The IARC Perspective on Colorectal Cancer Screening

Colorectal cancer, which is the third most common cancer in men and the second most common in women, represents almost 10% of the annual global cancer incidence. Incidence rates of colorectal cancer show a strong positive gradient with an increasing level of economic development. Even so, the net 5-year rate of survival decreases with lower levels of income, with rates reaching 60% in high-income countries but falling to 30% or less in low-income countries. Established risk factors for colorectal cancer include consumption of processed meats, consumption of alcoholic beverages, tobacco smoking, and excess body fat, whereas consumption of dietary fiber and dairy products and increased levels of physical activity decrease the risk. In addition, certain subgroups of the population are at increased risk owing to genetic predisposition (e.g., the Lynch syndrome), a family or personal history of colorectal neoplasia, or medical conditions (e.g., inflammatory bowel disease) that have been associated with colorectal cancer

ECIBC at a Glance: European Commission Initiative on Breast Cancer

This document is a brochure explaining the EICBC initiative to a middle-informed audience. ECIBC provides evidence based guidelines and a European Quality assurance scheme for breast cancer.JRC.F.1-Health in Societ

The Future of Cities

This report is an initiative of the Joint Research Centre (JRC), the science and knowledge service of the European Commission (EC), and supported by the Commission's Directorate-General for Regional and Urban Policy (DG REGIO). It highlights drivers shaping the urban future, identifying both the key challenges cities will have to address and the strengths they can capitalise on to proactively build their desired futures. The main aim of this report is to raise open questions and steer discussions on what the future of cities can, and should be, both within the science and policymaker communities. While addressing mainly European cities, examples from other world regions are also given since many challenges and solutions have a global relevance. The report is particularly novel in two ways. First, it was developed in an inclusive manner – close collaboration with the EC’s Community of Practice on Cities (CoP-CITIES) provided insights from the broader research community and city networks, including individual municipalities, as well as Commission services and international organisations. It was also extensively reviewed by an Editorial Board. Secondly, the report is supported by an online ‘living’ platform which will host future updates, including additional analyses, discussions, case studies, comments and interactive maps that go beyond the scope of the current version of the report. Steered by the JRC, the platform will offer a permanent virtual space to the research, practice and policymaking community for sharing and accumulating knowledge on the future of cities. This report is produced in the framework of the EC Knowledge Centre for Territorial Policies and is part of a wider series of flagship Science for Policy reports by the JRC, investigating future perspectives concerning Artificial Intelligence, the Future of Road Transport, Resilience, Cybersecurity and Fairness Interactive online platform : https://urban.jrc.ec.europa.eu/thefutureofcitiesJRC.B.3-Territorial Developmen

In utero exposure to xenoestrogens, associated health outcomes and epigenetic mechanisms in children

The prenatal period is a stage of special sensitivity to the adverse effects of environmental agents for the developing fetus. The human placenta is an organ that, in the interface between mother and fetus, plays a key role in fetal growth and development and, as such, affects the fetal programming underlying subsequent disease vulnerability in adulthood. There is increasing epidemiological evidence linking prenatal exposure to endocrine disrupting chemicals (EDCs) and adverse health outcomes in children, although mechanisms remain still unclear. Xenoestrogens are a group of endocrine disrupting chemicals that target the estrogenic signaling pathway and include a large number of compounds, both man-made and of natural origin, ubiquitously present in the environment, often at low doses. Xenoestrogen exposure has been related both in humans and in animal models to adverse health endpoints, most especially obesity and metabolic disorders, reproductive problems, increased risk for several types of cancers and neurobehavioral abnormalities. Prenatal epigenetic dysregulation has been proposed as a possible causal mechanism. The main objective of this thesis has been to evaluate the effects of prenatal exposure to mixtures of xenoestrogens on growth related and neuropsychological outcomes in children from the prospective Spanish birth cohort study INMA, INfancia y Medio Ambiente (Childhood and the Environment) Project, and to analyze whether in utero exposure to mixtures produces changes in placental DNA methylation, both globally or at specific genes and/or nearby regions. For that purpose, the Total Effective Xenoestrogen Burden (TEXB-alpha), a biomarker of the cumulative exposure to xenoestrogens, was measured in placental tissue using the E-Screen biossay. Information on birth outcomes was recorded by pediatricians or nurses at birth and at following time points, and neuropsychological assessment was conducted by trained psychologists using two different scales when children were around 2 and 4 years of age. DNA methylation was measured on DNA extracted from placenta for a sub-group of children using quantitative methods. We evaluated global DNA methylation by bisulfite pyrosequencing of several retrotransposons (repetitive elements that make up around 42% of the human genome); and genome-wide DNA methylation was scanned with a comprehensive array provided by Illumina, the HumanMethylation450 BeadChip, in which practically all human genes and many regulatory regions are represented. Associations were tested using linear regression, mixed-effects regression or robust linear regression models accordingly, always adjusting for potential confounders and sex specific effects were investigated. Overall, we found significant associations between TEXB-alpha exposure in boys but not in girls and the outcomes studied: higher TEXB-alpha levels were associated with increasing birthweight and with a decrease in motor performance at age 1-2 years, which did not persist at age 4. Additionally, we found some evidence that xenoestrogen exposure produced a decrease in placenta global DNA methylation in an Alu element in boys and, although non-significant after multiple testing correction, induced changes in DNA methylation in boys in CpG sites located in several genes (i.e. LRPAP1, HAGH, PPARGC1B,KCNQ1 and KCNQ1DN), previously associated either to birthweight and Type 2 Diabetes, obesity or to steroid hormone metabolism and signalling. Results from this work on chidren from the general Spanish population suggest that low-level exposure to mixtures of hormonally active estrogenic compounds may produce growth-related changes and some adverse effects on the early development of motor tasks in the male population, and are suggestive of epigenetic disruption in global methylation in the same group, while the association with specific genes in boys remains unclear and needs to be evaluated in larger samples and using alternative methods. This thesis has analyzed for the first time in an epidemiological study a biomarker of exposure to mixtures of xenoestrogens in placenta in relation to birthweight, children growth, body mass index and neuropsychological development, adding knowledge to the limited evidence that prenatal xenoestrogen exposure could be relevant in terms of children health outcomes, that epigenetic alterations may play a mechanistic role and highlights the importance to take into account possible sex-related vulnerability to EDCs during pregnancy.El període prenatal és una etapa sensible als efectes de l’exposició a agents ambientals. La placenta humana, un òrgan que comunica la mare i el fetus i que, durant aquest període, juga un paper clau en el creixement i el desenvolupament fetal. Com a tal, la placenta podria estar implicada en alteracions fenotípiques ja visibles en la infància i amb possibles efectes en salut a llarg termini. Existeix evidència epidemiològica que relaciona l’exposició prenatal a pertorbadors endocrins (EDCs, de l’ anglés endocrine disrupting chemicals) amb diferents indicadors de salut infantil, tot i que els mecanismes d’acció són encara poc coneguts. Els xenoestrògens són un grup d’EDCs que interfereixen amb les vies de senyalització de les hormones estrogèniques. Inclouen un ampli ventall de compostos, alguns d’origen natural i d’altres sintètic, omnipresents en el medi ambient, sovint a baixes concentracions. Un nombre important d’estudis científics han trobat associacions, tant en humans com en models animals, entre l’exposició prenatal a aquests compostos i alteracions metabòliques, obesitat, problemes reproductius, un augment de risc de patir diferents tipus de càncer i alteracions en el desenvolupament de funcions neuropsicològiques. Un possible mecanisme molecular proposat per molts investigadors que podria explicar, almenys en part, aquestes associacions és l’alteració de patrons epigenètics durant el període prenatal. L’objectiu principal d’aquest projecte de tesi ha estat avaluar l’associació entre l’exposició prenatal a mescles de compostos xenoestrogènics i el pes al naixement, la velocitat de creixement durant els 6 primers mesos i l’índex de massa corporal als 14 mesos, així com el desenvolupament neuropsicològic a diferents edats en nens de la cohort espanyola de naixement INMA (INfància i Medi Ambient), i també estudiar si aquesta exposició produeix canvis en la metilació del DNA en la placenta, a nivell global i/o en gens específics o possibles regions reguladores del genoma. Amb aquest propòsit, vam mesurar en placenta l’efecte estrogènic degut a mescles de compostos ambientals mitjançant un biomarcador anomenat Total Effective Xenoestrogen Burden (TEXB-alfa) usant l’assaig E-Screen, basat en la proliferació de cèl.lules tumorals MCF que responen a estrògens. La informació referent al pes al néixer i altres variables de creixement va ser recollida per pediatres i/o infermeres i l’avaluació neuropsicològica va ser realitzada per psicòlegs entrenats amb experiència prèvia en l’administració de les dues escales utilitzades. En un subgrup de nens, es va analitzar la metilació del DNA en placenta amb diferents mètodes quantitatius. A nivell global la vam estimar mesurant el percentatge de citosines metilades en unes seqüències repetides que constitueixen fins a un 42% del total del genoma humà anomenades retrotransposons usant la tècnica de piroseqüenciació i, per altra banda, es van mesurar els nivells de metilació de forma quantitativa en un gran nombre de citosines distribuïdes al llarg de tot el genoma, incloent pràcticament tots els gens descrits i moltes regions reguladores, amb un array produït per la casa comercial Illumina anomenat HumanMethylation450 BeadChip. Les corresponents associacions van ser analitzades usant models de regressió lineals, models de regressió lineal mixta (per a tenir en compte mesures repetides o correlacionades) i regressions lineals robustes, ajustant per potencials variables confusores. En tots els casos es va estudiar l’existència d’efectes diferents en funció del sexe dels nens. Els resultats obtinguts en aquesta tesi mostren l’existència d’associacions entre l’exposició prenatal a TEXB-alpha i els diferents fenotips estudiats en els nens però no en les nenes: en aquests, nivells alts de TEXB-alpha es relacionaven amb un augment significatiu del pes al néixer i alteracions neuropsicològiques, concretament una disminució en les puntuacions de l’escala motora al voltant dels 2 anys, tot i que aquest últim efecte ja no el trobàvem als 4 anys d’edat. També vam observar una disminució en els nens amb nivells alts de TEXB-alpha en la metilació en placenta d’un element repetitiu anomenat AluYb8, que representa un indicador de la metilació global del genoma i, tot i no ser significatius a nivell estadístic, vam trobar canvis en la metilació en nens en uns CpGs situats en gens (LRPAP1, HAGH, PPARGC1B, KCNQ1 i KCNQ1DN) que en estudis anteriors s’havien relacionat amb el pes al néixer, la obesitat, la diabetis de tipus II i el metabolisme i la resposta a hormones esteroides com l’estrògen. Aquests resultats, obtinguts en població general infantil espanyola, suggereixen que l’exposició constant i a baixes dosis a mescles de compostos actius a nivell hormonal podrien afectar el creixement i tenir un impacte en el desenvolupament inicial de funcions cerebrals en la població masculina, i aporten evidència de canvis en els nivells de metilació global en aquesta població, mentre que les associacions observades en relació a gens concrets són incertes i caldran més estudis en altres cohorts més nombroses i validacions tècniques usant altres mètodes. Finalment, aquesta tesi ha realitzat per primer cop un estudi epidemiològic usant un biomarcador d’exposició conjunta a mescles de xenoestrògens en placenta en relació a variables de creixement i desenvolupament neuropsicològic, i aporta nou coneixement a l’evidència científica existent, tot i que limitada, de què l’exposició prenatal a xenoestrògens pot tenir un impacte en la salut infantil, que alteracions en la metilació del DNA podrien jugar un paper mecanístic en aquests efectes observats i, finalment, destaquen la importància d’estudiar la possible vulnerabilitat diferencial entre nens i nenes a l’exposició in utero a pertorbadors endocrins

Storage conditions and stability of global DNA methylation in placental tissue

AIM: The placenta is an informative and easily available tissue for many epidemiological studies. We analyzed the extent to which storage delay affects DNA methylation. MATERIAL & METHODS: Biopsies from two placentas were sequentially stored at -80°C after standing at room temperature for 30 min, 1 h, 2 h, 6 h and 24 h. Global DNA methylation was measured by bisulfite pyrosequencing of repetitive elements and the luminometric methylation assay. RESULTS: Small changes in global DNA methylation in relation to time-to-storage were observed by pyrosequencing, with a coefficient of variation (COV) of 2.49% (placenta 1) and 2.86% (placenta 2), similar to the mean technical variation observed for pyrosequencing (COV: 1.91 and 1.51%, respectively). A luminometric methylation assay yielded more variable results in the two placentas analyzed, both among time points (COV: 9.13 and 10.35%, respectively) and technical replicates (COV: 11.60 and 9.80%, respectively). CONCLUSION: Global DNA methylation is stable at room temperature. However, some techniques to measure methylation might be confounded by DNA degradation caused by a delay in storage.This study was funded by grants from the Spanish Ministry of Health (FIS-PI041436 and PI11/00610), Instituto de Salud Carlos III (Red Infancia y MedioAmbiente G03/176 and CB06/02/0041) and the Generalitat de Catalunya-Comissió Interdepartamental de Recerca i Innovació Tecnològica 1999SGR 00241. AA Baccarelli receives support from the Harvard School of Public Health and National Institute of Environmental Health Sciences Center for Environmental Health (ES000002). N Vilahur was supported by a Formación de Personal Investigador Grant from the Spanish Ministry of Health and a Formación de Personal Investigador Grant for Short Research Stays in Foreign Institutions (BES-2009-023933) and MF Fernandez by the Ramon y Cajal Research Grant from the Spanish Ministry of Educatio

Storage conditions and stability of global DNA methylation in placental tissue

AIM: The placenta is an informative and easily available tissue for many epidemiological studies. We analyzed the extent to which storage delay affects DNA methylation. MATERIAL & METHODS: Biopsies from two placentas were sequentially stored at -80°C after standing at room temperature for 30 min, 1 h, 2 h, 6 h and 24 h. Global DNA methylation was measured by bisulfite pyrosequencing of repetitive elements and the luminometric methylation assay. RESULTS: Small changes in global DNA methylation in relation to time-to-storage were observed by pyrosequencing, with a coefficient of variation (COV) of 2.49% (placenta 1) and 2.86% (placenta 2), similar to the mean technical variation observed for pyrosequencing (COV: 1.91 and 1.51%, respectively). A luminometric methylation assay yielded more variable results in the two placentas analyzed, both among time points (COV: 9.13 and 10.35%, respectively) and technical replicates (COV: 11.60 and 9.80%, respectively). CONCLUSION: Global DNA methylation is stable at room temperature. However, some techniques to measure methylation might be confounded by DNA degradation caused by a delay in storage.This study was funded by grants from the Spanish Ministry of Health (FIS-PI041436 and PI11/00610), Instituto de Salud Carlos III (Red Infancia y MedioAmbiente G03/176 and CB06/02/0041) and the Generalitat de Catalunya-Comissió Interdepartamental de Recerca i Innovació Tecnològica 1999SGR 00241. AA Baccarelli receives support from the Harvard School of Public Health and National Institute of Environmental Health Sciences Center for Environmental Health (ES000002). N Vilahur was supported by a Formación de Personal Investigador Grant from the Spanish Ministry of Health and a Formación de Personal Investigador Grant for Short Research Stays in Foreign Institutions (BES-2009-023933) and MF Fernandez by the Ramon y Cajal Research Grant from the Spanish Ministry of Educatio

Welding fumes and lung cancer a meta-analysis of case-control and cohort studies

International audienceBackground - An estimated 110 million workers are exposed to welding fumes worldwide. Welding fumes are classified by the International Agency for Research on Cancer as (group 1), based on of lung cancer from epidemiological studies. Objective - To conduct a meta-analysis of case-control and cohort studies on welding or exposure to welding fumes and risk of lung cancer, accounting for confounding by exposure to asbestos and tobacco smoking. Methods - The literature was searched comprehensively in PubMed, reference lists of relevant publications and additional databases. Overlapping populations were removed. Meta-relative risks (mRRs) were calculated using random effects models. Publication bias was assessed using funnel plot, Eggers's test and Begg's test. Results - Forty-five studies met the inclusion criteria (20 case-control, 25 cohort/nested case-control), which reduced to 37 when overlapping study populations were removed. For 'ever' compared with 'never' being a welder or exposed to welding fumes, mRRs and 95% CIs were 1.29 (1.20 to 1.39; I=26.4%; 22 studies) for cohort studies, 1.87 (1.53 to 2.29; I=44.1%; 15 studies) for case-control studies and 1.17 (1.04 to 1.38; I=41.2%) for 8 case-control studies that adjusted for smoking and asbestos exposure. The mRRs were 1.32 (95% CI 1.20 to 1.45; I=6.3%; 15 studies) among 'shipyard welders', 1.44 (95% CI 1.07 to 1.95; I=35.8%; 3 studies) for 'mild steel welders' and 1.38 (95% CI 0.89 to 2.13; I=68.1%; 5 studies) among 'stainless steel welders'. Increased risks persisted regardless of time period, geographic location, study design, occupational setting, exposure assessment method and histological subtype. Conclusions - These results support the conclusion that exposure to welding fumes increases the risk of lung cancer, regardless of the type of steel welded, the welding method (arc vs gas welding) and independent of exposure to asbestos or tobacco smoking