Impact of Oxidative Stress Biomarkers and Carboxymethyllysine (an Advanced Glycation End Product) on Prostate Cancer: A Prospective Study

Abstract

Introduction Biomarkers of oxidative stress and advanced glycation end products (AGE) have been linked to the development of prostate cancer, but evidence from human studies is either scarce or controversial. Materials and Methods We conducted a prospective nested case-control study among 48 men (24 prostate cancer cases and 24 controls) aged 48–76 years at baseline. The participants of our study were a part of the Fernald Community Cohort (FCC). Prostate cancer cases and controls were matched individually on age (± 3 years) with 1:1 ratio. Biomarkers included urine F2-isoprostanes (markers of lipid oxidation), plasma fluorescent oxidation products (FlOPs; markers of global oxidation) and carboxymethyllysine (CML; a major end-stage AGE). Results At baseline, cases had similar age, body mass index, proportion of family history of prostate cancer, history of benign prostatic hyperplasia, history of hypertension, history of diabetes, smokers and plasma glucose levels as compared to controls. Levels of plasma CML were significantly higher in cases than in controls (182 vs. 152 μg/ml, P < 0.05). In the conditional logistic regression model, an increase in CML equivalent to one standard deviation was associated with increased risk of incident prostate cancer (Relative risk = 1.79, 95% confidence interval = 1.00–3.21), and accounted for ~8% variance of prostate cancer liability. Urine F2-isoprostanes and plasma FlOPs were not associated with prostate cancer incidence. Conclusion Higher levels of plasma CML were associated with increased risk of prostate cancer. This suggests a potential new pathway for prostate cancer prediction and treatment.

Pre‐diagnostic derivatives of reactive oxygen metabolites and the occurrence of lung, colorectal, breast and prostate cancer: An individual participant data meta‐analysis of two large population‐based studies

“…Therefore, the reports in the literature about oxidative stress biomarkers and BC risk remain controversial and more large studies are needed. In line with our finding for d‐ROM and PrC, it was previously shown that neither 8‐isoprostane levels nor FlOP were statistically significantly associated with PrC incidence in the main analyses using the total cohort's populations …”

“…In line with our finding for d-ROM and PrC, it was previously shown that neither 8-isoprostane levels nor FlOP were statistically significantly associated with PrC incidence in the main analyses using the total cohort's populations. 23,31 As aforementioned, the d-ROM test assesses the total organic hydroperoxides concentration in fluids. Hydroperoxides are a battery of biomolecules generated by the oxidation of mainly lipids but also proteins and nucleic acids.…”

Redox Signaling and Advanced Glycation Endproducts (AGEs) in Diet-Related Diseases

“…Last but not least, in the last few years, the potential implication of AGEs in carcinogenesis has drawn the attention of investigators, and the presence of AGEs has already been described in several types of cancer [161][162][163]. Moreover, it has been found that the circulating levels of AGEs were increased in patients with prostate cancer when compared with healthy patients, with the highest levels of AGEs corresponding with high-grade prostate cancer patients, according to the Gleason score [162,164,165].…”

Glycative stress from advanced glycation end products (AGEs) and dicarbonyls: An emerging biological factor in cancer onset and progression

“…Systematic reviews indicate that a high-AGE diet that often recognized as a Western-style diet containing high-fat/high-sugar foods, refined grains, and red meat [25] or an unhealthy/sedentary lifestyle may increase the body's AGE pool, thereby increasing the risk of cancers such as prostate and pancreatic cancer [25][26][27][42][43][44]. In addition, a series of epidemiological studies have elucidated the association of biological AGE levels with the risk of cancer in smokers [45][46][47][48] and cancer patients [49][50][51]. Studies in Finnish male smokers found that serum CML levels were not associated with the risk of pancreatic or colorectal cancer and were inversely associated with the risk of liver cancer [45][46][47].…”