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Background and Objective : Nutrimetabolomics may reveal novel insights into early metabolic alterations and the role of dietary exposures on prostate cancer (PCa) risk. We aimed to prospectively investigate the associations between plasma metabolite concentrations and PCa risk, including clinically relevant tumor subtypes. Methods : We used a targeted and large-scale metabolomics approach to analyze plasma samples of 851 matched PCa case-control pairs from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Associations between metabolite concentrations and PCa risk were estimated by multivariate conditional logistic regression analysis. False discovery rate (FDR) was used to control for multiple testing correction. Results : Thirty-one metabolites (predominately derivatives of food intake and microbial metabolism) were associated with overall PCa risk and its clinical subtypes ( p < 0.05), but none of the associations exceeded the FDR threshold. The strongest positive and negative associations were for dimethylglycine (OR = 2.13; 95% CI 1.16-3.91) with advanced PCa risk (n = 157) and indole-3-lactic acid (OR = 0.28; 95% CI 0.09-0.87) with fatal PCa risk (n = 57), respectively; however, these associations did not survive correction for multiple testing. Conclusions : The results from the current nutrimetabolomics study suggest that apart from early metabolic deregulations, some biomarkers of food intake might be related to PCa risk, especially advanced and fatal PCa. Further independent and larger studies are needed to validate our results.

Introduction: Dietary intake of (poly)phenols has been linked to reduced adiposity and body weight (BW) in several epidemiological studies. However, epidemiological evidence on (poly)phenol biomarkers, particularly plasma concentrations, is scarce. We aimed to investigate the associations between plasma (poly)phenols and prospective BW change in participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort., Methods: This study included 761 participants with data on BW at baseline and after 5 years of follow-up. Plasma concentrations of 36 (poly)phenols were measured at baseline using liquid chromatography-tandem mass spectrometry. Associations were assessed through general linear mixed models and multinomial logistic regression models, using change in BW as a continuous or as a categorical variable (BW loss, maintenance, gain), respectively. Plasma (poly)phenols were assessed as log2-transformed continuous variables. The false discovery rate (FDR) was used to control for multiple comparisons., Results: Doubling plasma (poly)phenol concentrations showed a borderline trend towards a positive association with BW loss. Plasma vanillic acid showed the strongest association (-0.53 kg/5 years; 95% confidence interval [CI]: -0.99, -0.07). Similar results were observed for plasma naringenin comparing BW loss versus BW maintenance (odds ratio: 1.1; 95% CI: 1.0, 1.2). These results did not remain significant after FDR correction., Conclusion: Higher concentrations of plasma (poly)phenols suggested a tendency towards 5-year BW maintenance or loss. While certain associations seemed promising, they did not withstand FDR correction, indicating the need for caution in interpreting these results. Further studies using (poly)phenol biomarkers are needed to confirm these suggestive protective trends., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Existing epidemiological evidence regarding the potential role of (poly)phenol intake in prostate cancer (PCa) risk is scarce and, in the case of flavonoids, it has been suggested that their intake may increase PCa risk. We investigated the associations between the intake of the total and individual classes and subclasses of (poly)phenols and the risk of PCa, including clinically relevant subtypes. The European Prospective Investigation into Cancer and Nutrition (EPIC) cohort included 131,425 adult men from seven European countries. (Poly)phenol intake at baseline was assessed by combining validated center/country-specific dietary questionnaires and the Phenol-Explorer database. Multivariable-adjusted Cox proportional hazards models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CI). In total, 6939 incident PCa cases (including 3501 low-grade and 710 high-grade, 2446 localized and 1268 advanced, and 914 fatal Pca cases) were identified during a mean follow-up of 14 years. No associations were observed between the total intake of (poly)phenols and the risk of PCa, either overall (HR log2 = 0.99, 95% CI 0.94-1.04) or according to PCa subtype. Null associations were also found between all classes (phenolic acids, flavonoids, lignans, and stilbenes) and subclasses of (poly)phenol intake and the risk of PCa, overall and according to PCa subtype. The results of the current large prospective cohort study do not support any association between (poly)phenol intake and PCa incidence.

This study analyzed the correlations between the acute and habitual intake of dietary tyrosols, their main food sources, and 24 h urine excretions of tyrosol (Tyr) and hydroxytyrosol (OHTyr) in participants from the European Prospective Investigation into Cancer and Nutrition study (EPIC). Participants (n = 419) were healthy men and women aged from 34 to 73 years from 8 EPIC centers belonging to France, Italy, and Germany. Acute and habitual dietary data were collected using a standardized 24 h dietary recall software and validated country-specific dietary questionnaires, respectively. The intake of 13 dietary tyrosols was estimated using the Phenol-Explorer database. Excretions of Tyr and OHTyr in a single 24 h urine sample were analyzed using tandem mass spectrometry. Urinary excretions of Tyr, OHTyr, and their sum (Tyr + OHTyr) correlated more strongly with their corresponding acute (rho partial ~0.63) rather than habitual intakes (rho partial ~0.47). In addition, individual and combined urinary excretions of Tyr and OHTyr were weakly to moderately correlated with the acute and habitual intake of other individual tyrosol precursors (rho partial = 0.10-0.44) and especially with major food sources, such as wine (rho partial = 0.41-0.58), olive oil (rho partial = 0.25-0.44), and beer (rho partial = 0.14-0.23). Urinary Tyr + OHTyr excretions were similarly correlated with the acute intake of total tyrosols but differently correlated with food sources among countries. Based on these results, we conclude that 24 h urinary excretions of Tyr + OHTyr could be proposed as biomarkers of total tyrosol intake, preferably for acute intakes.

Purpose: This article summarizes natural products that target the MAPK-signaling pathway in cancer therapy. The classification, chemical structures, and anti-cancer mechanisms of these natural products are elucidated, and comprehensive information is provided on their potential use in cancer therapy. Methods: Using the PubMed database, we searched for keywords, including “tumor”, “cancer”, “natural product”, “phytochemistry”, “plant chemical components”, and “MAPK-signaling pathway”. We also screened for compounds with well-defined structures that targeting the MAPK-signaling pathway and have anti-cancer effects. We used Kingdraw software and Adobe Photoshop software to draw the chemical compound structural diagrams. Results: A total of 131 papers were searched, from which 85 compounds with well-defined structures were selected. These compounds have clear mechanisms for targeting cancer treatment and are mainly related to the MAPK-signaling pathway. Examples include eupatilin, carvacrol, oridonin, sophoridine, diosgenin, and juglone. These chemical components are classified as flavonoids, phenols, terpenoids, alkaloids, steroidal saponins, and quinones. Conclusions: Certain MAPK pathway inhibitors have been used for clinical treatment. However, the clinical feedback has not been promising because of genomic instability, drug resistance, and side effects. Natural products have few side effects, good medicinal efficacy, a wide range of sources, individual heterogeneity of biological activity, and are capable of treating disease from multiple targets. These characteristics make natural products promising drugs for cancer treatment. [ABSTRACT FROM AUTHOR]