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      Prevention in the age of personal responsibility: epigenetic risk-predictive screening for female cancers as a case study


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          Epigenetic markers could potentially be used for risk assessment in risk-stratified population-based cancer screening programmes. Whereas current screening programmes generally aim to detect existing cancer, epigenetic markers could be used to provide risk estimates for not-yet-existing cancers. Epigenetic risk-predictive tests may thus allow for new opportunities for risk assessment for developing cancer in the future. Since epigenetic changes are presumed to be modifiable, preventive measures, such as lifestyle modification, could be used to reduce the risk of cancer. Moreover, epigenetic markers might be used to monitor the response to risk-reducing interventions. In this article, we address ethical concerns related to personal responsibility raised by epigenetic risk-predictive tests in cancer population screening. Will individuals increasingly be held responsible for their health, that is, will they be held accountable for bad health outcomes? Will they be blamed or subject to moral sanctions? We will illustrate these ethical concerns by means of a Europe-wide research programme that develops an epigenetic risk-predictive test for female cancers. Subsequently, we investigate when we can hold someone responsible for her actions. We argue that the standard conception of personal responsibility does not provide an appropriate framework to address these concerns. A different, prospective account of responsibility meets part of our concerns, that is, concerns about inequality of opportunities, but does not meet all our concerns about personal responsibility. We argue that even if someone is responsible on grounds of a negative and/or prospective account of responsibility, there may be moral and practical reasons to abstain from moral sanctions.

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          Integrative analysis of 111 reference human epigenomes

          The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but a similar reference has lacked for epigenomic studies. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection to-date of human epigenomes for primary cells and tissues. Here, we describe the integrative analysis of 111 reference human epigenomes generated as part of the program, profiled for histone modification patterns, DNA accessibility, DNA methylation, and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically-relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation, and human disease.
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            DNA methylation: roles in mammalian development.

            DNA methylation is among the best studied epigenetic modifications and is essential to mammalian development. Although the methylation status of most CpG dinucleotides in the genome is stably propagated through mitosis, improvements to methods for measuring methylation have identified numerous regions in which it is dynamically regulated. In this Review, we discuss key concepts in the function of DNA methylation in mammals, stemming from more than two decades of research, including many recent studies that have elucidated when and where DNA methylation has a regulatory role in the genome. We include insights from early development, embryonic stem cells and adult lineages, particularly haematopoiesis, to highlight the general features of this modification as it participates in both global and localized epigenetic regulation.
              • Record: found
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              Health literacy in Europe: comparative results of the European health literacy survey (HLS-EU)

              Background: Health literacy concerns the capacities of people to meet the complex demands of health in modern society. In spite of the growing attention for the concept among European health policymakers, researchers and practitioners, information about the status of health literacy in Europe remains scarce. This article presents selected findings from the first European comparative survey on health literacy in populations. Methods: The European health literacy survey (HLS-EU) was conducted in eight countries: Austria, Bulgaria, Germany, Greece, Ireland, the Netherlands, Poland and Spain (n = 1000 per country, n = 8000 total sample). Data collection was based on Eurobarometer standards and the implementation of the HLS-EU-Q (questionnaire) in computer-assisted or paper-assisted personal interviews. Results: The HLS-EU-Q constructed four levels of health literacy: insufficient, problematic, sufficient and excellent. At least 1 in 10 (12%) respondents showed insufficient health literacy and almost 1 in 2 (47%) had limited (insufficient or problematic) health literacy. However, the distribution of levels differed substantially across countries (29–62%). Subgroups within the population, defined by financial deprivation, low social status, low education or old age, had higher proportions of people with limited health literacy, suggesting the presence of a social gradient which was also confirmed by raw bivariate correlations and a multivariate linear regression model. Discussion: Limited health literacy represents an important challenge for health policies and practices across Europe, but to a different degree for different countries. The social gradient in health literacy must be taken into account when developing public health strategies to improve health equity in Europe.

                Author and article information

                J Med Ethics
                J Med Ethics
                Journal of Medical Ethics
                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                December 2021
                18 November 2020
                : 47
                : 12
                : e46
                [1 ] departmentDepartment of Medical Ethics, Philosophy and History of Medicine , Erasmus MC , Rotterdam, The Netherlands
                [2 ] departmentUCL Department of Applied Health Research , University College London , London, UK
                [3 ] departmentDepartment of Women's Cancer , University College London , London, UK
                Author notes
                [Correspondence to ] Dr Ineke Bolt, Department of Medical Ethics, Philosophy and History of Medicine, Erasmus MC, Rotterdam 3000 CA, The Netherlands; L.Bolt@ 123456erasmusmc.nl
                © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

                This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

                : 14 February 2020
                : 18 August 2020
                : 23 August 2020
                Funded by: European Union’s Horizon 2020 research and innovation programme;
                Award ID: No. 634570
                Funded by: NWO-MVI programme;
                Award ID: 313-99-332
                Original Research
                Custom metadata

                technology/risk assessment,genetic screening/testing
                technology/risk assessment, genetic screening/testing


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