Urinary estrogen metabolites and prostate cancer : a case-control study and meta-analysis

Objective: To investigate prostate cancer (Pca) risk in relation to estrogen metabolism, expressed as urinary 2-hydroxyestrone (2-OHE1), 16α-hydroxyestrone (16α-OHE1) and 2-OHE1 to 16α-OHE1 ratio. Methods: We conducted a case-control study within the Western New York Health Cohort Study (WNYHCS) from 1996 to 2001. From January 2003 through September 2004, we completed the re-call and follow-up of 1092 cohort participants. Cases (n = 26) and controls (n = 110) were matched on age, race and recruitment period according to a 1:4 ratio. We used the unconditional logistic regression to compute crude and adjusted odds ratios (OR) and 95% confident interval (CI) of Pca in relation to 2-OHE1, 16αOHE1 and 2-OHE1 to 16α-OHE1 by tertiles of urine concentrations (stored in a biorepository for an average of 4 years). We identified age, race, education and body mass index as covariates. We also conducted a systematic review of the literature which revealed no additional studies, but we pooled the results from this study with those from a previously conducted case-control study using the DerSimonian-Laird random effects method. Results: We observed a non-significant risk reduction in the highest tertile of 2-OHE1 (OR 0.72, 95% CI 0.25-2.10). Conversely, the odds in the highest tertile of 16α-OHE1 showed a non-significant risk increase (OR 1.76 95% CI 0.62-4.98). There was a suggestion of reduced Pca risk for men in the highest tertile of 2-OHE1 to 16α-OHE1 ratio (OR 0.56, 95% CI 0.19-1.68). The pooled estimates confirmed the association between an increased Pca risk and higher urinary levels of 16α-OHE1 (third vs. first tertile: OR 1.82, 95% CI 1.09-3.05) and the protective effect of a higher 2-OHE 1 to 16α-OHE1 ratio (third vs. first tertile: OR 0.53, 95% CI 0.31-0.90). Conclusion: Our study and the pooled results provide evidence for a differential role of the estrogen hydroxylation pathway in Pca development and encourage further study

Intake of Natural Compounds and Circulating microRNA Expression Levels: Their Relationship Investigated in Healthy Subjects With Different Dietary Habits

Diet has a strong influence on many physiological processes, which in turn have important implications on a variety of pathological conditions. In this respect, microRNAs (miRNAs), a class of small non-coding RNAs playing a relevant epigenetic role in controlling gene expression, may represent mediators between the dietary intake and the healthy status. Despite great advances in the field of nutri-epigenomics, it remains unclear how miRNA expression is modulated by the diet and, specifically, the intake of specific nutrients. We investigated the whole circulating miRNome by small RNA-sequencing performed on plasma samples of 120 healthy volunteers with different dietary habits (vegans, vegetarians, and omnivores). Dietary intakes of specific nutrients were estimated for each subject from the information reported in the food-frequency questionnaire previously validated in the EPIC study. We focused hereby on the intake of 23 natural compounds (NCs) of the classes of lipids, micro-elements, and vitamins. We identified 78 significant correlations (rho > 0.300, p-value < 0.05) among the estimated daily intake of 13 NCs and the expression levels of 58 plasma miRNAs. Overall, vitamin D, sodium, and vitamin E correlated with the largest number of miRNAs. All the identified correlations were consistent among the three dietary groups and 22 of them were confirmed as significant (p-value < 0.05) by age-, gender-, and body-mass index-adjusted Generalized Linear regression Model analysis. miR-23a-3p expression levels were related with different NCs including a significant positive correlation with sodium (rho = 0.377) and significant negative correlations with lipid-related NCs and vitamin E. Conversely, the estimated intake of vitamin D was negatively correlated with the expression of the highest number of circulating miRNAs, particularly miR-1277-5p (rho = −0.393) and miR-144-3p (rho = −0.393). Functional analysis of the targets of sodium intake-correlated miRNAs highlighted terms related to cardiac development. A similar approach on targets of those miRNAs correlated with vitamin D intake showed an enrichment in genes involved in hormone metabolisms, while the response to chronic inflammation was among the top enriched processes involving targets of miRNAs negatively related with vitamin E intake. Our findings show that nutrients through the habitual diet influence circulating miRNA profiles and highlight that this aspect must be considered in the nutri-epigenomic research

Biomarkers of inflammation and breast cancer risk: A case-control study nested in the EPIC-Varese cohort

Abstract Breast cancer (BC) is the leading cause of cancer death in women. Adipokines, and other inflammation molecules linked to adiposity, are suspected to be involved in breast carcinogenesis, however prospective findings are inconclusive. In a prospective nested case-control study within the EPIC-Varese cohort, we used conditional logistic regression to estimate rate ratios (RRs) for BC, with 95% confidence intervals (CI), in relation to plasma levels of C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), interleukin-6, leptin, and adiponectin, controlling for BC risk factors. After a median 14.9 years, 351 BC cases were identified and matched to 351 controls. No marker was significantly associated with BC risk overall. Significant interactions between menopausal status and CRP, leptin, and adiponectin were found. Among postmenopausal women, high CRP was significantly associated with increased BC risk, and high adiponectin with significantly reduced risk. Among premenopausal women, high TNF-α was associated with significantly increased risk, and high leptin with reduced risk; interleukin-6 was associated with increased risk only in a continuous model. These findings constitute further evidence that inflammation plays a role in breast cancer. Interventions to lower CRP, TNF-α, and interleukin-6 and increase adiponectin levels may contribute to preventing BC

Life-course socioeconomic status and DNA methylation of genes regulating inflammation

Background: In humans, low socioeconomic status (SES) across the life course is associated with greater diurnal cortisol production, increased inflammatory activity and higher circulating antibodies for several pathogens, all suggesting a dampened immune response. Recent evidence suggests that DNA methylation of pro-inflammatory genes may be implicated in the biological embedding of the social environment. Methods: The present study examines the association between life-course SES and DNA methylation of candidate genes, selected on the basis of their involvement in SES-related inflammation, in the context of a genome-wide methylation study. Participants were 857 healthy individuals sampled from the EPIC Italy prospective cohort study. Results: Indicators of SES were associated with DNA methylation of genes involved in inflammation. NFATC1, in particular, was consistently found to be less methylated in individuals with low vs high SES, in a dose-dependent manner. IL1A, GPR132 and genes belonging to the MAPK family were also less methylated among individuals with low SES. In addition, associations were found between SES and CXCL2 and PTGS2, but these genes were consistently more methylated among low SES individuals. Conclusions: Our findings support the hypothesis that the social environment leaves an epigenetic signature in cells. Although the functional significance of SES-related DNA methylation is still unclear, we hypothesize that it may link SES to chronic disease ris

Lifestyle, dietary factors and antibody levels to oral bacteria in cancer-free participants of a European cohort study

Background—Increasing evidence suggests that oral microbiota play a pivotal role in chronic diseases, in addition to the well-established role in periodontal disease. Moreover, recent studies suggest that oral bacteria may also be involved in carcinogenesis; periodontal disease has been linked several cancers. In this study, we examined whether lifestyle factors have an impact on antibody levels to oral bacteria. Methods—Data on demographic characteristics, lifestyle factors, and medical conditions were obtained at the time of blood sample collection. For the current analysis, we measured antibody levels to 25 oral bacteria in 395 cancer-free individuals using an immunoblot array. Combined total immunglobin G (IgG) levels were obtained by summing concentrations for all oral bacteria measured. Results—IgG antibody levels were substantially lower among current and former smokers (1697 and 1677 ng/mL, respectively) than never smokers (1960 ng/mL; p-trend = 0.01), but did not vary by other factors, including BMI, diabetes, physical activity, or by dietary factors, after adjusting for age, sex, education, country and smoking status. The highest levels of total IgG were found among individuals with low education (2419 ng/mL). Conclusions—Our findings on smoking are consistent with previous studies and support the notion that smokers have a compromised humoral immune response. Moreover, other major factors known to be associated with inflammatory markers, including obesity, were not associated with antibody levels to a large number of oral bacteria

Urinary excretions of 34 dietary polyphenols and their associations with lifestyle factors in the EPIC cohort study.

Urinary excretion of 34 dietary polyphenols and their variations according to diet and other lifestyle factors were measured by tandem mass spectrometry in 475 adult participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) cross-sectional study. A single 24-hour urine sample was analysed for each subject from 4 European countries. The highest median levels were observed for phenolic acids such as 4-hydroxyphenylacetic acid (157 μmol/24 h), followed by 3-hydroxyphenylacetic, ferulic, vanillic and homovanillic acids (20-50 μmol/24 h). The lowest concentrations were observed for equol, apigenin and resveratrol ( 0.5) observed between urinary polyphenols and the intake of their main food sources (e.g., resveratrol and gallic acid ethyl ester with red wine intake; caffeic, protocatechuic and ferulic acids with coffee consumption; and hesperetin and naringenin with citrus fruit intake). The large variations in urinary polyphenols observed are largely determined by food preferences. These polyphenol biomarkers should allow more accurate evaluation of the relationships between polyphenol exposure and the risk of chronic diseases in large epidemiological studies

Diseño activista, a 50 años del Mayo francés "La belleza esta en la calle"

El gesto de los estudiantes de arte y de literatura en Mayo del ´68 al apropiarse del discurso de la publicidad, retornándolo a la poesía, nos invitó una vez más a pensar el diseño. Y a reivindicar aquel acontecimiento desde tan lejos en el tiempo y el espacio. Desde el Taller de Diseño en Comunicación Visual C de la Facultad de Bellas Artes de la UNLP, articulamos los contenidos de cada ciclo lectivo en torno a un tema que nos movilice. Es así que el año pasado, el cincuentenario del Mayo francés fue motivo para realizar la jornada “La belleza está en la calle”. Vivimos en la sociedad del espectáculo que anticipó Guy Debord y cuestionaron aquellos jóvenes. Se actualizan entonces las preguntas sobre para qué y a quién sirve lo que hacemos. Se vuelve necesario pensar las relaciones entre diseño, arte, política y cultura ¿Dónde está el legado de aquellos afichistas en nuestro presente latinoamericano? ¿qué marcas trazó entre la protesta social y el diseño del campo académico profesional? ¿cómo se escriben en la actualidad las posibilidades discursivas otras del diseño? A 50 años, muchas preguntas y una certeza: aún hoy, la belleza está en la calle.Facultad de Bellas Artes (FBA

Diseño activista, a 50 años del Mayo francés "La belleza esta en la calle"

El gesto de los estudiantes de arte y de literatura en Mayo del ´68 al apropiarse del discurso de la publicidad, retornándolo a la poesía, nos invitó una vez más a pensar el diseño. Y a reivindicar aquel acontecimiento desde tan lejos en el tiempo y el espacio. Desde el Taller de Diseño en Comunicación Visual C de la Facultad de Bellas Artes de la UNLP, articulamos los contenidos de cada ciclo lectivo en torno a un tema que nos movilice. Es así que el año pasado, el cincuentenario del Mayo francés fue motivo para realizar la jornada “La belleza está en la calle”. Vivimos en la sociedad del espectáculo que anticipó Guy Debord y cuestionaron aquellos jóvenes. Se actualizan entonces las preguntas sobre para qué y a quién sirve lo que hacemos. Se vuelve necesario pensar las relaciones entre diseño, arte, política y cultura ¿Dónde está el legado de aquellos afichistas en nuestro presente latinoamericano? ¿qué marcas trazó entre la protesta social y el diseño del campo académico profesional? ¿cómo se escriben en la actualidad las posibilidades discursivas otras del diseño? A 50 años, muchas preguntas y una certeza: aún hoy, la belleza está en la calle.Facultad de Bellas Artes (FBA