Germline HOXB13 mutations p.G84E and p.R217C do not confer an increased breast cancer risk

In breast cancer, high levels of homeobox protein Hox-B13 (HOXB13) have been associated with disease progression of ER-positive breast cancer patients and resistance to tamoxifen treatment. Since HOXB13 p.G84E is a prostate cancer risk allele, we evaluated the association between HOXB13 germline mutations and breast cancer risk in a previous study consisting of 3,270 familial non-BRCA1/2 breast cancer cases and 2,327 controls from the Netherlands. Although both recurrent HOXB13 mutations p.G84E and p.R217C were not associated with breast cancer risk, the risk estimation for p.R217C was not very precise. To provide more conclusive evidence regarding the role of HOXB13 in breast cancer susceptibility, we here evaluated the association between HOXB13 mutations and increased breast cancer risk within 81 studies of the international Breast Cancer Association Consortium containing 68,521 invasive breast cancer patients and 54,865 controls. Both HOXB13 p.G84E and p.R217C did not associate with the development of breast cancer in European women, neither in the overall analysis (OR = 1.035, 95% CI = 0.859-1.246, P = 0.718 and OR = 0.798, 95% CI = 0.482-1.322, P = 0.381 respectively), nor in specific high-risk subgroups or breast cancer subtypes. Thus, although involved in breast cancer progression, HOXB13 is not a material breast cancer susceptibility gene.Peer reviewe

Germline HOXB13 mutations p.G84E and p.R217C do not confer an increased breast cancer risk

Abstract: In breast cancer, high levels of homeobox protein Hox-B13 (HOXB13) have been associated with disease progression of ER-positive breast cancer patients and resistance to tamoxifen treatment. Since HOXB13 p.G84E is a prostate cancer risk allele, we evaluated the association between HOXB13 germline mutations and breast cancer risk in a previous study consisting of 3,270 familial non-BRCA1/2 breast cancer cases and 2,327 controls from the Netherlands. Although both recurrent HOXB13 mutations p.G84E and p.R217C were not associated with breast cancer risk, the risk estimation for p.R217C was not very precise. To provide more conclusive evidence regarding the role of HOXB13 in breast cancer susceptibility, we here evaluated the association between HOXB13 mutations and increased breast cancer risk within 81 studies of the international Breast Cancer Association Consortium containing 68,521 invasive breast cancer patients and 54,865 controls. Both HOXB13 p.G84E and p.R217C did not associate with the development of breast cancer in European women, neither in the overall analysis (OR = 1.035, 95% CI = 0.859–1.246, P = 0.718 and OR = 0.798, 95% CI = 0.482–1.322, P = 0.381 respectively), nor in specific high-risk subgroups or breast cancer subtypes. Thus, although involved in breast cancer progression, HOXB13 is not a material breast cancer susceptibility gene

CYP3A7*1C allele: linking premenopausal oestrone and progesterone levels with risk of hormone receptor-positive breast cancers

Funder: Breast Cancer Now (BCN); doi: https://doi.org/10.13039/100009794Funder: Cancer Research UK (CRUK); doi: https://doi.org/10.13039/501100000289Funder: RCUK | Medical Research Council (MRC); doi: https://doi.org/10.13039/501100000265Funder: U.S. Department of Health & Human Services | National Institutes of Health (NIH)Funder: Wellcome Trust (Wellcome); doi: https://doi.org/10.13039/100004440Funder: EC | EC Seventh Framework Programm | FP7 Ideas: European Research Council (FP7-IDEAS-ERC - Specific Programme: "Ideas" Implementing the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities (2007 to 2013)); doi: https://doi.org/10.13039/100011199; Grant(s): HEALTH-F2-2009-223175, HEALTH-F2-2009-223175Funder: Genome Canada (Génome Canada); doi: https://doi.org/10.13039/100008762Funder: Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada); doi: https://doi.org/10.13039/501100000024Funder: Quebec Breast cancer Foundation Genome QuebecFunder: U.S. Department of Health & Human Services | NIH | U.S. National Library of Medicine (NLM); doi: https://doi.org/10.13039/100000092Funder: EC | EC Seventh Framework Programm | FP7 Ideas: European Research Council (FP7-IDEAS-ERC - Specific Programme: "Ideas" Implementing the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities (2007 to 2013))Funder: European Union’s Horizon 2020Funder: Deutsche Krebshilfe (German Cancer Aid); doi: https://doi.org/10.13039/501100005972Funder: BCAST - European Union’s Horizon 2020Funder: Breast Cancer Now; doi: https://doi.org/10.13039/501100007913Abstract: Background: Epidemiological studies provide strong evidence for a role of endogenous sex hormones in the aetiology of breast cancer. The aim of this analysis was to identify genetic variants that are associated with urinary sex-hormone levels and breast cancer risk. Methods: We carried out a genome-wide association study of urinary oestrone-3-glucuronide and pregnanediol-3-glucuronide levels in 560 premenopausal women, with additional analysis of progesterone levels in 298 premenopausal women. To test for the association with breast cancer risk, we carried out follow-up genotyping in 90,916 cases and 89,893 controls from the Breast Cancer Association Consortium. All women were of European ancestry. Results: For pregnanediol-3-glucuronide, there were no genome-wide significant associations; for oestrone-3-glucuronide, we identified a single peak mapping to the CYP3A locus, annotated by rs45446698. The minor rs45446698-C allele was associated with lower oestrone-3-glucuronide (−49.2%, 95% CI −56.1% to −41.1%, P = 3.1 × 10–18); in follow-up analyses, rs45446698-C was also associated with lower progesterone (−26.7%, 95% CI −39.4% to −11.6%, P = 0.001) and reduced risk of oestrogen and progesterone receptor-positive breast cancer (OR = 0.86, 95% CI 0.82–0.91, P = 6.9 × 10–8). Conclusions: The CYP3A7*1C allele is associated with reduced risk of hormone receptor-positive breast cancer possibly mediated via an effect on the metabolism of endogenous sex hormones in premenopausal women

Alexander Pope’s Dunciad and Ned Ward’s London Spy: Experiments in Text Visualization

Text visualization is the technique of using graphs and charts to examine text as data. Often, these do not represent a text directly and instead display an output based on word counts, word sequences, and so on. This technique can provide insights into important keywords in a text, provide an overview of textual content, or reveal trends and patterns within one text or across many texts. This paper describes recent development of and experiments with several tools for the Grub Street Project to generate visualizations of eighteenth-century texts, especially in terms of the spatial relationships of words and entities on the pages of the original documents. Two examples are discussed in this article as test cases: Edward Ward’s The London Spy Compleat, in Eighteen Parts (1703) and Alexander Pope’s The Dunciad. With Notes Variorum (1729).La visualisation textuelle est une technique qui utilise des graphiques et des diagrammes afin d’examiner des textes sous la forme de données. Ces graphiques et diagrammes, en général, ne représentent pas les textes de manière directe, mais présentent des résultats fondés sur le nombre de mots, sur les termes en séquence, et ainsi de suite. Cette technique peut révéler des mots-clés importants, donner un aperçu du contenu textuel, faire émerger des tendances récurrentes dans un seul texte ou à travers un corpus. Cet article décrit les avancées récentes de ce champ de recherche et les expériences menées avec ces nouveaux outils pour le Grub Street Project, lesquelles consistent à générer des visualisations de textes du dix-huitième siècle, en portant notamment une attention particulière aux rapports spatiaux entre les mots et les entités dans les documents originaux. En guise d’exemple, deux études de cas sont abordées : The London Spy Compleat, in Eighteen Parts d’Edward Ward (1703) et The Dunciad. With Notes Variorum d’Alexander Pope (1729)

Twenty Years after the Death of the Book: Literature, the Humanities, and the Knowledge Economy

Twenty Years after the Death of the Book: Literature, the Humanities, and the Knowledge Econom

Chapter 14 Beyond GIS: On mapping early modern narratives and the chronotope

This essay examines the possibilities for creating digital editions as representations of social and topographical networks of time and space, rather than as standalone e-versions of printed books.   La présente dissertation étudie les possibilités de créer des éditions numériques comme représentations de réseaux sociaux et topographiques dans le temps et l’espace, plutôt que comme versions électroniques autonomes de livres imprimés

The Enlightenment cyborg : aspects and origins of the postmodern man-machine metaphor

Popular media, literature, and theory suggests that technology has induced a newly evolved, posthuman and postmodern (or "post-Enlightenment") cyborg consciousness. I suggest, as an alternative reading to the notion that we are evolving towards a disembodied posthuman state which will revolutionise what it means to be human, that the literature of cyborgs incorporates and reinscribes traditional narratives about human identity. This project analyses representative tropes of the cyborg in contemporary discourse from an explicitly historical perspective. Although dualisms such as mind/matter or soul/body are recognised in current theorising of the cyborg, little has been written about the historical relationship of mechanism and humanity in the ongoing discussion of cyborg mind/body ontology. The cyborg in much of our literature throughout a wide range of genres is represented by the exaggerated and horrifying effacement of human embodiment to embellish an underlying concern about the consequences to the human spirit when we can be reproduced by technological means. This thesis argues that much of the discourse about the novelty of the "postmodern" human-machine, however, is not unprecedented. Cyborg literature re-presents themes and concerns regarding the man-machine of the seventeenth and eighteenth centuries, and continues to reflect a religious debate about the spirit within the material body. Beginning with current notions of the supposed obsolescence of the body, this thesis explores how the contemporary cyborg functions as a device to reflect traditional (frequently Christian) values. Drawing on eighteenth-century medical philosophy and the satirical literary responses to mechanist definitions of body and soul, I demonstrate literary connections between medical and literary metaphors of the Enlightenment man-machine and the postmodern cyborg in popular media, fiction, and theory. The debate surrounding eighteenth-century materialism, primarily metaphorical and analogical in its representation of the body's mechanisms, contributed directly to current notions of figurative disembodiment and the status of the human soul in contemporary literature. I conclude that the cyborg as a figure of literature does not indicate a revolutionary change in social consciousness but repeatedly is a device used to affirm traditional religious concepts of human reproduction, individual free will, spirit and body, and life after death

Electronic Scholarly Editing in the University Classroom: an Approach to Project-based Learning

This paper describes a project-based senior undergraduate course in electronic scholarly editing at the University of Saskatchewan. Students used HTML to prepare and publish on the World Wide Web electronic documentary editions of two seventeenth-century books: the anonymous 'Eighth Liberal Science: or a New-found Art and Order of Drinking '[1650], and Edward Whitaker's 'Directions for Brewing Malt Liquors' [1700]. The course offered students the benefits of project-based pedagogy—collaboration, original research, independent decision making, and preparation of a concrete product with real-world usefulness. The paper also describes the editions produced by the class, with particular emphasis on the textual issues that emerged, and the students' technological and editorial resolution of those issues. It concludes with a discussion of the benefits of project-based pedagogy in the undergraduate humanities classroom