AGE treatment prompted RAGE dimerization in activated fibroblasts AGEs elicited RAGE-mediated sustenance and augmentation of migratory capacity of cancer cells RAGE depletion in tumour stroma blocked AGE-driven cancer expansion
| [39] |
| In cancer cells—in vitro |
| Analysis of glycation in MCF-7 cells by mass spectrometry | | [49] |
| Analysis of proteins in liver cancer cells by mass spectrometry | Fructosamine-3-kinase (FN3K) sensitive glycation of 110 proteins—transcription factors, splicing factors, histones, DNA- and RNA-binding proteins, HSPs; HSP90AA1, HSP90AA4, translation factors (eIF4A1, eIF1, eIF3G), transcription factors (NRF-2), replication and repair proteins (HELB, MCM3), splicing factors (SRSF7, PUF60) and more importantly, enzymes involved in glucose metabolism (LDHA, LDHC), were identified
| [17] |
