Genetically Modified Circulating Levels of Advanced Glycation End-Products and Their Soluble Receptor (AGEs-RAGE Axis) with Risk and Mortality of Breast Cancer

Abstract

The interaction of advanced glycation end-products (AGEs) with their receptor (RAGE) elicits oxidative stress and inflammation, which is involved in the development of breast cancer. However, large-scale population-based evidence exploring genetically modified circulating levels of AGEs-RAGE axis with risk and mortality of breast cancer is scarce. We recruited 1051 pairs of age-matched breast cancers and controls and measured plasma AGEs and sRAGE concentrations by enzyme-linked immunosorbent assay (ELISA). Multivariate logistic regression and Cox proportional hazard model were used to calculate the effects of plasma levels and genetic variants of the AGEs-RAGE axis and their combined effects on breast cancer risk and prognosis, respectively. Furthermore, linear regression was performed to assess the modifications in plasma AGEs/sRAGE levels by genetic predisposition. Higher levels of AGEs and AGEs/sRAGE-ratio were associated with an increased risk of breast cancer, but sRAGE levels were negatively associated with breast cancer risk, especially in women <60 years. We also observed a positive association between AGEs and the bad prognosis of breast cancer. Although we did not observe a significant contribution of genetic variants to breast cancer risk, rs2070600 and rs1800624 in the AGER gene were dose-dependently correlated with sRAGE levels. Further, compared to the haplotype CT at the lowest quartile of AGEs, haplotypes TT and TA were prominently associated with breast cancer risk in the highest quartile of AGEs. This study depicted a significant association between circulating levels of AGEs-RAGE axis and breast cancer risk and mortality and revealed the potential of plasma AGEs, especially coupled with AGER polymorphism as biomarkers of breast cancer.

Non-Genomic Hallmarks of Aging—The Review

“…Higher levels of AGEs and the AGEs/RAGE ratio were associated with an increased risk of breast cancer. The authors also documented a positive association between AGEs and poor prognosis [69].…”

Plasma One-Carbon Metabolism-Related Micronutrients and the Risk of Breast Cancer: Involvement of DNA Methylation

“…The study population consisted of 107 paired breast cancer patients and controls, simply randomly extracted from a hospital-based case–control study we set up [ 26 ]. As described in our previous study [ 27 ], the cases were patients with newly diagnosed and histologically confirmed breast cancer from Tianjin Medical University Cancer Institute and Hospital since 1 January 2003. They had no history of other malignancies, no reception of any treatment before admission, and no history of blood transfusion in the last 6 months prior to blood sample collection.…”

AGEs and RAGE: metabolic and molecular signatures of the glycation-inflammation axis in malignant or metastatic cancers

“…Oral vitamin D3 (50,000 IU), administered once every 8 weeks, was found to augment sRAGE levels in women with PCOS, as reported in a recent phase IV clinical trial conducted by Maimonides Medical Center, USA [ 130 ]. Now this result is highly crucial with respect to the fact that reduced sRAGE levels and high plasma AGEs have been reported in patients with breast cancer [ 41 ]. In this most recent study conducted in Tianjin Medical University Cancer Institute and Hospital, China, decreased sRAGE and elevated AGE levels were found to increase breast cancer risk, thereby establishing negative concomitance of sRAGE and positive association of AGEs, respectively, with breast cancer.…”