Author: "Torres, Diana" / Database: OAIster - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"Torres, Diana"' showing total 397 results

Start Over Author "Torres, Diana" Database OAIster

397 results on '"Torres, Diana"'

1. A novel barcoded nanopore sequencing workflow of high-quality, full-length bacterial 16S amplicons for taxonomic annotation of bacterial isolates and complex microbial communities

Author: Howe, Adina, Howe, A ( Adina ), Dommann, Julian; https://orcid.org/0009-0008-2448-3795, Kerbl-Knapp, Jakob; https://orcid.org/0009-0001-5463-2762, Albertos Torres, Diana; https://orcid.org/0000-0002-0490-3974, Egli, Adrian; https://orcid.org/0000-0002-3564-8603, Keiser, Jennifer; https://orcid.org/0000-0003-0290-3521, Schneeberger, Pierre H H; https://orcid.org/0000-0002-8586-4937, Howe, Adina, Howe, A ( Adina ), Dommann, Julian; https://orcid.org/0009-0008-2448-3795, Kerbl-Knapp, Jakob; https://orcid.org/0009-0001-5463-2762, Albertos Torres, Diana; https://orcid.org/0000-0002-0490-3974, Egli, Adrian; https://orcid.org/0000-0002-3564-8603, Keiser, Jennifer; https://orcid.org/0000-0003-0290-3521, and Schneeberger, Pierre H H; https://orcid.org/0000-0002-8586-4937
Abstract: Due to recent improvements, Nanopore sequencing has become a promising method for experiments relying on amplicon sequencing. We describe a flexible workflow to generate and annotate high-quality, full-length 16S rDNA amplicons. We evaluated it for two applications, namely, (i) identification of bacterial isolates and (ii) species-level profiling of microbial communities. We assessed the identification of single bacterial isolates by sequencing, using a set of barcoded full-length 16S rRNA gene primer pairs (pair A), on 47 isolates encompassing multiple genera and compared those results with matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS)-based identification. Species-level community profiling was tested with two sets of barcoded full-length 16S primer pairs (A and B) and compared to the results obtained with shotgun Illumina sequencing using 27 stool samples. We developed a Nextflow pipeline to retain high-quality reads and taxonomically annotate them. We found high agreement between our workflow and MALDI-TOF data for isolate identification (positive predictive value = 0.90, Cramér’s V = 0.857, and Theil’s U= 0.316). For species-level community profiling, we found strong correlations (r$_{s}$ > 0.6) of alpha diversity indices between the two primer sets and Illumina sequencing. At the community level, we found significant but small differences when comparing sequencing techniques. Finally, we found a moderate to strong correlation when comparing the relative abundances of individual species (average r$_{s}$ = 0.6 and 0.533 for primers A and B). Despite identified shortcomings, the proposed workflow enabled accurate identification of single bacterial isolates and prominent features in microbial communities, making it a worthwhile alternative to MALDI-TOF MS and Illumina sequencing. IMPORTANCE A quick, robust, simple, and cost-effective method to identify bacterial isolates and communities in each sample is indisp
Published: 2024

2. Anti-SARS-CoV-2 total immunoglobulin and neutralising antibody responses in healthy blood donors throughout the COVID-19 pandemic: a longitudinal observational study

Author: Gütlin, Yukino, Albertos Torres, Diana, Gensch, Alexander, Schlotterbeck, Ann-Kathrin, Stöger, Laurent, Heller, Stefanie, Infanti, Laura, Barut, Güliz Tuba, Thiel, Volker; https://orcid.org/0000-0002-5783-0887, Leuzinger, Karoline; https://orcid.org/0000-0002-5654-9356, Hirsch, Hans H; https://orcid.org/0000-0003-0883-0423, Buser, Andreas, Egli, Adrian; https://orcid.org/0000-0002-3564-8603, Gütlin, Yukino, Albertos Torres, Diana, Gensch, Alexander, Schlotterbeck, Ann-Kathrin, Stöger, Laurent, Heller, Stefanie, Infanti, Laura, Barut, Güliz Tuba, Thiel, Volker; https://orcid.org/0000-0002-5783-0887, Leuzinger, Karoline; https://orcid.org/0000-0002-5654-9356, Hirsch, Hans H; https://orcid.org/0000-0003-0883-0423, Buser, Andreas, and Egli, Adrian; https://orcid.org/0000-0002-3564-8603
Abstract: INTRODUCTION: Quantifying antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and neutralising antibodies may help to understand protection at the individual and population levels. Determination of neutralising antibodies using classical virus neutralisation tests (VNT) is considered the gold standard, but they are costly and time-intensive. Enzyme-linked immunosorbent assay (ELISA)-based surrogate VNTs (sVNT) or anti-SARS-CoV-2 spike protein receptor binding domain immunoglobulins (anti-S-RBD Ig) may be suitable alternatives to VNTs. We aimed to (a) explore the correlations between anti-S-RBD Ig, VNT, and sVNT measurements and (b) describe humoral immunity against SARS-CoV-2 after vaccination, natural infection, and vaccine breakthrough infection in healthy blood donors. METHODS: We measured total anti-SARS-CoV-2 Ig in 5714 serum samples from 2748 healthy individuals visiting the Swiss Red Cross Blood Donation Centre in Basel from 03/2020 to 04/2022. We used the Elecsys® Anti-SARS-CoV-2 immunoassay (Roche) against the N- and S-receptor binding domain (RBD) proteins. In a subset of 548 samples from 123 donors, we conducted sVNTs against the Wuhan wild-type SARS-CoV-2 (SARS-CoV-2 Neutralizing Antibodies Detection Kit; Adipogen™). In 100 samples from 40 donors, we correlated sVNT and VNTs against the wild-type (D614G WU1) virus. Surveys were sent to the blood donors to collect data on their SARS-CoV-2 infection and vaccination status. Using this data, donors were categorised as “vaccination only”, “infection before vaccination”, “post-vaccine breakthrough infection”, and “natural infection only”. RESULTS: Our longitudinal observation study cohort consisted of 50.7% males with a median age of 31 years (range 18–75 y). Anti-SARS-CoV-2 N protein positivity rates per month indicate 57.1% (88/154) of the cohort was infected up to 04/2022. No differences in seropositivity were found between sexes, age groups, blood types (AB0 or RhD), and cytomeg
Published: 2024

3. Predominant technical actions used in the European judo championship

Author: Batista, Marco Alexandre da Silva, da Silva, Carlos Manuel Marques, Torres, Diana, Conceiçao, Ana, Borrego, Carla, Louro, Hugo, Batista, Marco Alexandre da Silva, da Silva, Carlos Manuel Marques, Torres, Diana, Conceiçao, Ana, Borrego, Carla, and Louro, Hugo
Abstract: Judo is an Olympic combat sport that is divided into male and female weight categories. Each weight category implies significant differences in technical and strategic dimensions, as well as physiological, performance, and body composition among com-petitors. This study aimed to determine the technical actions predominance used by judokas in the European Judo Championship 2021. We observed 398 judo combats, in the various weight categories male and female, disputed in the European Judo Championship 2021. It was used an observation system in accordance with the classification of judo techniques proposed by Kodokan. An observation system was used according to the Kodokan classification of judo techniques. In Nage-Waza combat, there was a predominance leg technique (Ashi-Waza), arm technique (Te-Waza), hip technique (Koshi-Waza), side sacrifice techniques (Yoko-Sutemi-Waza) and frontal sacri-fice techniques (Ma-Sutemi-Waza). When we focused our observation on the effectiveness of applied techniques, we observed more techniques scored with Ippon than Wazari. We can also observe that Shido was the significantly more recurrent punishment during male combats.
Published: 2024

4. El garantismo y la filosofía del derecho

Author: Ramírez Torres, Diana Gissella and Ramírez Torres, Diana Gissella
Abstract: El mundo de la filosofía implica pasearse por los principios generales que dan vida al conocimiento de la realidad circundante, es buscar el sentido que impulsa las acciones humanas, es vincular la filosofía con el derecho, es profundizar en esas acciones del hombre, puesto que la filosofía del derecho implica penetrar en el estudio del fenómeno jurídico, desde lo abstracto, buscar una visión integral del mismo; es decir, incluir aspectos como lo normativo, lo institucional pero también, lo social y lo moral. Hablar de garantismo es entenderlo como un modelo que asegura el cumplimiento de los derechos establecidos en el ordenamiento jurídico, significando el ideal de legalidad y legitimidad imperante en la sociedad, logrando la observancia de los derechos fundamentales. El artículo tiene como objetivo analizar el Garantismo y la filosofía del Derecho. Se apoyó en una investigación documental. Se concluyó que el garantismo como forma de ideología jurídica, orientada a la representación, comprensión, interpretación y explicación del derecho, alcanza una fuerte conexión con la filosofía del derecho al tener esta también una concepción de análisis profundo del derecho, para con ello brindar nociones a las distintas disciplinas jurídicas y así lograr una mejor comprensión y aplicación del derecho.
Published: 2024

5. Los mecanismos de solución de controversias en los derechos humanos

Author: Ramírez Torres, Diana Gissella and Ramírez Torres, Diana Gissella
Abstract: Los mecanismos de solución de controversias, constituyen una serie de procedimientos, que permiten que los ciudadanos resuelvan sus divergencias, sin la participación de un órgano jurisdiccional. Pueden mencionarse dentro de estos, la negociación, mediación, conciliación y el arbitraje. Ahora bien, ubicarse en los derechos humanos, indica, que son prerrogativas, de la persona humana, las cuales toda autoridad tiene la obligación de respetar, proteger y defender. Dentro de estos derechos se encuentran el de la vida, la libertad, la salud, la educación, entre otros; sin embargo, es fundamental mencionar el derecho al acceso a la justicia, englobando esto, el hecho que toda persona tiene el derecho que se le imparta justicia prontamente, sin dilaciones indebidas, sin discriminaciones, respetando los lapsos y términos estipulados por las leyes. Esta atención especial al acceso a la justicia, incluye en algunos casos el empleo de los denominados mecanismos alternativos de solución de controversias o medios alternativos de resolución de conflictos, como una forma de solventar divergencias de manera más rápida, económica, obteniendo resultados útiles y estables. Partiendo de lo anteriormente señalado, el presente artículo tuvo como propósito analizar los mecanismos de solución de controversias en los derechos humanos. Se empleó para el desarrollo de la investigación una metodología de tipo documental, de nivel analítico. Una vez realizada la revisión de diversos materiales escritos se concluyó que los mecanismos de solución de conflictos emergen al margen de los tribunales, sin embargo, ofrecen la posibilidad de resolver conflictos, sin los traumas que genera un proceso judicial.
Published: 2024

6. UCI EyeMobile Exam Findings from School Children Following on-Site Screening

Author: Hong,John, Choi,Elliot, Suh,Susie, Bui,Joseph, Storch,Annabelle, Walker,Kimberly, Shahraki,Kourosh, Yanez,Carolina, Torres,Diana, Espinoza,Jennifer, Molina,Iliana, Suh,Donny, Hong,John, Choi,Elliot, Suh,Susie, Bui,Joseph, Storch,Annabelle, Walker,Kimberly, Shahraki,Kourosh, Yanez,Carolina, Torres,Diana, Espinoza,Jennifer, Molina,Iliana, and Suh,Donny
Abstract: John D Hong,1 Elliot H Choi,1 Susie Suh,1 Joseph H Bui,1 Annabelle M Storch,1 Kimberly R Walker,1 Kourosh Shahraki,1 Carolina Yanez,1 Diana Torres,1 Jennifer Espinoza,1 Iliana Molina,2,&ast; Donny W Suh1,&ast; 1Gavin Herbert Eye Institute, Department of Ophthalmology, University of California, Irvine, CA, USA; 2Shiley Eye Institute, Department of Ophthalmology, University of California, San Diego, CA, USA&ast;These authors contributed equally to this workCorrespondence: Donny W Suh, Gavin Herbert Eye Institute, Department of Ophthalmology, University of California, Irvine, 850 Health Sciences Road, Irvine, CA, 92697, USA, Tel +1 949 824-4122, Email donnys@hs.uci.edu Iliana Molina, Shiley Eye Institute, Department of Ophthalmology, University of California, San Diego, 9415 Campus Point Dr, San Diego, CA, 92037, USA, Tel +1 858 822-2585, Email imolina@health.ucsd.eduPurpose: Uncorrected refractive errors (REs) and amblyopia can lead to visual impairment with deleterious effects on quality of life and academic performance. Early detection and treatment by community vision care programs, such as the UCI EyeMobile for Children, can aid in addressing preventable vision loss.Methods: A total of 5074 children between the ages of 3 and 10 years were screened at 153 locations, including preschools, head start programs, and elementary schools within Orange County (OC), California (CA). Subsequently, 1024 children presented for comprehensive eye examinations. A retrospective analysis of all examined children was conducted, determining the frequency and severity of REs and amblyopia and the spectacle prescription rate by age. Propensity score matching analysis evaluated the effect of median household income on RE and amblyopia frequency.Results: Among those who failed initial screening and were subsequently examined, significant rates of REs and amblyopia were detected: myopia (24.4%), hyperopia (35.4%), astigmatism (71.8%), anisometropia (8.9%), amblyopia (7.0%), an
Published: 2024

7. El salón de reinos a escena en el Museo del Prado: El Brasil restituido de Lope de Vega por el Instituto del Teatro de Madrid

Author: Martínez Valderas, Jara, Álvarez Barco, Mario, Caparrós Rodríguez, Marta, Clemente Sánchez, Raquel, Fernández Villanueva, Juan José, Florensa Tomasi, Mónica, García García, Bernardo José, García Molero,Patricia, Gil Carrera, Micaela Teresa, González Vigara, Paula, Herranz Sotoca, Irene, Ruíz Moya, Itziar, Ruíz Torres, Diana Carolina, Velasquez Serrano, Jhonnathan Josseph, Vélez Sáinz, José Julio, Martínez Valderas, Jara, Álvarez Barco, Mario, Caparrós Rodríguez, Marta, Clemente Sánchez, Raquel, Fernández Villanueva, Juan José, Florensa Tomasi, Mónica, García García, Bernardo José, García Molero,Patricia, Gil Carrera, Micaela Teresa, González Vigara, Paula, Herranz Sotoca, Irene, Ruíz Moya, Itziar, Ruíz Torres, Diana Carolina, Velasquez Serrano, Jhonnathan Josseph, and Vélez Sáinz, José Julio
Abstract: En el Salón de Reinos, quedó inmortalizado en el lienzo de fray Juan Bautista Maíno, considerado por los contemporáneos como la obra magna de esta extraordinaria galería del Palacio del Buen Retiro. Este volumen, centrado en la conquista holandesa de 1624 y la recuperación luso-española de Salvador de Bahía de 1625, es el segundo de la colección El salón de Reinos en las noticias y el teatro. Proporciona al lector una visión rigurosa y contextualizada de cómo fue recibida la noticia y reinterpretada a través de los relatos, impresos o manuscritos que se difundieron en la época y su posterior representación en la ficción teatral y pictórica. En la primera parte José Manuel Santos Pérez e Irene María Vicente Martín sitúan el suceso en el panorama internacional, mercado por el reinicio de las hostilidades hispano-neerlandesas en el Atlántico, y en el ámbito local, determinado por la creciente importancia geopolítica de Brasil y, más concretamente, el Salvador, en el complejo entramado territorial de la Monarquía Hispánica. Incluye también el más completo listado de relaciones de sucesos, tanto holandeses, luso-castellanas de los acontecimientos de 1624-1625, y ediciones críticas de las más significativas. Por su parte Enrique Rodrigues-Moura edita y analiza dos de las obras de teatro que se escribieron y representaron sobre aquellas victorias annus mirabilis de 1625, El Brasil restituido de Lope de Vega y Pérdida y restauración de la Bahía de Todos Santos de Juan Antonio Correa. Lope de Vega terminó su comedia en octubre de 1625, pocos días antes de la llegada del grueso de la flota a Cádiz utilizando algunas de aquellas relaciones.
Published: 2023

8. Producción y cuantificación de carbohidratos a partir de residuos lignocelulósicos por hongos del género aspergillus

Author: Ríos Torres, Diana Nicole, Salmerón, Ivan, Quintero Ramos, Armando, Pérez Vega, Samuel B., Cisneros de la Cueva, Sergio, Ríos Torres, Diana Nicole, Salmerón, Ivan, Quintero Ramos, Armando, Pérez Vega, Samuel B., and Cisneros de la Cueva, Sergio
Abstract: Uno de los principales residuos generados en México son los desechos urbanos de jardinería, principalmente compuestos de residuos lignocelulosicos que contienen azúcares que no se encuentran disponibles para ser utilizados por los microorganismos y aprovecharlos para generar compuestos químicos de alto valor agregado. En este estudio por fermentación en medio sólido utilizando los residuos de jardinería como sustrato, se evaluó la capacidad de degradación de lignina y producción de azúcares como glucosa, galactosa y xilosa, probando tres diferentes especies de hongos del género Aspergillus a humedades de 60%, 70% y 80%. Las diferentes especies de hongos del género Aspergillus fueron designados como cepas A1, A2 y A3. Los máximos valores de degradación de lignina de 60.29±0.57% y producción de glucosa de 116.52±0.99 ppm, galactosa de 50.86±0.51ppm y xilosa de 38.27±0.47 ppm fueron obtenidos para la cepa A1 a una humedad de 70%.
Published: 2023

9. La clase de Español-literatura: espacio idóneo para fortalecer la educación ambiental

Author: Aparicio Torres, Diana Esther, Dominguez Hernandez, Elimey, Aparicio Torres, Diana Esther, and Dominguez Hernandez, Elimey
Abstract: Environmental education as a management tool in the context of the Spanish-Literature subject favors the development of sensitivity in relation to the environment and the making of critical evaluations, and also expresses the apprehension of a different relationship between literature and the environment. It is a topical issue and in correspondence to this, the training model of Basic Secondary students, plans and projects curricular strategies that emerge from the educational strategies and the conception of the disciplines of the curriculum, becoming essential axes to be treated from the classes, that is why the article was aimed at offering a set of teaching activities with an interdisciplinary and integrative nature, aimed at strengthening the environmental education of students. Methods of the theoretical level were used: historical-logical, analysis-synthesis, inductive-deductive; the empirical level methods: observation, survey, interview, document analysis and the mathematical method for the percentage calculation procedure in the quantitative analysis of the results produced by the applied instruments. The existence of problems related to the topic under investigation made it possible to project actions aimed at its treatment; It is worth highlighting their potential as active readers who have communication skills, responsibility and enthusiasm to face the activities and tasks assigned to them., A educação ambiental como ferramenta de gestão no contexto da disciplina de Literatura Espanhola favorece o desenvolvimento da sensibilidade em relação ao meio ambiente e a realização de avaliações críticas, e também expressa a apreensão de uma relação diferente entre a literatura e o meio ambiente.É um tema atual e em correspondência a isso, o modelo de formação dos alunos do Secundário Básico, planeja e projeta estratégias curriculares que emergem das estratégias educacionais e da concepção das disciplinas do currículo, tornando-se eixos essenciais a serem tratados desde as aulas, por isso o artigo teve como objetivo oferecer um conjunto de atividades didáticas de caráter interdisciplinar e integrador, visando fortalecer a educação ambiental dos alunos.Foram utilizados métodos do nível teórico: histórico-lógico, análise-síntese, indutivo-dedutivo;os métodos de nível empírico: observação, levantamento, entrevista, análise documental e o método matemático para o procedimento de cálculo percentual na análise quantitativa dos resultados produzidos pelos instrumentos aplicados.A existência de problemas relacionados ao tema investigado possibilitou projetar ações voltadas ao seu tratamento;Vale destacar seu potencial como leitores ativos, que possuem capacidade de comunicação, responsabilidade e entusiasmo para enfrentar as atividades e tarefas que lhes são atribuídas., La educación ambiental como herramienta de gestión en el contexto de la asignatura Español- Literatura favorece el desarrollo de la sensibilidad en relación con el entorno y a la realización de valoraciones críticas con respecto a este, además expresa la aprehensión de una relación diferente entre literatura y medio ambiente. Es una temática de actualidad y en correspondencia a ello, el modelo de formación de los estudiantes de Secundaria Básica, planifica y proyecta estrategias curriculares que emergen desde las estrategias educativas y la concepción de las disciplinas del currículo convirtiéndose en ejes esenciales para ser tratados desde las clases. En la investigación se emplearon los métodos del nivel teórico: histórico-lógico, análisis-síntesis, inductivo-deductivo; los métodos del nivel empírico: la observación pedagógica, el cuestionario, la entrevista, el análisis de fondos bibliográficos y de los documentos normativos; y el método matemático: el procedimiento del cálculo porcentual en el análisis cuantitativo de los resultados que arrojaron los instrumentos aplicados. La experiencia propuesta permitió corroborar la existencia de problemas referidos al conocimiento de los problemas ambientales y la manifestación de conductas incorrectas en los estudiantes que permitieron proyectar acciones para su erradicación. A pesar de todo ello cabe resaltar las potencialidades de ellos como: son lectores activos, tienen habilidades comunicativas, responsabilidad y entusiasmo para enfrentar las actividades y tareas que se les asignan.
Published: 2023

10. Towards a Theory of Interoperability of Software Systems

Author: Torres, Diana M., Chen, David, Villavicencio, Mónica, Zapata Jaramillo, Carlos Mario, Torres, Diana M., Chen, David, Villavicencio, Mónica, and Zapata Jaramillo, Carlos Mario
Abstract: Interoperability is a property of software quality that is related to the cooperation between software systems for exchanging information. However, this concept is not well explained or understood. A theory would be useful to explain interoperability in terms of its essential elements and propositions. Theoretical contributions of interoperability are intended to formalize this concept by using common frameworks, models, and meta-models. However, tentative contributions developed in the past have failed to propose a theory of interoperability due to four reasons: (1) a disunified vocabulary is used, (2) the essential elements for describing interoperability are not well identified, (3) only a single level of interoperability is assessed, and (4) interoperability principles are not well formalized. This paper tentatively proposes an axiomatic theory of interoperability as a complementary approach to the existing knowledge. The proposed theory seeks to better formalize the concepts of interoperability and suggest actions aimed at establishing interoperability. After a brief review of related works and the state of the art, a set of axioms and propositions is presented. This theory is evaluated by a group of experts, and an example is presented to illustrate its use. Conclusions and future works are outlined at the end of the paper., La interoperabilidad es una propiedad de calidad del software que tiene que ver con la cooperación entre sistemas de software para intercambiar información. Sin embargo, este concepto carece de una explicación o un completo entendimiento. Una teoría permitiría explicar la interoperabilidad en términos de sus elementos esenciales y proposiciones. Las contribuciones teóricas acerca de la interoperabilidad proponen formalizar este concepto utilizando marcos comunes, modelos y metamodelos. No obstante, las contribuciones tentativas desarrolladas en el pasado no logran proponer una teoría. Esto, debido a cuatro razones: (1) usan un vocabulario desunificado, (2) omiten los elementos esenciales para describir la interoperabilidad, (3) se enfocan en un nivel particular de interoperabilidad y (4) presentan una formalización incompleta con respecto a los principios de interoperabilidad. En este artículo se propone una teoría axiomática de interoperabilidad como un enfoque complementario al conocimiento existente. Con la teoría propuesta se pretende formalizar los conceptos de interoperabilidad y sugerir acciones para establecer la interoperabilidad. Con base en una revisión de los trabajos relacionados y el estado del arte, se define un conjunto de axiomas y proposiciones. Un conjunto de expertos valida la teoría, y se expone un ejemplo para ilustrar su uso. Las conclusiones y los trabajos futuros se describen al final del artículo.
Published: 2023

11. Ejea: Proyectos y realidades: Una mirada a la evolución del urbanismo de Ejea de los Caballeros con motivo del I Centenario de la inauguración de su Ensanche

Author: Espada Torres, Diana Mª and Espada Torres, Diana Mª
Abstract: Es reseña del libro: "Ejea: Proyectos y realidades: Una mirada a la evolución del urbanismo de Ejea de los Caballeros con motivo del I Centenario de la inauguración de su Ensanche" ISBN 978-84-9911-529-0
Published: 2023

12. Ejea: Proyectos y realidades: Una mirada a la evolución del urbanismo de Ejea de los Caballeros con motivo del I Centenario de la inauguración de su Ensanche

Author: Espada Torres, Diana Mª and Espada Torres, Diana Mª
Abstract: Es reseña del libro: "Ejea: Proyectos y realidades: Una mirada a la evolución del urbanismo de Ejea de los Caballeros con motivo del I Centenario de la inauguración de su Ensanche" ISBN 978-84-9911-529-0
Published: 2023

13. Towards a Theory of Interoperability of Software Systems

Author: Torres, Diana M., Chen, David, Villavicencio, Mónica, Zapata Jaramillo, Carlos Mario, Torres, Diana M., Chen, David, Villavicencio, Mónica, and Zapata Jaramillo, Carlos Mario
Abstract: Interoperability is a property of software quality that is related to the cooperation between software systems for exchanging information. However, this concept is not well explained or understood. A theory would be useful to explain interoperability in terms of its essential elements and propositions. Theoretical contributions of interoperability are intended to formalize this concept by using common frameworks, models, and meta-models. However, tentative contributions developed in the past have failed to propose a theory of interoperability due to four reasons: (1) a disunified vocabulary is used, (2) the essential elements for describing interoperability are not well identified, (3) only a single level of interoperability is assessed, and (4) interoperability principles are not well formalized. This paper tentatively proposes an axiomatic theory of interoperability as a complementary approach to the existing knowledge. The proposed theory seeks to better formalize the concepts of interoperability and suggest actions aimed at establishing interoperability. After a brief review of related works and the state of the art, a set of axioms and propositions is presented. This theory is evaluated by a group of experts, and an example is presented to illustrate its use. Conclusions and future works are outlined at the end of the paper., La interoperabilidad es una propiedad de calidad del software que tiene que ver con la cooperación entre sistemas de software para intercambiar información. Sin embargo, este concepto carece de una explicación o un completo entendimiento. Una teoría permitiría explicar la interoperabilidad en términos de sus elementos esenciales y proposiciones. Las contribuciones teóricas acerca de la interoperabilidad proponen formalizar este concepto utilizando marcos comunes, modelos y metamodelos. No obstante, las contribuciones tentativas desarrolladas en el pasado no logran proponer una teoría. Esto, debido a cuatro razones: (1) usan un vocabulario desunificado, (2) omiten los elementos esenciales para describir la interoperabilidad, (3) se enfocan en un nivel particular de interoperabilidad y (4) presentan una formalización incompleta con respecto a los principios de interoperabilidad. En este artículo se propone una teoría axiomática de interoperabilidad como un enfoque complementario al conocimiento existente. Con la teoría propuesta se pretende formalizar los conceptos de interoperabilidad y sugerir acciones para establecer la interoperabilidad. Con base en una revisión de los trabajos relacionados y el estado del arte, se define un conjunto de axiomas y proposiciones. Un conjunto de expertos valida la teoría, y se expone un ejemplo para ilustrar su uso. Las conclusiones y los trabajos futuros se describen al final del artículo.
Published: 2023

14. Aggregation tests identify new gene associations with breast cancer in populations with diverse ancestry

Author: Mueller, Stefanie H., Lai, Alvina G., Valkovskaya, Maria, Michailidou, Kyriaki, Bolla, Manjeet K., Wang, Qin, Dennis, Joe, Lush, Michael, Abu-Ful, Zomoruda, Ahearn, Thomas U., Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Arndt, Volker, Aronson, Kristan J., Augustinsson, Annelie, Baert, Thais, Freeman, Laura E. Beane, Beckmann, Matthias W., Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Bogdanova, Natalia, V, Bojesen, Stig E., Bonanni, Bernardo, Brenner, Hermann, Brucker, Sara Y., Buys, Saundra S., Castelao, Jose E., Chan, Tsun L., Chang-Claude, Jenny, Chanock, Stephen J., Choi, Ji-Yeob, Chung, Wendy K., Colonna, Sarah, V, Cornelissen, Sten, Couch, Fergus J., Czene, Kamila, Daly, Mary B., Devilee, Peter, Dork, Thilo, Dossus, Laure, Dwek, Miriam, Eccles, Diana M., Ekici, Arif B., Eliassen, A. Heather, Engel, Christoph, Evans, D. Gareth, Fasching, Peter A., Fletcher, Olivia, Flyger, Henrik, Gago-Dominguez, Manuela, Gao, Yu-Tang, Garcia-Closas, Montserrat, Garcia-Saenz, Jose A., Genkinger, Jeanine, Gentry-Maharaj, Aleksandra, Grassmann, Felix, Guenel, Pascal, Gundert, Melanie, Haeberle, Lothar, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hall, Per, Harkness, Elaine F., Harrington, Patricia A., Hartikainen, Jaana M., Hartman, Mikael, Hein, Alexander, Ho, Weang-Kee, Hooning, Maartje J., Hoppe, Reiner, Hopper, John L., Houlston, Richard S., Howell, Anthony, Hunter, David J., Huo, Dezheng, Investigators, Abctb, Ito, Hidemi, Iwasaki, Motoki, Jakubowska, Anna, Janni, Wolfgang, John, Esther M., Jones, Michael E., Jung, Audrey, Kaaks, Rudolf, Kang, Daehee, Khusnutdinova, Elza K., Kim, Sung-Won, Kitahara, Cari M., Koutros, Stella, Kraft, Peter, Kristensen, Vessela N., Kubelka-Sabit, Katerina, Kurian, Allison W., Kwong, Ava, Lacey, James, V, Lambrechts, Diether, Le Marchand, Loic, Li, Jingmei, Linet, Martha, Lo, Wing-Yee, Long, Jirong, Lophatananon, Artitaya, Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, Matsuo, Keitaro, Mavroudis, Dimitrios, Menon, Usha, Muir, Kenneth, Murphy, Rachel A., Nevanlinna, Heli, Newman, William G., Niederacher, Dieter, O'Brien, Katie M., Obi, Nadia, Offit, Kenneth, Olopade, Olufunmilayo, I, Olshan, Andrew F., Olsson, Hakan, Park, Sue K., Patel, Alpa, V, Patel, Achal, Perou, Charles M., Peto, Julian, Pharoah, Paul D. P., Plaseska-Karanfilska, Dijana, Presneau, Nadege, Rack, Brigitte, Radice, Paolo, Ramachandran, Dhanya, Rashid, Muhammad U., Rennert, Gad, Romero, Atocha, Ruddy, Kathryn J., Ruebner, Matthias, Saloustros, Emmanouil, Sandler, Dale P., Sawyer, Elinor J., Schmidt, Marjanka K., Schmutzler, Rita K., Schneider, Michael O., Scott, Christopher, Shah, Mitul, Sharma, Priyanka, Shen, Chen-Yang, Shu, Xiao-Ou, Simard, Jacques, Surowy, Harald, Tamimi, Rulla M., Tapper, William J., Taylor, Jack A., Teo, Soo Hwang, Teras, Lauren R., Toland, Amanda E., Tollenaar, Rob A. E. M., Torres, Diana, Torres-Mejia, Gabriela, Troester, Melissa A., Truong, Therese, Vachon, Celine M., Vijai, Joseph, Weinberg, Clarice R., Wendt, Camilla, Winqvist, Robert, Wolk, Alicja, Wu, Anna H., Yamaji, Taiki, Yang, Xiaohong R., Yu, Jyh-Cherng, Zheng, Wei, Ziogas, Argyrios, Ziv, Elad, Dunning, Alison M., Easton, Douglas F., Hemingway, Harry, Hamann, Ute, Kuchenbaecker, Karoline B., Mueller, Stefanie H., Lai, Alvina G., Valkovskaya, Maria, Michailidou, Kyriaki, Bolla, Manjeet K., Wang, Qin, Dennis, Joe, Lush, Michael, Abu-Ful, Zomoruda, Ahearn, Thomas U., Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Arndt, Volker, Aronson, Kristan J., Augustinsson, Annelie, Baert, Thais, Freeman, Laura E. Beane, Beckmann, Matthias W., Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Bogdanova, Natalia, V, Bojesen, Stig E., Bonanni, Bernardo, Brenner, Hermann, Brucker, Sara Y., Buys, Saundra S., Castelao, Jose E., Chan, Tsun L., Chang-Claude, Jenny, Chanock, Stephen J., Choi, Ji-Yeob, Chung, Wendy K., Colonna, Sarah, V, Cornelissen, Sten, Couch, Fergus J., Czene, Kamila, Daly, Mary B., Devilee, Peter, Dork, Thilo, Dossus, Laure, Dwek, Miriam, Eccles, Diana M., Ekici, Arif B., Eliassen, A. Heather, Engel, Christoph, Evans, D. Gareth, Fasching, Peter A., Fletcher, Olivia, Flyger, Henrik, Gago-Dominguez, Manuela, Gao, Yu-Tang, Garcia-Closas, Montserrat, Garcia-Saenz, Jose A., Genkinger, Jeanine, Gentry-Maharaj, Aleksandra, Grassmann, Felix, Guenel, Pascal, Gundert, Melanie, Haeberle, Lothar, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hall, Per, Harkness, Elaine F., Harrington, Patricia A., Hartikainen, Jaana M., Hartman, Mikael, Hein, Alexander, Ho, Weang-Kee, Hooning, Maartje J., Hoppe, Reiner, Hopper, John L., Houlston, Richard S., Howell, Anthony, Hunter, David J., Huo, Dezheng, Investigators, Abctb, Ito, Hidemi, Iwasaki, Motoki, Jakubowska, Anna, Janni, Wolfgang, John, Esther M., Jones, Michael E., Jung, Audrey, Kaaks, Rudolf, Kang, Daehee, Khusnutdinova, Elza K., Kim, Sung-Won, Kitahara, Cari M., Koutros, Stella, Kraft, Peter, Kristensen, Vessela N., Kubelka-Sabit, Katerina, Kurian, Allison W., Kwong, Ava, Lacey, James, V, Lambrechts, Diether, Le Marchand, Loic, Li, Jingmei, Linet, Martha, Lo, Wing-Yee, Long, Jirong, Lophatananon, Artitaya, Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, Matsuo, Keitaro, Mavroudis, Dimitrios, Menon, Usha, Muir, Kenneth, Murphy, Rachel A., Nevanlinna, Heli, Newman, William G., Niederacher, Dieter, O'Brien, Katie M., Obi, Nadia, Offit, Kenneth, Olopade, Olufunmilayo, I, Olshan, Andrew F., Olsson, Hakan, Park, Sue K., Patel, Alpa, V, Patel, Achal, Perou, Charles M., Peto, Julian, Pharoah, Paul D. P., Plaseska-Karanfilska, Dijana, Presneau, Nadege, Rack, Brigitte, Radice, Paolo, Ramachandran, Dhanya, Rashid, Muhammad U., Rennert, Gad, Romero, Atocha, Ruddy, Kathryn J., Ruebner, Matthias, Saloustros, Emmanouil, Sandler, Dale P., Sawyer, Elinor J., Schmidt, Marjanka K., Schmutzler, Rita K., Schneider, Michael O., Scott, Christopher, Shah, Mitul, Sharma, Priyanka, Shen, Chen-Yang, Shu, Xiao-Ou, Simard, Jacques, Surowy, Harald, Tamimi, Rulla M., Tapper, William J., Taylor, Jack A., Teo, Soo Hwang, Teras, Lauren R., Toland, Amanda E., Tollenaar, Rob A. E. M., Torres, Diana, Torres-Mejia, Gabriela, Troester, Melissa A., Truong, Therese, Vachon, Celine M., Vijai, Joseph, Weinberg, Clarice R., Wendt, Camilla, Winqvist, Robert, Wolk, Alicja, Wu, Anna H., Yamaji, Taiki, Yang, Xiaohong R., Yu, Jyh-Cherng, Zheng, Wei, Ziogas, Argyrios, Ziv, Elad, Dunning, Alison M., Easton, Douglas F., Hemingway, Harry, Hamann, Ute, and Kuchenbaecker, Karoline B.
Abstract: Background: Low-frequency variants play an important role in breast cancer (BC) susceptibility. Gene-based methods can increase power by combining multiple variants in the same gene and help identify target genes. Methods: We evaluated the potential of gene-based aggregation in the Breast Cancer Association Consortium cohorts including 83,471 cases and 59,199 controls. Low-frequency variants were aggregated for individual genes' coding and regulatory regions. Association results in European ancestry samples were compared to single-marker association results in the same cohort. Gene-based associations were also combined in meta-analysis across individuals with European, Asian, African, and Latin American and Hispanic ancestry. Results: In European ancestry samples, 14 genes were significantly associated (q < 0.05) with BC. Of those, two genes, FMNL3 (P = 6.11 x 10(-6)) and AC058822.1 (P = 1.47 x 10(-4)), represent new associations. High FMNL3 expression has previously been linked to poor prognosis in several other cancers. Meta-analysis of samples with diverse ancestry discovered further associations including established candidate genes ESR1 and CBLB. Furthermore, literature review and database query found further support for a biologically plausible link with cancer for genes CBLB, FMNL3, FGFR2, LSP1, MAP3K1, and SRGAP2C. Conclusions: Using extended gene-based aggregation tests including coding and regulatory variation, we report identification of plausible target genes for previously identified single-marker associations with BC as well as the discovery of novel genes implicated in BC development. Including multi ancestral cohorts in this study enabled the identification of otherwise missed disease associations as ESR1 (P = 1.31 x 10(-5)), demonstrating the importance of diversifying study cohorts.
Published: 2023
Full Text: View/download PDF

15. Aggregation tests identify new gene associations with breast cancer in populations with diverse ancestry

Author: Mueller, Stefanie H., Lai, Alvina G., Valkovskaya, Maria, Michailidou, Kyriaki, Bolla, Manjeet K., Wang, Qin, Dennis, Joe, Lush, Michael, Abu-Ful, Zomoruda, Ahearn, Thomas U., Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Arndt, Volker, Aronson, Kristan J., Augustinsson, Annelie, Baert, Thais, Freeman, Laura E. Beane, Beckmann, Matthias W., Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Bogdanova, Natalia, V, Bojesen, Stig E., Bonanni, Bernardo, Brenner, Hermann, Brucker, Sara Y., Buys, Saundra S., Castelao, Jose E., Chan, Tsun L., Chang-Claude, Jenny, Chanock, Stephen J., Choi, Ji-Yeob, Chung, Wendy K., Colonna, Sarah, V, Cornelissen, Sten, Couch, Fergus J., Czene, Kamila, Daly, Mary B., Devilee, Peter, Dork, Thilo, Dossus, Laure, Dwek, Miriam, Eccles, Diana M., Ekici, Arif B., Eliassen, A. Heather, Engel, Christoph, Evans, D. Gareth, Fasching, Peter A., Fletcher, Olivia, Flyger, Henrik, Gago-Dominguez, Manuela, Gao, Yu-Tang, Garcia-Closas, Montserrat, Garcia-Saenz, Jose A., Genkinger, Jeanine, Gentry-Maharaj, Aleksandra, Grassmann, Felix, Guenel, Pascal, Gundert, Melanie, Haeberle, Lothar, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hall, Per, Harkness, Elaine F., Harrington, Patricia A., Hartikainen, Jaana M., Hartman, Mikael, Hein, Alexander, Ho, Weang-Kee, Hooning, Maartje J., Hoppe, Reiner, Hopper, John L., Houlston, Richard S., Howell, Anthony, Hunter, David J., Huo, Dezheng, Investigators, Abctb, Ito, Hidemi, Iwasaki, Motoki, Jakubowska, Anna, Janni, Wolfgang, John, Esther M., Jones, Michael E., Jung, Audrey, Kaaks, Rudolf, Kang, Daehee, Khusnutdinova, Elza K., Kim, Sung-Won, Kitahara, Cari M., Koutros, Stella, Kraft, Peter, Kristensen, Vessela N., Kubelka-Sabit, Katerina, Kurian, Allison W., Kwong, Ava, Lacey, James, V, Lambrechts, Diether, Le Marchand, Loic, Li, Jingmei, Linet, Martha, Lo, Wing-Yee, Long, Jirong, Lophatananon, Artitaya, Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, Matsuo, Keitaro, Mavroudis, Dimitrios, Menon, Usha, Muir, Kenneth, Murphy, Rachel A., Nevanlinna, Heli, Newman, William G., Niederacher, Dieter, O'Brien, Katie M., Obi, Nadia, Offit, Kenneth, Olopade, Olufunmilayo, I, Olshan, Andrew F., Olsson, Hakan, Park, Sue K., Patel, Alpa, V, Patel, Achal, Perou, Charles M., Peto, Julian, Pharoah, Paul D. P., Plaseska-Karanfilska, Dijana, Presneau, Nadege, Rack, Brigitte, Radice, Paolo, Ramachandran, Dhanya, Rashid, Muhammad U., Rennert, Gad, Romero, Atocha, Ruddy, Kathryn J., Ruebner, Matthias, Saloustros, Emmanouil, Sandler, Dale P., Sawyer, Elinor J., Schmidt, Marjanka K., Schmutzler, Rita K., Schneider, Michael O., Scott, Christopher, Shah, Mitul, Sharma, Priyanka, Shen, Chen-Yang, Shu, Xiao-Ou, Simard, Jacques, Surowy, Harald, Tamimi, Rulla M., Tapper, William J., Taylor, Jack A., Teo, Soo Hwang, Teras, Lauren R., Toland, Amanda E., Tollenaar, Rob A. E. M., Torres, Diana, Torres-Mejia, Gabriela, Troester, Melissa A., Truong, Therese, Vachon, Celine M., Vijai, Joseph, Weinberg, Clarice R., Wendt, Camilla, Winqvist, Robert, Wolk, Alicja, Wu, Anna H., Yamaji, Taiki, Yang, Xiaohong R., Yu, Jyh-Cherng, Zheng, Wei, Ziogas, Argyrios, Ziv, Elad, Dunning, Alison M., Easton, Douglas F., Hemingway, Harry, Hamann, Ute, Kuchenbaecker, Karoline B., Mueller, Stefanie H., Lai, Alvina G., Valkovskaya, Maria, Michailidou, Kyriaki, Bolla, Manjeet K., Wang, Qin, Dennis, Joe, Lush, Michael, Abu-Ful, Zomoruda, Ahearn, Thomas U., Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Arndt, Volker, Aronson, Kristan J., Augustinsson, Annelie, Baert, Thais, Freeman, Laura E. Beane, Beckmann, Matthias W., Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Bogdanova, Natalia, V, Bojesen, Stig E., Bonanni, Bernardo, Brenner, Hermann, Brucker, Sara Y., Buys, Saundra S., Castelao, Jose E., Chan, Tsun L., Chang-Claude, Jenny, Chanock, Stephen J., Choi, Ji-Yeob, Chung, Wendy K., Colonna, Sarah, V, Cornelissen, Sten, Couch, Fergus J., Czene, Kamila, Daly, Mary B., Devilee, Peter, Dork, Thilo, Dossus, Laure, Dwek, Miriam, Eccles, Diana M., Ekici, Arif B., Eliassen, A. Heather, Engel, Christoph, Evans, D. Gareth, Fasching, Peter A., Fletcher, Olivia, Flyger, Henrik, Gago-Dominguez, Manuela, Gao, Yu-Tang, Garcia-Closas, Montserrat, Garcia-Saenz, Jose A., Genkinger, Jeanine, Gentry-Maharaj, Aleksandra, Grassmann, Felix, Guenel, Pascal, Gundert, Melanie, Haeberle, Lothar, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hall, Per, Harkness, Elaine F., Harrington, Patricia A., Hartikainen, Jaana M., Hartman, Mikael, Hein, Alexander, Ho, Weang-Kee, Hooning, Maartje J., Hoppe, Reiner, Hopper, John L., Houlston, Richard S., Howell, Anthony, Hunter, David J., Huo, Dezheng, Investigators, Abctb, Ito, Hidemi, Iwasaki, Motoki, Jakubowska, Anna, Janni, Wolfgang, John, Esther M., Jones, Michael E., Jung, Audrey, Kaaks, Rudolf, Kang, Daehee, Khusnutdinova, Elza K., Kim, Sung-Won, Kitahara, Cari M., Koutros, Stella, Kraft, Peter, Kristensen, Vessela N., Kubelka-Sabit, Katerina, Kurian, Allison W., Kwong, Ava, Lacey, James, V, Lambrechts, Diether, Le Marchand, Loic, Li, Jingmei, Linet, Martha, Lo, Wing-Yee, Long, Jirong, Lophatananon, Artitaya, Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, Matsuo, Keitaro, Mavroudis, Dimitrios, Menon, Usha, Muir, Kenneth, Murphy, Rachel A., Nevanlinna, Heli, Newman, William G., Niederacher, Dieter, O'Brien, Katie M., Obi, Nadia, Offit, Kenneth, Olopade, Olufunmilayo, I, Olshan, Andrew F., Olsson, Hakan, Park, Sue K., Patel, Alpa, V, Patel, Achal, Perou, Charles M., Peto, Julian, Pharoah, Paul D. P., Plaseska-Karanfilska, Dijana, Presneau, Nadege, Rack, Brigitte, Radice, Paolo, Ramachandran, Dhanya, Rashid, Muhammad U., Rennert, Gad, Romero, Atocha, Ruddy, Kathryn J., Ruebner, Matthias, Saloustros, Emmanouil, Sandler, Dale P., Sawyer, Elinor J., Schmidt, Marjanka K., Schmutzler, Rita K., Schneider, Michael O., Scott, Christopher, Shah, Mitul, Sharma, Priyanka, Shen, Chen-Yang, Shu, Xiao-Ou, Simard, Jacques, Surowy, Harald, Tamimi, Rulla M., Tapper, William J., Taylor, Jack A., Teo, Soo Hwang, Teras, Lauren R., Toland, Amanda E., Tollenaar, Rob A. E. M., Torres, Diana, Torres-Mejia, Gabriela, Troester, Melissa A., Truong, Therese, Vachon, Celine M., Vijai, Joseph, Weinberg, Clarice R., Wendt, Camilla, Winqvist, Robert, Wolk, Alicja, Wu, Anna H., Yamaji, Taiki, Yang, Xiaohong R., Yu, Jyh-Cherng, Zheng, Wei, Ziogas, Argyrios, Ziv, Elad, Dunning, Alison M., Easton, Douglas F., Hemingway, Harry, Hamann, Ute, and Kuchenbaecker, Karoline B.
Abstract: Background: Low-frequency variants play an important role in breast cancer (BC) susceptibility. Gene-based methods can increase power by combining multiple variants in the same gene and help identify target genes. Methods: We evaluated the potential of gene-based aggregation in the Breast Cancer Association Consortium cohorts including 83,471 cases and 59,199 controls. Low-frequency variants were aggregated for individual genes' coding and regulatory regions. Association results in European ancestry samples were compared to single-marker association results in the same cohort. Gene-based associations were also combined in meta-analysis across individuals with European, Asian, African, and Latin American and Hispanic ancestry. Results: In European ancestry samples, 14 genes were significantly associated (q < 0.05) with BC. Of those, two genes, FMNL3 (P = 6.11 x 10(-6)) and AC058822.1 (P = 1.47 x 10(-4)), represent new associations. High FMNL3 expression has previously been linked to poor prognosis in several other cancers. Meta-analysis of samples with diverse ancestry discovered further associations including established candidate genes ESR1 and CBLB. Furthermore, literature review and database query found further support for a biologically plausible link with cancer for genes CBLB, FMNL3, FGFR2, LSP1, MAP3K1, and SRGAP2C. Conclusions: Using extended gene-based aggregation tests including coding and regulatory variation, we report identification of plausible target genes for previously identified single-marker associations with BC as well as the discovery of novel genes implicated in BC development. Including multi ancestral cohorts in this study enabled the identification of otherwise missed disease associations as ESR1 (P = 1.31 x 10(-5)), demonstrating the importance of diversifying study cohorts.
Published: 2023
Full Text: View/download PDF

16. Aggregation tests identify new gene associations with breast cancer in populations with diverse ancestry

Author: Mueller, Stefanie H., Lai, Alvina G., Valkovskaya, Maria, Michailidou, Kyriaki, Bolla, Manjeet K., Wang, Qin, Dennis, Joe, Lush, Michael, Abu-Ful, Zomoruda, Ahearn, Thomas U., Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Arndt, Volker, Aronson, Kristan J., Augustinsson, Annelie, Baert, Thais, Freeman, Laura E. Beane, Beckmann, Matthias W., Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Bogdanova, Natalia, V, Bojesen, Stig E., Bonanni, Bernardo, Brenner, Hermann, Brucker, Sara Y., Buys, Saundra S., Castelao, Jose E., Chan, Tsun L., Chang-Claude, Jenny, Chanock, Stephen J., Choi, Ji-Yeob, Chung, Wendy K., Colonna, Sarah, V, Cornelissen, Sten, Couch, Fergus J., Czene, Kamila, Daly, Mary B., Devilee, Peter, Dork, Thilo, Dossus, Laure, Dwek, Miriam, Eccles, Diana M., Ekici, Arif B., Eliassen, A. Heather, Engel, Christoph, Evans, D. Gareth, Fasching, Peter A., Fletcher, Olivia, Flyger, Henrik, Gago-Dominguez, Manuela, Gao, Yu-Tang, Garcia-Closas, Montserrat, Garcia-Saenz, Jose A., Genkinger, Jeanine, Gentry-Maharaj, Aleksandra, Grassmann, Felix, Guenel, Pascal, Gundert, Melanie, Haeberle, Lothar, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hall, Per, Harkness, Elaine F., Harrington, Patricia A., Hartikainen, Jaana M., Hartman, Mikael, Hein, Alexander, Ho, Weang-Kee, Hooning, Maartje J., Hoppe, Reiner, Hopper, John L., Houlston, Richard S., Howell, Anthony, Hunter, David J., Huo, Dezheng, Investigators, Abctb, Ito, Hidemi, Iwasaki, Motoki, Jakubowska, Anna, Janni, Wolfgang, John, Esther M., Jones, Michael E., Jung, Audrey, Kaaks, Rudolf, Kang, Daehee, Khusnutdinova, Elza K., Kim, Sung-Won, Kitahara, Cari M., Koutros, Stella, Kraft, Peter, Kristensen, Vessela N., Kubelka-Sabit, Katerina, Kurian, Allison W., Kwong, Ava, Lacey, James, V, Lambrechts, Diether, Le Marchand, Loic, Li, Jingmei, Linet, Martha, Lo, Wing-Yee, Long, Jirong, Lophatananon, Artitaya, Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, Matsuo, Keitaro, Mavroudis, Dimitrios, Menon, Usha, Muir, Kenneth, Murphy, Rachel A., Nevanlinna, Heli, Newman, William G., Niederacher, Dieter, O'Brien, Katie M., Obi, Nadia, Offit, Kenneth, Olopade, Olufunmilayo, I, Olshan, Andrew F., Olsson, Hakan, Park, Sue K., Patel, Alpa, V, Patel, Achal, Perou, Charles M., Peto, Julian, Pharoah, Paul D. P., Plaseska-Karanfilska, Dijana, Presneau, Nadege, Rack, Brigitte, Radice, Paolo, Ramachandran, Dhanya, Rashid, Muhammad U., Rennert, Gad, Romero, Atocha, Ruddy, Kathryn J., Ruebner, Matthias, Saloustros, Emmanouil, Sandler, Dale P., Sawyer, Elinor J., Schmidt, Marjanka K., Schmutzler, Rita K., Schneider, Michael O., Scott, Christopher, Shah, Mitul, Sharma, Priyanka, Shen, Chen-Yang, Shu, Xiao-Ou, Simard, Jacques, Surowy, Harald, Tamimi, Rulla M., Tapper, William J., Taylor, Jack A., Teo, Soo Hwang, Teras, Lauren R., Toland, Amanda E., Tollenaar, Rob A. E. M., Torres, Diana, Torres-Mejia, Gabriela, Troester, Melissa A., Truong, Therese, Vachon, Celine M., Vijai, Joseph, Weinberg, Clarice R., Wendt, Camilla, Winqvist, Robert, Wolk, Alicja, Wu, Anna H., Yamaji, Taiki, Yang, Xiaohong R., Yu, Jyh-Cherng, Zheng, Wei, Ziogas, Argyrios, Ziv, Elad, Dunning, Alison M., Easton, Douglas F., Hemingway, Harry, Hamann, Ute, Kuchenbaecker, Karoline B., Mueller, Stefanie H., Lai, Alvina G., Valkovskaya, Maria, Michailidou, Kyriaki, Bolla, Manjeet K., Wang, Qin, Dennis, Joe, Lush, Michael, Abu-Ful, Zomoruda, Ahearn, Thomas U., Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Arndt, Volker, Aronson, Kristan J., Augustinsson, Annelie, Baert, Thais, Freeman, Laura E. Beane, Beckmann, Matthias W., Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Bogdanova, Natalia, V, Bojesen, Stig E., Bonanni, Bernardo, Brenner, Hermann, Brucker, Sara Y., Buys, Saundra S., Castelao, Jose E., Chan, Tsun L., Chang-Claude, Jenny, Chanock, Stephen J., Choi, Ji-Yeob, Chung, Wendy K., Colonna, Sarah, V, Cornelissen, Sten, Couch, Fergus J., Czene, Kamila, Daly, Mary B., Devilee, Peter, Dork, Thilo, Dossus, Laure, Dwek, Miriam, Eccles, Diana M., Ekici, Arif B., Eliassen, A. Heather, Engel, Christoph, Evans, D. Gareth, Fasching, Peter A., Fletcher, Olivia, Flyger, Henrik, Gago-Dominguez, Manuela, Gao, Yu-Tang, Garcia-Closas, Montserrat, Garcia-Saenz, Jose A., Genkinger, Jeanine, Gentry-Maharaj, Aleksandra, Grassmann, Felix, Guenel, Pascal, Gundert, Melanie, Haeberle, Lothar, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hall, Per, Harkness, Elaine F., Harrington, Patricia A., Hartikainen, Jaana M., Hartman, Mikael, Hein, Alexander, Ho, Weang-Kee, Hooning, Maartje J., Hoppe, Reiner, Hopper, John L., Houlston, Richard S., Howell, Anthony, Hunter, David J., Huo, Dezheng, Investigators, Abctb, Ito, Hidemi, Iwasaki, Motoki, Jakubowska, Anna, Janni, Wolfgang, John, Esther M., Jones, Michael E., Jung, Audrey, Kaaks, Rudolf, Kang, Daehee, Khusnutdinova, Elza K., Kim, Sung-Won, Kitahara, Cari M., Koutros, Stella, Kraft, Peter, Kristensen, Vessela N., Kubelka-Sabit, Katerina, Kurian, Allison W., Kwong, Ava, Lacey, James, V, Lambrechts, Diether, Le Marchand, Loic, Li, Jingmei, Linet, Martha, Lo, Wing-Yee, Long, Jirong, Lophatananon, Artitaya, Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, Matsuo, Keitaro, Mavroudis, Dimitrios, Menon, Usha, Muir, Kenneth, Murphy, Rachel A., Nevanlinna, Heli, Newman, William G., Niederacher, Dieter, O'Brien, Katie M., Obi, Nadia, Offit, Kenneth, Olopade, Olufunmilayo, I, Olshan, Andrew F., Olsson, Hakan, Park, Sue K., Patel, Alpa, V, Patel, Achal, Perou, Charles M., Peto, Julian, Pharoah, Paul D. P., Plaseska-Karanfilska, Dijana, Presneau, Nadege, Rack, Brigitte, Radice, Paolo, Ramachandran, Dhanya, Rashid, Muhammad U., Rennert, Gad, Romero, Atocha, Ruddy, Kathryn J., Ruebner, Matthias, Saloustros, Emmanouil, Sandler, Dale P., Sawyer, Elinor J., Schmidt, Marjanka K., Schmutzler, Rita K., Schneider, Michael O., Scott, Christopher, Shah, Mitul, Sharma, Priyanka, Shen, Chen-Yang, Shu, Xiao-Ou, Simard, Jacques, Surowy, Harald, Tamimi, Rulla M., Tapper, William J., Taylor, Jack A., Teo, Soo Hwang, Teras, Lauren R., Toland, Amanda E., Tollenaar, Rob A. E. M., Torres, Diana, Torres-Mejia, Gabriela, Troester, Melissa A., Truong, Therese, Vachon, Celine M., Vijai, Joseph, Weinberg, Clarice R., Wendt, Camilla, Winqvist, Robert, Wolk, Alicja, Wu, Anna H., Yamaji, Taiki, Yang, Xiaohong R., Yu, Jyh-Cherng, Zheng, Wei, Ziogas, Argyrios, Ziv, Elad, Dunning, Alison M., Easton, Douglas F., Hemingway, Harry, Hamann, Ute, and Kuchenbaecker, Karoline B.
Abstract: Background: Low-frequency variants play an important role in breast cancer (BC) susceptibility. Gene-based methods can increase power by combining multiple variants in the same gene and help identify target genes. Methods: We evaluated the potential of gene-based aggregation in the Breast Cancer Association Consortium cohorts including 83,471 cases and 59,199 controls. Low-frequency variants were aggregated for individual genes' coding and regulatory regions. Association results in European ancestry samples were compared to single-marker association results in the same cohort. Gene-based associations were also combined in meta-analysis across individuals with European, Asian, African, and Latin American and Hispanic ancestry. Results: In European ancestry samples, 14 genes were significantly associated (q < 0.05) with BC. Of those, two genes, FMNL3 (P = 6.11 x 10(-6)) and AC058822.1 (P = 1.47 x 10(-4)), represent new associations. High FMNL3 expression has previously been linked to poor prognosis in several other cancers. Meta-analysis of samples with diverse ancestry discovered further associations including established candidate genes ESR1 and CBLB. Furthermore, literature review and database query found further support for a biologically plausible link with cancer for genes CBLB, FMNL3, FGFR2, LSP1, MAP3K1, and SRGAP2C. Conclusions: Using extended gene-based aggregation tests including coding and regulatory variation, we report identification of plausible target genes for previously identified single-marker associations with BC as well as the discovery of novel genes implicated in BC development. Including multi ancestral cohorts in this study enabled the identification of otherwise missed disease associations as ESR1 (P = 1.31 x 10(-5)), demonstrating the importance of diversifying study cohorts.
Published: 2023
Full Text: View/download PDF

17. Aggregation tests identify new gene associations with breast cancer in populations with diverse ancestry

Author: Mueller, Stefanie H., Lai, Alvina G., Valkovskaya, Maria, Michailidou, Kyriaki, Bolla, Manjeet K., Wang, Qin, Dennis, Joe, Lush, Michael, Abu-Ful, Zomoruda, Ahearn, Thomas U., Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Arndt, Volker, Aronson, Kristan J., Augustinsson, Annelie, Baert, Thais, Freeman, Laura E. Beane, Beckmann, Matthias W., Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Bogdanova, Natalia, V, Bojesen, Stig E., Bonanni, Bernardo, Brenner, Hermann, Brucker, Sara Y., Buys, Saundra S., Castelao, Jose E., Chan, Tsun L., Chang-Claude, Jenny, Chanock, Stephen J., Choi, Ji-Yeob, Chung, Wendy K., Colonna, Sarah, V, Cornelissen, Sten, Couch, Fergus J., Czene, Kamila, Daly, Mary B., Devilee, Peter, Dork, Thilo, Dossus, Laure, Dwek, Miriam, Eccles, Diana M., Ekici, Arif B., Eliassen, A. Heather, Engel, Christoph, Evans, D. Gareth, Fasching, Peter A., Fletcher, Olivia, Flyger, Henrik, Gago-Dominguez, Manuela, Gao, Yu-Tang, Garcia-Closas, Montserrat, Garcia-Saenz, Jose A., Genkinger, Jeanine, Gentry-Maharaj, Aleksandra, Grassmann, Felix, Guenel, Pascal, Gundert, Melanie, Haeberle, Lothar, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hall, Per, Harkness, Elaine F., Harrington, Patricia A., Hartikainen, Jaana M., Hartman, Mikael, Hein, Alexander, Ho, Weang-Kee, Hooning, Maartje J., Hoppe, Reiner, Hopper, John L., Houlston, Richard S., Howell, Anthony, Hunter, David J., Huo, Dezheng, Investigators, Abctb, Ito, Hidemi, Iwasaki, Motoki, Jakubowska, Anna, Janni, Wolfgang, John, Esther M., Jones, Michael E., Jung, Audrey, Kaaks, Rudolf, Kang, Daehee, Khusnutdinova, Elza K., Kim, Sung-Won, Kitahara, Cari M., Koutros, Stella, Kraft, Peter, Kristensen, Vessela N., Kubelka-Sabit, Katerina, Kurian, Allison W., Kwong, Ava, Lacey, James, V, Lambrechts, Diether, Le Marchand, Loic, Li, Jingmei, Linet, Martha, Lo, Wing-Yee, Long, Jirong, Lophatananon, Artitaya, Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, Matsuo, Keitaro, Mavroudis, Dimitrios, Menon, Usha, Muir, Kenneth, Murphy, Rachel A., Nevanlinna, Heli, Newman, William G., Niederacher, Dieter, O'Brien, Katie M., Obi, Nadia, Offit, Kenneth, Olopade, Olufunmilayo, I, Olshan, Andrew F., Olsson, Hakan, Park, Sue K., Patel, Alpa, V, Patel, Achal, Perou, Charles M., Peto, Julian, Pharoah, Paul D. P., Plaseska-Karanfilska, Dijana, Presneau, Nadege, Rack, Brigitte, Radice, Paolo, Ramachandran, Dhanya, Rashid, Muhammad U., Rennert, Gad, Romero, Atocha, Ruddy, Kathryn J., Ruebner, Matthias, Saloustros, Emmanouil, Sandler, Dale P., Sawyer, Elinor J., Schmidt, Marjanka K., Schmutzler, Rita K., Schneider, Michael O., Scott, Christopher, Shah, Mitul, Sharma, Priyanka, Shen, Chen-Yang, Shu, Xiao-Ou, Simard, Jacques, Surowy, Harald, Tamimi, Rulla M., Tapper, William J., Taylor, Jack A., Teo, Soo Hwang, Teras, Lauren R., Toland, Amanda E., Tollenaar, Rob A. E. M., Torres, Diana, Torres-Mejia, Gabriela, Troester, Melissa A., Truong, Therese, Vachon, Celine M., Vijai, Joseph, Weinberg, Clarice R., Wendt, Camilla, Winqvist, Robert, Wolk, Alicja, Wu, Anna H., Yamaji, Taiki, Yang, Xiaohong R., Yu, Jyh-Cherng, Zheng, Wei, Ziogas, Argyrios, Ziv, Elad, Dunning, Alison M., Easton, Douglas F., Hemingway, Harry, Hamann, Ute, Kuchenbaecker, Karoline B., Mueller, Stefanie H., Lai, Alvina G., Valkovskaya, Maria, Michailidou, Kyriaki, Bolla, Manjeet K., Wang, Qin, Dennis, Joe, Lush, Michael, Abu-Ful, Zomoruda, Ahearn, Thomas U., Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Arndt, Volker, Aronson, Kristan J., Augustinsson, Annelie, Baert, Thais, Freeman, Laura E. Beane, Beckmann, Matthias W., Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Bogdanova, Natalia, V, Bojesen, Stig E., Bonanni, Bernardo, Brenner, Hermann, Brucker, Sara Y., Buys, Saundra S., Castelao, Jose E., Chan, Tsun L., Chang-Claude, Jenny, Chanock, Stephen J., Choi, Ji-Yeob, Chung, Wendy K., Colonna, Sarah, V, Cornelissen, Sten, Couch, Fergus J., Czene, Kamila, Daly, Mary B., Devilee, Peter, Dork, Thilo, Dossus, Laure, Dwek, Miriam, Eccles, Diana M., Ekici, Arif B., Eliassen, A. Heather, Engel, Christoph, Evans, D. Gareth, Fasching, Peter A., Fletcher, Olivia, Flyger, Henrik, Gago-Dominguez, Manuela, Gao, Yu-Tang, Garcia-Closas, Montserrat, Garcia-Saenz, Jose A., Genkinger, Jeanine, Gentry-Maharaj, Aleksandra, Grassmann, Felix, Guenel, Pascal, Gundert, Melanie, Haeberle, Lothar, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hall, Per, Harkness, Elaine F., Harrington, Patricia A., Hartikainen, Jaana M., Hartman, Mikael, Hein, Alexander, Ho, Weang-Kee, Hooning, Maartje J., Hoppe, Reiner, Hopper, John L., Houlston, Richard S., Howell, Anthony, Hunter, David J., Huo, Dezheng, Investigators, Abctb, Ito, Hidemi, Iwasaki, Motoki, Jakubowska, Anna, Janni, Wolfgang, John, Esther M., Jones, Michael E., Jung, Audrey, Kaaks, Rudolf, Kang, Daehee, Khusnutdinova, Elza K., Kim, Sung-Won, Kitahara, Cari M., Koutros, Stella, Kraft, Peter, Kristensen, Vessela N., Kubelka-Sabit, Katerina, Kurian, Allison W., Kwong, Ava, Lacey, James, V, Lambrechts, Diether, Le Marchand, Loic, Li, Jingmei, Linet, Martha, Lo, Wing-Yee, Long, Jirong, Lophatananon, Artitaya, Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, Matsuo, Keitaro, Mavroudis, Dimitrios, Menon, Usha, Muir, Kenneth, Murphy, Rachel A., Nevanlinna, Heli, Newman, William G., Niederacher, Dieter, O'Brien, Katie M., Obi, Nadia, Offit, Kenneth, Olopade, Olufunmilayo, I, Olshan, Andrew F., Olsson, Hakan, Park, Sue K., Patel, Alpa, V, Patel, Achal, Perou, Charles M., Peto, Julian, Pharoah, Paul D. P., Plaseska-Karanfilska, Dijana, Presneau, Nadege, Rack, Brigitte, Radice, Paolo, Ramachandran, Dhanya, Rashid, Muhammad U., Rennert, Gad, Romero, Atocha, Ruddy, Kathryn J., Ruebner, Matthias, Saloustros, Emmanouil, Sandler, Dale P., Sawyer, Elinor J., Schmidt, Marjanka K., Schmutzler, Rita K., Schneider, Michael O., Scott, Christopher, Shah, Mitul, Sharma, Priyanka, Shen, Chen-Yang, Shu, Xiao-Ou, Simard, Jacques, Surowy, Harald, Tamimi, Rulla M., Tapper, William J., Taylor, Jack A., Teo, Soo Hwang, Teras, Lauren R., Toland, Amanda E., Tollenaar, Rob A. E. M., Torres, Diana, Torres-Mejia, Gabriela, Troester, Melissa A., Truong, Therese, Vachon, Celine M., Vijai, Joseph, Weinberg, Clarice R., Wendt, Camilla, Winqvist, Robert, Wolk, Alicja, Wu, Anna H., Yamaji, Taiki, Yang, Xiaohong R., Yu, Jyh-Cherng, Zheng, Wei, Ziogas, Argyrios, Ziv, Elad, Dunning, Alison M., Easton, Douglas F., Hemingway, Harry, Hamann, Ute, and Kuchenbaecker, Karoline B.
Abstract: Background: Low-frequency variants play an important role in breast cancer (BC) susceptibility. Gene-based methods can increase power by combining multiple variants in the same gene and help identify target genes. Methods: We evaluated the potential of gene-based aggregation in the Breast Cancer Association Consortium cohorts including 83,471 cases and 59,199 controls. Low-frequency variants were aggregated for individual genes' coding and regulatory regions. Association results in European ancestry samples were compared to single-marker association results in the same cohort. Gene-based associations were also combined in meta-analysis across individuals with European, Asian, African, and Latin American and Hispanic ancestry. Results: In European ancestry samples, 14 genes were significantly associated (q < 0.05) with BC. Of those, two genes, FMNL3 (P = 6.11 x 10(-6)) and AC058822.1 (P = 1.47 x 10(-4)), represent new associations. High FMNL3 expression has previously been linked to poor prognosis in several other cancers. Meta-analysis of samples with diverse ancestry discovered further associations including established candidate genes ESR1 and CBLB. Furthermore, literature review and database query found further support for a biologically plausible link with cancer for genes CBLB, FMNL3, FGFR2, LSP1, MAP3K1, and SRGAP2C. Conclusions: Using extended gene-based aggregation tests including coding and regulatory variation, we report identification of plausible target genes for previously identified single-marker associations with BC as well as the discovery of novel genes implicated in BC development. Including multi ancestral cohorts in this study enabled the identification of otherwise missed disease associations as ESR1 (P = 1.31 x 10(-5)), demonstrating the importance of diversifying study cohorts.
Published: 2023
Full Text: View/download PDF

18. El salón de reinos a escena en el Museo del Prado: El Brasil restituido de Lope de Vega por el Instituto del Teatro de Madrid

Author: Martínez Valderas, Jara, Álvarez Barco, Mario, Caparrós Rodríguez, Marta, Clemente Sánchez, Raquel, Fernández Villanueva, Juan josé, Florensa Tomasi, Mónica, García García, Bernardo José, García Molero,Patricia, Gil Carrera, Micaela Teresa, González Vigara, Paula, Herranz Sotoca, Irene, Ruíz Moya, Itziar, Ruíz Torres, Diana Carolina, Velasquez Serrano, Jhonnathan Josseph, Vélez Sáinz, José Julio, Martínez Valderas, Jara, Álvarez Barco, Mario, Caparrós Rodríguez, Marta, Clemente Sánchez, Raquel, Fernández Villanueva, Juan josé, Florensa Tomasi, Mónica, García García, Bernardo José, García Molero,Patricia, Gil Carrera, Micaela Teresa, González Vigara, Paula, Herranz Sotoca, Irene, Ruíz Moya, Itziar, Ruíz Torres, Diana Carolina, Velasquez Serrano, Jhonnathan Josseph, and Vélez Sáinz, José Julio
Abstract: En el Salón de Reinos, quedó inmortalizado en el lienzo de fray Juan Bautista Maíno, considerado por los contemporáneos como la obra magna de esta extraordinaria galería del Palacio del Buen Retiro. Este volumen, centrado en la conquista holandesa de 1624 y la recuperación luso-española de Salvador de Bahía de 1625, es el segundo de la colección El salón de Reinos en las noticias y el teatro. Proporciona al lector una visión rigurosa y contextualizada de cómo fue recibida la noticia y reinterpretada a través de los relatos, impresos o manuscritos que se difundieron en la época y su posterior representación en la ficción teatral y pictórica. En la primera parte José Manuel Santos Pérez e Irene María Vicente Martín sitúan el suceso en el panorama internacional, mercado por el reinicio de las hostilidades hispano-neerlandesas en el Atlántico, y en el ámbito local, determinado por la creciente importancia geopolítica de Brasil y, más concretamente, el Salvador, en el complejo entramado territorial de la Monarquía Hispánica. Incluye también el más completo listado de relaciones de sucesos, tanto holandeses, luso-castellanas de los acontecimientos de 1624-1625, y ediciones críticas de las más significativas. Por su parte Enrique Rodrigues-Moura edita y analiza dos de las obras de teatro que se escribieron y representaron sobre aquellas victorias annus mirabilis de 1625, El Brasil restituido de Lope de Vega y Pérdida y restauración de la Bahía de Todos Santos de Juan Antonio Correa. Lope de Vega terminó su comedia en octubre de 1625, pocos días antes de la llegada del grueso de la flota a Cádiz utilizando algunas de aquellas relaciones.
Published: 2023

19. Extensive phylogenomic discordance and the complex evolutionary history of the Neotropical cat genus Leopardus

Author: Lescroart, Jonas, Bonilla-Sánchez, Alejandra, Napolitano, Constanza, Buitrago-Torres, Diana L, Ramírez-Chaves, Héctor E, Pulido-Santacruz, Paola, Murphy, William J, Svardal, H. (Hannes), Eizirik, Eduardo, Lescroart, Jonas, Bonilla-Sánchez, Alejandra, Napolitano, Constanza, Buitrago-Torres, Diana L, Ramírez-Chaves, Héctor E, Pulido-Santacruz, Paola, Murphy, William J, Svardal, H. (Hannes), and Eizirik, Eduardo
Abstract: Even in the genomics era, the phylogeny of Neotropical small felids comprised in the genus Leopardus remains contentious. We used whole-genome resequencing data to construct a time-calibrated consensus phylogeny of this group, quantify phylogenomic discordance, test for interspecies introgression, and assess patterns of genetic diversity and demographic history. We infer that the Leopardus radiation started in the Early Pliocene as an initial speciation burst, followed by another in its subgenus Oncifelis during the Early Pleistocene. Our findings challenge the long-held notion that ocelot (Leopardus pardalis) and margay (L. wiedii) are sister species and instead indicate that margay is most closely related to the enigmatic Andean cat (L. jacobita), whose whole-genome data are reported here for the first time. In addition, we found that the newly sampled Andean tiger cat (L. tigrinus pardinoides) population from Colombia associates closely with Central American tiger cats (L. tigrinus oncilla). Genealogical discordance was largely attributable to incomplete lineage sorting, yet was augmented by strong gene flow between ocelot and the ancestral branch of Oncifelis, as well as between Geoffroy's cat (L. geoffroyi) and southern tiger cat (L. guttulus). Contrasting demographic trajectories have led to disparate levels of current genomic diversity, with a nearly tenfold difference in heterozygosity between Andean cat and ocelot, spanning the entire range of variability found in extant felids. Our analyses improved our understanding of the speciation history and diversity patterns in this felid radiation, and highlight the benefits to phylogenomic inference of embracing the many heterogeneous signals scattered across the genome.
Published: 2023
Full Text: View/download PDF

20. El workshop como estrategia de aprendizaje en planificación territorial

Author: Sauza Reyes, Adriana Catalina, Sevilla Torres, Diana Carolina, Sauza Reyes, Adriana Catalina, and Sevilla Torres, Diana Carolina
Abstract: The learning of territorial planning is a subject in process of consolidation and is relevant for the development of capacity building for the transformation of Latin American cities. Actually the experiences around the application of the workshop as a learning strategy are presented, incorporate it into the curricular plan of the postgraduate program, it has served to reinforce the research training processes, as well as to deepen and put in practice the skills acquired in other theoretical components. Therefore, this article shows how this experience has been carried out, fundamental aspects for its development and a series of results that show the benefits of implementing this practical workshop that leads its students to understand the territorial dynamics and problems to seek contextualized planning solutions for a specific territory from a systemic and interdisciplinary vision., L'enseignement de l'aménagement du territoire est un sujet en voie de consolidation et pertinent pour le développement des capacités de formation pour la transformation des villes latino-américaines. En ce sens, les expériences autour de l'application de l'atelier en tant que stratégie d'apprentissage sont présentées, de sorte qu'en l'intégrant dans le plan curriculaire du programme de deuxième cycle, il a servi à renforcer les processus de formation à la recherche, ainsi que d'approfondir et mettre en pratique les compétences acquises dans d'autres composantes théoriques. Ensuite, la manière dont cette expérience a été menée, les aspects fondamentaux pour son développement et une série de résultats qui montrent l'intérêt de la mise en œuvre de cet atelier pratique qui amène ses étudiants à comprendre les dynamiques et les problèmes territoriaux pour rechercher des solutions d'aménagement contextualisées pour un territoire spécifique dans une vision systémique et interdisciplinaire., O ensino do planejamento territorial é uma disciplina em processo de consolidação e relevante para o desenvolvimento de capacidades formativas para a transformação das cidades latinoamericanas. Nesse sentido, são apresentadas as experiências em torno da aplicação da oficina como estratégia de aprendizagem, de modo que, ao incorporá-la ao plano curricular da pós-graduação, tem servido para reforçar os processos de formação em pesquisa, bem como aprofundar e colocar na prática as competências adquiridas nas restantes componentes teóricas. A seguir, a forma como esta experiência foi realizada, os aspectos fundamentais para o seu desenvolvimento e uma série de resultados que mostram os benefícios da implementação desta oficina prática que leva seus alunos a compreender as dinâmicas e problemas territoriais para buscar soluções de planejamento contextualizadas para um território específico a partir de uma visão sistêmica e interdisciplinar., La enseñanza de la planificación territorial es un tema en proceso de consolidación y es de relevancia para el desarrollo de capacidades de formación para la transformación de las ciudades latinoamericanas. En este sentido, se presentan las experiencias en torno a la aplicación del workshop como estrategia de aprendizaje que, al ser incorporada dentro del plan curricular del programa de posgrado, ha servido para reforzar los procesos de formación en investigación, así como para profundizar y poner en práctica las competencias adquiridas en otros componentes teóricos. A continuación, se expone la forma como se ha llevado a cabo esta experiencia, los aspectos fundamentales para su desarrollo y una serie de resultados que muestran los beneficios de implementar este taller práctico para que los estudiantes comprendan las dinámicas y problemas territoriales y busquen soluciones contextualizadas de planificación de un territorio específico, a partir de una visión sistémica e interdisciplinaria.
Published: 2023

21. Aggregation tests identify new gene associations with breast cancer in populations with diverse ancestry

Author: Mueller, Stefanie H., Lai, Alvina G., Valkovskaya, Maria, Michailidou, Kyriaki, Bolla, Manjeet K., Wang, Qin, Dennis, Joe, Lush, Michael, Abu-Ful, Zomoruda, Ahearn, Thomas U., Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Arndt, Volker, Aronson, Kristan J., Augustinsson, Annelie, Baert, Thais, Freeman, Laura E. Beane, Beckmann, Matthias W., Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Bogdanova, Natalia, V, Bojesen, Stig E., Bonanni, Bernardo, Brenner, Hermann, Brucker, Sara Y., Buys, Saundra S., Castelao, Jose E., Chan, Tsun L., Chang-Claude, Jenny, Chanock, Stephen J., Choi, Ji-Yeob, Chung, Wendy K., Colonna, Sarah, V, Cornelissen, Sten, Couch, Fergus J., Czene, Kamila, Daly, Mary B., Devilee, Peter, Dork, Thilo, Dossus, Laure, Dwek, Miriam, Eccles, Diana M., Ekici, Arif B., Eliassen, A. Heather, Engel, Christoph, Evans, D. Gareth, Fasching, Peter A., Fletcher, Olivia, Flyger, Henrik, Gago-Dominguez, Manuela, Gao, Yu-Tang, Garcia-Closas, Montserrat, Garcia-Saenz, Jose A., Genkinger, Jeanine, Gentry-Maharaj, Aleksandra, Grassmann, Felix, Guenel, Pascal, Gundert, Melanie, Haeberle, Lothar, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hall, Per, Harkness, Elaine F., Harrington, Patricia A., Hartikainen, Jaana M., Hartman, Mikael, Hein, Alexander, Ho, Weang-Kee, Hooning, Maartje J., Hoppe, Reiner, Hopper, John L., Houlston, Richard S., Howell, Anthony, Hunter, David J., Huo, Dezheng, Investigators, Abctb, Ito, Hidemi, Iwasaki, Motoki, Jakubowska, Anna, Janni, Wolfgang, John, Esther M., Jones, Michael E., Jung, Audrey, Kaaks, Rudolf, Kang, Daehee, Khusnutdinova, Elza K., Kim, Sung-Won, Kitahara, Cari M., Koutros, Stella, Kraft, Peter, Kristensen, Vessela N., Kubelka-Sabit, Katerina, Kurian, Allison W., Kwong, Ava, Lacey, James, V, Lambrechts, Diether, Le Marchand, Loic, Li, Jingmei, Linet, Martha, Lo, Wing-Yee, Long, Jirong, Lophatananon, Artitaya, Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, Matsuo, Keitaro, Mavroudis, Dimitrios, Menon, Usha, Muir, Kenneth, Murphy, Rachel A., Nevanlinna, Heli, Newman, William G., Niederacher, Dieter, O'Brien, Katie M., Obi, Nadia, Offit, Kenneth, Olopade, Olufunmilayo, I, Olshan, Andrew F., Olsson, Hakan, Park, Sue K., Patel, Alpa, V, Patel, Achal, Perou, Charles M., Peto, Julian, Pharoah, Paul D. P., Plaseska-Karanfilska, Dijana, Presneau, Nadege, Rack, Brigitte, Radice, Paolo, Ramachandran, Dhanya, Rashid, Muhammad U., Rennert, Gad, Romero, Atocha, Ruddy, Kathryn J., Ruebner, Matthias, Saloustros, Emmanouil, Sandler, Dale P., Sawyer, Elinor J., Schmidt, Marjanka K., Schmutzler, Rita K., Schneider, Michael O., Scott, Christopher, Shah, Mitul, Sharma, Priyanka, Shen, Chen-Yang, Shu, Xiao-Ou, Simard, Jacques, Surowy, Harald, Tamimi, Rulla M., Tapper, William J., Taylor, Jack A., Teo, Soo Hwang, Teras, Lauren R., Toland, Amanda E., Tollenaar, Rob A. E. M., Torres, Diana, Torres-Mejia, Gabriela, Troester, Melissa A., Truong, Therese, Vachon, Celine M., Vijai, Joseph, Weinberg, Clarice R., Wendt, Camilla, Winqvist, Robert, Wolk, Alicja, Wu, Anna H., Yamaji, Taiki, Yang, Xiaohong R., Yu, Jyh-Cherng, Zheng, Wei, Ziogas, Argyrios, Ziv, Elad, Dunning, Alison M., Easton, Douglas F., Hemingway, Harry, Hamann, Ute, Kuchenbaecker, Karoline B., Mueller, Stefanie H., Lai, Alvina G., Valkovskaya, Maria, Michailidou, Kyriaki, Bolla, Manjeet K., Wang, Qin, Dennis, Joe, Lush, Michael, Abu-Ful, Zomoruda, Ahearn, Thomas U., Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Arndt, Volker, Aronson, Kristan J., Augustinsson, Annelie, Baert, Thais, Freeman, Laura E. Beane, Beckmann, Matthias W., Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Bogdanova, Natalia, V, Bojesen, Stig E., Bonanni, Bernardo, Brenner, Hermann, Brucker, Sara Y., Buys, Saundra S., Castelao, Jose E., Chan, Tsun L., Chang-Claude, Jenny, Chanock, Stephen J., Choi, Ji-Yeob, Chung, Wendy K., Colonna, Sarah, V, Cornelissen, Sten, Couch, Fergus J., Czene, Kamila, Daly, Mary B., Devilee, Peter, Dork, Thilo, Dossus, Laure, Dwek, Miriam, Eccles, Diana M., Ekici, Arif B., Eliassen, A. Heather, Engel, Christoph, Evans, D. Gareth, Fasching, Peter A., Fletcher, Olivia, Flyger, Henrik, Gago-Dominguez, Manuela, Gao, Yu-Tang, Garcia-Closas, Montserrat, Garcia-Saenz, Jose A., Genkinger, Jeanine, Gentry-Maharaj, Aleksandra, Grassmann, Felix, Guenel, Pascal, Gundert, Melanie, Haeberle, Lothar, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hall, Per, Harkness, Elaine F., Harrington, Patricia A., Hartikainen, Jaana M., Hartman, Mikael, Hein, Alexander, Ho, Weang-Kee, Hooning, Maartje J., Hoppe, Reiner, Hopper, John L., Houlston, Richard S., Howell, Anthony, Hunter, David J., Huo, Dezheng, Investigators, Abctb, Ito, Hidemi, Iwasaki, Motoki, Jakubowska, Anna, Janni, Wolfgang, John, Esther M., Jones, Michael E., Jung, Audrey, Kaaks, Rudolf, Kang, Daehee, Khusnutdinova, Elza K., Kim, Sung-Won, Kitahara, Cari M., Koutros, Stella, Kraft, Peter, Kristensen, Vessela N., Kubelka-Sabit, Katerina, Kurian, Allison W., Kwong, Ava, Lacey, James, V, Lambrechts, Diether, Le Marchand, Loic, Li, Jingmei, Linet, Martha, Lo, Wing-Yee, Long, Jirong, Lophatananon, Artitaya, Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, Matsuo, Keitaro, Mavroudis, Dimitrios, Menon, Usha, Muir, Kenneth, Murphy, Rachel A., Nevanlinna, Heli, Newman, William G., Niederacher, Dieter, O'Brien, Katie M., Obi, Nadia, Offit, Kenneth, Olopade, Olufunmilayo, I, Olshan, Andrew F., Olsson, Hakan, Park, Sue K., Patel, Alpa, V, Patel, Achal, Perou, Charles M., Peto, Julian, Pharoah, Paul D. P., Plaseska-Karanfilska, Dijana, Presneau, Nadege, Rack, Brigitte, Radice, Paolo, Ramachandran, Dhanya, Rashid, Muhammad U., Rennert, Gad, Romero, Atocha, Ruddy, Kathryn J., Ruebner, Matthias, Saloustros, Emmanouil, Sandler, Dale P., Sawyer, Elinor J., Schmidt, Marjanka K., Schmutzler, Rita K., Schneider, Michael O., Scott, Christopher, Shah, Mitul, Sharma, Priyanka, Shen, Chen-Yang, Shu, Xiao-Ou, Simard, Jacques, Surowy, Harald, Tamimi, Rulla M., Tapper, William J., Taylor, Jack A., Teo, Soo Hwang, Teras, Lauren R., Toland, Amanda E., Tollenaar, Rob A. E. M., Torres, Diana, Torres-Mejia, Gabriela, Troester, Melissa A., Truong, Therese, Vachon, Celine M., Vijai, Joseph, Weinberg, Clarice R., Wendt, Camilla, Winqvist, Robert, Wolk, Alicja, Wu, Anna H., Yamaji, Taiki, Yang, Xiaohong R., Yu, Jyh-Cherng, Zheng, Wei, Ziogas, Argyrios, Ziv, Elad, Dunning, Alison M., Easton, Douglas F., Hemingway, Harry, Hamann, Ute, and Kuchenbaecker, Karoline B.
Abstract: Background: Low-frequency variants play an important role in breast cancer (BC) susceptibility. Gene-based methods can increase power by combining multiple variants in the same gene and help identify target genes. Methods: We evaluated the potential of gene-based aggregation in the Breast Cancer Association Consortium cohorts including 83,471 cases and 59,199 controls. Low-frequency variants were aggregated for individual genes' coding and regulatory regions. Association results in European ancestry samples were compared to single-marker association results in the same cohort. Gene-based associations were also combined in meta-analysis across individuals with European, Asian, African, and Latin American and Hispanic ancestry. Results: In European ancestry samples, 14 genes were significantly associated (q < 0.05) with BC. Of those, two genes, FMNL3 (P = 6.11 x 10(-6)) and AC058822.1 (P = 1.47 x 10(-4)), represent new associations. High FMNL3 expression has previously been linked to poor prognosis in several other cancers. Meta-analysis of samples with diverse ancestry discovered further associations including established candidate genes ESR1 and CBLB. Furthermore, literature review and database query found further support for a biologically plausible link with cancer for genes CBLB, FMNL3, FGFR2, LSP1, MAP3K1, and SRGAP2C. Conclusions: Using extended gene-based aggregation tests including coding and regulatory variation, we report identification of plausible target genes for previously identified single-marker associations with BC as well as the discovery of novel genes implicated in BC development. Including multi ancestral cohorts in this study enabled the identification of otherwise missed disease associations as ESR1 (P = 1.31 x 10(-5)), demonstrating the importance of diversifying study cohorts.
Published: 2023
Full Text: View/download PDF

22. Endofitismo de especies de trichoderma y crecimiento radicular en dos variedades de banano in vitro: Endophytism of trichoderma in banano

Author: Ramírez Torres, Diana Carolina, Reyes López, Delfino, Domínguez Perales, Luis Antonio, Orduño Cruz, Nuvia, Grifaldo-Alcántara, Pedro Fabián, Hernández Domínguez, Carmela, Ramírez Torres, Diana Carolina, Reyes López, Delfino, Domínguez Perales, Luis Antonio, Orduño Cruz, Nuvia, Grifaldo-Alcántara, Pedro Fabián, and Hernández Domínguez, Carmela
Abstract: The endophytism of fungi in plants has beneficial effects and depends on several factors. In this study the individual endophytism and the consortium of five species of Trichoderma in root and bract were in Williams and French in vitro bananas were evaluate, after three months mortality, length and root diameter were evaluated too. Significant differences in root endophytism were observed (X21.00= 31.13, P<0.05); T. longibrachiatum y T. hamatum had 48% endophytism in the Williams variety and T. spirale 58% in the French variety. Treatment which consisted of five species of Trichoderma had 24% endophytism in the root of the Williams variety and 8% in the French variety. Relationship between endophytism and root diameter growth was observed (R2= 0.771, P<0.05), however the relationship between endophyte of Trichoderma species and plant mortality of both varieties of banana was not observed (R2 = 0.298, P <0.05), (R2 = 0.089). The endophyte effect of Trichoderma species on plant mortality of both varieties there was no relationship between these variables (R2 = 0.298, P0.05), (R2= 0.089)., El endofitismo de hongos en plantas tiene efectos benéficos y depende de varios factores. En este estudio se evaluó el endofitismo individual y el consorcio de cinco especies —Trichoderma spirale, T. longibrachiatum, T. parareesei, T. andinense y T. hamatum— en raíz y bráctea de banano Williams y Francés in vitro. La mortalidad, la longitud y el diámetro de raíz de plantas ex vitro fueron evaluados. Se observaron diferencias significativas de endofitismo en raíz (X21.00= 31.13, P<0.05); T. longibrachiatum y T. hamatum tuvieron 48 por ciento de endofitismo en la variedad Williams, y T. spirale, 58 por ciento en la variedad Francés. El tratamiento formado por las cinco especies presentó 24 por ciento de endofitismo en raíz de la variedad Williams y 8 por ciento en la variedad Francés. Se observó relación entre endofitismo y crecimiento de diámetro de raíz (R2= 0.771, P<0.05); sin embargo, no se observó relación (R2= 0.298, P<0.05), (R2= 0.089) entre endófitismo de especies de Trichoderma y mortalidad de plantas de banano de ambas variedades.
Published: 2022

23. Disentangling the relationship between prior knowledge and entrepreneurial orientation: a bibliometric study

Author: Espinoza Torres, Diana Lucía, Segarra Oña, Marival, Espinoza Torres, Diana Lucía, and Segarra Oña, Marival
Abstract: This paper analyzes the theoretical relationship between knowledge and entrepreneurship through a bibliometric study. Several indicators are drawn from the Web of Science database using the HistCite software for bibliometrics, including annual publications, citation density, and journals with the highest number of publications. For the empirical application, a qualitative approach was adopted through a case study of four companies located in Valencia with the application of a semi-structured interview. The Atlas.ti software was used to analyze the data. The results indicate a relationship between knowledge and entrepreneurship constructs through theoretical modeling, highlighting the importance of the origin of knowledge for new venture creation, knowledge commercialization processes through entrepreneurship opportunities, and the origin and transmission of knowledge in organizations with entrepreneurial orientation (EO). The main limitation is the dispersion of research topics and the exclusion of publications that did not address the investigated relationship directly. The theoretical model proposed in this study can be extended to different spheres to identify and generate entrepreneurship opportunities, especially in universities and incumbent firms. Future studies should further validate the model empirically, Este trabajo analiza la relación teórica entre conocimiento y emprendimiento a través de un estudio bibliométrico. Se extraen varios indicadores de la base de datos Web of Science utilizando el software HistCite para bibliometría, incluidas las publicaciones anuales, la densidad de citas y las revistas con el mayor número de publicaciones. Para la aplicación empírica se adoptó un enfoque cualitativo a través de un estudio de caso de cuatro empresas ubicadas en Valencia con la aplicación de una entrevista semiestructurada. El software Atlas.ti se utilizó para analizar los datos. Los resultados indican una relación entre el conocimiento y los constructos de emprendimiento a través de la modelación teórica, destacando la importancia del origen del conocimiento para la creación de nuevos emprendimientos, los procesos de comercialización del conocimiento a través de oportunidades de emprendimiento y el origen y transmisión del conocimiento en organizaciones con orientación emprendedora (EO). La principal limitación es la dispersión de los temas de investigación y la exclusión de publicaciones que no abordaban directamente la relación investigada. El modelo teórico propuesto en este estudio puede extenderse a diferentes ámbitos para identificar y generar oportunidades de emprendimiento, especialmente en universidades y empresas incumbentes. Los estudios futuros deberían validar aún más el modelo empíricamente
Published: 2022

24. Cancer Risks Associated With BRCA1 and BRCA2 Pathogenic Variants.

Author: Li, Shuai, Li, Shuai, Silvestri, Valentina, Leslie, Goska, Rebbeck, Timothy R, Neuhausen, Susan L, Hopper, John L, Nielsen, Henriette Roed, Lee, Andrew, Yang, Xin, McGuffog, Lesley, Parsons, Michael T, Andrulis, Irene L, Arnold, Norbert, Belotti, Muriel, Borg, Åke, Buecher, Bruno, Buys, Saundra S, Caputo, Sandrine M, Chung, Wendy K, Colas, Chrystelle, Colonna, Sarah V, Cook, Jackie, Daly, Mary B, de la Hoya, Miguel, de Pauw, Antoine, Delhomelle, Hélène, Eason, Jacqueline, Engel, Christoph, Evans, D Gareth, Faust, Ulrike, Fehm, Tanja N, Fostira, Florentia, Fountzilas, George, Frone, Megan, Garcia-Barberan, Vanesa, Garre, Pilar, Gauthier-Villars, Marion, Gehrig, Andrea, Glendon, Gord, Goldgar, David E, Golmard, Lisa, Greene, Mark H, Hahnen, Eric, Hamann, Ute, Hanson, Helen, Hassan, Tiara, Hentschel, Julia, Horvath, Judit, Izatt, Louise, Janavicius, Ramunas, Jiao, Yue, John, Esther M, Karlan, Beth Y, Kim, Sung-Won, Konstantopoulou, Irene, Kwong, Ava, Laugé, Anthony, Lee, Jong Won, Lesueur, Fabienne, Mebirouk, Noura, Meindl, Alfons, Mouret-Fourme, Emmanuelle, Musgrave, Hannah, Ngeow Yuen Yie, Joanne, Niederacher, Dieter, Park, Sue K, Pedersen, Inge Sokilde, Ramser, Juliane, Ramus, Susan J, Rantala, Johanna, Rashid, Muhammad U, Reichl, Florian, Ritter, Julia, Rump, Andreas, Santamariña, Marta, Saule, Claire, Schmidt, Gunnar, Schmutzler, Rita K, Senter, Leigha, Shariff, Saba, Singer, Christian F, Southey, Melissa C, Stoppa-Lyonnet, Dominique, Sutter, Christian, Tan, Yen, Teo, Soo Hwang, Terry, Mary Beth, Thomassen, Mads, Tischkowitz, Marc, Toland, Amanda E, Torres, Diana, Vega, Ana, Wagner, Sebastian A, Wang-Gohrke, Shan, Wappenschmidt, Barbara, Weber, Bernhard HF, Yannoukakos, Drakoulis, Spurdle, Amanda B, Easton, Douglas F, Chenevix-Trench, Georgia, Li, Shuai, Li, Shuai, Silvestri, Valentina, Leslie, Goska, Rebbeck, Timothy R, Neuhausen, Susan L, Hopper, John L, Nielsen, Henriette Roed, Lee, Andrew, Yang, Xin, McGuffog, Lesley, Parsons, Michael T, Andrulis, Irene L, Arnold, Norbert, Belotti, Muriel, Borg, Åke, Buecher, Bruno, Buys, Saundra S, Caputo, Sandrine M, Chung, Wendy K, Colas, Chrystelle, Colonna, Sarah V, Cook, Jackie, Daly, Mary B, de la Hoya, Miguel, de Pauw, Antoine, Delhomelle, Hélène, Eason, Jacqueline, Engel, Christoph, Evans, D Gareth, Faust, Ulrike, Fehm, Tanja N, Fostira, Florentia, Fountzilas, George, Frone, Megan, Garcia-Barberan, Vanesa, Garre, Pilar, Gauthier-Villars, Marion, Gehrig, Andrea, Glendon, Gord, Goldgar, David E, Golmard, Lisa, Greene, Mark H, Hahnen, Eric, Hamann, Ute, Hanson, Helen, Hassan, Tiara, Hentschel, Julia, Horvath, Judit, Izatt, Louise, Janavicius, Ramunas, Jiao, Yue, John, Esther M, Karlan, Beth Y, Kim, Sung-Won, Konstantopoulou, Irene, Kwong, Ava, Laugé, Anthony, Lee, Jong Won, Lesueur, Fabienne, Mebirouk, Noura, Meindl, Alfons, Mouret-Fourme, Emmanuelle, Musgrave, Hannah, Ngeow Yuen Yie, Joanne, Niederacher, Dieter, Park, Sue K, Pedersen, Inge Sokilde, Ramser, Juliane, Ramus, Susan J, Rantala, Johanna, Rashid, Muhammad U, Reichl, Florian, Ritter, Julia, Rump, Andreas, Santamariña, Marta, Saule, Claire, Schmidt, Gunnar, Schmutzler, Rita K, Senter, Leigha, Shariff, Saba, Singer, Christian F, Southey, Melissa C, Stoppa-Lyonnet, Dominique, Sutter, Christian, Tan, Yen, Teo, Soo Hwang, Terry, Mary Beth, Thomassen, Mads, Tischkowitz, Marc, Toland, Amanda E, Torres, Diana, Vega, Ana, Wagner, Sebastian A, Wang-Gohrke, Shan, Wappenschmidt, Barbara, Weber, Bernhard HF, Yannoukakos, Drakoulis, Spurdle, Amanda B, Easton, Douglas F, and Chenevix-Trench, Georgia
Abstract: PurposeTo provide precise age-specific risk estimates of cancers other than female breast and ovarian cancers associated with pathogenic variants (PVs) in BRCA1 and BRCA2 for effective cancer risk management.MethodsWe used data from 3,184 BRCA1 and 2,157 BRCA2 families in the Consortium of Investigators of Modifiers of BRCA1/2 to estimate age-specific relative (RR) and absolute risks for 22 first primary cancer types adjusting for family ascertainment.ResultsBRCA1 PVs were associated with risks of male breast (RR = 4.30; 95% CI, 1.09 to 16.96), pancreatic (RR = 2.36; 95% CI, 1.51 to 3.68), and stomach (RR = 2.17; 95% CI, 1.25 to 3.77) cancers. Associations with colorectal and gallbladder cancers were also suggested. BRCA2 PVs were associated with risks of male breast (RR = 44.0; 95% CI, 21.3 to 90.9), stomach (RR = 3.69; 95% CI, 2.40 to 5.67), pancreatic (RR = 3.34; 95% CI, 2.21 to 5.06), and prostate (RR = 2.22; 95% CI, 1.63 to 3.03) cancers. The stomach cancer RR was higher for females than males (6.89 v 2.76; P = .04). The absolute risks to age 80 years ranged from 0.4% for male breast cancer to approximately 2.5% for pancreatic cancer for BRCA1 carriers and from approximately 2.5% for pancreatic cancer to 27% for prostate cancer for BRCA2 carriers.ConclusionIn addition to female breast and ovarian cancers, BRCA1 and BRCA2 PVs are associated with increased risks of male breast, pancreatic, stomach, and prostate (only BRCA2 PVs) cancers, but not with the risks of other previously suggested cancers. The estimated age-specific risks will refine cancer risk management in men and women with BRCA1/2 PVs.
Published: 2022

25. Polygenic risk modeling for prediction of epithelial ovarian cancer risk

Author: Dareng, Eileen O., Tyrer, Jonathan P., Barnes, Daniel R., Jones, Michelle R., Yang, Xin, Aben, Katja K. H., Adank, Muriel A., Agata, Simona, Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Aravantinos, Gerasimos, Arun, Banu K., Augustinsson, Annelie, Balmana, Judith, Bandera, Elisa, V, Barkardottir, Rosa B., Barrowdale, Daniel, Beckmann, Matthias W., Beeghly-Fadiel, Alicia, Benitez, Javier, Bermisheva, Marina, Bernardini, Marcus Q., Bjorge, Line, Black, Amanda, Bogdanova, Natalia, V, Bonanni, Bernardo, Borg, Ake, Brenton, James D., Budzilowska, Agnieszka, Butzow, Ralf, Buys, Saundra S., Cai, Hui, Caligo, Maria A., Campbell, Ian, Cannioto, Rikki, Cassingham, Hayley, Chang-Claude, Jenny, Chanock, Stephen J., Chen, Kexin, Chiew, Yoke-Eng, Chung, Wendy K., Claes, Kathleen B. M., Colonna, Sarah, Cook, Linda S., Couch, Fergus J., Daly, Mary B., Dao, Fanny, Davies, Eleanor, de la Hoya, Miguel, de Putter, Robin, Dennis, Joe, DePersia, Allison, Devilee, Peter, Diez, Orland, Ding, Yuan Chun, Doherty, Jennifer A., Domchek, Susan M., Dork, Thilo, du Bois, Andreas, Durst, Matthias, Eccles, Diana M., Eliassen, Heather A., Engel, Christoph, Evans, Gareth D., Fasching, Peter A., Flanagan, James M., Fortner, ReneeT, Machackova, Eva, Friedman, Eitan, Ganz, Patricia A., Garber, Judy, Gensini, Francesca, Giles, Graham G., Glendon, Gord, Godwin, Andrew K., Goodman, Marc T., Greene, Mark H., Gronwald, Jacek, Group, Opal Study, Group, AOCS, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hamann, Ute, Hansen, Thomas V. O., Harris, Holly R., Hartman, Mikael, Heitz, Florian, Hildebrandt, Michelle A. T., Hogdall, Estrid, Hogdall, Claus K., Hopper, John L., Huang, Ruea-Yea, Huff, Chad, Hulick, Peter J., Huntsman, David G., Imyanitov, Evgeny N., Isaacs, Claudine, Jakubowska, Anna, James, Paul A., Janavicius, Ramunas, Jensen, Allan, Johannsson, Oskar Th, John, Esther M., Jones, Michael E., Kang, Daehee, Karlan, Beth Y., Karnezis, Anthony, Kelemen, Linda E., Khusnutdinova, Elza, Kiemeney, Lambertus A., Kim, Byoung-Gie, Kjaer, Susanne K., Komenaka, Ian, Kupryjanczyk, Jolanta, Kurian, Allison W., Kwong, Ava, Lambrechts, Diether, Larson, Melissa C., Lazaro, Conxi, Le, Nhu D., Leslie, Goska, Lester, Jenny, Lesueur, Fabienne, Levine, Douglas A., Li, Lian, Li, Jingmei, Loud, Jennifer T., Lu, Karen H., Mai, Phuong L., Manoukian, Siranoush, Marks, Jeffrey R., KimMatsuno, Rayna, Matsuo, Keitaro, May, Taymaa, McGuffog, Lesley, McLaughlin, John R., McNeish, Iain A., Mebirouk, Noura, Menon, Usha, Miller, Austin, Milne, Roger L., Minlikeeva, Albina, Modugno, Francesmary, Montagna, Marco, Moysich, Kirsten B., Munro, Elizabeth, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Yie, Joanne Ngeow Yuen, Nielsen, Henriette Roed, Nielsen, Finn C., Nikitina-Zake, Liene, Odunsi, Kunle, Offit, Kenneth, Olah, Edith, Olbrecht, Siel, Olopade, Olufunmilayo, I, Olson, Sara H., Olsson, Hakan, Osorio, Ana, Papi, Laura, Park, Sue K., Parsons, Michael T., Pathak, Harsha, Pedersen, Inge Sokilde, Peixoto, Ana, Pejovic, Tanja, Perez-Segura, Pedro, Permuth, Jennifer B., Peshkin, Beth, Peterlongo, Paolo, Piskorz, Anna, Prokofyeva, Darya, Radice, Paolo, Rantala, Johanna, Riggan, Marjorie J., Risch, Harvey A., Rodriguez-Antona, Cristina, Ross, Eric, Rossing, Mary Anne, Runnebaum, Ingo, Sandler, Dale P., Santamarina, Marta, Soucy, Penny, Schmutzler, Rita K., Setiawan, V. Wendy, Shan, Kang, Sieh, Weiva, Simard, Jacques, Singer, Christian F., Sokolenko, Anna P., Song, Honglin, Southey, Melissa C., Steed, Helen, Stoppa-Lyonnet, Dominique, Sutphen, Rebecca, Swerdlow, Anthony J., Tan, Yen Yen, Teixeira, Manuel R., Teo, Soo Hwang, Terry, Kathryn L., BethTerry, Mary, Thomassen, Mads, Thompson, Pamela J., Thomsen, Liv Cecilie Vestrheim, Thull, Darcy L., Tischkowitz, Marc, Titus, Linda, Toland, Amanda E., Torres, Diana, Trabert, Britton, Travis, Ruth, Tung, Nadine, Tworoger, Shelley S., Valen, Ellen, van Altena, Anne M., van der Hout, Annemieke H., Nieuwenhuysen, ElsVan, van Rensburg, Elizabeth J., Vega, Ana, Edwards, Digna Velez, Vierkant, Robert A., Wang, Frances, Wappenschmidt, Barbara, Webb, Penelope M., Weinberg, Clarice R., Weitzel, Jeffrey N., Wentzensen, Nicolas, White, Emily, Whittemore, Alice S., Winham, Stacey J., Wolk, Alicja, Woo, Yin-Ling, Wu, Anna H., Yan, Li, Yannoukakos, Drakoulis, Zavaglia, Katia M., Zheng, Wei, Ziogas, Argyrios, Zorn, Kristin K., Kleibl, Zdenek, Easton, Douglas, Lawrenson, Kate, DeFazio, Anna, Sellers, Thomas A., Ramus, Susan J., Pearce, Celeste L., Monteiro, Alvaro N., Cunningham, Julie, Goode, Ellen L., Schildkraut, Joellen M., Berchuck, Andrew, Chenevix-Trench, Georgia, Gayther, Simon A., Antoniou, Antonis C., Pharoah, Paul D. P., Dareng, Eileen O., Tyrer, Jonathan P., Barnes, Daniel R., Jones, Michelle R., Yang, Xin, Aben, Katja K. H., Adank, Muriel A., Agata, Simona, Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Aravantinos, Gerasimos, Arun, Banu K., Augustinsson, Annelie, Balmana, Judith, Bandera, Elisa, V, Barkardottir, Rosa B., Barrowdale, Daniel, Beckmann, Matthias W., Beeghly-Fadiel, Alicia, Benitez, Javier, Bermisheva, Marina, Bernardini, Marcus Q., Bjorge, Line, Black, Amanda, Bogdanova, Natalia, V, Bonanni, Bernardo, Borg, Ake, Brenton, James D., Budzilowska, Agnieszka, Butzow, Ralf, Buys, Saundra S., Cai, Hui, Caligo, Maria A., Campbell, Ian, Cannioto, Rikki, Cassingham, Hayley, Chang-Claude, Jenny, Chanock, Stephen J., Chen, Kexin, Chiew, Yoke-Eng, Chung, Wendy K., Claes, Kathleen B. M., Colonna, Sarah, Cook, Linda S., Couch, Fergus J., Daly, Mary B., Dao, Fanny, Davies, Eleanor, de la Hoya, Miguel, de Putter, Robin, Dennis, Joe, DePersia, Allison, Devilee, Peter, Diez, Orland, Ding, Yuan Chun, Doherty, Jennifer A., Domchek, Susan M., Dork, Thilo, du Bois, Andreas, Durst, Matthias, Eccles, Diana M., Eliassen, Heather A., Engel, Christoph, Evans, Gareth D., Fasching, Peter A., Flanagan, James M., Fortner, ReneeT, Machackova, Eva, Friedman, Eitan, Ganz, Patricia A., Garber, Judy, Gensini, Francesca, Giles, Graham G., Glendon, Gord, Godwin, Andrew K., Goodman, Marc T., Greene, Mark H., Gronwald, Jacek, Group, Opal Study, Group, AOCS, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hamann, Ute, Hansen, Thomas V. O., Harris, Holly R., Hartman, Mikael, Heitz, Florian, Hildebrandt, Michelle A. T., Hogdall, Estrid, Hogdall, Claus K., Hopper, John L., Huang, Ruea-Yea, Huff, Chad, Hulick, Peter J., Huntsman, David G., Imyanitov, Evgeny N., Isaacs, Claudine, Jakubowska, Anna, James, Paul A., Janavicius, Ramunas, Jensen, Allan, Johannsson, Oskar Th, John, Esther M., Jones, Michael E., Kang, Daehee, Karlan, Beth Y., Karnezis, Anthony, Kelemen, Linda E., Khusnutdinova, Elza, Kiemeney, Lambertus A., Kim, Byoung-Gie, Kjaer, Susanne K., Komenaka, Ian, Kupryjanczyk, Jolanta, Kurian, Allison W., Kwong, Ava, Lambrechts, Diether, Larson, Melissa C., Lazaro, Conxi, Le, Nhu D., Leslie, Goska, Lester, Jenny, Lesueur, Fabienne, Levine, Douglas A., Li, Lian, Li, Jingmei, Loud, Jennifer T., Lu, Karen H., Mai, Phuong L., Manoukian, Siranoush, Marks, Jeffrey R., KimMatsuno, Rayna, Matsuo, Keitaro, May, Taymaa, McGuffog, Lesley, McLaughlin, John R., McNeish, Iain A., Mebirouk, Noura, Menon, Usha, Miller, Austin, Milne, Roger L., Minlikeeva, Albina, Modugno, Francesmary, Montagna, Marco, Moysich, Kirsten B., Munro, Elizabeth, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Yie, Joanne Ngeow Yuen, Nielsen, Henriette Roed, Nielsen, Finn C., Nikitina-Zake, Liene, Odunsi, Kunle, Offit, Kenneth, Olah, Edith, Olbrecht, Siel, Olopade, Olufunmilayo, I, Olson, Sara H., Olsson, Hakan, Osorio, Ana, Papi, Laura, Park, Sue K., Parsons, Michael T., Pathak, Harsha, Pedersen, Inge Sokilde, Peixoto, Ana, Pejovic, Tanja, Perez-Segura, Pedro, Permuth, Jennifer B., Peshkin, Beth, Peterlongo, Paolo, Piskorz, Anna, Prokofyeva, Darya, Radice, Paolo, Rantala, Johanna, Riggan, Marjorie J., Risch, Harvey A., Rodriguez-Antona, Cristina, Ross, Eric, Rossing, Mary Anne, Runnebaum, Ingo, Sandler, Dale P., Santamarina, Marta, Soucy, Penny, Schmutzler, Rita K., Setiawan, V. Wendy, Shan, Kang, Sieh, Weiva, Simard, Jacques, Singer, Christian F., Sokolenko, Anna P., Song, Honglin, Southey, Melissa C., Steed, Helen, Stoppa-Lyonnet, Dominique, Sutphen, Rebecca, Swerdlow, Anthony J., Tan, Yen Yen, Teixeira, Manuel R., Teo, Soo Hwang, Terry, Kathryn L., BethTerry, Mary, Thomassen, Mads, Thompson, Pamela J., Thomsen, Liv Cecilie Vestrheim, Thull, Darcy L., Tischkowitz, Marc, Titus, Linda, Toland, Amanda E., Torres, Diana, Trabert, Britton, Travis, Ruth, Tung, Nadine, Tworoger, Shelley S., Valen, Ellen, van Altena, Anne M., van der Hout, Annemieke H., Nieuwenhuysen, ElsVan, van Rensburg, Elizabeth J., Vega, Ana, Edwards, Digna Velez, Vierkant, Robert A., Wang, Frances, Wappenschmidt, Barbara, Webb, Penelope M., Weinberg, Clarice R., Weitzel, Jeffrey N., Wentzensen, Nicolas, White, Emily, Whittemore, Alice S., Winham, Stacey J., Wolk, Alicja, Woo, Yin-Ling, Wu, Anna H., Yan, Li, Yannoukakos, Drakoulis, Zavaglia, Katia M., Zheng, Wei, Ziogas, Argyrios, Zorn, Kristin K., Kleibl, Zdenek, Easton, Douglas, Lawrenson, Kate, DeFazio, Anna, Sellers, Thomas A., Ramus, Susan J., Pearce, Celeste L., Monteiro, Alvaro N., Cunningham, Julie, Goode, Ellen L., Schildkraut, Joellen M., Berchuck, Andrew, Chenevix-Trench, Georgia, Gayther, Simon A., Antoniou, Antonis C., and Pharoah, Paul D. P.
Abstract: Polygenic risk scores (PRS) for epithelial ovarian cancer (EOC) have the potential to improve risk stratification. Joint estimation of Single Nucleotide Polymorphism (SNP) effects in models could improve predictive performance over standard approaches of PRS construction. Here, we implemented computationally efficient, penalized, logistic regression models (lasso, elastic net, stepwise) to individual level genotype data and a Bayesian framework with continuous shrinkage, "select and shrink for summary statistics" (S4), to summary level data for epithelial non-mucinous ovarian cancer risk prediction. We developed the models in a dataset consisting of 23,564 non-mucinous EOC cases and 40,138 controls participating in the Ovarian Cancer Association Consortium (OCAC) and validated the best models in three populations of different ancestries: prospective data from 198,101 women of European ancestries; 7,669 women of East Asian ancestries; 1,072 women of African ancestries, and in 18,915 BRCA1 and 12,337 BRCA2 pathogenic variant carriers of European ancestries. In the external validation data, the model with the strongest association for non-mucinous EOC risk derived from the OCAC model development data was the S4 model (27,240 SNPs) with odds ratios (OR) of 1.38 (95% CI: 1.28-1.48, AUC: 0.588) per unit standard deviation, in women of European ancestries; 1.14 (95% CI: 1.08-1.19, AUC: 0.538) in women of East Asian ancestries; 1.38 (95% CI: 1.21-1.58, AUC: 0.593) in women of African ancestries; hazard ratios of 1.36 (95% CI: 1.29-1.43, AUC: 0.592) in BRCA1 pathogenic variant carriers and 1.49 (95% CI: 1.35-1.64, AUC: 0.624) in BRCA2 pathogenic variant carriers. Incorporation of the S4 PRS in risk prediction models for ovarian cancer may have clinical utility in ovarian cancer prevention programs.
Published: 2022
Full Text: View/download PDF

26. Polygenic risk modeling for prediction of epithelial ovarian cancer risk

Author: Dareng, Eileen O., Tyrer, Jonathan P., Barnes, Daniel R., Jones, Michelle R., Yang, Xin, Aben, Katja K. H., Adank, Muriel A., Agata, Simona, Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Aravantinos, Gerasimos, Arun, Banu K., Augustinsson, Annelie, Balmana, Judith, Bandera, Elisa, V, Barkardottir, Rosa B., Barrowdale, Daniel, Beckmann, Matthias W., Beeghly-Fadiel, Alicia, Benitez, Javier, Bermisheva, Marina, Bernardini, Marcus Q., Bjorge, Line, Black, Amanda, Bogdanova, Natalia, V, Bonanni, Bernardo, Borg, Ake, Brenton, James D., Budzilowska, Agnieszka, Butzow, Ralf, Buys, Saundra S., Cai, Hui, Caligo, Maria A., Campbell, Ian, Cannioto, Rikki, Cassingham, Hayley, Chang-Claude, Jenny, Chanock, Stephen J., Chen, Kexin, Chiew, Yoke-Eng, Chung, Wendy K., Claes, Kathleen B. M., Colonna, Sarah, Cook, Linda S., Couch, Fergus J., Daly, Mary B., Dao, Fanny, Davies, Eleanor, de la Hoya, Miguel, de Putter, Robin, Dennis, Joe, DePersia, Allison, Devilee, Peter, Diez, Orland, Ding, Yuan Chun, Doherty, Jennifer A., Domchek, Susan M., Dork, Thilo, du Bois, Andreas, Durst, Matthias, Eccles, Diana M., Eliassen, Heather A., Engel, Christoph, Evans, Gareth D., Fasching, Peter A., Flanagan, James M., Fortner, ReneeT, Machackova, Eva, Friedman, Eitan, Ganz, Patricia A., Garber, Judy, Gensini, Francesca, Giles, Graham G., Glendon, Gord, Godwin, Andrew K., Goodman, Marc T., Greene, Mark H., Gronwald, Jacek, Group, Opal Study, Group, AOCS, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hamann, Ute, Hansen, Thomas V. O., Harris, Holly R., Hartman, Mikael, Heitz, Florian, Hildebrandt, Michelle A. T., Hogdall, Estrid, Hogdall, Claus K., Hopper, John L., Huang, Ruea-Yea, Huff, Chad, Hulick, Peter J., Huntsman, David G., Imyanitov, Evgeny N., Isaacs, Claudine, Jakubowska, Anna, James, Paul A., Janavicius, Ramunas, Jensen, Allan, Johannsson, Oskar Th, John, Esther M., Jones, Michael E., Kang, Daehee, Karlan, Beth Y., Karnezis, Anthony, Kelemen, Linda E., Khusnutdinova, Elza, Kiemeney, Lambertus A., Kim, Byoung-Gie, Kjaer, Susanne K., Komenaka, Ian, Kupryjanczyk, Jolanta, Kurian, Allison W., Kwong, Ava, Lambrechts, Diether, Larson, Melissa C., Lazaro, Conxi, Le, Nhu D., Leslie, Goska, Lester, Jenny, Lesueur, Fabienne, Levine, Douglas A., Li, Lian, Li, Jingmei, Loud, Jennifer T., Lu, Karen H., Mai, Phuong L., Manoukian, Siranoush, Marks, Jeffrey R., KimMatsuno, Rayna, Matsuo, Keitaro, May, Taymaa, McGuffog, Lesley, McLaughlin, John R., McNeish, Iain A., Mebirouk, Noura, Menon, Usha, Miller, Austin, Milne, Roger L., Minlikeeva, Albina, Modugno, Francesmary, Montagna, Marco, Moysich, Kirsten B., Munro, Elizabeth, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Yie, Joanne Ngeow Yuen, Nielsen, Henriette Roed, Nielsen, Finn C., Nikitina-Zake, Liene, Odunsi, Kunle, Offit, Kenneth, Olah, Edith, Olbrecht, Siel, Olopade, Olufunmilayo, I, Olson, Sara H., Olsson, Hakan, Osorio, Ana, Papi, Laura, Park, Sue K., Parsons, Michael T., Pathak, Harsha, Pedersen, Inge Sokilde, Peixoto, Ana, Pejovic, Tanja, Perez-Segura, Pedro, Permuth, Jennifer B., Peshkin, Beth, Peterlongo, Paolo, Piskorz, Anna, Prokofyeva, Darya, Radice, Paolo, Rantala, Johanna, Riggan, Marjorie J., Risch, Harvey A., Rodriguez-Antona, Cristina, Ross, Eric, Rossing, Mary Anne, Runnebaum, Ingo, Sandler, Dale P., Santamarina, Marta, Soucy, Penny, Schmutzler, Rita K., Setiawan, V. Wendy, Shan, Kang, Sieh, Weiva, Simard, Jacques, Singer, Christian F., Sokolenko, Anna P., Song, Honglin, Southey, Melissa C., Steed, Helen, Stoppa-Lyonnet, Dominique, Sutphen, Rebecca, Swerdlow, Anthony J., Tan, Yen Yen, Teixeira, Manuel R., Teo, Soo Hwang, Terry, Kathryn L., BethTerry, Mary, Thomassen, Mads, Thompson, Pamela J., Thomsen, Liv Cecilie Vestrheim, Thull, Darcy L., Tischkowitz, Marc, Titus, Linda, Toland, Amanda E., Torres, Diana, Trabert, Britton, Travis, Ruth, Tung, Nadine, Tworoger, Shelley S., Valen, Ellen, van Altena, Anne M., van der Hout, Annemieke H., Nieuwenhuysen, ElsVan, van Rensburg, Elizabeth J., Vega, Ana, Edwards, Digna Velez, Vierkant, Robert A., Wang, Frances, Wappenschmidt, Barbara, Webb, Penelope M., Weinberg, Clarice R., Weitzel, Jeffrey N., Wentzensen, Nicolas, White, Emily, Whittemore, Alice S., Winham, Stacey J., Wolk, Alicja, Woo, Yin-Ling, Wu, Anna H., Yan, Li, Yannoukakos, Drakoulis, Zavaglia, Katia M., Zheng, Wei, Ziogas, Argyrios, Zorn, Kristin K., Kleibl, Zdenek, Easton, Douglas, Lawrenson, Kate, DeFazio, Anna, Sellers, Thomas A., Ramus, Susan J., Pearce, Celeste L., Monteiro, Alvaro N., Cunningham, Julie, Goode, Ellen L., Schildkraut, Joellen M., Berchuck, Andrew, Chenevix-Trench, Georgia, Gayther, Simon A., Antoniou, Antonis C., Pharoah, Paul D. P., Dareng, Eileen O., Tyrer, Jonathan P., Barnes, Daniel R., Jones, Michelle R., Yang, Xin, Aben, Katja K. H., Adank, Muriel A., Agata, Simona, Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Aravantinos, Gerasimos, Arun, Banu K., Augustinsson, Annelie, Balmana, Judith, Bandera, Elisa, V, Barkardottir, Rosa B., Barrowdale, Daniel, Beckmann, Matthias W., Beeghly-Fadiel, Alicia, Benitez, Javier, Bermisheva, Marina, Bernardini, Marcus Q., Bjorge, Line, Black, Amanda, Bogdanova, Natalia, V, Bonanni, Bernardo, Borg, Ake, Brenton, James D., Budzilowska, Agnieszka, Butzow, Ralf, Buys, Saundra S., Cai, Hui, Caligo, Maria A., Campbell, Ian, Cannioto, Rikki, Cassingham, Hayley, Chang-Claude, Jenny, Chanock, Stephen J., Chen, Kexin, Chiew, Yoke-Eng, Chung, Wendy K., Claes, Kathleen B. M., Colonna, Sarah, Cook, Linda S., Couch, Fergus J., Daly, Mary B., Dao, Fanny, Davies, Eleanor, de la Hoya, Miguel, de Putter, Robin, Dennis, Joe, DePersia, Allison, Devilee, Peter, Diez, Orland, Ding, Yuan Chun, Doherty, Jennifer A., Domchek, Susan M., Dork, Thilo, du Bois, Andreas, Durst, Matthias, Eccles, Diana M., Eliassen, Heather A., Engel, Christoph, Evans, Gareth D., Fasching, Peter A., Flanagan, James M., Fortner, ReneeT, Machackova, Eva, Friedman, Eitan, Ganz, Patricia A., Garber, Judy, Gensini, Francesca, Giles, Graham G., Glendon, Gord, Godwin, Andrew K., Goodman, Marc T., Greene, Mark H., Gronwald, Jacek, Group, Opal Study, Group, AOCS, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hamann, Ute, Hansen, Thomas V. O., Harris, Holly R., Hartman, Mikael, Heitz, Florian, Hildebrandt, Michelle A. T., Hogdall, Estrid, Hogdall, Claus K., Hopper, John L., Huang, Ruea-Yea, Huff, Chad, Hulick, Peter J., Huntsman, David G., Imyanitov, Evgeny N., Isaacs, Claudine, Jakubowska, Anna, James, Paul A., Janavicius, Ramunas, Jensen, Allan, Johannsson, Oskar Th, John, Esther M., Jones, Michael E., Kang, Daehee, Karlan, Beth Y., Karnezis, Anthony, Kelemen, Linda E., Khusnutdinova, Elza, Kiemeney, Lambertus A., Kim, Byoung-Gie, Kjaer, Susanne K., Komenaka, Ian, Kupryjanczyk, Jolanta, Kurian, Allison W., Kwong, Ava, Lambrechts, Diether, Larson, Melissa C., Lazaro, Conxi, Le, Nhu D., Leslie, Goska, Lester, Jenny, Lesueur, Fabienne, Levine, Douglas A., Li, Lian, Li, Jingmei, Loud, Jennifer T., Lu, Karen H., Mai, Phuong L., Manoukian, Siranoush, Marks, Jeffrey R., KimMatsuno, Rayna, Matsuo, Keitaro, May, Taymaa, McGuffog, Lesley, McLaughlin, John R., McNeish, Iain A., Mebirouk, Noura, Menon, Usha, Miller, Austin, Milne, Roger L., Minlikeeva, Albina, Modugno, Francesmary, Montagna, Marco, Moysich, Kirsten B., Munro, Elizabeth, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Yie, Joanne Ngeow Yuen, Nielsen, Henriette Roed, Nielsen, Finn C., Nikitina-Zake, Liene, Odunsi, Kunle, Offit, Kenneth, Olah, Edith, Olbrecht, Siel, Olopade, Olufunmilayo, I, Olson, Sara H., Olsson, Hakan, Osorio, Ana, Papi, Laura, Park, Sue K., Parsons, Michael T., Pathak, Harsha, Pedersen, Inge Sokilde, Peixoto, Ana, Pejovic, Tanja, Perez-Segura, Pedro, Permuth, Jennifer B., Peshkin, Beth, Peterlongo, Paolo, Piskorz, Anna, Prokofyeva, Darya, Radice, Paolo, Rantala, Johanna, Riggan, Marjorie J., Risch, Harvey A., Rodriguez-Antona, Cristina, Ross, Eric, Rossing, Mary Anne, Runnebaum, Ingo, Sandler, Dale P., Santamarina, Marta, Soucy, Penny, Schmutzler, Rita K., Setiawan, V. Wendy, Shan, Kang, Sieh, Weiva, Simard, Jacques, Singer, Christian F., Sokolenko, Anna P., Song, Honglin, Southey, Melissa C., Steed, Helen, Stoppa-Lyonnet, Dominique, Sutphen, Rebecca, Swerdlow, Anthony J., Tan, Yen Yen, Teixeira, Manuel R., Teo, Soo Hwang, Terry, Kathryn L., BethTerry, Mary, Thomassen, Mads, Thompson, Pamela J., Thomsen, Liv Cecilie Vestrheim, Thull, Darcy L., Tischkowitz, Marc, Titus, Linda, Toland, Amanda E., Torres, Diana, Trabert, Britton, Travis, Ruth, Tung, Nadine, Tworoger, Shelley S., Valen, Ellen, van Altena, Anne M., van der Hout, Annemieke H., Nieuwenhuysen, ElsVan, van Rensburg, Elizabeth J., Vega, Ana, Edwards, Digna Velez, Vierkant, Robert A., Wang, Frances, Wappenschmidt, Barbara, Webb, Penelope M., Weinberg, Clarice R., Weitzel, Jeffrey N., Wentzensen, Nicolas, White, Emily, Whittemore, Alice S., Winham, Stacey J., Wolk, Alicja, Woo, Yin-Ling, Wu, Anna H., Yan, Li, Yannoukakos, Drakoulis, Zavaglia, Katia M., Zheng, Wei, Ziogas, Argyrios, Zorn, Kristin K., Kleibl, Zdenek, Easton, Douglas, Lawrenson, Kate, DeFazio, Anna, Sellers, Thomas A., Ramus, Susan J., Pearce, Celeste L., Monteiro, Alvaro N., Cunningham, Julie, Goode, Ellen L., Schildkraut, Joellen M., Berchuck, Andrew, Chenevix-Trench, Georgia, Gayther, Simon A., Antoniou, Antonis C., and Pharoah, Paul D. P.
Abstract: Polygenic risk scores (PRS) for epithelial ovarian cancer (EOC) have the potential to improve risk stratification. Joint estimation of Single Nucleotide Polymorphism (SNP) effects in models could improve predictive performance over standard approaches of PRS construction. Here, we implemented computationally efficient, penalized, logistic regression models (lasso, elastic net, stepwise) to individual level genotype data and a Bayesian framework with continuous shrinkage, "select and shrink for summary statistics" (S4), to summary level data for epithelial non-mucinous ovarian cancer risk prediction. We developed the models in a dataset consisting of 23,564 non-mucinous EOC cases and 40,138 controls participating in the Ovarian Cancer Association Consortium (OCAC) and validated the best models in three populations of different ancestries: prospective data from 198,101 women of European ancestries; 7,669 women of East Asian ancestries; 1,072 women of African ancestries, and in 18,915 BRCA1 and 12,337 BRCA2 pathogenic variant carriers of European ancestries. In the external validation data, the model with the strongest association for non-mucinous EOC risk derived from the OCAC model development data was the S4 model (27,240 SNPs) with odds ratios (OR) of 1.38 (95% CI: 1.28-1.48, AUC: 0.588) per unit standard deviation, in women of European ancestries; 1.14 (95% CI: 1.08-1.19, AUC: 0.538) in women of East Asian ancestries; 1.38 (95% CI: 1.21-1.58, AUC: 0.593) in women of African ancestries; hazard ratios of 1.36 (95% CI: 1.29-1.43, AUC: 0.592) in BRCA1 pathogenic variant carriers and 1.49 (95% CI: 1.35-1.64, AUC: 0.624) in BRCA2 pathogenic variant carriers. Incorporation of the S4 PRS in risk prediction models for ovarian cancer may have clinical utility in ovarian cancer prevention programs.
Published: 2022
Full Text: View/download PDF

27. Polygenic risk modeling for prediction of epithelial ovarian cancer risk

Author: Dareng, Eileen O., Tyrer, Jonathan P., Barnes, Daniel R., Jones, Michelle R., Yang, Xin, Aben, Katja K. H., Adank, Muriel A., Agata, Simona, Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Aravantinos, Gerasimos, Arun, Banu K., Augustinsson, Annelie, Balmana, Judith, Bandera, Elisa, V, Barkardottir, Rosa B., Barrowdale, Daniel, Beckmann, Matthias W., Beeghly-Fadiel, Alicia, Benitez, Javier, Bermisheva, Marina, Bernardini, Marcus Q., Bjorge, Line, Black, Amanda, Bogdanova, Natalia, V, Bonanni, Bernardo, Borg, Ake, Brenton, James D., Budzilowska, Agnieszka, Butzow, Ralf, Buys, Saundra S., Cai, Hui, Caligo, Maria A., Campbell, Ian, Cannioto, Rikki, Cassingham, Hayley, Chang-Claude, Jenny, Chanock, Stephen J., Chen, Kexin, Chiew, Yoke-Eng, Chung, Wendy K., Claes, Kathleen B. M., Colonna, Sarah, Cook, Linda S., Couch, Fergus J., Daly, Mary B., Dao, Fanny, Davies, Eleanor, de la Hoya, Miguel, de Putter, Robin, Dennis, Joe, DePersia, Allison, Devilee, Peter, Diez, Orland, Ding, Yuan Chun, Doherty, Jennifer A., Domchek, Susan M., Dork, Thilo, du Bois, Andreas, Durst, Matthias, Eccles, Diana M., Eliassen, Heather A., Engel, Christoph, Evans, Gareth D., Fasching, Peter A., Flanagan, James M., Fortner, ReneeT, Machackova, Eva, Friedman, Eitan, Ganz, Patricia A., Garber, Judy, Gensini, Francesca, Giles, Graham G., Glendon, Gord, Godwin, Andrew K., Goodman, Marc T., Greene, Mark H., Gronwald, Jacek, Group, Opal Study, Group, AOCS, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hamann, Ute, Hansen, Thomas V. O., Harris, Holly R., Hartman, Mikael, Heitz, Florian, Hildebrandt, Michelle A. T., Hogdall, Estrid, Hogdall, Claus K., Hopper, John L., Huang, Ruea-Yea, Huff, Chad, Hulick, Peter J., Huntsman, David G., Imyanitov, Evgeny N., Isaacs, Claudine, Jakubowska, Anna, James, Paul A., Janavicius, Ramunas, Jensen, Allan, Johannsson, Oskar Th, John, Esther M., Jones, Michael E., Kang, Daehee, Karlan, Beth Y., Karnezis, Anthony, Kelemen, Linda E., Khusnutdinova, Elza, Kiemeney, Lambertus A., Kim, Byoung-Gie, Kjaer, Susanne K., Komenaka, Ian, Kupryjanczyk, Jolanta, Kurian, Allison W., Kwong, Ava, Lambrechts, Diether, Larson, Melissa C., Lazaro, Conxi, Le, Nhu D., Leslie, Goska, Lester, Jenny, Lesueur, Fabienne, Levine, Douglas A., Li, Lian, Li, Jingmei, Loud, Jennifer T., Lu, Karen H., Mai, Phuong L., Manoukian, Siranoush, Marks, Jeffrey R., KimMatsuno, Rayna, Matsuo, Keitaro, May, Taymaa, McGuffog, Lesley, McLaughlin, John R., McNeish, Iain A., Mebirouk, Noura, Menon, Usha, Miller, Austin, Milne, Roger L., Minlikeeva, Albina, Modugno, Francesmary, Montagna, Marco, Moysich, Kirsten B., Munro, Elizabeth, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Yie, Joanne Ngeow Yuen, Nielsen, Henriette Roed, Nielsen, Finn C., Nikitina-Zake, Liene, Odunsi, Kunle, Offit, Kenneth, Olah, Edith, Olbrecht, Siel, Olopade, Olufunmilayo, I, Olson, Sara H., Olsson, Hakan, Osorio, Ana, Papi, Laura, Park, Sue K., Parsons, Michael T., Pathak, Harsha, Pedersen, Inge Sokilde, Peixoto, Ana, Pejovic, Tanja, Perez-Segura, Pedro, Permuth, Jennifer B., Peshkin, Beth, Peterlongo, Paolo, Piskorz, Anna, Prokofyeva, Darya, Radice, Paolo, Rantala, Johanna, Riggan, Marjorie J., Risch, Harvey A., Rodriguez-Antona, Cristina, Ross, Eric, Rossing, Mary Anne, Runnebaum, Ingo, Sandler, Dale P., Santamarina, Marta, Soucy, Penny, Schmutzler, Rita K., Setiawan, V. Wendy, Shan, Kang, Sieh, Weiva, Simard, Jacques, Singer, Christian F., Sokolenko, Anna P., Song, Honglin, Southey, Melissa C., Steed, Helen, Stoppa-Lyonnet, Dominique, Sutphen, Rebecca, Swerdlow, Anthony J., Tan, Yen Yen, Teixeira, Manuel R., Teo, Soo Hwang, Terry, Kathryn L., BethTerry, Mary, Thomassen, Mads, Thompson, Pamela J., Thomsen, Liv Cecilie Vestrheim, Thull, Darcy L., Tischkowitz, Marc, Titus, Linda, Toland, Amanda E., Torres, Diana, Trabert, Britton, Travis, Ruth, Tung, Nadine, Tworoger, Shelley S., Valen, Ellen, van Altena, Anne M., van der Hout, Annemieke H., Nieuwenhuysen, ElsVan, van Rensburg, Elizabeth J., Vega, Ana, Edwards, Digna Velez, Vierkant, Robert A., Wang, Frances, Wappenschmidt, Barbara, Webb, Penelope M., Weinberg, Clarice R., Weitzel, Jeffrey N., Wentzensen, Nicolas, White, Emily, Whittemore, Alice S., Winham, Stacey J., Wolk, Alicja, Woo, Yin-Ling, Wu, Anna H., Yan, Li, Yannoukakos, Drakoulis, Zavaglia, Katia M., Zheng, Wei, Ziogas, Argyrios, Zorn, Kristin K., Kleibl, Zdenek, Easton, Douglas, Lawrenson, Kate, DeFazio, Anna, Sellers, Thomas A., Ramus, Susan J., Pearce, Celeste L., Monteiro, Alvaro N., Cunningham, Julie, Goode, Ellen L., Schildkraut, Joellen M., Berchuck, Andrew, Chenevix-Trench, Georgia, Gayther, Simon A., Antoniou, Antonis C., Pharoah, Paul D. P., Dareng, Eileen O., Tyrer, Jonathan P., Barnes, Daniel R., Jones, Michelle R., Yang, Xin, Aben, Katja K. H., Adank, Muriel A., Agata, Simona, Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Aravantinos, Gerasimos, Arun, Banu K., Augustinsson, Annelie, Balmana, Judith, Bandera, Elisa, V, Barkardottir, Rosa B., Barrowdale, Daniel, Beckmann, Matthias W., Beeghly-Fadiel, Alicia, Benitez, Javier, Bermisheva, Marina, Bernardini, Marcus Q., Bjorge, Line, Black, Amanda, Bogdanova, Natalia, V, Bonanni, Bernardo, Borg, Ake, Brenton, James D., Budzilowska, Agnieszka, Butzow, Ralf, Buys, Saundra S., Cai, Hui, Caligo, Maria A., Campbell, Ian, Cannioto, Rikki, Cassingham, Hayley, Chang-Claude, Jenny, Chanock, Stephen J., Chen, Kexin, Chiew, Yoke-Eng, Chung, Wendy K., Claes, Kathleen B. M., Colonna, Sarah, Cook, Linda S., Couch, Fergus J., Daly, Mary B., Dao, Fanny, Davies, Eleanor, de la Hoya, Miguel, de Putter, Robin, Dennis, Joe, DePersia, Allison, Devilee, Peter, Diez, Orland, Ding, Yuan Chun, Doherty, Jennifer A., Domchek, Susan M., Dork, Thilo, du Bois, Andreas, Durst, Matthias, Eccles, Diana M., Eliassen, Heather A., Engel, Christoph, Evans, Gareth D., Fasching, Peter A., Flanagan, James M., Fortner, ReneeT, Machackova, Eva, Friedman, Eitan, Ganz, Patricia A., Garber, Judy, Gensini, Francesca, Giles, Graham G., Glendon, Gord, Godwin, Andrew K., Goodman, Marc T., Greene, Mark H., Gronwald, Jacek, Group, Opal Study, Group, AOCS, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hamann, Ute, Hansen, Thomas V. O., Harris, Holly R., Hartman, Mikael, Heitz, Florian, Hildebrandt, Michelle A. T., Hogdall, Estrid, Hogdall, Claus K., Hopper, John L., Huang, Ruea-Yea, Huff, Chad, Hulick, Peter J., Huntsman, David G., Imyanitov, Evgeny N., Isaacs, Claudine, Jakubowska, Anna, James, Paul A., Janavicius, Ramunas, Jensen, Allan, Johannsson, Oskar Th, John, Esther M., Jones, Michael E., Kang, Daehee, Karlan, Beth Y., Karnezis, Anthony, Kelemen, Linda E., Khusnutdinova, Elza, Kiemeney, Lambertus A., Kim, Byoung-Gie, Kjaer, Susanne K., Komenaka, Ian, Kupryjanczyk, Jolanta, Kurian, Allison W., Kwong, Ava, Lambrechts, Diether, Larson, Melissa C., Lazaro, Conxi, Le, Nhu D., Leslie, Goska, Lester, Jenny, Lesueur, Fabienne, Levine, Douglas A., Li, Lian, Li, Jingmei, Loud, Jennifer T., Lu, Karen H., Mai, Phuong L., Manoukian, Siranoush, Marks, Jeffrey R., KimMatsuno, Rayna, Matsuo, Keitaro, May, Taymaa, McGuffog, Lesley, McLaughlin, John R., McNeish, Iain A., Mebirouk, Noura, Menon, Usha, Miller, Austin, Milne, Roger L., Minlikeeva, Albina, Modugno, Francesmary, Montagna, Marco, Moysich, Kirsten B., Munro, Elizabeth, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Yie, Joanne Ngeow Yuen, Nielsen, Henriette Roed, Nielsen, Finn C., Nikitina-Zake, Liene, Odunsi, Kunle, Offit, Kenneth, Olah, Edith, Olbrecht, Siel, Olopade, Olufunmilayo, I, Olson, Sara H., Olsson, Hakan, Osorio, Ana, Papi, Laura, Park, Sue K., Parsons, Michael T., Pathak, Harsha, Pedersen, Inge Sokilde, Peixoto, Ana, Pejovic, Tanja, Perez-Segura, Pedro, Permuth, Jennifer B., Peshkin, Beth, Peterlongo, Paolo, Piskorz, Anna, Prokofyeva, Darya, Radice, Paolo, Rantala, Johanna, Riggan, Marjorie J., Risch, Harvey A., Rodriguez-Antona, Cristina, Ross, Eric, Rossing, Mary Anne, Runnebaum, Ingo, Sandler, Dale P., Santamarina, Marta, Soucy, Penny, Schmutzler, Rita K., Setiawan, V. Wendy, Shan, Kang, Sieh, Weiva, Simard, Jacques, Singer, Christian F., Sokolenko, Anna P., Song, Honglin, Southey, Melissa C., Steed, Helen, Stoppa-Lyonnet, Dominique, Sutphen, Rebecca, Swerdlow, Anthony J., Tan, Yen Yen, Teixeira, Manuel R., Teo, Soo Hwang, Terry, Kathryn L., BethTerry, Mary, Thomassen, Mads, Thompson, Pamela J., Thomsen, Liv Cecilie Vestrheim, Thull, Darcy L., Tischkowitz, Marc, Titus, Linda, Toland, Amanda E., Torres, Diana, Trabert, Britton, Travis, Ruth, Tung, Nadine, Tworoger, Shelley S., Valen, Ellen, van Altena, Anne M., van der Hout, Annemieke H., Nieuwenhuysen, ElsVan, van Rensburg, Elizabeth J., Vega, Ana, Edwards, Digna Velez, Vierkant, Robert A., Wang, Frances, Wappenschmidt, Barbara, Webb, Penelope M., Weinberg, Clarice R., Weitzel, Jeffrey N., Wentzensen, Nicolas, White, Emily, Whittemore, Alice S., Winham, Stacey J., Wolk, Alicja, Woo, Yin-Ling, Wu, Anna H., Yan, Li, Yannoukakos, Drakoulis, Zavaglia, Katia M., Zheng, Wei, Ziogas, Argyrios, Zorn, Kristin K., Kleibl, Zdenek, Easton, Douglas, Lawrenson, Kate, DeFazio, Anna, Sellers, Thomas A., Ramus, Susan J., Pearce, Celeste L., Monteiro, Alvaro N., Cunningham, Julie, Goode, Ellen L., Schildkraut, Joellen M., Berchuck, Andrew, Chenevix-Trench, Georgia, Gayther, Simon A., Antoniou, Antonis C., and Pharoah, Paul D. P.
Abstract: Polygenic risk scores (PRS) for epithelial ovarian cancer (EOC) have the potential to improve risk stratification. Joint estimation of Single Nucleotide Polymorphism (SNP) effects in models could improve predictive performance over standard approaches of PRS construction. Here, we implemented computationally efficient, penalized, logistic regression models (lasso, elastic net, stepwise) to individual level genotype data and a Bayesian framework with continuous shrinkage, "select and shrink for summary statistics" (S4), to summary level data for epithelial non-mucinous ovarian cancer risk prediction. We developed the models in a dataset consisting of 23,564 non-mucinous EOC cases and 40,138 controls participating in the Ovarian Cancer Association Consortium (OCAC) and validated the best models in three populations of different ancestries: prospective data from 198,101 women of European ancestries; 7,669 women of East Asian ancestries; 1,072 women of African ancestries, and in 18,915 BRCA1 and 12,337 BRCA2 pathogenic variant carriers of European ancestries. In the external validation data, the model with the strongest association for non-mucinous EOC risk derived from the OCAC model development data was the S4 model (27,240 SNPs) with odds ratios (OR) of 1.38 (95% CI: 1.28-1.48, AUC: 0.588) per unit standard deviation, in women of European ancestries; 1.14 (95% CI: 1.08-1.19, AUC: 0.538) in women of East Asian ancestries; 1.38 (95% CI: 1.21-1.58, AUC: 0.593) in women of African ancestries; hazard ratios of 1.36 (95% CI: 1.29-1.43, AUC: 0.592) in BRCA1 pathogenic variant carriers and 1.49 (95% CI: 1.35-1.64, AUC: 0.624) in BRCA2 pathogenic variant carriers. Incorporation of the S4 PRS in risk prediction models for ovarian cancer may have clinical utility in ovarian cancer prevention programs.
Published: 2022
Full Text: View/download PDF

28. Common variants in breast cancer risk loci predispose to distinct tumor subtypes

Author: Ahearn, Thomas U., Zhang, Haoyu, Michailidou, Kyriaki, Milne, Roger L., Bolla, Manjeet K., Dennis, Joe, Dunning, Alison M., Lush, Michael, Wang, Qin, Andrulis, Irene L., Anton-Culver, Hoda, Arndt, Volker, Aronson, Kristan J., Auer, Paul L., Augustinsson, Annelie, Baten, Adinda, Becher, Heiko, Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Bojesen, Stig E., Bonanni, Bernardo, Borresen-Dale, Anne-Lise, Brauch, Hiltrud, Brenner, Hermann, Brooks-Wilson, Angela, Bruening, Thomas, Burwinkel, Barbara, Buys, Saundra S., Canzian, Federico, Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Chenevix-Trench, Georgia, Clarke, Christine L., Collee, J. Margriet, Cox, Angela, Cross, Simon S., Czene, Kamila, Daly, Mary B., Devilee, Peter, Dork, Thilo, Dwek, Miriam, Eccles, Diana M., Evans, D. Gareth, Fasching, Peter A., Figueroa, Jonine, Floris, Giuseppe, Gago-Dominguez, Manuela, Gapstur, Susan M., Garcia-Saenz, Jose A., Gaudet, Mia M., Giles, Graham G., Goldberg, Mark S., Gonzalez-Neira, Anna, Alnaes, Grethe I. Grenaker, Grip, Mervi, Guenel, Pascal, Haiman, Christopher A., Hall, Per, Hamann, Ute, Harkness, Elaine F., Heemskerk-Gerritsen, Bernadette A. M., Holleczek, Bernd, Hollestelle, Antoinette, Hooning, Maartje J., Hoover, Robert N., Hopper, John L., Howell, Anthony, Jakimovska, Milena, Jakubowska, Anna, John, Esther M., Jones, Michael E., Jung, Audrey, Kaaks, Rudolf, Kauppila, Saila, Keeman, Renske, Khusnutdinova, Elza, Kitahara, Cari M., Ko, Yon-Dschun, Koutros, Stella, Kristensen, Vessela N., Kruger, Ute, Kubelka-Sabit, Katerina, Kurian, Allison W., Kyriacou, Kyriacos, Lambrechts, Diether, Lee, Derrick G., Lindblom, Annika, Linet, Martha, Lissowska, Jolanta, Llaneza, Ana, Lo, Wing-Yee, MacInnis, Robert J., Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, Martinez, Maria Elena, McLean, Catriona, Meindl, Alfons, Menon, Usha, Nevanlinna, Heli, Newman, William G., Nodora, Jesse, Offit, Kenneth, Olsson, Hakan, Orr, Nick, Park-Simon, Tjoung-Won, Patel, Alpa, V, Peto, Julian, Pita, Guillermo, Plaseska-Karanfilska, Dijana, Prentice, Ross, Punie, Kevin, Pylkas, Katri, Radice, Paolo, Rennert, Gad, Romero, Atocha, Ruediger, Thomas, Saloustros, Emmanouil, Sampson, Sarah, Sandler, Dale P., Sawyer, Elinor J., Schmutzler, Rita K., Schoemaker, Minouk J., Schottker, Ben, Sherman, Mark E., Shu, Xiao-Ou, Smichkoska, Snezhana, Southey, Melissa C., Spinelli, John J., Swerdlow, Anthony J., Tamimi, Rulla M., Tapper, William J., Taylor, Jack A., Teras, Lauren R., Terry, Mary Beth, Torres, Diana, Troester, Melissa A., Vachon, Celine M., van Deurzen, Carolien H. M., van Veen, Elke M., Wagner, Philippe, Weinberg, Clarice R., Wendt, Camilla, Wesseling, Jelle, Winqvist, Robert, Wolk, Alicja, Yang, Xiaohong R., Zheng, Wei, Couch, Fergus J., Simard, Jacques, Kraft, Peter, Easton, Douglas F., Pharoah, Paul D. P., Schmidt, Marjanka K., Garcia-Closas, Montserrat, Chatterjee, Nilanjan, Ahearn, Thomas U., Zhang, Haoyu, Michailidou, Kyriaki, Milne, Roger L., Bolla, Manjeet K., Dennis, Joe, Dunning, Alison M., Lush, Michael, Wang, Qin, Andrulis, Irene L., Anton-Culver, Hoda, Arndt, Volker, Aronson, Kristan J., Auer, Paul L., Augustinsson, Annelie, Baten, Adinda, Becher, Heiko, Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Bojesen, Stig E., Bonanni, Bernardo, Borresen-Dale, Anne-Lise, Brauch, Hiltrud, Brenner, Hermann, Brooks-Wilson, Angela, Bruening, Thomas, Burwinkel, Barbara, Buys, Saundra S., Canzian, Federico, Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Chenevix-Trench, Georgia, Clarke, Christine L., Collee, J. Margriet, Cox, Angela, Cross, Simon S., Czene, Kamila, Daly, Mary B., Devilee, Peter, Dork, Thilo, Dwek, Miriam, Eccles, Diana M., Evans, D. Gareth, Fasching, Peter A., Figueroa, Jonine, Floris, Giuseppe, Gago-Dominguez, Manuela, Gapstur, Susan M., Garcia-Saenz, Jose A., Gaudet, Mia M., Giles, Graham G., Goldberg, Mark S., Gonzalez-Neira, Anna, Alnaes, Grethe I. Grenaker, Grip, Mervi, Guenel, Pascal, Haiman, Christopher A., Hall, Per, Hamann, Ute, Harkness, Elaine F., Heemskerk-Gerritsen, Bernadette A. M., Holleczek, Bernd, Hollestelle, Antoinette, Hooning, Maartje J., Hoover, Robert N., Hopper, John L., Howell, Anthony, Jakimovska, Milena, Jakubowska, Anna, John, Esther M., Jones, Michael E., Jung, Audrey, Kaaks, Rudolf, Kauppila, Saila, Keeman, Renske, Khusnutdinova, Elza, Kitahara, Cari M., Ko, Yon-Dschun, Koutros, Stella, Kristensen, Vessela N., Kruger, Ute, Kubelka-Sabit, Katerina, Kurian, Allison W., Kyriacou, Kyriacos, Lambrechts, Diether, Lee, Derrick G., Lindblom, Annika, Linet, Martha, Lissowska, Jolanta, Llaneza, Ana, Lo, Wing-Yee, MacInnis, Robert J., Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, Martinez, Maria Elena, McLean, Catriona, Meindl, Alfons, Menon, Usha, Nevanlinna, Heli, Newman, William G., Nodora, Jesse, Offit, Kenneth, Olsson, Hakan, Orr, Nick, Park-Simon, Tjoung-Won, Patel, Alpa, V, Peto, Julian, Pita, Guillermo, Plaseska-Karanfilska, Dijana, Prentice, Ross, Punie, Kevin, Pylkas, Katri, Radice, Paolo, Rennert, Gad, Romero, Atocha, Ruediger, Thomas, Saloustros, Emmanouil, Sampson, Sarah, Sandler, Dale P., Sawyer, Elinor J., Schmutzler, Rita K., Schoemaker, Minouk J., Schottker, Ben, Sherman, Mark E., Shu, Xiao-Ou, Smichkoska, Snezhana, Southey, Melissa C., Spinelli, John J., Swerdlow, Anthony J., Tamimi, Rulla M., Tapper, William J., Taylor, Jack A., Teras, Lauren R., Terry, Mary Beth, Torres, Diana, Troester, Melissa A., Vachon, Celine M., van Deurzen, Carolien H. M., van Veen, Elke M., Wagner, Philippe, Weinberg, Clarice R., Wendt, Camilla, Wesseling, Jelle, Winqvist, Robert, Wolk, Alicja, Yang, Xiaohong R., Zheng, Wei, Couch, Fergus J., Simard, Jacques, Kraft, Peter, Easton, Douglas F., Pharoah, Paul D. P., Schmidt, Marjanka K., Garcia-Closas, Montserrat, and Chatterjee, Nilanjan
Abstract: Background Genome-wide association studies (GWAS) have identified multiple common breast cancer susceptibility variants. Many of these variants have differential associations by estrogen receptor (ER) status, but how these variants relate with other tumor features and intrinsic molecular subtypes is unclear. Methods Among 106,571 invasive breast cancer cases and 95,762 controls of European ancestry with data on 173 breast cancer variants identified in previous GWAS, we used novel two-stage polytomous logistic regression models to evaluate variants in relation to multiple tumor features (ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and grade) adjusting for each other, and to intrinsic-like subtypes. Results Eighty-five of 173 variants were associated with at least one tumor feature (false discovery rate < 5%), most commonly ER and grade, followed by PR and HER2. Models for intrinsic-like subtypes found nearly all of these variants (83 of 85) associated at p < 0.05 with risk for at least one luminal-like subtype, and approximately half (41 of 85) of the variants were associated with risk of at least one non-luminal subtype, including 32 variants associated with triple-negative (TN) disease. Ten variants were associated with risk of all subtypes in different magnitude. Five variants were associated with risk of luminal A-like and TN subtypes in opposite directions. Conclusion This report demonstrates a high level of complexity in the etiology heterogeneity of breast cancer susceptibility variants and can inform investigations of subtype-specific risk prediction.
Published: 2022
Full Text: View/download PDF

29. Common variants in breast cancer risk loci predispose to distinct tumor subtypes

Author: Ahearn, Thomas U., Zhang, Haoyu, Michailidou, Kyriaki, Milne, Roger L., Bolla, Manjeet K., Dennis, Joe, Dunning, Alison M., Lush, Michael, Wang, Qin, Andrulis, Irene L., Anton-Culver, Hoda, Arndt, Volker, Aronson, Kristan J., Auer, Paul L., Augustinsson, Annelie, Baten, Adinda, Becher, Heiko, Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Bojesen, Stig E., Bonanni, Bernardo, Borresen-Dale, Anne-Lise, Brauch, Hiltrud, Brenner, Hermann, Brooks-Wilson, Angela, Bruening, Thomas, Burwinkel, Barbara, Buys, Saundra S., Canzian, Federico, Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Chenevix-Trench, Georgia, Clarke, Christine L., Collee, J. Margriet, Cox, Angela, Cross, Simon S., Czene, Kamila, Daly, Mary B., Devilee, Peter, Dork, Thilo, Dwek, Miriam, Eccles, Diana M., Evans, D. Gareth, Fasching, Peter A., Figueroa, Jonine, Floris, Giuseppe, Gago-Dominguez, Manuela, Gapstur, Susan M., Garcia-Saenz, Jose A., Gaudet, Mia M., Giles, Graham G., Goldberg, Mark S., Gonzalez-Neira, Anna, Alnaes, Grethe I. Grenaker, Grip, Mervi, Guenel, Pascal, Haiman, Christopher A., Hall, Per, Hamann, Ute, Harkness, Elaine F., Heemskerk-Gerritsen, Bernadette A. M., Holleczek, Bernd, Hollestelle, Antoinette, Hooning, Maartje J., Hoover, Robert N., Hopper, John L., Howell, Anthony, Jakimovska, Milena, Jakubowska, Anna, John, Esther M., Jones, Michael E., Jung, Audrey, Kaaks, Rudolf, Kauppila, Saila, Keeman, Renske, Khusnutdinova, Elza, Kitahara, Cari M., Ko, Yon-Dschun, Koutros, Stella, Kristensen, Vessela N., Kruger, Ute, Kubelka-Sabit, Katerina, Kurian, Allison W., Kyriacou, Kyriacos, Lambrechts, Diether, Lee, Derrick G., Lindblom, Annika, Linet, Martha, Lissowska, Jolanta, Llaneza, Ana, Lo, Wing-Yee, MacInnis, Robert J., Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, Martinez, Maria Elena, McLean, Catriona, Meindl, Alfons, Menon, Usha, Nevanlinna, Heli, Newman, William G., Nodora, Jesse, Offit, Kenneth, Olsson, Hakan, Orr, Nick, Park-Simon, Tjoung-Won, Patel, Alpa, V, Peto, Julian, Pita, Guillermo, Plaseska-Karanfilska, Dijana, Prentice, Ross, Punie, Kevin, Pylkas, Katri, Radice, Paolo, Rennert, Gad, Romero, Atocha, Ruediger, Thomas, Saloustros, Emmanouil, Sampson, Sarah, Sandler, Dale P., Sawyer, Elinor J., Schmutzler, Rita K., Schoemaker, Minouk J., Schottker, Ben, Sherman, Mark E., Shu, Xiao-Ou, Smichkoska, Snezhana, Southey, Melissa C., Spinelli, John J., Swerdlow, Anthony J., Tamimi, Rulla M., Tapper, William J., Taylor, Jack A., Teras, Lauren R., Terry, Mary Beth, Torres, Diana, Troester, Melissa A., Vachon, Celine M., van Deurzen, Carolien H. M., van Veen, Elke M., Wagner, Philippe, Weinberg, Clarice R., Wendt, Camilla, Wesseling, Jelle, Winqvist, Robert, Wolk, Alicja, Yang, Xiaohong R., Zheng, Wei, Couch, Fergus J., Simard, Jacques, Kraft, Peter, Easton, Douglas F., Pharoah, Paul D. P., Schmidt, Marjanka K., Garcia-Closas, Montserrat, Chatterjee, Nilanjan, Ahearn, Thomas U., Zhang, Haoyu, Michailidou, Kyriaki, Milne, Roger L., Bolla, Manjeet K., Dennis, Joe, Dunning, Alison M., Lush, Michael, Wang, Qin, Andrulis, Irene L., Anton-Culver, Hoda, Arndt, Volker, Aronson, Kristan J., Auer, Paul L., Augustinsson, Annelie, Baten, Adinda, Becher, Heiko, Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Bojesen, Stig E., Bonanni, Bernardo, Borresen-Dale, Anne-Lise, Brauch, Hiltrud, Brenner, Hermann, Brooks-Wilson, Angela, Bruening, Thomas, Burwinkel, Barbara, Buys, Saundra S., Canzian, Federico, Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Chenevix-Trench, Georgia, Clarke, Christine L., Collee, J. Margriet, Cox, Angela, Cross, Simon S., Czene, Kamila, Daly, Mary B., Devilee, Peter, Dork, Thilo, Dwek, Miriam, Eccles, Diana M., Evans, D. Gareth, Fasching, Peter A., Figueroa, Jonine, Floris, Giuseppe, Gago-Dominguez, Manuela, Gapstur, Susan M., Garcia-Saenz, Jose A., Gaudet, Mia M., Giles, Graham G., Goldberg, Mark S., Gonzalez-Neira, Anna, Alnaes, Grethe I. Grenaker, Grip, Mervi, Guenel, Pascal, Haiman, Christopher A., Hall, Per, Hamann, Ute, Harkness, Elaine F., Heemskerk-Gerritsen, Bernadette A. M., Holleczek, Bernd, Hollestelle, Antoinette, Hooning, Maartje J., Hoover, Robert N., Hopper, John L., Howell, Anthony, Jakimovska, Milena, Jakubowska, Anna, John, Esther M., Jones, Michael E., Jung, Audrey, Kaaks, Rudolf, Kauppila, Saila, Keeman, Renske, Khusnutdinova, Elza, Kitahara, Cari M., Ko, Yon-Dschun, Koutros, Stella, Kristensen, Vessela N., Kruger, Ute, Kubelka-Sabit, Katerina, Kurian, Allison W., Kyriacou, Kyriacos, Lambrechts, Diether, Lee, Derrick G., Lindblom, Annika, Linet, Martha, Lissowska, Jolanta, Llaneza, Ana, Lo, Wing-Yee, MacInnis, Robert J., Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, Martinez, Maria Elena, McLean, Catriona, Meindl, Alfons, Menon, Usha, Nevanlinna, Heli, Newman, William G., Nodora, Jesse, Offit, Kenneth, Olsson, Hakan, Orr, Nick, Park-Simon, Tjoung-Won, Patel, Alpa, V, Peto, Julian, Pita, Guillermo, Plaseska-Karanfilska, Dijana, Prentice, Ross, Punie, Kevin, Pylkas, Katri, Radice, Paolo, Rennert, Gad, Romero, Atocha, Ruediger, Thomas, Saloustros, Emmanouil, Sampson, Sarah, Sandler, Dale P., Sawyer, Elinor J., Schmutzler, Rita K., Schoemaker, Minouk J., Schottker, Ben, Sherman, Mark E., Shu, Xiao-Ou, Smichkoska, Snezhana, Southey, Melissa C., Spinelli, John J., Swerdlow, Anthony J., Tamimi, Rulla M., Tapper, William J., Taylor, Jack A., Teras, Lauren R., Terry, Mary Beth, Torres, Diana, Troester, Melissa A., Vachon, Celine M., van Deurzen, Carolien H. M., van Veen, Elke M., Wagner, Philippe, Weinberg, Clarice R., Wendt, Camilla, Wesseling, Jelle, Winqvist, Robert, Wolk, Alicja, Yang, Xiaohong R., Zheng, Wei, Couch, Fergus J., Simard, Jacques, Kraft, Peter, Easton, Douglas F., Pharoah, Paul D. P., Schmidt, Marjanka K., Garcia-Closas, Montserrat, and Chatterjee, Nilanjan
Abstract: Background Genome-wide association studies (GWAS) have identified multiple common breast cancer susceptibility variants. Many of these variants have differential associations by estrogen receptor (ER) status, but how these variants relate with other tumor features and intrinsic molecular subtypes is unclear. Methods Among 106,571 invasive breast cancer cases and 95,762 controls of European ancestry with data on 173 breast cancer variants identified in previous GWAS, we used novel two-stage polytomous logistic regression models to evaluate variants in relation to multiple tumor features (ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and grade) adjusting for each other, and to intrinsic-like subtypes. Results Eighty-five of 173 variants were associated with at least one tumor feature (false discovery rate < 5%), most commonly ER and grade, followed by PR and HER2. Models for intrinsic-like subtypes found nearly all of these variants (83 of 85) associated at p < 0.05 with risk for at least one luminal-like subtype, and approximately half (41 of 85) of the variants were associated with risk of at least one non-luminal subtype, including 32 variants associated with triple-negative (TN) disease. Ten variants were associated with risk of all subtypes in different magnitude. Five variants were associated with risk of luminal A-like and TN subtypes in opposite directions. Conclusion This report demonstrates a high level of complexity in the etiology heterogeneity of breast cancer susceptibility variants and can inform investigations of subtype-specific risk prediction.
Published: 2022
Full Text: View/download PDF

30. Common variants in breast cancer risk loci predispose to distinct tumor subtypes

Author: Ahearn, Thomas U., Zhang, Haoyu, Michailidou, Kyriaki, Milne, Roger L., Bolla, Manjeet K., Dennis, Joe, Dunning, Alison M., Lush, Michael, Wang, Qin, Andrulis, Irene L., Anton-Culver, Hoda, Arndt, Volker, Aronson, Kristan J., Auer, Paul L., Augustinsson, Annelie, Baten, Adinda, Becher, Heiko, Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Bojesen, Stig E., Bonanni, Bernardo, Borresen-Dale, Anne-Lise, Brauch, Hiltrud, Brenner, Hermann, Brooks-Wilson, Angela, Bruening, Thomas, Burwinkel, Barbara, Buys, Saundra S., Canzian, Federico, Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Chenevix-Trench, Georgia, Clarke, Christine L., Collee, J. Margriet, Cox, Angela, Cross, Simon S., Czene, Kamila, Daly, Mary B., Devilee, Peter, Dork, Thilo, Dwek, Miriam, Eccles, Diana M., Evans, D. Gareth, Fasching, Peter A., Figueroa, Jonine, Floris, Giuseppe, Gago-Dominguez, Manuela, Gapstur, Susan M., Garcia-Saenz, Jose A., Gaudet, Mia M., Giles, Graham G., Goldberg, Mark S., Gonzalez-Neira, Anna, Alnaes, Grethe I. Grenaker, Grip, Mervi, Guenel, Pascal, Haiman, Christopher A., Hall, Per, Hamann, Ute, Harkness, Elaine F., Heemskerk-Gerritsen, Bernadette A. M., Holleczek, Bernd, Hollestelle, Antoinette, Hooning, Maartje J., Hoover, Robert N., Hopper, John L., Howell, Anthony, Jakimovska, Milena, Jakubowska, Anna, John, Esther M., Jones, Michael E., Jung, Audrey, Kaaks, Rudolf, Kauppila, Saila, Keeman, Renske, Khusnutdinova, Elza, Kitahara, Cari M., Ko, Yon-Dschun, Koutros, Stella, Kristensen, Vessela N., Kruger, Ute, Kubelka-Sabit, Katerina, Kurian, Allison W., Kyriacou, Kyriacos, Lambrechts, Diether, Lee, Derrick G., Lindblom, Annika, Linet, Martha, Lissowska, Jolanta, Llaneza, Ana, Lo, Wing-Yee, MacInnis, Robert J., Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, Martinez, Maria Elena, McLean, Catriona, Meindl, Alfons, Menon, Usha, Nevanlinna, Heli, Newman, William G., Nodora, Jesse, Offit, Kenneth, Olsson, Hakan, Orr, Nick, Park-Simon, Tjoung-Won, Patel, Alpa, V, Peto, Julian, Pita, Guillermo, Plaseska-Karanfilska, Dijana, Prentice, Ross, Punie, Kevin, Pylkas, Katri, Radice, Paolo, Rennert, Gad, Romero, Atocha, Ruediger, Thomas, Saloustros, Emmanouil, Sampson, Sarah, Sandler, Dale P., Sawyer, Elinor J., Schmutzler, Rita K., Schoemaker, Minouk J., Schottker, Ben, Sherman, Mark E., Shu, Xiao-Ou, Smichkoska, Snezhana, Southey, Melissa C., Spinelli, John J., Swerdlow, Anthony J., Tamimi, Rulla M., Tapper, William J., Taylor, Jack A., Teras, Lauren R., Terry, Mary Beth, Torres, Diana, Troester, Melissa A., Vachon, Celine M., van Deurzen, Carolien H. M., van Veen, Elke M., Wagner, Philippe, Weinberg, Clarice R., Wendt, Camilla, Wesseling, Jelle, Winqvist, Robert, Wolk, Alicja, Yang, Xiaohong R., Zheng, Wei, Couch, Fergus J., Simard, Jacques, Kraft, Peter, Easton, Douglas F., Pharoah, Paul D. P., Schmidt, Marjanka K., Garcia-Closas, Montserrat, Chatterjee, Nilanjan, Ahearn, Thomas U., Zhang, Haoyu, Michailidou, Kyriaki, Milne, Roger L., Bolla, Manjeet K., Dennis, Joe, Dunning, Alison M., Lush, Michael, Wang, Qin, Andrulis, Irene L., Anton-Culver, Hoda, Arndt, Volker, Aronson, Kristan J., Auer, Paul L., Augustinsson, Annelie, Baten, Adinda, Becher, Heiko, Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Bojesen, Stig E., Bonanni, Bernardo, Borresen-Dale, Anne-Lise, Brauch, Hiltrud, Brenner, Hermann, Brooks-Wilson, Angela, Bruening, Thomas, Burwinkel, Barbara, Buys, Saundra S., Canzian, Federico, Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Chenevix-Trench, Georgia, Clarke, Christine L., Collee, J. Margriet, Cox, Angela, Cross, Simon S., Czene, Kamila, Daly, Mary B., Devilee, Peter, Dork, Thilo, Dwek, Miriam, Eccles, Diana M., Evans, D. Gareth, Fasching, Peter A., Figueroa, Jonine, Floris, Giuseppe, Gago-Dominguez, Manuela, Gapstur, Susan M., Garcia-Saenz, Jose A., Gaudet, Mia M., Giles, Graham G., Goldberg, Mark S., Gonzalez-Neira, Anna, Alnaes, Grethe I. Grenaker, Grip, Mervi, Guenel, Pascal, Haiman, Christopher A., Hall, Per, Hamann, Ute, Harkness, Elaine F., Heemskerk-Gerritsen, Bernadette A. M., Holleczek, Bernd, Hollestelle, Antoinette, Hooning, Maartje J., Hoover, Robert N., Hopper, John L., Howell, Anthony, Jakimovska, Milena, Jakubowska, Anna, John, Esther M., Jones, Michael E., Jung, Audrey, Kaaks, Rudolf, Kauppila, Saila, Keeman, Renske, Khusnutdinova, Elza, Kitahara, Cari M., Ko, Yon-Dschun, Koutros, Stella, Kristensen, Vessela N., Kruger, Ute, Kubelka-Sabit, Katerina, Kurian, Allison W., Kyriacou, Kyriacos, Lambrechts, Diether, Lee, Derrick G., Lindblom, Annika, Linet, Martha, Lissowska, Jolanta, Llaneza, Ana, Lo, Wing-Yee, MacInnis, Robert J., Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, Martinez, Maria Elena, McLean, Catriona, Meindl, Alfons, Menon, Usha, Nevanlinna, Heli, Newman, William G., Nodora, Jesse, Offit, Kenneth, Olsson, Hakan, Orr, Nick, Park-Simon, Tjoung-Won, Patel, Alpa, V, Peto, Julian, Pita, Guillermo, Plaseska-Karanfilska, Dijana, Prentice, Ross, Punie, Kevin, Pylkas, Katri, Radice, Paolo, Rennert, Gad, Romero, Atocha, Ruediger, Thomas, Saloustros, Emmanouil, Sampson, Sarah, Sandler, Dale P., Sawyer, Elinor J., Schmutzler, Rita K., Schoemaker, Minouk J., Schottker, Ben, Sherman, Mark E., Shu, Xiao-Ou, Smichkoska, Snezhana, Southey, Melissa C., Spinelli, John J., Swerdlow, Anthony J., Tamimi, Rulla M., Tapper, William J., Taylor, Jack A., Teras, Lauren R., Terry, Mary Beth, Torres, Diana, Troester, Melissa A., Vachon, Celine M., van Deurzen, Carolien H. M., van Veen, Elke M., Wagner, Philippe, Weinberg, Clarice R., Wendt, Camilla, Wesseling, Jelle, Winqvist, Robert, Wolk, Alicja, Yang, Xiaohong R., Zheng, Wei, Couch, Fergus J., Simard, Jacques, Kraft, Peter, Easton, Douglas F., Pharoah, Paul D. P., Schmidt, Marjanka K., Garcia-Closas, Montserrat, and Chatterjee, Nilanjan
Abstract: Background Genome-wide association studies (GWAS) have identified multiple common breast cancer susceptibility variants. Many of these variants have differential associations by estrogen receptor (ER) status, but how these variants relate with other tumor features and intrinsic molecular subtypes is unclear. Methods Among 106,571 invasive breast cancer cases and 95,762 controls of European ancestry with data on 173 breast cancer variants identified in previous GWAS, we used novel two-stage polytomous logistic regression models to evaluate variants in relation to multiple tumor features (ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and grade) adjusting for each other, and to intrinsic-like subtypes. Results Eighty-five of 173 variants were associated with at least one tumor feature (false discovery rate < 5%), most commonly ER and grade, followed by PR and HER2. Models for intrinsic-like subtypes found nearly all of these variants (83 of 85) associated at p < 0.05 with risk for at least one luminal-like subtype, and approximately half (41 of 85) of the variants were associated with risk of at least one non-luminal subtype, including 32 variants associated with triple-negative (TN) disease. Ten variants were associated with risk of all subtypes in different magnitude. Five variants were associated with risk of luminal A-like and TN subtypes in opposite directions. Conclusion This report demonstrates a high level of complexity in the etiology heterogeneity of breast cancer susceptibility variants and can inform investigations of subtype-specific risk prediction.
Published: 2022
Full Text: View/download PDF

31. Cancer Risks Associated With BRCA1 and BRCA2 Pathogenic Variants.

Author: Li, Shuai, Li, Shuai, Silvestri, Valentina, Leslie, Goska, Rebbeck, Timothy R, Neuhausen, Susan L, Hopper, John L, Nielsen, Henriette Roed, Lee, Andrew, Yang, Xin, McGuffog, Lesley, Parsons, Michael T, Andrulis, Irene L, Arnold, Norbert, Belotti, Muriel, Borg, Åke, Buecher, Bruno, Buys, Saundra S, Caputo, Sandrine M, Chung, Wendy K, Colas, Chrystelle, Colonna, Sarah V, Cook, Jackie, Daly, Mary B, de la Hoya, Miguel, de Pauw, Antoine, Delhomelle, Hélène, Eason, Jacqueline, Engel, Christoph, Evans, D Gareth, Faust, Ulrike, Fehm, Tanja N, Fostira, Florentia, Fountzilas, George, Frone, Megan, Garcia-Barberan, Vanesa, Garre, Pilar, Gauthier-Villars, Marion, Gehrig, Andrea, Glendon, Gord, Goldgar, David E, Golmard, Lisa, Greene, Mark H, Hahnen, Eric, Hamann, Ute, Hanson, Helen, Hassan, Tiara, Hentschel, Julia, Horvath, Judit, Izatt, Louise, Janavicius, Ramunas, Jiao, Yue, John, Esther M, Karlan, Beth Y, Kim, Sung-Won, Konstantopoulou, Irene, Kwong, Ava, Laugé, Anthony, Lee, Jong Won, Lesueur, Fabienne, Mebirouk, Noura, Meindl, Alfons, Mouret-Fourme, Emmanuelle, Musgrave, Hannah, Ngeow Yuen Yie, Joanne, Niederacher, Dieter, Park, Sue K, Pedersen, Inge Sokilde, Ramser, Juliane, Ramus, Susan J, Rantala, Johanna, Rashid, Muhammad U, Reichl, Florian, Ritter, Julia, Rump, Andreas, Santamariña, Marta, Saule, Claire, Schmidt, Gunnar, Schmutzler, Rita K, Senter, Leigha, Shariff, Saba, Singer, Christian F, Southey, Melissa C, Stoppa-Lyonnet, Dominique, Sutter, Christian, Tan, Yen, Teo, Soo Hwang, Terry, Mary Beth, Thomassen, Mads, Tischkowitz, Marc, Toland, Amanda E, Torres, Diana, Vega, Ana, Wagner, Sebastian A, Wang-Gohrke, Shan, Wappenschmidt, Barbara, Weber, Bernhard HF, Yannoukakos, Drakoulis, Spurdle, Amanda B, Easton, Douglas F, Chenevix-Trench, Georgia, Li, Shuai, Li, Shuai, Silvestri, Valentina, Leslie, Goska, Rebbeck, Timothy R, Neuhausen, Susan L, Hopper, John L, Nielsen, Henriette Roed, Lee, Andrew, Yang, Xin, McGuffog, Lesley, Parsons, Michael T, Andrulis, Irene L, Arnold, Norbert, Belotti, Muriel, Borg, Åke, Buecher, Bruno, Buys, Saundra S, Caputo, Sandrine M, Chung, Wendy K, Colas, Chrystelle, Colonna, Sarah V, Cook, Jackie, Daly, Mary B, de la Hoya, Miguel, de Pauw, Antoine, Delhomelle, Hélène, Eason, Jacqueline, Engel, Christoph, Evans, D Gareth, Faust, Ulrike, Fehm, Tanja N, Fostira, Florentia, Fountzilas, George, Frone, Megan, Garcia-Barberan, Vanesa, Garre, Pilar, Gauthier-Villars, Marion, Gehrig, Andrea, Glendon, Gord, Goldgar, David E, Golmard, Lisa, Greene, Mark H, Hahnen, Eric, Hamann, Ute, Hanson, Helen, Hassan, Tiara, Hentschel, Julia, Horvath, Judit, Izatt, Louise, Janavicius, Ramunas, Jiao, Yue, John, Esther M, Karlan, Beth Y, Kim, Sung-Won, Konstantopoulou, Irene, Kwong, Ava, Laugé, Anthony, Lee, Jong Won, Lesueur, Fabienne, Mebirouk, Noura, Meindl, Alfons, Mouret-Fourme, Emmanuelle, Musgrave, Hannah, Ngeow Yuen Yie, Joanne, Niederacher, Dieter, Park, Sue K, Pedersen, Inge Sokilde, Ramser, Juliane, Ramus, Susan J, Rantala, Johanna, Rashid, Muhammad U, Reichl, Florian, Ritter, Julia, Rump, Andreas, Santamariña, Marta, Saule, Claire, Schmidt, Gunnar, Schmutzler, Rita K, Senter, Leigha, Shariff, Saba, Singer, Christian F, Southey, Melissa C, Stoppa-Lyonnet, Dominique, Sutter, Christian, Tan, Yen, Teo, Soo Hwang, Terry, Mary Beth, Thomassen, Mads, Tischkowitz, Marc, Toland, Amanda E, Torres, Diana, Vega, Ana, Wagner, Sebastian A, Wang-Gohrke, Shan, Wappenschmidt, Barbara, Weber, Bernhard HF, Yannoukakos, Drakoulis, Spurdle, Amanda B, Easton, Douglas F, and Chenevix-Trench, Georgia
Abstract: PurposeTo provide precise age-specific risk estimates of cancers other than female breast and ovarian cancers associated with pathogenic variants (PVs) in BRCA1 and BRCA2 for effective cancer risk management.MethodsWe used data from 3,184 BRCA1 and 2,157 BRCA2 families in the Consortium of Investigators of Modifiers of BRCA1/2 to estimate age-specific relative (RR) and absolute risks for 22 first primary cancer types adjusting for family ascertainment.ResultsBRCA1 PVs were associated with risks of male breast (RR = 4.30; 95% CI, 1.09 to 16.96), pancreatic (RR = 2.36; 95% CI, 1.51 to 3.68), and stomach (RR = 2.17; 95% CI, 1.25 to 3.77) cancers. Associations with colorectal and gallbladder cancers were also suggested. BRCA2 PVs were associated with risks of male breast (RR = 44.0; 95% CI, 21.3 to 90.9), stomach (RR = 3.69; 95% CI, 2.40 to 5.67), pancreatic (RR = 3.34; 95% CI, 2.21 to 5.06), and prostate (RR = 2.22; 95% CI, 1.63 to 3.03) cancers. The stomach cancer RR was higher for females than males (6.89 v 2.76; P = .04). The absolute risks to age 80 years ranged from 0.4% for male breast cancer to approximately 2.5% for pancreatic cancer for BRCA1 carriers and from approximately 2.5% for pancreatic cancer to 27% for prostate cancer for BRCA2 carriers.ConclusionIn addition to female breast and ovarian cancers, BRCA1 and BRCA2 PVs are associated with increased risks of male breast, pancreatic, stomach, and prostate (only BRCA2 PVs) cancers, but not with the risks of other previously suggested cancers. The estimated age-specific risks will refine cancer risk management in men and women with BRCA1/2 PVs.
Published: 2022

32. Workshop as a learning strategy for territorial planning

Author: Sevilla Torres, Diana Carolina, Sauza Reyes, Adriana Catalina, Sevilla Torres, Diana Carolina, and Sauza Reyes, Adriana Catalina
Abstract: The learning of territorial planning is a subject in process of consolidation and is relevant for the development of capacity building for the transformation of Latin American cities. Actually the experiences around the application of the workshop as a learning strategy are presented, incorporate it into the curricular plan of the postgraduate program, it has served to reinforce the research training processes, as well as to deepen and put in practice the skills acquired in other theoretical components. Therefore, this article shows how this experience has been carried out, fundamental aspects for its development and a series of results that show the benefits of implementing this practical workshop that leads its students to understand the territorial dynamics and problems to seek contextualized planning solutions for a specific territory from a systemic and interdisciplinary vision., La enseñanza de la planificación territorial es un tema en proceso de consolidación y es de relevancia para el desarrollo de capacidades de formación para la transformación de las ciudades latinoamericanas. En este sentido, se presentan las experiencias en torno a la aplicación del workshop como estrategia de aprendizaje que, al ser incorporada dentro del plan curricular del programa de posgrado, ha servido para reforzar los procesos de formación en investigación, así como para profundizar y poner en práctica las competencias adquiridas en otros componentes teóricos. A continuación, se expone la forma como se ha llevado a cabo esta experiencia, los aspectos fundamentales para su desarrollo y una serie de resultados que muestran los beneficios de implementar este taller práctico para que los estudiantes comprendan las dinámicas y problemas territoriales y busquen soluciones contextualizadas de planificación de un territorio específico, a partir de una visión sistémica e interdisciplinaria., L'enseignement de l'aménagement du territoire est un sujet en voie de consolidation et pertinent pour le développement des capacités de formation pour la transformation des villes latino-américaines. En ce sens, les expériences autour de l'application de l'atelier en tant que stratégie d'apprentissage sont présentées, de sorte qu'en l'intégrant dans le plan curriculaire du programme de deuxième cycle, il a servi à renforcer les processus de formation à la recherche, ainsi que d'approfondir et mettre en pratique les compétences acquises dans d'autres composantes théoriques. Ensuite, la manière dont cette expérience a été menée, les aspects fondamentaux pour son développement et une série de résultats qui montrent l'intérêt de la mise en œuvre de cet atelier pratique qui amène ses étudiants à comprendre les dynamiques et les problèmes territoriaux pour rechercher des solutions d'aménagement contextualisées pour un territoire spécifique dans une vision systémique et interdisciplinaire., O ensino do planejamento territorial é uma disciplina em processo de consolidação e relevante para o desenvolvimento de capacidades formativas para a transformação das cidades latinoamericanas. Nesse sentido, são apresentadas as experiências em torno da aplicação da oficina como estratégia de aprendizagem, de modo que, ao incorporá-la ao plano curricular da pós-graduação, tem servido para reforçar os processos de formação em pesquisa, bem como aprofundar e colocar na prática as competências adquiridas nas restantes componentes teóricas. A seguir, a forma como esta experiência foi realizada, os aspectos fundamentais para o seu desenvolvimento e uma série de resultados que mostram os benefícios da implementação desta oficina prática que leva seus alunos a compreender as dinâmicas e problemas territoriais para buscar soluções de planejamento contextualizadas para um território específico a partir de uma visão sistêmica e interdisciplinar.
Published: 2022

33. Polygenic risk modeling for prediction of epithelial ovarian cancer risk

Author: Dareng, Eileen O., Tyrer, Jonathan P., Barnes, Daniel R., Jones, Michelle R., Yang, Xin, Aben, Katja K. H., Adank, Muriel A., Agata, Simona, Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Aravantinos, Gerasimos, Arun, Banu K., Augustinsson, Annelie, Balmana, Judith, Bandera, Elisa, V, Barkardottir, Rosa B., Barrowdale, Daniel, Beckmann, Matthias W., Beeghly-Fadiel, Alicia, Benitez, Javier, Bermisheva, Marina, Bernardini, Marcus Q., Bjorge, Line, Black, Amanda, Bogdanova, Natalia, V, Bonanni, Bernardo, Borg, Ake, Brenton, James D., Budzilowska, Agnieszka, Butzow, Ralf, Buys, Saundra S., Cai, Hui, Caligo, Maria A., Campbell, Ian, Cannioto, Rikki, Cassingham, Hayley, Chang-Claude, Jenny, Chanock, Stephen J., Chen, Kexin, Chiew, Yoke-Eng, Chung, Wendy K., Claes, Kathleen B. M., Colonna, Sarah, Cook, Linda S., Couch, Fergus J., Daly, Mary B., Dao, Fanny, Davies, Eleanor, de la Hoya, Miguel, de Putter, Robin, Dennis, Joe, DePersia, Allison, Devilee, Peter, Diez, Orland, Ding, Yuan Chun, Doherty, Jennifer A., Domchek, Susan M., Dork, Thilo, du Bois, Andreas, Durst, Matthias, Eccles, Diana M., Eliassen, Heather A., Engel, Christoph, Evans, Gareth D., Fasching, Peter A., Flanagan, James M., Fortner, ReneeT, Machackova, Eva, Friedman, Eitan, Ganz, Patricia A., Garber, Judy, Gensini, Francesca, Giles, Graham G., Glendon, Gord, Godwin, Andrew K., Goodman, Marc T., Greene, Mark H., Gronwald, Jacek, Group, Opal Study, Group, AOCS, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hamann, Ute, Hansen, Thomas V. O., Harris, Holly R., Hartman, Mikael, Heitz, Florian, Hildebrandt, Michelle A. T., Hogdall, Estrid, Hogdall, Claus K., Hopper, John L., Huang, Ruea-Yea, Huff, Chad, Hulick, Peter J., Huntsman, David G., Imyanitov, Evgeny N., Isaacs, Claudine, Jakubowska, Anna, James, Paul A., Janavicius, Ramunas, Jensen, Allan, Johannsson, Oskar Th, John, Esther M., Jones, Michael E., Kang, Daehee, Karlan, Beth Y., Karnezis, Anthony, Kelemen, Linda E., Khusnutdinova, Elza, Kiemeney, Lambertus A., Kim, Byoung-Gie, Kjaer, Susanne K., Komenaka, Ian, Kupryjanczyk, Jolanta, Kurian, Allison W., Kwong, Ava, Lambrechts, Diether, Larson, Melissa C., Lazaro, Conxi, Le, Nhu D., Leslie, Goska, Lester, Jenny, Lesueur, Fabienne, Levine, Douglas A., Li, Lian, Li, Jingmei, Loud, Jennifer T., Lu, Karen H., Mai, Phuong L., Manoukian, Siranoush, Marks, Jeffrey R., KimMatsuno, Rayna, Matsuo, Keitaro, May, Taymaa, McGuffog, Lesley, McLaughlin, John R., McNeish, Iain A., Mebirouk, Noura, Menon, Usha, Miller, Austin, Milne, Roger L., Minlikeeva, Albina, Modugno, Francesmary, Montagna, Marco, Moysich, Kirsten B., Munro, Elizabeth, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Yie, Joanne Ngeow Yuen, Nielsen, Henriette Roed, Nielsen, Finn C., Nikitina-Zake, Liene, Odunsi, Kunle, Offit, Kenneth, Olah, Edith, Olbrecht, Siel, Olopade, Olufunmilayo, I, Olson, Sara H., Olsson, Hakan, Osorio, Ana, Papi, Laura, Park, Sue K., Parsons, Michael T., Pathak, Harsha, Pedersen, Inge Sokilde, Peixoto, Ana, Pejovic, Tanja, Perez-Segura, Pedro, Permuth, Jennifer B., Peshkin, Beth, Peterlongo, Paolo, Piskorz, Anna, Prokofyeva, Darya, Radice, Paolo, Rantala, Johanna, Riggan, Marjorie J., Risch, Harvey A., Rodriguez-Antona, Cristina, Ross, Eric, Rossing, Mary Anne, Runnebaum, Ingo, Sandler, Dale P., Santamarina, Marta, Soucy, Penny, Schmutzler, Rita K., Setiawan, V. Wendy, Shan, Kang, Sieh, Weiva, Simard, Jacques, Singer, Christian F., Sokolenko, Anna P., Song, Honglin, Southey, Melissa C., Steed, Helen, Stoppa-Lyonnet, Dominique, Sutphen, Rebecca, Swerdlow, Anthony J., Tan, Yen Yen, Teixeira, Manuel R., Teo, Soo Hwang, Terry, Kathryn L., BethTerry, Mary, Thomassen, Mads, Thompson, Pamela J., Thomsen, Liv Cecilie Vestrheim, Thull, Darcy L., Tischkowitz, Marc, Titus, Linda, Toland, Amanda E., Torres, Diana, Trabert, Britton, Travis, Ruth, Tung, Nadine, Tworoger, Shelley S., Valen, Ellen, van Altena, Anne M., van der Hout, Annemieke H., Nieuwenhuysen, ElsVan, van Rensburg, Elizabeth J., Vega, Ana, Edwards, Digna Velez, Vierkant, Robert A., Wang, Frances, Wappenschmidt, Barbara, Webb, Penelope M., Weinberg, Clarice R., Weitzel, Jeffrey N., Wentzensen, Nicolas, White, Emily, Whittemore, Alice S., Winham, Stacey J., Wolk, Alicja, Woo, Yin-Ling, Wu, Anna H., Yan, Li, Yannoukakos, Drakoulis, Zavaglia, Katia M., Zheng, Wei, Ziogas, Argyrios, Zorn, Kristin K., Kleibl, Zdenek, Easton, Douglas, Lawrenson, Kate, DeFazio, Anna, Sellers, Thomas A., Ramus, Susan J., Pearce, Celeste L., Monteiro, Alvaro N., Cunningham, Julie, Goode, Ellen L., Schildkraut, Joellen M., Berchuck, Andrew, Chenevix-Trench, Georgia, Gayther, Simon A., Antoniou, Antonis C., Pharoah, Paul D. P., Dareng, Eileen O., Tyrer, Jonathan P., Barnes, Daniel R., Jones, Michelle R., Yang, Xin, Aben, Katja K. H., Adank, Muriel A., Agata, Simona, Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Aravantinos, Gerasimos, Arun, Banu K., Augustinsson, Annelie, Balmana, Judith, Bandera, Elisa, V, Barkardottir, Rosa B., Barrowdale, Daniel, Beckmann, Matthias W., Beeghly-Fadiel, Alicia, Benitez, Javier, Bermisheva, Marina, Bernardini, Marcus Q., Bjorge, Line, Black, Amanda, Bogdanova, Natalia, V, Bonanni, Bernardo, Borg, Ake, Brenton, James D., Budzilowska, Agnieszka, Butzow, Ralf, Buys, Saundra S., Cai, Hui, Caligo, Maria A., Campbell, Ian, Cannioto, Rikki, Cassingham, Hayley, Chang-Claude, Jenny, Chanock, Stephen J., Chen, Kexin, Chiew, Yoke-Eng, Chung, Wendy K., Claes, Kathleen B. M., Colonna, Sarah, Cook, Linda S., Couch, Fergus J., Daly, Mary B., Dao, Fanny, Davies, Eleanor, de la Hoya, Miguel, de Putter, Robin, Dennis, Joe, DePersia, Allison, Devilee, Peter, Diez, Orland, Ding, Yuan Chun, Doherty, Jennifer A., Domchek, Susan M., Dork, Thilo, du Bois, Andreas, Durst, Matthias, Eccles, Diana M., Eliassen, Heather A., Engel, Christoph, Evans, Gareth D., Fasching, Peter A., Flanagan, James M., Fortner, ReneeT, Machackova, Eva, Friedman, Eitan, Ganz, Patricia A., Garber, Judy, Gensini, Francesca, Giles, Graham G., Glendon, Gord, Godwin, Andrew K., Goodman, Marc T., Greene, Mark H., Gronwald, Jacek, Group, Opal Study, Group, AOCS, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hamann, Ute, Hansen, Thomas V. O., Harris, Holly R., Hartman, Mikael, Heitz, Florian, Hildebrandt, Michelle A. T., Hogdall, Estrid, Hogdall, Claus K., Hopper, John L., Huang, Ruea-Yea, Huff, Chad, Hulick, Peter J., Huntsman, David G., Imyanitov, Evgeny N., Isaacs, Claudine, Jakubowska, Anna, James, Paul A., Janavicius, Ramunas, Jensen, Allan, Johannsson, Oskar Th, John, Esther M., Jones, Michael E., Kang, Daehee, Karlan, Beth Y., Karnezis, Anthony, Kelemen, Linda E., Khusnutdinova, Elza, Kiemeney, Lambertus A., Kim, Byoung-Gie, Kjaer, Susanne K., Komenaka, Ian, Kupryjanczyk, Jolanta, Kurian, Allison W., Kwong, Ava, Lambrechts, Diether, Larson, Melissa C., Lazaro, Conxi, Le, Nhu D., Leslie, Goska, Lester, Jenny, Lesueur, Fabienne, Levine, Douglas A., Li, Lian, Li, Jingmei, Loud, Jennifer T., Lu, Karen H., Mai, Phuong L., Manoukian, Siranoush, Marks, Jeffrey R., KimMatsuno, Rayna, Matsuo, Keitaro, May, Taymaa, McGuffog, Lesley, McLaughlin, John R., McNeish, Iain A., Mebirouk, Noura, Menon, Usha, Miller, Austin, Milne, Roger L., Minlikeeva, Albina, Modugno, Francesmary, Montagna, Marco, Moysich, Kirsten B., Munro, Elizabeth, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Yie, Joanne Ngeow Yuen, Nielsen, Henriette Roed, Nielsen, Finn C., Nikitina-Zake, Liene, Odunsi, Kunle, Offit, Kenneth, Olah, Edith, Olbrecht, Siel, Olopade, Olufunmilayo, I, Olson, Sara H., Olsson, Hakan, Osorio, Ana, Papi, Laura, Park, Sue K., Parsons, Michael T., Pathak, Harsha, Pedersen, Inge Sokilde, Peixoto, Ana, Pejovic, Tanja, Perez-Segura, Pedro, Permuth, Jennifer B., Peshkin, Beth, Peterlongo, Paolo, Piskorz, Anna, Prokofyeva, Darya, Radice, Paolo, Rantala, Johanna, Riggan, Marjorie J., Risch, Harvey A., Rodriguez-Antona, Cristina, Ross, Eric, Rossing, Mary Anne, Runnebaum, Ingo, Sandler, Dale P., Santamarina, Marta, Soucy, Penny, Schmutzler, Rita K., Setiawan, V. Wendy, Shan, Kang, Sieh, Weiva, Simard, Jacques, Singer, Christian F., Sokolenko, Anna P., Song, Honglin, Southey, Melissa C., Steed, Helen, Stoppa-Lyonnet, Dominique, Sutphen, Rebecca, Swerdlow, Anthony J., Tan, Yen Yen, Teixeira, Manuel R., Teo, Soo Hwang, Terry, Kathryn L., BethTerry, Mary, Thomassen, Mads, Thompson, Pamela J., Thomsen, Liv Cecilie Vestrheim, Thull, Darcy L., Tischkowitz, Marc, Titus, Linda, Toland, Amanda E., Torres, Diana, Trabert, Britton, Travis, Ruth, Tung, Nadine, Tworoger, Shelley S., Valen, Ellen, van Altena, Anne M., van der Hout, Annemieke H., Nieuwenhuysen, ElsVan, van Rensburg, Elizabeth J., Vega, Ana, Edwards, Digna Velez, Vierkant, Robert A., Wang, Frances, Wappenschmidt, Barbara, Webb, Penelope M., Weinberg, Clarice R., Weitzel, Jeffrey N., Wentzensen, Nicolas, White, Emily, Whittemore, Alice S., Winham, Stacey J., Wolk, Alicja, Woo, Yin-Ling, Wu, Anna H., Yan, Li, Yannoukakos, Drakoulis, Zavaglia, Katia M., Zheng, Wei, Ziogas, Argyrios, Zorn, Kristin K., Kleibl, Zdenek, Easton, Douglas, Lawrenson, Kate, DeFazio, Anna, Sellers, Thomas A., Ramus, Susan J., Pearce, Celeste L., Monteiro, Alvaro N., Cunningham, Julie, Goode, Ellen L., Schildkraut, Joellen M., Berchuck, Andrew, Chenevix-Trench, Georgia, Gayther, Simon A., Antoniou, Antonis C., and Pharoah, Paul D. P.
Abstract: Polygenic risk scores (PRS) for epithelial ovarian cancer (EOC) have the potential to improve risk stratification. Joint estimation of Single Nucleotide Polymorphism (SNP) effects in models could improve predictive performance over standard approaches of PRS construction. Here, we implemented computationally efficient, penalized, logistic regression models (lasso, elastic net, stepwise) to individual level genotype data and a Bayesian framework with continuous shrinkage, "select and shrink for summary statistics" (S4), to summary level data for epithelial non-mucinous ovarian cancer risk prediction. We developed the models in a dataset consisting of 23,564 non-mucinous EOC cases and 40,138 controls participating in the Ovarian Cancer Association Consortium (OCAC) and validated the best models in three populations of different ancestries: prospective data from 198,101 women of European ancestries; 7,669 women of East Asian ancestries; 1,072 women of African ancestries, and in 18,915 BRCA1 and 12,337 BRCA2 pathogenic variant carriers of European ancestries. In the external validation data, the model with the strongest association for non-mucinous EOC risk derived from the OCAC model development data was the S4 model (27,240 SNPs) with odds ratios (OR) of 1.38 (95% CI: 1.28-1.48, AUC: 0.588) per unit standard deviation, in women of European ancestries; 1.14 (95% CI: 1.08-1.19, AUC: 0.538) in women of East Asian ancestries; 1.38 (95% CI: 1.21-1.58, AUC: 0.593) in women of African ancestries; hazard ratios of 1.36 (95% CI: 1.29-1.43, AUC: 0.592) in BRCA1 pathogenic variant carriers and 1.49 (95% CI: 1.35-1.64, AUC: 0.624) in BRCA2 pathogenic variant carriers. Incorporation of the S4 PRS in risk prediction models for ovarian cancer may have clinical utility in ovarian cancer prevention programs.
Published: 2022
Full Text: View/download PDF

34. Incorporating progesterone receptor expression into the PREDICT breast prognostic model.

Author: Grootes, Isabelle, Grootes, Isabelle, Keeman, Renske, Blows, Fiona M, Milne, Roger L, Giles, Graham G, Swerdlow, Anthony J, Fasching, Peter A, Abubakar, Mustapha, Andrulis, Irene L, Anton-Culver, Hoda, Beckmann, Matthias W, Blomqvist, Carl, Bojesen, Stig E, Bolla, Manjeet K, Bonanni, Bernardo, Briceno, Ignacio, Burwinkel, Barbara, Camp, Nicola J, Castelao, Jose E, Choi, Ji-Yeob, Clarke, Christine L, Couch, Fergus J, Cox, Angela, Cross, Simon S, Czene, Kamila, Devilee, Peter, Dörk, Thilo, Dunning, Alison M, Dwek, Miriam, Easton, Douglas F, Eccles, Diana M, Eriksson, Mikael, Ernst, Kristina, Evans, D Gareth, Figueroa, Jonine D, Fink, Visnja, Floris, Giuseppe, Fox, Stephen, Gabrielson, Marike, Gago-Dominguez, Manuela, García-Sáenz, José A, González-Neira, Anna, Haeberle, Lothar, Haiman, Christopher A, Hall, Per, Hamann, Ute, Harkness, Elaine F, Hartman, Mikael, Hein, Alexander, Hooning, Maartje J, Hou, Ming-Feng, Howell, Sacha J, ABCTB Investigators, kConFab Investigators, Ito, Hidemi, Jakubowska, Anna, Janni, Wolfgang, John, Esther M, Jung, Audrey, Kang, Daehee, Kristensen, Vessela N, Kwong, Ava, Lambrechts, Diether, Li, Jingmei, Lubiński, Jan, Manoochehri, Mehdi, Margolin, Sara, Matsuo, Keitaro, Taib, Nur Aishah Mohd, Mulligan, Anna Marie, Nevanlinna, Heli, Newman, William G, Offit, Kenneth, Osorio, Ana, Park, Sue K, Park-Simon, Tjoung-Won, Patel, Alpa V, Presneau, Nadege, Pylkäs, Katri, Rack, Brigitte, Radice, Paolo, Rennert, Gad, Romero, Atocha, Saloustros, Emmanouil, Sawyer, Elinor J, Schneeweiss, Andreas, Schochter, Fabienne, Schoemaker, Minouk J, Shen, Chen-Yang, Shibli, Rana, Sinn, Peter, Tapper, William J, Tawfiq, Essa, Teo, Soo Hwang, Teras, Lauren R, Torres, Diana, Vachon, Celine M, van Deurzen, Carolien HM, Wendt, Camilla, Williams, Justin A, Grootes, Isabelle, Grootes, Isabelle, Keeman, Renske, Blows, Fiona M, Milne, Roger L, Giles, Graham G, Swerdlow, Anthony J, Fasching, Peter A, Abubakar, Mustapha, Andrulis, Irene L, Anton-Culver, Hoda, Beckmann, Matthias W, Blomqvist, Carl, Bojesen, Stig E, Bolla, Manjeet K, Bonanni, Bernardo, Briceno, Ignacio, Burwinkel, Barbara, Camp, Nicola J, Castelao, Jose E, Choi, Ji-Yeob, Clarke, Christine L, Couch, Fergus J, Cox, Angela, Cross, Simon S, Czene, Kamila, Devilee, Peter, Dörk, Thilo, Dunning, Alison M, Dwek, Miriam, Easton, Douglas F, Eccles, Diana M, Eriksson, Mikael, Ernst, Kristina, Evans, D Gareth, Figueroa, Jonine D, Fink, Visnja, Floris, Giuseppe, Fox, Stephen, Gabrielson, Marike, Gago-Dominguez, Manuela, García-Sáenz, José A, González-Neira, Anna, Haeberle, Lothar, Haiman, Christopher A, Hall, Per, Hamann, Ute, Harkness, Elaine F, Hartman, Mikael, Hein, Alexander, Hooning, Maartje J, Hou, Ming-Feng, Howell, Sacha J, ABCTB Investigators, kConFab Investigators, Ito, Hidemi, Jakubowska, Anna, Janni, Wolfgang, John, Esther M, Jung, Audrey, Kang, Daehee, Kristensen, Vessela N, Kwong, Ava, Lambrechts, Diether, Li, Jingmei, Lubiński, Jan, Manoochehri, Mehdi, Margolin, Sara, Matsuo, Keitaro, Taib, Nur Aishah Mohd, Mulligan, Anna Marie, Nevanlinna, Heli, Newman, William G, Offit, Kenneth, Osorio, Ana, Park, Sue K, Park-Simon, Tjoung-Won, Patel, Alpa V, Presneau, Nadege, Pylkäs, Katri, Rack, Brigitte, Radice, Paolo, Rennert, Gad, Romero, Atocha, Saloustros, Emmanouil, Sawyer, Elinor J, Schneeweiss, Andreas, Schochter, Fabienne, Schoemaker, Minouk J, Shen, Chen-Yang, Shibli, Rana, Sinn, Peter, Tapper, William J, Tawfiq, Essa, Teo, Soo Hwang, Teras, Lauren R, Torres, Diana, Vachon, Celine M, van Deurzen, Carolien HM, Wendt, Camilla, and Williams, Justin A
Abstract: BackgroundPredict Breast (www.predict.nhs.uk) is an online prognostication and treatment benefit tool for early invasive breast cancer. The aim of this study was to incorporate the prognostic effect of progesterone receptor (PR) status into a new version of PREDICT and to compare its performance to the current version (2.2).MethodThe prognostic effect of PR status was based on the analysis of data from 45,088 European patients with breast cancer from 49 studies in the Breast Cancer Association Consortium. Cox proportional hazard models were used to estimate the hazard ratio for PR status. Data from a New Zealand study of 11,365 patients with early invasive breast cancer were used for external validation. Model calibration and discrimination were used to test the model performance.ResultsHaving a PR-positive tumour was associated with a 23% and 28% lower risk of dying from breast cancer for women with oestrogen receptor (ER)-negative and ER-positive breast cancer, respectively. The area under the ROC curve increased with the addition of PR status from 0.807 to 0.809 for patients with ER-negative tumours (p = 0.023) and from 0.898 to 0.902 for patients with ER-positive tumours (p = 2.3 × 10-6) in the New Zealand cohort. Model calibration was modest with 940 observed deaths compared to 1151 predicted.ConclusionThe inclusion of the prognostic effect of PR status to PREDICT Breast has led to an improvement of model performance and more accurate absolute treatment benefit predictions for individual patients. Further studies should determine whether the baseline hazard function requires recalibration.
Published: 2022

35. Recomendaciones de buenas prácticas para mejorar employee experience en compañías pymes en Colombia

Author: Espinel Suárez, Ana María, Peñuela Torres, Diana Angélica, Mora Hurtado, Natalia, Espinel Suárez, Ana María, Peñuela Torres, Diana Angélica, and Mora Hurtado, Natalia
Abstract: Con el transcurrir de los tiempos las empresas han gestionado estrategias dependiendo de las demandas del mercado para mantenerse o crecer dentro del mismo. Hoy en día donde el mercado es cada vez más competitivo las empresas optan por estrategias no solo dirigidas al cliente externo si no también al cliente interno, siendo este protagonista en el funcionamiento de toda organización. Teniendo en cuenta lo anterior muchas empresas exitosas hoy en día trabajan para que sus colaboradores sientan ese protagonismo a través de programas de bienestar, capacitación, desarrollo y fidelización; de esta manera lograr que su experiencia al interior de las mismas sea gratificante además de cumplir sus expectativas y esto sea reflejo en su labor y crecimiento tanto personal como profesional, siendo esto benéfico también para los intereses de toda organización.
Published: 2022

36. DM Design

Author: Riveros Rodríguez, Jean Rene / Tutor, Valbuena Torres, Diana Milena, Riveros Rodríguez, Jean Rene / Tutor, and Valbuena Torres, Diana Milena
Abstract: DM DESIGN es un proyecto de emprendimiento de Diseño de Espacios laborales y Comerciales que inicia en el 2021, este proyecto se desarrolla en la etapa de planeación teniendo como base las herramientas para la gestión de proyectos en la realización de un modelo de negocio, donde se definen y organizan todas las actividades que se deben tener en cuenta para el desarrollo del proyecto, se realizan análisis de mercado donde exploran los diferentes segmentos y se define el nicho al que se va a dirigir nuestro producto. Por medio de las herramientas para la gestión de proyectos estudiamos a nuestro cliente y desarrollamos una propuesta de valor que cumple con los objetivos del proyecto de emprendimiento que es crear espacios basados en las necesidades e ideologías de cada cliente para de este manera generar identidad de entre lo que representa su marca y el espacio que se crea para la marca o empresa., DM DESIGN is an entrepreneurship project of Design of Work and Commercial Spaces that starts in 2021, this project is developed in the planning stage based on the tools for project management in the realization of a business model, where all the activities that must be taken into account for the development of the project are defined and organized, market analysis is performed where different segments are explored and the niche to which our product will be directed is defined. Through the tools for project management we study our client and develop a value proposition that meets the objectives of the project, which is to create spaces based on the needs and ideologies of each client in order to generate identity between what represents their brand and the space that is created for the brand or company
Published: 2022

37. DM Design

Author: Riveros Rodríguez, Jean Rene / Tutor, Valbuena Torres, Diana Milena, Riveros Rodríguez, Jean Rene / Tutor, and Valbuena Torres, Diana Milena
Abstract: DM DESIGN es un proyecto de emprendimiento de Diseño de Espacios laborales y Comerciales que inicia en el 2021, este proyecto se desarrolla en la etapa de planeación teniendo como base las herramientas para la gestión de proyectos en la realización de un modelo de negocio, donde se definen y organizan todas las actividades que se deben tener en cuenta para el desarrollo del proyecto, se realizan análisis de mercado donde exploran los diferentes segmentos y se define el nicho al que se va a dirigir nuestro producto. Por medio de las herramientas para la gestión de proyectos estudiamos a nuestro cliente y desarrollamos una propuesta de valor que cumple con los objetivos del proyecto de emprendimiento que es crear espacios basados en las necesidades e ideologías de cada cliente para de este manera generar identidad de entre lo que representa su marca y el espacio que se crea para la marca o empresa., DM DESIGN is an entrepreneurship project of Design of Work and Commercial Spaces that starts in 2021, this project is developed in the planning stage based on the tools for project management in the realization of a business model, where all the activities that must be taken into account for the development of the project are defined and organized, market analysis is performed where different segments are explored and the niche to which our product will be directed is defined. Through the tools for project management we study our client and develop a value proposition that meets the objectives of the project, which is to create spaces based on the needs and ideologies of each client in order to generate identity between what represents their brand and the space that is created for the brand or company
Published: 2022

38. Common variants in breast cancer risk loci predispose to distinct tumor subtypes

Author: Ahearn, Thomas U., Zhang, Haoyu, Michailidou, Kyriaki, Milne, Roger L., Bolla, Manjeet K., Dennis, Joe, Dunning, Alison M., Lush, Michael, Wang, Qin, Andrulis, Irene L., Anton-Culver, Hoda, Arndt, Volker, Aronson, Kristan J., Auer, Paul L., Augustinsson, Annelie, Baten, Adinda, Becher, Heiko, Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Bojesen, Stig E., Bonanni, Bernardo, Borresen-Dale, Anne-Lise, Brauch, Hiltrud, Brenner, Hermann, Brooks-Wilson, Angela, Bruening, Thomas, Burwinkel, Barbara, Buys, Saundra S., Canzian, Federico, Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Chenevix-Trench, Georgia, Clarke, Christine L., Collee, J. Margriet, Cox, Angela, Cross, Simon S., Czene, Kamila, Daly, Mary B., Devilee, Peter, Dork, Thilo, Dwek, Miriam, Eccles, Diana M., Evans, D. Gareth, Fasching, Peter A., Figueroa, Jonine, Floris, Giuseppe, Gago-Dominguez, Manuela, Gapstur, Susan M., Garcia-Saenz, Jose A., Gaudet, Mia M., Giles, Graham G., Goldberg, Mark S., Gonzalez-Neira, Anna, Alnaes, Grethe I. Grenaker, Grip, Mervi, Guenel, Pascal, Haiman, Christopher A., Hall, Per, Hamann, Ute, Harkness, Elaine F., Heemskerk-Gerritsen, Bernadette A. M., Holleczek, Bernd, Hollestelle, Antoinette, Hooning, Maartje J., Hoover, Robert N., Hopper, John L., Howell, Anthony, Jakimovska, Milena, Jakubowska, Anna, John, Esther M., Jones, Michael E., Jung, Audrey, Kaaks, Rudolf, Kauppila, Saila, Keeman, Renske, Khusnutdinova, Elza, Kitahara, Cari M., Ko, Yon-Dschun, Koutros, Stella, Kristensen, Vessela N., Kruger, Ute, Kubelka-Sabit, Katerina, Kurian, Allison W., Kyriacou, Kyriacos, Lambrechts, Diether, Lee, Derrick G., Lindblom, Annika, Linet, Martha, Lissowska, Jolanta, Llaneza, Ana, Lo, Wing-Yee, MacInnis, Robert J., Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, Martinez, Maria Elena, McLean, Catriona, Meindl, Alfons, Menon, Usha, Nevanlinna, Heli, Newman, William G., Nodora, Jesse, Offit, Kenneth, Olsson, Hakan, Orr, Nick, Park-Simon, Tjoung-Won, Patel, Alpa, V, Peto, Julian, Pita, Guillermo, Plaseska-Karanfilska, Dijana, Prentice, Ross, Punie, Kevin, Pylkas, Katri, Radice, Paolo, Rennert, Gad, Romero, Atocha, Ruediger, Thomas, Saloustros, Emmanouil, Sampson, Sarah, Sandler, Dale P., Sawyer, Elinor J., Schmutzler, Rita K., Schoemaker, Minouk J., Schottker, Ben, Sherman, Mark E., Shu, Xiao-Ou, Smichkoska, Snezhana, Southey, Melissa C., Spinelli, John J., Swerdlow, Anthony J., Tamimi, Rulla M., Tapper, William J., Taylor, Jack A., Teras, Lauren R., Terry, Mary Beth, Torres, Diana, Troester, Melissa A., Vachon, Celine M., van Deurzen, Carolien H. M., van Veen, Elke M., Wagner, Philippe, Weinberg, Clarice R., Wendt, Camilla, Wesseling, Jelle, Winqvist, Robert, Wolk, Alicja, Yang, Xiaohong R., Zheng, Wei, Couch, Fergus J., Simard, Jacques, Kraft, Peter, Easton, Douglas F., Pharoah, Paul D. P., Schmidt, Marjanka K., Garcia-Closas, Montserrat, Chatterjee, Nilanjan, Ahearn, Thomas U., Zhang, Haoyu, Michailidou, Kyriaki, Milne, Roger L., Bolla, Manjeet K., Dennis, Joe, Dunning, Alison M., Lush, Michael, Wang, Qin, Andrulis, Irene L., Anton-Culver, Hoda, Arndt, Volker, Aronson, Kristan J., Auer, Paul L., Augustinsson, Annelie, Baten, Adinda, Becher, Heiko, Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Bojesen, Stig E., Bonanni, Bernardo, Borresen-Dale, Anne-Lise, Brauch, Hiltrud, Brenner, Hermann, Brooks-Wilson, Angela, Bruening, Thomas, Burwinkel, Barbara, Buys, Saundra S., Canzian, Federico, Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Chenevix-Trench, Georgia, Clarke, Christine L., Collee, J. Margriet, Cox, Angela, Cross, Simon S., Czene, Kamila, Daly, Mary B., Devilee, Peter, Dork, Thilo, Dwek, Miriam, Eccles, Diana M., Evans, D. Gareth, Fasching, Peter A., Figueroa, Jonine, Floris, Giuseppe, Gago-Dominguez, Manuela, Gapstur, Susan M., Garcia-Saenz, Jose A., Gaudet, Mia M., Giles, Graham G., Goldberg, Mark S., Gonzalez-Neira, Anna, Alnaes, Grethe I. Grenaker, Grip, Mervi, Guenel, Pascal, Haiman, Christopher A., Hall, Per, Hamann, Ute, Harkness, Elaine F., Heemskerk-Gerritsen, Bernadette A. M., Holleczek, Bernd, Hollestelle, Antoinette, Hooning, Maartje J., Hoover, Robert N., Hopper, John L., Howell, Anthony, Jakimovska, Milena, Jakubowska, Anna, John, Esther M., Jones, Michael E., Jung, Audrey, Kaaks, Rudolf, Kauppila, Saila, Keeman, Renske, Khusnutdinova, Elza, Kitahara, Cari M., Ko, Yon-Dschun, Koutros, Stella, Kristensen, Vessela N., Kruger, Ute, Kubelka-Sabit, Katerina, Kurian, Allison W., Kyriacou, Kyriacos, Lambrechts, Diether, Lee, Derrick G., Lindblom, Annika, Linet, Martha, Lissowska, Jolanta, Llaneza, Ana, Lo, Wing-Yee, MacInnis, Robert J., Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, Martinez, Maria Elena, McLean, Catriona, Meindl, Alfons, Menon, Usha, Nevanlinna, Heli, Newman, William G., Nodora, Jesse, Offit, Kenneth, Olsson, Hakan, Orr, Nick, Park-Simon, Tjoung-Won, Patel, Alpa, V, Peto, Julian, Pita, Guillermo, Plaseska-Karanfilska, Dijana, Prentice, Ross, Punie, Kevin, Pylkas, Katri, Radice, Paolo, Rennert, Gad, Romero, Atocha, Ruediger, Thomas, Saloustros, Emmanouil, Sampson, Sarah, Sandler, Dale P., Sawyer, Elinor J., Schmutzler, Rita K., Schoemaker, Minouk J., Schottker, Ben, Sherman, Mark E., Shu, Xiao-Ou, Smichkoska, Snezhana, Southey, Melissa C., Spinelli, John J., Swerdlow, Anthony J., Tamimi, Rulla M., Tapper, William J., Taylor, Jack A., Teras, Lauren R., Terry, Mary Beth, Torres, Diana, Troester, Melissa A., Vachon, Celine M., van Deurzen, Carolien H. M., van Veen, Elke M., Wagner, Philippe, Weinberg, Clarice R., Wendt, Camilla, Wesseling, Jelle, Winqvist, Robert, Wolk, Alicja, Yang, Xiaohong R., Zheng, Wei, Couch, Fergus J., Simard, Jacques, Kraft, Peter, Easton, Douglas F., Pharoah, Paul D. P., Schmidt, Marjanka K., Garcia-Closas, Montserrat, and Chatterjee, Nilanjan
Abstract: Background Genome-wide association studies (GWAS) have identified multiple common breast cancer susceptibility variants. Many of these variants have differential associations by estrogen receptor (ER) status, but how these variants relate with other tumor features and intrinsic molecular subtypes is unclear. Methods Among 106,571 invasive breast cancer cases and 95,762 controls of European ancestry with data on 173 breast cancer variants identified in previous GWAS, we used novel two-stage polytomous logistic regression models to evaluate variants in relation to multiple tumor features (ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and grade) adjusting for each other, and to intrinsic-like subtypes. Results Eighty-five of 173 variants were associated with at least one tumor feature (false discovery rate < 5%), most commonly ER and grade, followed by PR and HER2. Models for intrinsic-like subtypes found nearly all of these variants (83 of 85) associated at p < 0.05 with risk for at least one luminal-like subtype, and approximately half (41 of 85) of the variants were associated with risk of at least one non-luminal subtype, including 32 variants associated with triple-negative (TN) disease. Ten variants were associated with risk of all subtypes in different magnitude. Five variants were associated with risk of luminal A-like and TN subtypes in opposite directions. Conclusion This report demonstrates a high level of complexity in the etiology heterogeneity of breast cancer susceptibility variants and can inform investigations of subtype-specific risk prediction.
Published: 2022
Full Text: View/download PDF

39. Endofitismo de especies de Trichoderma y crecimiento radicular en dos variedades de banano in vitro

Author: Ramírez Torres, Diana Carolina, Reyes López, Delfino, Domínguez Perales, Luis Antonio, Orduño Cruz, Nuvia, Grifaldo-Alcántara, Pedro Fabián, Hernández Domínguez, Carmela, Ramírez Torres, Diana Carolina, Reyes López, Delfino, Domínguez Perales, Luis Antonio, Orduño Cruz, Nuvia, Grifaldo-Alcántara, Pedro Fabián, and Hernández Domínguez, Carmela
Abstract: Endophytism of fungi in plants has beneficial effects and depends on several factors. In this study, we evaluated individual endophytism and the consortium of five species—Trichoderma spirale, T. longibrachiatum, T. parareesei, T. andinense and T. hamatum—in root and bract in Williams and French bananas in vitro. Mortality, length and root diameter were evaluated on ex vitro plants. We observed significant differences in root endophytism (X21.00= 31.13, P<0.05). Trichoderma longi-brachiatum and T. hamatum had 48% endophytism in the Williams variety, while T. spirale,58% in the French variety. The treatment which consisted of the five species of Trichoderma had 24% en-dophytism in the root of the Williams variety, and 8% in the French variety. Correlation between endophytism and root diameter growth was observed (R2= 0.771, P<0.05). However, relation (R2 = 0.298, P <0.05), (R2 = 0.089) was not observed between endophyte of Trichoderma species and plant mortality of both banana varieties., El endofitismo de hongos en plantas tiene efectos benéficos y depende de varios factores. En este estudio se evaluó el endofitismo individual y el consorcio de cinco especies —Trichoderma spirale,T. longibrachiatum, T. parareesei, T. andinense y T. hamatum— en raíz y bráctea de banano Williams y Francés in vitro. La mortalidad, la longitud y el diámetro de raíz de plantas ex vitro fueron evaluados. Se observaron diferencias significativas de endofitismo en raíz (X21.00= 31.13, P<0.05); T. longibrachiatum y T. hamatum tuvieron 48 por ciento de endofitismo en la variedad Williams, y T. spirale,58 por ciento en la variedad Francés. El tratamiento formado por las cinco especies presentó 24 por ciento de endofitismo en raíz de la variedad Williams y 8 por ciento en la varie-dad Francés. Se observó relación entre endofitismo y crecimiento de diámetro de raíz (R2= 0.771, P<0.05); sin embargo, no se observó relación (R2= 0.298, P<0.05), (R2= 0.089) entre endófitismo de especies de Trichoderma y mortalidad de plantas de banano de ambas variedades.
Published: 2022

40. La fracción como operador: resolución de problemas, dificultades asociadas y conocimiento didáctico del contenido

Author: Herreros Torres, Diana, Sanz, María T., Gómez Ferragud, Carlos B., Herreros Torres, Diana, Sanz, María T., and Gómez Ferragud, Carlos B.
Abstract: An exploratory research is presented that seeks to detect the difficulties present in the development of one of the basic contents of Primary Education: the fraction as an operator. A group of 40 teachers recently graduated in Teaching participated in the study. Based on two specific tests, it was intended to inquire about their disciplinary knowledge in solving problems with fractions where they act as an operator, as well as about their didactic content knowledge about fractions. Better results were evidenced in the arithmetic resolution versus the graph and when the fraction operates on a natural number than when it operates on a fraction. Pedagogical content knowledge levels were very low, with percentages below 40%. From these results, the need to reconsider the functionality that is given to the mathematical content under study in the different curricula is suggested., Se presenta una investigación de carácter exploratorio que busca detectar las dificultades presentes en el desarrollo de uno de los contenidos básicos de la Educación Primaria: la fracción como operador. Participaron en el estudio un grupo de 40 docentes recién graduados en Magisterio. A partir de dos pruebas específicas se pretendió indagar acerca de su conocimiento disciplinar en resolución de problemas con fracciones donde estas actúan como operador, así como acerca de su conocimiento didáctico del contenido sobre fracciones. Se evidenciaron mejores resultados en la resolución aritmética frente a la gráfica y cuando la fracción opera sobre un número natural que cuando opera sobre un fraccionario. Los niveles de conocimiento didáctico del contenido fueron muy bajos, con porcentajes inferiores al 40%. A partir de estos resultados, se sugiere la necesidad de reconsiderar la funcionalidad que se le otorga al contenido matemático objeto de estudio en los diferentes currículos.
Published: 2022

41. Common variants in breast cancer risk loci predispose to distinct tumor subtypes

Author: Ahearn, Thomas U., Zhang, Haoyu, Michailidou, Kyriaki, Milne, Roger L., Bolla, Manjeet K., Dennis, Joe, Dunning, Alison M., Lush, Michael, Wang, Qin, Andrulis, Irene L., Anton-Culver, Hoda, Arndt, Volker, Aronson, Kristan J., Auer, Paul L., Augustinsson, Annelie, Baten, Adinda, Becher, Heiko, Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Bojesen, Stig E., Bonanni, Bernardo, Borresen-Dale, Anne-Lise, Brauch, Hiltrud, Brenner, Hermann, Brooks-Wilson, Angela, Bruening, Thomas, Burwinkel, Barbara, Buys, Saundra S., Canzian, Federico, Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Chenevix-Trench, Georgia, Clarke, Christine L., Collee, J. Margriet, Cox, Angela, Cross, Simon S., Czene, Kamila, Daly, Mary B., Devilee, Peter, Dork, Thilo, Dwek, Miriam, Eccles, Diana M., Evans, D. Gareth, Fasching, Peter A., Figueroa, Jonine, Floris, Giuseppe, Gago-Dominguez, Manuela, Gapstur, Susan M., Garcia-Saenz, Jose A., Gaudet, Mia M., Giles, Graham G., Goldberg, Mark S., Gonzalez-Neira, Anna, Alnaes, Grethe I. Grenaker, Grip, Mervi, Guenel, Pascal, Haiman, Christopher A., Hall, Per, Hamann, Ute, Harkness, Elaine F., Heemskerk-Gerritsen, Bernadette A. M., Holleczek, Bernd, Hollestelle, Antoinette, Hooning, Maartje J., Hoover, Robert N., Hopper, John L., Howell, Anthony, Jakimovska, Milena, Jakubowska, Anna, John, Esther M., Jones, Michael E., Jung, Audrey, Kaaks, Rudolf, Kauppila, Saila, Keeman, Renske, Khusnutdinova, Elza, Kitahara, Cari M., Ko, Yon-Dschun, Koutros, Stella, Kristensen, Vessela N., Kruger, Ute, Kubelka-Sabit, Katerina, Kurian, Allison W., Kyriacou, Kyriacos, Lambrechts, Diether, Lee, Derrick G., Lindblom, Annika, Linet, Martha, Lissowska, Jolanta, Llaneza, Ana, Lo, Wing-Yee, MacInnis, Robert J., Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, Martinez, Maria Elena, McLean, Catriona, Meindl, Alfons, Menon, Usha, Nevanlinna, Heli, Newman, William G., Nodora, Jesse, Offit, Kenneth, Olsson, Hakan, Orr, Nick, Park-Simon, Tjoung-Won, Patel, Alpa, V, Peto, Julian, Pita, Guillermo, Plaseska-Karanfilska, Dijana, Prentice, Ross, Punie, Kevin, Pylkas, Katri, Radice, Paolo, Rennert, Gad, Romero, Atocha, Ruediger, Thomas, Saloustros, Emmanouil, Sampson, Sarah, Sandler, Dale P., Sawyer, Elinor J., Schmutzler, Rita K., Schoemaker, Minouk J., Schottker, Ben, Sherman, Mark E., Shu, Xiao-Ou, Smichkoska, Snezhana, Southey, Melissa C., Spinelli, John J., Swerdlow, Anthony J., Tamimi, Rulla M., Tapper, William J., Taylor, Jack A., Teras, Lauren R., Terry, Mary Beth, Torres, Diana, Troester, Melissa A., Vachon, Celine M., van Deurzen, Carolien H. M., van Veen, Elke M., Wagner, Philippe, Weinberg, Clarice R., Wendt, Camilla, Wesseling, Jelle, Winqvist, Robert, Wolk, Alicja, Yang, Xiaohong R., Zheng, Wei, Couch, Fergus J., Simard, Jacques, Kraft, Peter, Easton, Douglas F., Pharoah, Paul D. P., Schmidt, Marjanka K., Garcia-Closas, Montserrat, Chatterjee, Nilanjan, Ahearn, Thomas U., Zhang, Haoyu, Michailidou, Kyriaki, Milne, Roger L., Bolla, Manjeet K., Dennis, Joe, Dunning, Alison M., Lush, Michael, Wang, Qin, Andrulis, Irene L., Anton-Culver, Hoda, Arndt, Volker, Aronson, Kristan J., Auer, Paul L., Augustinsson, Annelie, Baten, Adinda, Becher, Heiko, Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Bojesen, Stig E., Bonanni, Bernardo, Borresen-Dale, Anne-Lise, Brauch, Hiltrud, Brenner, Hermann, Brooks-Wilson, Angela, Bruening, Thomas, Burwinkel, Barbara, Buys, Saundra S., Canzian, Federico, Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Chenevix-Trench, Georgia, Clarke, Christine L., Collee, J. Margriet, Cox, Angela, Cross, Simon S., Czene, Kamila, Daly, Mary B., Devilee, Peter, Dork, Thilo, Dwek, Miriam, Eccles, Diana M., Evans, D. Gareth, Fasching, Peter A., Figueroa, Jonine, Floris, Giuseppe, Gago-Dominguez, Manuela, Gapstur, Susan M., Garcia-Saenz, Jose A., Gaudet, Mia M., Giles, Graham G., Goldberg, Mark S., Gonzalez-Neira, Anna, Alnaes, Grethe I. Grenaker, Grip, Mervi, Guenel, Pascal, Haiman, Christopher A., Hall, Per, Hamann, Ute, Harkness, Elaine F., Heemskerk-Gerritsen, Bernadette A. M., Holleczek, Bernd, Hollestelle, Antoinette, Hooning, Maartje J., Hoover, Robert N., Hopper, John L., Howell, Anthony, Jakimovska, Milena, Jakubowska, Anna, John, Esther M., Jones, Michael E., Jung, Audrey, Kaaks, Rudolf, Kauppila, Saila, Keeman, Renske, Khusnutdinova, Elza, Kitahara, Cari M., Ko, Yon-Dschun, Koutros, Stella, Kristensen, Vessela N., Kruger, Ute, Kubelka-Sabit, Katerina, Kurian, Allison W., Kyriacou, Kyriacos, Lambrechts, Diether, Lee, Derrick G., Lindblom, Annika, Linet, Martha, Lissowska, Jolanta, Llaneza, Ana, Lo, Wing-Yee, MacInnis, Robert J., Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, Martinez, Maria Elena, McLean, Catriona, Meindl, Alfons, Menon, Usha, Nevanlinna, Heli, Newman, William G., Nodora, Jesse, Offit, Kenneth, Olsson, Hakan, Orr, Nick, Park-Simon, Tjoung-Won, Patel, Alpa, V, Peto, Julian, Pita, Guillermo, Plaseska-Karanfilska, Dijana, Prentice, Ross, Punie, Kevin, Pylkas, Katri, Radice, Paolo, Rennert, Gad, Romero, Atocha, Ruediger, Thomas, Saloustros, Emmanouil, Sampson, Sarah, Sandler, Dale P., Sawyer, Elinor J., Schmutzler, Rita K., Schoemaker, Minouk J., Schottker, Ben, Sherman, Mark E., Shu, Xiao-Ou, Smichkoska, Snezhana, Southey, Melissa C., Spinelli, John J., Swerdlow, Anthony J., Tamimi, Rulla M., Tapper, William J., Taylor, Jack A., Teras, Lauren R., Terry, Mary Beth, Torres, Diana, Troester, Melissa A., Vachon, Celine M., van Deurzen, Carolien H. M., van Veen, Elke M., Wagner, Philippe, Weinberg, Clarice R., Wendt, Camilla, Wesseling, Jelle, Winqvist, Robert, Wolk, Alicja, Yang, Xiaohong R., Zheng, Wei, Couch, Fergus J., Simard, Jacques, Kraft, Peter, Easton, Douglas F., Pharoah, Paul D. P., Schmidt, Marjanka K., Garcia-Closas, Montserrat, and Chatterjee, Nilanjan
Abstract: Background Genome-wide association studies (GWAS) have identified multiple common breast cancer susceptibility variants. Many of these variants have differential associations by estrogen receptor (ER) status, but how these variants relate with other tumor features and intrinsic molecular subtypes is unclear. Methods Among 106,571 invasive breast cancer cases and 95,762 controls of European ancestry with data on 173 breast cancer variants identified in previous GWAS, we used novel two-stage polytomous logistic regression models to evaluate variants in relation to multiple tumor features (ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and grade) adjusting for each other, and to intrinsic-like subtypes. Results Eighty-five of 173 variants were associated with at least one tumor feature (false discovery rate < 5%), most commonly ER and grade, followed by PR and HER2. Models for intrinsic-like subtypes found nearly all of these variants (83 of 85) associated at p < 0.05 with risk for at least one luminal-like subtype, and approximately half (41 of 85) of the variants were associated with risk of at least one non-luminal subtype, including 32 variants associated with triple-negative (TN) disease. Ten variants were associated with risk of all subtypes in different magnitude. Five variants were associated with risk of luminal A-like and TN subtypes in opposite directions. Conclusion This report demonstrates a high level of complexity in the etiology heterogeneity of breast cancer susceptibility variants and can inform investigations of subtype-specific risk prediction.
Published: 2022

42. Polygenic risk modeling for prediction of epithelial ovarian cancer risk

Author: Dareng, Eileen O., Tyrer, Jonathan P., Barnes, Daniel R., Jones, Michelle R., Yang, Xin, Aben, Katja K. H., Adank, Muriel A., Agata, Simona, Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Aravantinos, Gerasimos, Arun, Banu K., Augustinsson, Annelie, Balmana, Judith, Bandera, Elisa, V, Barkardottir, Rosa B., Barrowdale, Daniel, Beckmann, Matthias W., Beeghly-Fadiel, Alicia, Benitez, Javier, Bermisheva, Marina, Bernardini, Marcus Q., Bjorge, Line, Black, Amanda, Bogdanova, Natalia, V, Bonanni, Bernardo, Borg, Ake, Brenton, James D., Budzilowska, Agnieszka, Butzow, Ralf, Buys, Saundra S., Cai, Hui, Caligo, Maria A., Campbell, Ian, Cannioto, Rikki, Cassingham, Hayley, Chang-Claude, Jenny, Chanock, Stephen J., Chen, Kexin, Chiew, Yoke-Eng, Chung, Wendy K., Claes, Kathleen B. M., Colonna, Sarah, Cook, Linda S., Couch, Fergus J., Daly, Mary B., Dao, Fanny, Davies, Eleanor, de la Hoya, Miguel, de Putter, Robin, Dennis, Joe, DePersia, Allison, Devilee, Peter, Diez, Orland, Ding, Yuan Chun, Doherty, Jennifer A., Domchek, Susan M., Dork, Thilo, du Bois, Andreas, Durst, Matthias, Eccles, Diana M., Eliassen, Heather A., Engel, Christoph, Evans, Gareth D., Fasching, Peter A., Flanagan, James M., Fortner, ReneeT, Machackova, Eva, Friedman, Eitan, Ganz, Patricia A., Garber, Judy, Gensini, Francesca, Giles, Graham G., Glendon, Gord, Godwin, Andrew K., Goodman, Marc T., Greene, Mark H., Gronwald, Jacek, Group, Opal Study, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hamann, Ute, Hansen, Thomas V. O., Harris, Holly R., Hartman, Mikael, Heitz, Florian, Hildebrandt, Michelle A. T., Hogdall, Estrid, Hogdall, Claus K., Hopper, John L., Huang, Ruea-Yea, Huff, Chad, Hulick, Peter J., Huntsman, David G., Imyanitov, Evgeny N., Isaacs, Claudine, Jakubowska, Anna, James, Paul A., Janavicius, Ramunas, Jensen, Allan, Johannsson, Oskar Th, John, Esther M., Jones, Michael E., Kang, Daehee, Karlan, Beth Y., Karnezis, Anthony, Kelemen, Linda E., Khusnutdinova, Elza, Kiemeney, Lambertus A., Kim, Byoung-Gie, Kjaer, Susanne K., Komenaka, Ian, Kupryjanczyk, Jolanta, Kurian, Allison W., Kwong, Ava, Lambrechts, Diether, Larson, Melissa C., Lazaro, Conxi, Le, Nhu D., Leslie, Goska, Lester, Jenny, Lesueur, Fabienne, Levine, Douglas A., Li, Lian, Li, Jingmei, Loud, Jennifer T., Lu, Karen H., Mai, Phuong L., Manoukian, Siranoush, Marks, Jeffrey R., KimMatsuno, Rayna, Matsuo, Keitaro, May, Taymaa, McGuffog, Lesley, McLaughlin, John R., McNeish, Iain A., Mebirouk, Noura, Menon, Usha, Miller, Austin, Milne, Roger L., Minlikeeva, Albina, Modugno, Francesmary, Montagna, Marco, Moysich, Kirsten B., Munro, Elizabeth, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Yie, Joanne Ngeow Yuen, Nielsen, Henriette Roed, Nielsen, Finn C., Nikitina-Zake, Liene, Odunsi, Kunle, Offit, Kenneth, Olah, Edith, Olbrecht, Siel, Olopade, Olufunmilayo, I, Olson, Sara H., Olsson, Hakan, Osorio, Ana, Papi, Laura, Park, Sue K., Parsons, Michael T., Pathak, Harsha, Pedersen, Inge Sokilde, Peixoto, Ana, Pejovic, Tanja, Perez-Segura, Pedro, Permuth, Jennifer B., Peshkin, Beth, Peterlongo, Paolo, Piskorz, Anna, Prokofyeva, Darya, Radice, Paolo, Rantala, Johanna, Riggan, Marjorie J., Risch, Harvey A., Rodriguez-Antona, Cristina, Ross, Eric, Rossing, Mary Anne, Runnebaum, Ingo, Sandler, Dale P., Santamarina, Marta, Soucy, Penny, Schmutzler, Rita K., Setiawan, V. Wendy, Shan, Kang, Sieh, Weiva, Simard, Jacques, Singer, Christian F., Sokolenko, Anna P., Song, Honglin, Southey, Melissa C., Steed, Helen, Stoppa-Lyonnet, Dominique, Sutphen, Rebecca, Swerdlow, Anthony J., Tan, Yen Yen, Teixeira, Manuel R., Teo, Soo Hwang, Terry, Kathryn L., BethTerry, Mary, Thomassen, Mads, Thompson, Pamela J., Thomsen, Liv Cecilie Vestrheim, Thull, Darcy L., Tischkowitz, Marc, Titus, Linda, Toland, Amanda E., Torres, Diana, Trabert, Britton, Travis, Ruth, Tung, Nadine, Tworoger, Shelley S., Valen, Ellen, van Altena, Anne M., van der Hout, Annemieke H., Nieuwenhuysen, ElsVan, van Rensburg, Elizabeth J., Vega, Ana, Edwards, Digna Velez, Vierkant, Robert A., Wang, Frances, Wappenschmidt, Barbara, Webb, Penelope M., Weinberg, Clarice R., Weitzel, Jeffrey N., Wentzensen, Nicolas, White, Emily, Whittemore, Alice S., Winham, Stacey J., Wolk, Alicja, Woo, Yin-Ling, Wu, Anna H., Yan, Li, Yannoukakos, Drakoulis, Zavaglia, Katia M., Zheng, Wei, Ziogas, Argyrios, Zorn, Kristin K., Kleibl, Zdenek, Easton, Douglas, Lawrenson, Kate, DeFazio, Anna, Sellers, Thomas A., Ramus, Susan J., Pearce, Celeste L., Monteiro, Alvaro N., Cunningham, Julie, Goode, Ellen L., Schildkraut, Joellen M., Berchuck, Andrew, Chenevix-Trench, Georgia, Gayther, Simon A., Antoniou, Antonis C., Pharoah, Paul D. P., Dareng, Eileen O., Tyrer, Jonathan P., Barnes, Daniel R., Jones, Michelle R., Yang, Xin, Aben, Katja K. H., Adank, Muriel A., Agata, Simona, Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Aravantinos, Gerasimos, Arun, Banu K., Augustinsson, Annelie, Balmana, Judith, Bandera, Elisa, V, Barkardottir, Rosa B., Barrowdale, Daniel, Beckmann, Matthias W., Beeghly-Fadiel, Alicia, Benitez, Javier, Bermisheva, Marina, Bernardini, Marcus Q., Bjorge, Line, Black, Amanda, Bogdanova, Natalia, V, Bonanni, Bernardo, Borg, Ake, Brenton, James D., Budzilowska, Agnieszka, Butzow, Ralf, Buys, Saundra S., Cai, Hui, Caligo, Maria A., Campbell, Ian, Cannioto, Rikki, Cassingham, Hayley, Chang-Claude, Jenny, Chanock, Stephen J., Chen, Kexin, Chiew, Yoke-Eng, Chung, Wendy K., Claes, Kathleen B. M., Colonna, Sarah, Cook, Linda S., Couch, Fergus J., Daly, Mary B., Dao, Fanny, Davies, Eleanor, de la Hoya, Miguel, de Putter, Robin, Dennis, Joe, DePersia, Allison, Devilee, Peter, Diez, Orland, Ding, Yuan Chun, Doherty, Jennifer A., Domchek, Susan M., Dork, Thilo, du Bois, Andreas, Durst, Matthias, Eccles, Diana M., Eliassen, Heather A., Engel, Christoph, Evans, Gareth D., Fasching, Peter A., Flanagan, James M., Fortner, ReneeT, Machackova, Eva, Friedman, Eitan, Ganz, Patricia A., Garber, Judy, Gensini, Francesca, Giles, Graham G., Glendon, Gord, Godwin, Andrew K., Goodman, Marc T., Greene, Mark H., Gronwald, Jacek, Group, Opal Study, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hamann, Ute, Hansen, Thomas V. O., Harris, Holly R., Hartman, Mikael, Heitz, Florian, Hildebrandt, Michelle A. T., Hogdall, Estrid, Hogdall, Claus K., Hopper, John L., Huang, Ruea-Yea, Huff, Chad, Hulick, Peter J., Huntsman, David G., Imyanitov, Evgeny N., Isaacs, Claudine, Jakubowska, Anna, James, Paul A., Janavicius, Ramunas, Jensen, Allan, Johannsson, Oskar Th, John, Esther M., Jones, Michael E., Kang, Daehee, Karlan, Beth Y., Karnezis, Anthony, Kelemen, Linda E., Khusnutdinova, Elza, Kiemeney, Lambertus A., Kim, Byoung-Gie, Kjaer, Susanne K., Komenaka, Ian, Kupryjanczyk, Jolanta, Kurian, Allison W., Kwong, Ava, Lambrechts, Diether, Larson, Melissa C., Lazaro, Conxi, Le, Nhu D., Leslie, Goska, Lester, Jenny, Lesueur, Fabienne, Levine, Douglas A., Li, Lian, Li, Jingmei, Loud, Jennifer T., Lu, Karen H., Mai, Phuong L., Manoukian, Siranoush, Marks, Jeffrey R., KimMatsuno, Rayna, Matsuo, Keitaro, May, Taymaa, McGuffog, Lesley, McLaughlin, John R., McNeish, Iain A., Mebirouk, Noura, Menon, Usha, Miller, Austin, Milne, Roger L., Minlikeeva, Albina, Modugno, Francesmary, Montagna, Marco, Moysich, Kirsten B., Munro, Elizabeth, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Yie, Joanne Ngeow Yuen, Nielsen, Henriette Roed, Nielsen, Finn C., Nikitina-Zake, Liene, Odunsi, Kunle, Offit, Kenneth, Olah, Edith, Olbrecht, Siel, Olopade, Olufunmilayo, I, Olson, Sara H., Olsson, Hakan, Osorio, Ana, Papi, Laura, Park, Sue K., Parsons, Michael T., Pathak, Harsha, Pedersen, Inge Sokilde, Peixoto, Ana, Pejovic, Tanja, Perez-Segura, Pedro, Permuth, Jennifer B., Peshkin, Beth, Peterlongo, Paolo, Piskorz, Anna, Prokofyeva, Darya, Radice, Paolo, Rantala, Johanna, Riggan, Marjorie J., Risch, Harvey A., Rodriguez-Antona, Cristina, Ross, Eric, Rossing, Mary Anne, Runnebaum, Ingo, Sandler, Dale P., Santamarina, Marta, Soucy, Penny, Schmutzler, Rita K., Setiawan, V. Wendy, Shan, Kang, Sieh, Weiva, Simard, Jacques, Singer, Christian F., Sokolenko, Anna P., Song, Honglin, Southey, Melissa C., Steed, Helen, Stoppa-Lyonnet, Dominique, Sutphen, Rebecca, Swerdlow, Anthony J., Tan, Yen Yen, Teixeira, Manuel R., Teo, Soo Hwang, Terry, Kathryn L., BethTerry, Mary, Thomassen, Mads, Thompson, Pamela J., Thomsen, Liv Cecilie Vestrheim, Thull, Darcy L., Tischkowitz, Marc, Titus, Linda, Toland, Amanda E., Torres, Diana, Trabert, Britton, Travis, Ruth, Tung, Nadine, Tworoger, Shelley S., Valen, Ellen, van Altena, Anne M., van der Hout, Annemieke H., Nieuwenhuysen, ElsVan, van Rensburg, Elizabeth J., Vega, Ana, Edwards, Digna Velez, Vierkant, Robert A., Wang, Frances, Wappenschmidt, Barbara, Webb, Penelope M., Weinberg, Clarice R., Weitzel, Jeffrey N., Wentzensen, Nicolas, White, Emily, Whittemore, Alice S., Winham, Stacey J., Wolk, Alicja, Woo, Yin-Ling, Wu, Anna H., Yan, Li, Yannoukakos, Drakoulis, Zavaglia, Katia M., Zheng, Wei, Ziogas, Argyrios, Zorn, Kristin K., Kleibl, Zdenek, Easton, Douglas, Lawrenson, Kate, DeFazio, Anna, Sellers, Thomas A., Ramus, Susan J., Pearce, Celeste L., Monteiro, Alvaro N., Cunningham, Julie, Goode, Ellen L., Schildkraut, Joellen M., Berchuck, Andrew, Chenevix-Trench, Georgia, Gayther, Simon A., Antoniou, Antonis C., and Pharoah, Paul D. P.
Abstract: Polygenic risk scores (PRS) for epithelial ovarian cancer (EOC) have the potential to improve risk stratification. Joint estimation of Single Nucleotide Polymorphism (SNP) effects in models could improve predictive performance over standard approaches of PRS construction. Here, we implemented computationally efficient, penalized, logistic regression models (lasso, elastic net, stepwise) to individual level genotype data and a Bayesian framework with continuous shrinkage, select and shrink for summary statistics (S4), to summary level data for epithelial non-mucinous ovarian cancer risk prediction. We developed the models in a dataset consisting of 23,564 non-mucinous EOC cases and 40,138 controls participating in the Ovarian Cancer Association Consortium (OCAC) and validated the best models in three populations of different ancestries: prospective data from 198,101 women of European ancestries; 7,669 women of East Asian ancestries; 1,072 women of African ancestries, and in 18,915 BRCA1 and 12,337 BRCA2 pathogenic variant carriers of European ancestries. In the external validation data, the model with the strongest association for non-mucinous EOC risk derived from the OCAC model development data was the S4 model (27,240 SNPs) with odds ratios (OR) of 1.38 (95% CI: 1.28-1.48, AUC: 0.588) per unit standard deviation, in women of European ancestries; 1.14 (95% CI: 1.08-1.19, AUC: 0.538) in women of East Asian ancestries; 1.38 (95% CI: 1.21-1.58, AUC: 0.593) in women of African ancestries; hazard ratios of 1.36 (95% CI: 1.29-1.43, AUC: 0.592) in BRCA1 pathogenic variant carriers and 1.49 (95% CI: 1.35-1.64, AUC: 0.624) in BRCA2 pathogenic variant carriers. Incorporation of the S4 PRS in risk prediction models for ovarian cancer may have clinical utility in ovarian cancer prevention programs.
Published: 2022

43. Breast cancer risks associated with missense variants in breast cancer susceptibility genes

Author: Dorling, Leila, Carvalho, Sara, Allen, Jamie, Parsons, Michael T., Fortuno, Cristina, Gonzalez-Neira, Anna, Heijl, Stephan M., Adank, Muriel A., Ahearn, Thomas U., Andrulis, Irene L., Auvinen, Paivi, Becher, Heiko, Beckmann, Matthias W., Behrens, Sabine, Bermisheva, Marina, Bogdanova, Natalia V., Bojesen, Stig E., Bolla, Manjeet K., Bremer, Michael, Briceno, Ignacio, Camp, Nicola J., Campbell, Archie, Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Chenevix-Trench, Georgia, Collee, J. Margriet, Czene, Kamila, Dennis, Joe, Dork, Thilo, Eriksson, Mikael, Evans, D. Gareth, Fasching, Peter A., Figueroa, Jonine, Flyger, Henrik, Gabrielson, Marike, Gago-Dominguez, Manuela, Garcia-Closas, Montserrat, Giles, Graham G., Glendon, Gord, Guenel, Pascal, Gundert, Melanie, Hadjisavvas, Andreas, Hahnen, Eric, Hall, Per, Hamann, Ute, Harkness, Elaine F., Hartman, Mikael, Hogervorst, Frans B. L., Hollestelle, Antoinette, Hoppe, Reiner, Howell, Anthony, Jakubowska, Anna, Jung, Audrey, Khusnutdinova, Elza, Kim, Sung-Won, Ko, Yon-Dschun, Kristensen, Vessela N., Lakeman, Inge M. M., Li, Jingmei, Lindblom, Annika, Loizidou, Maria A., Lophatananon, Artitaya, Lubinski, Jan, Luccarini, Craig, Madsen, Michael J., Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, Mavroudis, Dimitrios, Milne, Roger L., Mohd Taib, Nur Aishah, Muir, Kenneth, Nevanlinna, Heli, Newman, William G., Oosterwijk, Jan C., Park, Sue K., Peterlongo, Paolo, Radice, Paolo, Saloustros, Emmanouil, Sawyer, Elinor J., Schmutzler, Rita K., Shah, Mitul, Sim, Xueling, Southey, Melissa C., Surowy, Harald, Suvanto, Maija, Tomlinson, Ian, Torres, Diana, Truong, Therese, van Asperen, Christi J., Waltes, Regina, Wang, Qin, Yang, Xiaohong R., Pharoah, Paul D. P., Schmidt, Marjanka K., Benitez, Javier, Vroling, Bas, Dunning, Alison M., Teo, Soo Hwang, Kvist, Anders, de la Hoya, Miguel, Devilee, Peter, Spurdle, Amanda B., Vreeswijk, Maaike P. G., Easton, Douglas F., Dorling, Leila, Carvalho, Sara, Allen, Jamie, Parsons, Michael T., Fortuno, Cristina, Gonzalez-Neira, Anna, Heijl, Stephan M., Adank, Muriel A., Ahearn, Thomas U., Andrulis, Irene L., Auvinen, Paivi, Becher, Heiko, Beckmann, Matthias W., Behrens, Sabine, Bermisheva, Marina, Bogdanova, Natalia V., Bojesen, Stig E., Bolla, Manjeet K., Bremer, Michael, Briceno, Ignacio, Camp, Nicola J., Campbell, Archie, Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Chenevix-Trench, Georgia, Collee, J. Margriet, Czene, Kamila, Dennis, Joe, Dork, Thilo, Eriksson, Mikael, Evans, D. Gareth, Fasching, Peter A., Figueroa, Jonine, Flyger, Henrik, Gabrielson, Marike, Gago-Dominguez, Manuela, Garcia-Closas, Montserrat, Giles, Graham G., Glendon, Gord, Guenel, Pascal, Gundert, Melanie, Hadjisavvas, Andreas, Hahnen, Eric, Hall, Per, Hamann, Ute, Harkness, Elaine F., Hartman, Mikael, Hogervorst, Frans B. L., Hollestelle, Antoinette, Hoppe, Reiner, Howell, Anthony, Jakubowska, Anna, Jung, Audrey, Khusnutdinova, Elza, Kim, Sung-Won, Ko, Yon-Dschun, Kristensen, Vessela N., Lakeman, Inge M. M., Li, Jingmei, Lindblom, Annika, Loizidou, Maria A., Lophatananon, Artitaya, Lubinski, Jan, Luccarini, Craig, Madsen, Michael J., Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, Mavroudis, Dimitrios, Milne, Roger L., Mohd Taib, Nur Aishah, Muir, Kenneth, Nevanlinna, Heli, Newman, William G., Oosterwijk, Jan C., Park, Sue K., Peterlongo, Paolo, Radice, Paolo, Saloustros, Emmanouil, Sawyer, Elinor J., Schmutzler, Rita K., Shah, Mitul, Sim, Xueling, Southey, Melissa C., Surowy, Harald, Suvanto, Maija, Tomlinson, Ian, Torres, Diana, Truong, Therese, van Asperen, Christi J., Waltes, Regina, Wang, Qin, Yang, Xiaohong R., Pharoah, Paul D. P., Schmidt, Marjanka K., Benitez, Javier, Vroling, Bas, Dunning, Alison M., Teo, Soo Hwang, Kvist, Anders, de la Hoya, Miguel, Devilee, Peter, Spurdle, Amanda B., Vreeswijk, Maaike P. G., and Easton, Douglas F.
Abstract: Background Protein truncating variants in ATM, BRCA1, BRCA2, CHEK2, and PALB2 are associated with increased breast cancer risk, but risks associated with missense variants in these genes are uncertain. Methods We analyzed data on 59,639 breast cancer cases and 53,165 controls from studies participating in the Breast Cancer Association Consortium BRIDGES project. We sampled training (80%) and validation (20%) sets to analyze rare missense variants in ATM (1146 training variants), BRCA1 (644), BRCA2 (1425), CHEK2 (325), and PALB2 (472). We evaluated breast cancer risks according to five in silico prediction-of-deleteriousness algorithms, functional protein domain, and frequency, using logistic regression models and also mixture models in which a subset of variants was assumed to be risk-associated. Results The most predictive in silico algorithms were Helix (BRCA1, BRCA2 and CHEK2) and CADD (ATM). Increased risks appeared restricted to functional protein domains for ATM (FAT and PIK domains) and BRCA1 (RING and BRCT domains). For ATM, BRCA1, and BRCA2, data were compatible with small subsets (approximately 7%, 2%, and 0.6%, respectively) of rare missense variants giving similar risk to those of protein truncating variants in the same gene. For CHEK2, data were more consistent with a large fraction (approximately 60%) of rare missense variants giving a lower risk (OR 1.75, 95% CI (1.47-2.08)) than CHEK2 protein truncating variants. There was little evidence for an association with risk for missense variants in PALB2. The best fitting models were well calibrated in the validation set. Conclusions These results will inform risk prediction models and the selection of candidate variants for functional assays and could contribute to the clinical reporting of gene panel testing for breast cancer susceptibility.
Published: 2022

44. Cancer Risks Associated With BRCA1 and BRCA2 Pathogenic Variants

Author: Li, Shuai, Silvestri, Valentina, Leslie, Goska, Rebbeck, Timothy R., Neuhausen, Susan L., Hopper, John L., Nielsen, Henriette Roed, Lee, Andrew, Yang, Xin, McGuffog, Lesley, Parsons, Michael T., Andrulis, Irene L., Arnold, Norbert, Belotti, Muriel, Borg, Ake, Buecher, Bruno, Buys, Saundra S., Caputo, Sandrine M., Chung, Wendy K., Colas, Chrystelle, Colonna, Sarah, V, Cook, Jackie, Daly, Mary B., de la Hoya, Miguel, de Pauw, Antoine, Delhomelle, Helene, Eason, Jacqueline, Engel, Christoph, Evans, D. Gareth, Faust, Ulrike, Fehm, Tanja N., Fostira, Florentia, Fountzilas, George, Frone, Megan, Garcia-Barberan, Vanesa, Garre, Pilar, Gauthier-Villars, Marion, Gehrig, Andrea, Glendon, Gord, Goldgar, David E., Golmard, Lisa, Greene, Mark H., Hahnen, Eric, Hamann, Ute, Hanson, Helen, Hassan, Tiara, Hentschel, Julia, Horvath, Judit, Izatt, Louise, Janavicius, Ramunas, Jiao, Yue, John, Esther M., Karlan, Beth Y., Kim, Sung-Won, Konstantopoulou, Irene, Kwong, Ava, Lauge, Anthony, Lee, Jong Won, Lesueur, Fabienne, Mebirouk, Noura, Meindl, Alfons, Mouret-Fourme, Emmanuelle, Musgrave, Hannah, Yie, Joanne Ngeow Yuen, Niederacher, Dieter, Park, Sue K., Pedersen, Inge Sokilde, Ramser, Juliane, Ramus, Susan J., Rantala, Johanna, Rashid, Muhammad U., Reichl, Florian, Ritter, Julia, Rump, Andreas, Santamarina, Marta, Saule, Claire, Schmidt, Gunnar, Schmutzler, Rita K., Senter, Leigha, Shariff, Saba, Singer, Christian F., Southey, Melissa C., Stoppa-Lyonnet, Dominique, Sutter, Christian, Tan, Yen, Teo, Soo Hwang, Terry, Mary Beth, Thomassen, Mads, Tischkowitz, Marc, Toland, Amanda E., Torres, Diana, Vega, Ana, Wagner, Sebastian A., Wang-Gohrke, Shan, Wappenschmidt, Barbara, Weber, Bernhard H. F., Yannoukakos, Drakoulis, Spurdle, Amanda B., Easton, Douglas F., Chenevix-Trench, Georgia, Ottini, Laura, Antoniou, Antonis C., Li, Shuai, Silvestri, Valentina, Leslie, Goska, Rebbeck, Timothy R., Neuhausen, Susan L., Hopper, John L., Nielsen, Henriette Roed, Lee, Andrew, Yang, Xin, McGuffog, Lesley, Parsons, Michael T., Andrulis, Irene L., Arnold, Norbert, Belotti, Muriel, Borg, Ake, Buecher, Bruno, Buys, Saundra S., Caputo, Sandrine M., Chung, Wendy K., Colas, Chrystelle, Colonna, Sarah, V, Cook, Jackie, Daly, Mary B., de la Hoya, Miguel, de Pauw, Antoine, Delhomelle, Helene, Eason, Jacqueline, Engel, Christoph, Evans, D. Gareth, Faust, Ulrike, Fehm, Tanja N., Fostira, Florentia, Fountzilas, George, Frone, Megan, Garcia-Barberan, Vanesa, Garre, Pilar, Gauthier-Villars, Marion, Gehrig, Andrea, Glendon, Gord, Goldgar, David E., Golmard, Lisa, Greene, Mark H., Hahnen, Eric, Hamann, Ute, Hanson, Helen, Hassan, Tiara, Hentschel, Julia, Horvath, Judit, Izatt, Louise, Janavicius, Ramunas, Jiao, Yue, John, Esther M., Karlan, Beth Y., Kim, Sung-Won, Konstantopoulou, Irene, Kwong, Ava, Lauge, Anthony, Lee, Jong Won, Lesueur, Fabienne, Mebirouk, Noura, Meindl, Alfons, Mouret-Fourme, Emmanuelle, Musgrave, Hannah, Yie, Joanne Ngeow Yuen, Niederacher, Dieter, Park, Sue K., Pedersen, Inge Sokilde, Ramser, Juliane, Ramus, Susan J., Rantala, Johanna, Rashid, Muhammad U., Reichl, Florian, Ritter, Julia, Rump, Andreas, Santamarina, Marta, Saule, Claire, Schmidt, Gunnar, Schmutzler, Rita K., Senter, Leigha, Shariff, Saba, Singer, Christian F., Southey, Melissa C., Stoppa-Lyonnet, Dominique, Sutter, Christian, Tan, Yen, Teo, Soo Hwang, Terry, Mary Beth, Thomassen, Mads, Tischkowitz, Marc, Toland, Amanda E., Torres, Diana, Vega, Ana, Wagner, Sebastian A., Wang-Gohrke, Shan, Wappenschmidt, Barbara, Weber, Bernhard H. F., Yannoukakos, Drakoulis, Spurdle, Amanda B., Easton, Douglas F., Chenevix-Trench, Georgia, Ottini, Laura, and Antoniou, Antonis C.
Abstract: PURPOSE To provide precise age-specific risk estimates of cancers other than female breast and ovarian cancers associated with pathogenic variants (PVs) in BRCA1 and BRCA2 for effective cancer risk management. METHODS We used data from 3,184 BRCA1 and 2,157 BRCA2 families in the Consortium of Investigators of Modifiers of BRCA1/2 to estimate age-specific relative (RR) and absolute risks for 22 first primary cancer types adjusting for family ascertainment. RESULTS BRCA1 PVs were associated with risks of male breast (RR = 4.30; 95% CI, 1.09 to 16.96), pancreatic (RR = 2.36; 95% CI, 1.51 to 3.68), and stomach (RR = 2.17; 95% CI, 1.25 to 3.77) cancers. Associations with colorectal and gallbladder cancers were also suggested. BRCA2 PVs were associated with risks of male breast (RR = 44.0; 95% CI, 21.3 to 90.9), stomach (RR = 3.69; 95% CI, 2.40 to 5.67), pancreatic (RR = 3.34; 95% CI, 2.21 to 5.06), and prostate (RR = 2.22; 95% CI, 1.63 to 3.03) cancers. The stomach cancer RR was higher for females than males (6.89 v 2.76; P = .04). The absolute risks to age 80 years ranged from 0.4% for male breast cancer to approximately 2.5% for pancreatic cancer for BRCA1 carriers and from approximately 2.5% for pancreatic cancer to 27% for prostate cancer for BRCA2 carriers. CONCLUSION In addition to female breast and ovarian cancers, BRCA1 and BRCA2 PVs are associated with increased risks of male breast, pancreatic, stomach, and prostate (only BRCA2 PVs) cancers, but not with the risks of other previously suggested cancers. The estimated age-specific risks will refine cancer risk management in men and women with BRCA1/2 PVs.
Published: 2022

45. Pathology of Tumors Associated With Pathogenic Germline Variants in 9 Breast Cancer Susceptibility Genes

Author: Mavaddat, Nasim, Dorling, Leila, Carvalho, Sara, Allen, Jamie, Gonzalez-Neira, Anna, Keeman, Renske, Bolla, Manjeet K., Dennis, Joe, Wang, Qin, Ahearn, Thomas U., Andrulis, Irene L., Beckmann, Matthias W., Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Bogdanova, Natalia, V, Bojesen, Stig E., Briceno, Ignacio, Bruning, Thomas, Camp, Nicola J., Campbell, Archie, Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Chenevix-Trench, Georgia, Christiansen, Hans, Czene, Kamila, Dork, Thilo, Eriksson, Mikael, Evans, D. Gareth, Fasching, Peter A., Figueroa, Jonine D., Flyger, Henrik, Gabrielson, Marike, Gago-Dominguez, Manuela, Geisler, Jurgen, Giles, Graham G., Guenel, Pascal, Hadjisavvas, Andreas, Hahnen, Eric, Hall, Per, Hamann, Ute, Hartikainen, Jaana M., Hartman, Mikael, Hoppe, Reiner, Howell, Anthony, Jakubowska, Anna, Jung, Audrey, Khusnutdinova, Elza K., Kristensen, Vessela N., Li, Jingmei, Lim, Swee Ho, Lindblom, Annika, Loizidou, Maria A., Lophatananon, Artitaya, Lubinski, Jan, Madsen, Michael J., Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, Mavroudis, Dimitrios, Milne, Roger L., Taib, Nur Aishah Mohd, Morra, Anna, Muir, Kenneth, Obi, Nadia, Osorio, Ana, Park-Simon, Tjoung-Won, Peterlongo, Paolo, Radice, Paolo, Saloustros, Emmanouil, Sawyer, Elinor J., Schmutzler, Rita K., Shah, Mitul, Sim, Xueling, Southey, Melissa C., Thorne, Heather, Tomlinson, Ian, Torres, Diana, Truong, Therese, Yip, Cheng Har, Spurdle, Amanda B., Vreeswijk, Maaike P. G., Dunning, Alison M., Garcia-Closas, Montserrat, Pharoah, Paul D. P., Kvist, Anders, Muranen, Taru A., Nevanlinna, Heli, Teo, Soo Hwang, Devilee, Peter, Schmidt, Marjanka K., Easton, Douglas F., Mavaddat, Nasim, Dorling, Leila, Carvalho, Sara, Allen, Jamie, Gonzalez-Neira, Anna, Keeman, Renske, Bolla, Manjeet K., Dennis, Joe, Wang, Qin, Ahearn, Thomas U., Andrulis, Irene L., Beckmann, Matthias W., Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Bogdanova, Natalia, V, Bojesen, Stig E., Briceno, Ignacio, Bruning, Thomas, Camp, Nicola J., Campbell, Archie, Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Chenevix-Trench, Georgia, Christiansen, Hans, Czene, Kamila, Dork, Thilo, Eriksson, Mikael, Evans, D. Gareth, Fasching, Peter A., Figueroa, Jonine D., Flyger, Henrik, Gabrielson, Marike, Gago-Dominguez, Manuela, Geisler, Jurgen, Giles, Graham G., Guenel, Pascal, Hadjisavvas, Andreas, Hahnen, Eric, Hall, Per, Hamann, Ute, Hartikainen, Jaana M., Hartman, Mikael, Hoppe, Reiner, Howell, Anthony, Jakubowska, Anna, Jung, Audrey, Khusnutdinova, Elza K., Kristensen, Vessela N., Li, Jingmei, Lim, Swee Ho, Lindblom, Annika, Loizidou, Maria A., Lophatananon, Artitaya, Lubinski, Jan, Madsen, Michael J., Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, Mavroudis, Dimitrios, Milne, Roger L., Taib, Nur Aishah Mohd, Morra, Anna, Muir, Kenneth, Obi, Nadia, Osorio, Ana, Park-Simon, Tjoung-Won, Peterlongo, Paolo, Radice, Paolo, Saloustros, Emmanouil, Sawyer, Elinor J., Schmutzler, Rita K., Shah, Mitul, Sim, Xueling, Southey, Melissa C., Thorne, Heather, Tomlinson, Ian, Torres, Diana, Truong, Therese, Yip, Cheng Har, Spurdle, Amanda B., Vreeswijk, Maaike P. G., Dunning, Alison M., Garcia-Closas, Montserrat, Pharoah, Paul D. P., Kvist, Anders, Muranen, Taru A., Nevanlinna, Heli, Teo, Soo Hwang, Devilee, Peter, Schmidt, Marjanka K., and Easton, Douglas F.
Abstract: IMPORTANCE Rare germline genetic variants in several genes are associated with increased breast cancer (BC) risk, but their precise contributions to different disease subtypes are unclear. This information is relevant to guidelines for gene panel testing and risk prediction. OBJECTIVE To characterize tumors associated with BC susceptibility genes in large-scale population- or hospital-based studies. DESIGN, SETTING, AND PARTICIPANTS The multicenter, international case-control analysis of the BRIDGES study included 42 680 patients and 46 387 control participants, comprising women aged 18 to 79 years who were sampled independently of family history from 38 studies. Studies were conducted between 1991and 2016. Sequencing and analysis took place between 2016 and 2021. EXPOSURES Protein-truncating variants and likely pathogenic missense variants in ATM, BARD1, BRCA1, BRCA2, CHEK2, PALB2, RAD51C, RAD51D, and TP53. MAIN OUTCOMES AND MEASURES The intrinsic-like BC subtypes as defined by estrogen receptor, progesterone receptor, and ERBB2 (formerly known as HER2) status, and tumor grade; morphology; size; stage; lymph node involvement; subtype-specific odds ratios (ORs) for carrying protein-truncating variants and pathogenic missense variants in the 9 BC susceptibility genes. RESULTS The mean (SD) ages at interview (control participants) and diagnosis (cases) were 55.1(11.9) and 55.8 (10.6) years, respectively; all participants were of European or East Asian ethnicity. There was substantial heterogeneity in the distribution of intrinsic subtypes by gene. RAD51C, RAD51D, and BARD1 variants were associated mainly with triple-negative disease (OR, 6.19 [95% CI, 3.17-12.12]; OR, 6.19 [95% CI, 2.99-12.79]; and OR, 10.05 [95% CI, 5.27-19.19], respectively). CHEK2 variants were associated with all subtypes (with ORs ranging from 2.21-3.17) except for triple-negative disease. For ATM variants, the association was strongest for the hormone receptor (HR)(+)ERBB2(-) high-grade subtype
Published: 2022

46. Breast cancer risks associated with missense variants in breast cancer susceptibility genes

Author: Dorling, Leila, Carvalho, Sara, Allen, Jamie, Parsons, Michael T, Fortuno, Cristina, González-Neira, Anna, Heijl, Stephan M., Adank, Muriel A., Ahearn, Thomas U, Andrulis, Irene L., Auvinen, Päivi, Becher, Heiko, Beckmann, Matthias W., Behrens, Sabine, Bermisheva, Marina, Bogdanova, Natalia V., Bojesen, Stig E., Bolla, Manjeet K., Bremer, Michael, Briceno, Ignacio, Camp, Nicola J, Campbell, Archie, Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Chenevix-Trench, Georgia, Collée, J Margriet, Czene, Kamila, Dennis, Joe, Dörk, Thilo, Eriksson, Mikael, Evans, D. Gareth, Fasching, Peter A., Figueroa, Jonine, Flyger, Henrik, Gabrielson, Marike, Gago-Dominguez, Manuela, García-Closas, Montserrat, Giles, Graham G, Glendon, Gord, Guénel, Pascal, Gündert, Melanie, Hadjisavvas, Andreas, Hahnen, Eric, Hall, Per, Hamann, Ute, Harkness, Elaine F., Hartman, Mikael, Hogervorst, Frans B L, Hollestelle, Antoinette, Hoppe, Reiner, Howell, Anthony, Jakubowska, Anna, Jung, Audrey, Khusnutdinova, Elza, Kim, Sung-Won, Ko, Yon-Dschun, Kristensen, Vessela N, Lakeman, Inge M. M., Li, Jingmei, Lindblom, Annika, Loizidou, Maria A., Lophatananon, Artitaya, Lubiński, Jan, Luccarini, Craig, Madsen, Michael J., Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, Mavroudis, Dimitrios, Milne, Roger L, Taib, Nur Aishah Mohd, Muir, Kenneth, Nevanlinna, Heli, Newman, William G., Oosterwijk, Jan C, Park, Sue K, Peterlongo, Paolo, Radice, Paolo, Saloustros, Emmanouil, Sawyer, Elinor J., Schmutzler, Rita K., Shah, Mitul, Sim, Xueling, Southey, Melissa C, Surowy, Harald, Suvanto, Maija, Tomlinson, Ian, Torres, Diana, Truong, Thérèse, van Asperen, Christi J, Waltes, Regina, Wang, Qin, Yang, Xiaohong R, Pharoah, Paul D P, Schmidt, Marjanka K., Benitez, Javier, Vroling, Bas, Dunning, Alison M., Teo, Soo Hwang, Kvist, Anders, de la Hoya, Miguel, Devilee, Peter, Spurdle, Amanda B, Vreeswijk, Maaike P G, Easton, Douglas F., Dorling, Leila, Carvalho, Sara, Allen, Jamie, Parsons, Michael T, Fortuno, Cristina, González-Neira, Anna, Heijl, Stephan M., Adank, Muriel A., Ahearn, Thomas U, Andrulis, Irene L., Auvinen, Päivi, Becher, Heiko, Beckmann, Matthias W., Behrens, Sabine, Bermisheva, Marina, Bogdanova, Natalia V., Bojesen, Stig E., Bolla, Manjeet K., Bremer, Michael, Briceno, Ignacio, Camp, Nicola J, Campbell, Archie, Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Chenevix-Trench, Georgia, Collée, J Margriet, Czene, Kamila, Dennis, Joe, Dörk, Thilo, Eriksson, Mikael, Evans, D. Gareth, Fasching, Peter A., Figueroa, Jonine, Flyger, Henrik, Gabrielson, Marike, Gago-Dominguez, Manuela, García-Closas, Montserrat, Giles, Graham G, Glendon, Gord, Guénel, Pascal, Gündert, Melanie, Hadjisavvas, Andreas, Hahnen, Eric, Hall, Per, Hamann, Ute, Harkness, Elaine F., Hartman, Mikael, Hogervorst, Frans B L, Hollestelle, Antoinette, Hoppe, Reiner, Howell, Anthony, Jakubowska, Anna, Jung, Audrey, Khusnutdinova, Elza, Kim, Sung-Won, Ko, Yon-Dschun, Kristensen, Vessela N, Lakeman, Inge M. M., Li, Jingmei, Lindblom, Annika, Loizidou, Maria A., Lophatananon, Artitaya, Lubiński, Jan, Luccarini, Craig, Madsen, Michael J., Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, Mavroudis, Dimitrios, Milne, Roger L, Taib, Nur Aishah Mohd, Muir, Kenneth, Nevanlinna, Heli, Newman, William G., Oosterwijk, Jan C, Park, Sue K, Peterlongo, Paolo, Radice, Paolo, Saloustros, Emmanouil, Sawyer, Elinor J., Schmutzler, Rita K., Shah, Mitul, Sim, Xueling, Southey, Melissa C, Surowy, Harald, Suvanto, Maija, Tomlinson, Ian, Torres, Diana, Truong, Thérèse, van Asperen, Christi J, Waltes, Regina, Wang, Qin, Yang, Xiaohong R, Pharoah, Paul D P, Schmidt, Marjanka K., Benitez, Javier, Vroling, Bas, Dunning, Alison M., Teo, Soo Hwang, Kvist, Anders, de la Hoya, Miguel, Devilee, Peter, Spurdle, Amanda B, Vreeswijk, Maaike P G, and Easton, Douglas F.
Abstract: Background: Protein truncating variants in ATM, BRCA1, BRCA2, CHEK2, and PALB2 are associated with increased breast cancer risk, but risks associated with missense variants in these genes are uncertain. Methods: We analyzed data on 59,639 breast cancer cases and 53,165 controls from studies participating in the Breast Cancer Association Consortium BRIDGES project. We sampled training (80%) and validation (20%) sets to analyze rare missense variants in ATM (1146 training variants), BRCA1 (644), BRCA2 (1425), CHEK2 (325), and PALB2 (472). We evaluated breast cancer risks according to five in silico prediction-of-deleteriousness algorithms, functional protein domain, and frequency, using logistic regression models and also mixture models in which a subset of variants was assumed to be risk-associated. Results: The most predictive in silico algorithms were Helix (BRCA1, BRCA2 and CHEK2) and CADD (ATM). Increased risks appeared restricted to functional protein domains for ATM (FAT and PIK domains) and BRCA1 (RING and BRCT domains). For ATM, BRCA1, and BRCA2, data were compatible with small subsets (approximately 7%, 2%, and 0.6%, respectively) of rare missense variants giving similar risk to those of protein truncating variants in the same gene. For CHEK2, data were more consistent with a large fraction (approximately 60%) of rare missense variants giving a lower risk (OR 1.75, 95% CI (1.47–2.08)) than CHEK2 protein truncating variants. There was little evidence for an association with risk for missense variants in PALB2. The best fitting models were well calibrated in the validation set. Conclusions: These results will inform risk prediction models and the selection of candidate variants for functional assays and could contribute to the clinical reporting of gene panel testing for breast cancer susceptibility.
Published: 2022

47. Breast cancer risks associated with missense variants in breast cancer susceptibility genes

Author: Dorling, Leila, Carvalho, Sara, Allen, Jamie, Parsons, Michael T, Fortuno, Cristina, González-Neira, Anna, Heijl, Stephan M., Adank, Muriel A., Ahearn, Thomas U, Andrulis, Irene L., Auvinen, Päivi, Becher, Heiko, Beckmann, Matthias W., Behrens, Sabine, Bermisheva, Marina, Bogdanova, Natalia V., Bojesen, Stig E., Bolla, Manjeet K., Bremer, Michael, Briceno, Ignacio, Camp, Nicola J, Campbell, Archie, Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Chenevix-Trench, Georgia, Collée, J Margriet, Czene, Kamila, Dennis, Joe, Dörk, Thilo, Eriksson, Mikael, Evans, D. Gareth, Fasching, Peter A., Figueroa, Jonine, Flyger, Henrik, Gabrielson, Marike, Gago-Dominguez, Manuela, García-Closas, Montserrat, Giles, Graham G, Glendon, Gord, Guénel, Pascal, Gündert, Melanie, Hadjisavvas, Andreas, Hahnen, Eric, Hall, Per, Hamann, Ute, Harkness, Elaine F., Hartman, Mikael, Hogervorst, Frans B L, Hollestelle, Antoinette, Hoppe, Reiner, Howell, Anthony, Jakubowska, Anna, Jung, Audrey, Khusnutdinova, Elza, Kim, Sung-Won, Ko, Yon-Dschun, Kristensen, Vessela N, Lakeman, Inge M. M., Li, Jingmei, Lindblom, Annika, Loizidou, Maria A., Lophatananon, Artitaya, Lubiński, Jan, Luccarini, Craig, Madsen, Michael J., Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, Mavroudis, Dimitrios, Milne, Roger L, Taib, Nur Aishah Mohd, Muir, Kenneth, Nevanlinna, Heli, Newman, William G., Oosterwijk, Jan C, Park, Sue K, Peterlongo, Paolo, Radice, Paolo, Saloustros, Emmanouil, Sawyer, Elinor J., Schmutzler, Rita K., Shah, Mitul, Sim, Xueling, Southey, Melissa C, Surowy, Harald, Suvanto, Maija, Tomlinson, Ian, Torres, Diana, Truong, Thérèse, van Asperen, Christi J, Waltes, Regina, Wang, Qin, Yang, Xiaohong R, Pharoah, Paul D P, Schmidt, Marjanka K., Benitez, Javier, Vroling, Bas, Dunning, Alison M., Teo, Soo Hwang, Kvist, Anders, de la Hoya, Miguel, Devilee, Peter, Spurdle, Amanda B, Vreeswijk, Maaike P G, Easton, Douglas F., Dorling, Leila, Carvalho, Sara, Allen, Jamie, Parsons, Michael T, Fortuno, Cristina, González-Neira, Anna, Heijl, Stephan M., Adank, Muriel A., Ahearn, Thomas U, Andrulis, Irene L., Auvinen, Päivi, Becher, Heiko, Beckmann, Matthias W., Behrens, Sabine, Bermisheva, Marina, Bogdanova, Natalia V., Bojesen, Stig E., Bolla, Manjeet K., Bremer, Michael, Briceno, Ignacio, Camp, Nicola J, Campbell, Archie, Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Chenevix-Trench, Georgia, Collée, J Margriet, Czene, Kamila, Dennis, Joe, Dörk, Thilo, Eriksson, Mikael, Evans, D. Gareth, Fasching, Peter A., Figueroa, Jonine, Flyger, Henrik, Gabrielson, Marike, Gago-Dominguez, Manuela, García-Closas, Montserrat, Giles, Graham G, Glendon, Gord, Guénel, Pascal, Gündert, Melanie, Hadjisavvas, Andreas, Hahnen, Eric, Hall, Per, Hamann, Ute, Harkness, Elaine F., Hartman, Mikael, Hogervorst, Frans B L, Hollestelle, Antoinette, Hoppe, Reiner, Howell, Anthony, Jakubowska, Anna, Jung, Audrey, Khusnutdinova, Elza, Kim, Sung-Won, Ko, Yon-Dschun, Kristensen, Vessela N, Lakeman, Inge M. M., Li, Jingmei, Lindblom, Annika, Loizidou, Maria A., Lophatananon, Artitaya, Lubiński, Jan, Luccarini, Craig, Madsen, Michael J., Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, Mavroudis, Dimitrios, Milne, Roger L, Taib, Nur Aishah Mohd, Muir, Kenneth, Nevanlinna, Heli, Newman, William G., Oosterwijk, Jan C, Park, Sue K, Peterlongo, Paolo, Radice, Paolo, Saloustros, Emmanouil, Sawyer, Elinor J., Schmutzler, Rita K., Shah, Mitul, Sim, Xueling, Southey, Melissa C, Surowy, Harald, Suvanto, Maija, Tomlinson, Ian, Torres, Diana, Truong, Thérèse, van Asperen, Christi J, Waltes, Regina, Wang, Qin, Yang, Xiaohong R, Pharoah, Paul D P, Schmidt, Marjanka K., Benitez, Javier, Vroling, Bas, Dunning, Alison M., Teo, Soo Hwang, Kvist, Anders, de la Hoya, Miguel, Devilee, Peter, Spurdle, Amanda B, Vreeswijk, Maaike P G, and Easton, Douglas F.
Abstract: Background: Protein truncating variants in ATM, BRCA1, BRCA2, CHEK2, and PALB2 are associated with increased breast cancer risk, but risks associated with missense variants in these genes are uncertain. Methods: We analyzed data on 59,639 breast cancer cases and 53,165 controls from studies participating in the Breast Cancer Association Consortium BRIDGES project. We sampled training (80%) and validation (20%) sets to analyze rare missense variants in ATM (1146 training variants), BRCA1 (644), BRCA2 (1425), CHEK2 (325), and PALB2 (472). We evaluated breast cancer risks according to five in silico prediction-of-deleteriousness algorithms, functional protein domain, and frequency, using logistic regression models and also mixture models in which a subset of variants was assumed to be risk-associated. Results: The most predictive in silico algorithms were Helix (BRCA1, BRCA2 and CHEK2) and CADD (ATM). Increased risks appeared restricted to functional protein domains for ATM (FAT and PIK domains) and BRCA1 (RING and BRCT domains). For ATM, BRCA1, and BRCA2, data were compatible with small subsets (approximately 7%, 2%, and 0.6%, respectively) of rare missense variants giving similar risk to those of protein truncating variants in the same gene. For CHEK2, data were more consistent with a large fraction (approximately 60%) of rare missense variants giving a lower risk (OR 1.75, 95% CI (1.47–2.08)) than CHEK2 protein truncating variants. There was little evidence for an association with risk for missense variants in PALB2. The best fitting models were well calibrated in the validation set. Conclusions: These results will inform risk prediction models and the selection of candidate variants for functional assays and could contribute to the clinical reporting of gene panel testing for breast cancer susceptibility.
Published: 2022

48. Polygenic risk modeling for prediction of epithelial ovarian cancer risk

Author: Dareng, Eileen O., Tyrer, Jonathan P., Barnes, Daniel R., Jones, Michelle R., Yang, Xin, Aben, Katja K. H., Adank, Muriel A., Agata, Simona, Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Aravantinos, Gerasimos, Arun, Banu K., Augustinsson, Annelie, Balmana, Judith, Bandera, Elisa, V, Barkardottir, Rosa B., Barrowdale, Daniel, Beckmann, Matthias W., Beeghly-Fadiel, Alicia, Benitez, Javier, Bermisheva, Marina, Bernardini, Marcus Q., Bjorge, Line, Black, Amanda, Bogdanova, Natalia, V, Bonanni, Bernardo, Borg, Ake, Brenton, James D., Budzilowska, Agnieszka, Butzow, Ralf, Buys, Saundra S., Cai, Hui, Caligo, Maria A., Campbell, Ian, Cannioto, Rikki, Cassingham, Hayley, Chang-Claude, Jenny, Chanock, Stephen J., Chen, Kexin, Chiew, Yoke-Eng, Chung, Wendy K., Claes, Kathleen B. M., Colonna, Sarah, Cook, Linda S., Couch, Fergus J., Daly, Mary B., Dao, Fanny, Davies, Eleanor, de la Hoya, Miguel, de Putter, Robin, Dennis, Joe, DePersia, Allison, Devilee, Peter, Diez, Orland, Ding, Yuan Chun, Doherty, Jennifer A., Domchek, Susan M., Dork, Thilo, du Bois, Andreas, Durst, Matthias, Eccles, Diana M., Eliassen, Heather A., Engel, Christoph, Evans, Gareth D., Fasching, Peter A., Flanagan, James M., Fortner, ReneeT, Machackova, Eva, Friedman, Eitan, Ganz, Patricia A., Garber, Judy, Gensini, Francesca, Giles, Graham G., Glendon, Gord, Godwin, Andrew K., Goodman, Marc T., Greene, Mark H., Gronwald, Jacek, Group, Opal Study, Group, AOCS, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hamann, Ute, Hansen, Thomas V. O., Harris, Holly R., Hartman, Mikael, Heitz, Florian, Hildebrandt, Michelle A. T., Hogdall, Estrid, Hogdall, Claus K., Hopper, John L., Huang, Ruea-Yea, Huff, Chad, Hulick, Peter J., Huntsman, David G., Imyanitov, Evgeny N., Isaacs, Claudine, Jakubowska, Anna, James, Paul A., Janavicius, Ramunas, Jensen, Allan, Johannsson, Oskar Th, John, Esther M., Jones, Michael E., Kang, Daehee, Karlan, Beth Y., Karnezis, Anthony, Kelemen, Linda E., Khusnutdinova, Elza, Kiemeney, Lambertus A., Kim, Byoung-Gie, Kjaer, Susanne K., Komenaka, Ian, Kupryjanczyk, Jolanta, Kurian, Allison W., Kwong, Ava, Lambrechts, Diether, Larson, Melissa C., Lazaro, Conxi, Le, Nhu D., Leslie, Goska, Lester, Jenny, Lesueur, Fabienne, Levine, Douglas A., Li, Lian, Li, Jingmei, Loud, Jennifer T., Lu, Karen H., Mai, Phuong L., Manoukian, Siranoush, Marks, Jeffrey R., KimMatsuno, Rayna, Matsuo, Keitaro, May, Taymaa, McGuffog, Lesley, McLaughlin, John R., McNeish, Iain A., Mebirouk, Noura, Menon, Usha, Miller, Austin, Milne, Roger L., Minlikeeva, Albina, Modugno, Francesmary, Montagna, Marco, Moysich, Kirsten B., Munro, Elizabeth, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Yie, Joanne Ngeow Yuen, Nielsen, Henriette Roed, Nielsen, Finn C., Nikitina-Zake, Liene, Odunsi, Kunle, Offit, Kenneth, Olah, Edith, Olbrecht, Siel, Olopade, Olufunmilayo, I, Olson, Sara H., Olsson, Hakan, Osorio, Ana, Papi, Laura, Park, Sue K., Parsons, Michael T., Pathak, Harsha, Pedersen, Inge Sokilde, Peixoto, Ana, Pejovic, Tanja, Perez-Segura, Pedro, Permuth, Jennifer B., Peshkin, Beth, Peterlongo, Paolo, Piskorz, Anna, Prokofyeva, Darya, Radice, Paolo, Rantala, Johanna, Riggan, Marjorie J., Risch, Harvey A., Rodriguez-Antona, Cristina, Ross, Eric, Rossing, Mary Anne, Runnebaum, Ingo, Sandler, Dale P., Santamarina, Marta, Soucy, Penny, Schmutzler, Rita K., Setiawan, V. Wendy, Shan, Kang, Sieh, Weiva, Simard, Jacques, Singer, Christian F., Sokolenko, Anna P., Song, Honglin, Southey, Melissa C., Steed, Helen, Stoppa-Lyonnet, Dominique, Sutphen, Rebecca, Swerdlow, Anthony J., Tan, Yen Yen, Teixeira, Manuel R., Teo, Soo Hwang, Terry, Kathryn L., BethTerry, Mary, Thomassen, Mads, Thompson, Pamela J., Thomsen, Liv Cecilie Vestrheim, Thull, Darcy L., Tischkowitz, Marc, Titus, Linda, Toland, Amanda E., Torres, Diana, Trabert, Britton, Travis, Ruth, Tung, Nadine, Tworoger, Shelley S., Valen, Ellen, van Altena, Anne M., van der Hout, Annemieke H., Nieuwenhuysen, ElsVan, van Rensburg, Elizabeth J., Vega, Ana, Edwards, Digna Velez, Vierkant, Robert A., Wang, Frances, Wappenschmidt, Barbara, Webb, Penelope M., Weinberg, Clarice R., Weitzel, Jeffrey N., Wentzensen, Nicolas, White, Emily, Whittemore, Alice S., Winham, Stacey J., Wolk, Alicja, Woo, Yin-Ling, Wu, Anna H., Yan, Li, Yannoukakos, Drakoulis, Zavaglia, Katia M., Zheng, Wei, Ziogas, Argyrios, Zorn, Kristin K., Kleibl, Zdenek, Easton, Douglas, Lawrenson, Kate, DeFazio, Anna, Sellers, Thomas A., Ramus, Susan J., Pearce, Celeste L., Monteiro, Alvaro N., Cunningham, Julie, Goode, Ellen L., Schildkraut, Joellen M., Berchuck, Andrew, Chenevix-Trench, Georgia, Gayther, Simon A., Antoniou, Antonis C., Pharoah, Paul D. P., Dareng, Eileen O., Tyrer, Jonathan P., Barnes, Daniel R., Jones, Michelle R., Yang, Xin, Aben, Katja K. H., Adank, Muriel A., Agata, Simona, Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Aravantinos, Gerasimos, Arun, Banu K., Augustinsson, Annelie, Balmana, Judith, Bandera, Elisa, V, Barkardottir, Rosa B., Barrowdale, Daniel, Beckmann, Matthias W., Beeghly-Fadiel, Alicia, Benitez, Javier, Bermisheva, Marina, Bernardini, Marcus Q., Bjorge, Line, Black, Amanda, Bogdanova, Natalia, V, Bonanni, Bernardo, Borg, Ake, Brenton, James D., Budzilowska, Agnieszka, Butzow, Ralf, Buys, Saundra S., Cai, Hui, Caligo, Maria A., Campbell, Ian, Cannioto, Rikki, Cassingham, Hayley, Chang-Claude, Jenny, Chanock, Stephen J., Chen, Kexin, Chiew, Yoke-Eng, Chung, Wendy K., Claes, Kathleen B. M., Colonna, Sarah, Cook, Linda S., Couch, Fergus J., Daly, Mary B., Dao, Fanny, Davies, Eleanor, de la Hoya, Miguel, de Putter, Robin, Dennis, Joe, DePersia, Allison, Devilee, Peter, Diez, Orland, Ding, Yuan Chun, Doherty, Jennifer A., Domchek, Susan M., Dork, Thilo, du Bois, Andreas, Durst, Matthias, Eccles, Diana M., Eliassen, Heather A., Engel, Christoph, Evans, Gareth D., Fasching, Peter A., Flanagan, James M., Fortner, ReneeT, Machackova, Eva, Friedman, Eitan, Ganz, Patricia A., Garber, Judy, Gensini, Francesca, Giles, Graham G., Glendon, Gord, Godwin, Andrew K., Goodman, Marc T., Greene, Mark H., Gronwald, Jacek, Group, Opal Study, Group, AOCS, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hamann, Ute, Hansen, Thomas V. O., Harris, Holly R., Hartman, Mikael, Heitz, Florian, Hildebrandt, Michelle A. T., Hogdall, Estrid, Hogdall, Claus K., Hopper, John L., Huang, Ruea-Yea, Huff, Chad, Hulick, Peter J., Huntsman, David G., Imyanitov, Evgeny N., Isaacs, Claudine, Jakubowska, Anna, James, Paul A., Janavicius, Ramunas, Jensen, Allan, Johannsson, Oskar Th, John, Esther M., Jones, Michael E., Kang, Daehee, Karlan, Beth Y., Karnezis, Anthony, Kelemen, Linda E., Khusnutdinova, Elza, Kiemeney, Lambertus A., Kim, Byoung-Gie, Kjaer, Susanne K., Komenaka, Ian, Kupryjanczyk, Jolanta, Kurian, Allison W., Kwong, Ava, Lambrechts, Diether, Larson, Melissa C., Lazaro, Conxi, Le, Nhu D., Leslie, Goska, Lester, Jenny, Lesueur, Fabienne, Levine, Douglas A., Li, Lian, Li, Jingmei, Loud, Jennifer T., Lu, Karen H., Mai, Phuong L., Manoukian, Siranoush, Marks, Jeffrey R., KimMatsuno, Rayna, Matsuo, Keitaro, May, Taymaa, McGuffog, Lesley, McLaughlin, John R., McNeish, Iain A., Mebirouk, Noura, Menon, Usha, Miller, Austin, Milne, Roger L., Minlikeeva, Albina, Modugno, Francesmary, Montagna, Marco, Moysich, Kirsten B., Munro, Elizabeth, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Yie, Joanne Ngeow Yuen, Nielsen, Henriette Roed, Nielsen, Finn C., Nikitina-Zake, Liene, Odunsi, Kunle, Offit, Kenneth, Olah, Edith, Olbrecht, Siel, Olopade, Olufunmilayo, I, Olson, Sara H., Olsson, Hakan, Osorio, Ana, Papi, Laura, Park, Sue K., Parsons, Michael T., Pathak, Harsha, Pedersen, Inge Sokilde, Peixoto, Ana, Pejovic, Tanja, Perez-Segura, Pedro, Permuth, Jennifer B., Peshkin, Beth, Peterlongo, Paolo, Piskorz, Anna, Prokofyeva, Darya, Radice, Paolo, Rantala, Johanna, Riggan, Marjorie J., Risch, Harvey A., Rodriguez-Antona, Cristina, Ross, Eric, Rossing, Mary Anne, Runnebaum, Ingo, Sandler, Dale P., Santamarina, Marta, Soucy, Penny, Schmutzler, Rita K., Setiawan, V. Wendy, Shan, Kang, Sieh, Weiva, Simard, Jacques, Singer, Christian F., Sokolenko, Anna P., Song, Honglin, Southey, Melissa C., Steed, Helen, Stoppa-Lyonnet, Dominique, Sutphen, Rebecca, Swerdlow, Anthony J., Tan, Yen Yen, Teixeira, Manuel R., Teo, Soo Hwang, Terry, Kathryn L., BethTerry, Mary, Thomassen, Mads, Thompson, Pamela J., Thomsen, Liv Cecilie Vestrheim, Thull, Darcy L., Tischkowitz, Marc, Titus, Linda, Toland, Amanda E., Torres, Diana, Trabert, Britton, Travis, Ruth, Tung, Nadine, Tworoger, Shelley S., Valen, Ellen, van Altena, Anne M., van der Hout, Annemieke H., Nieuwenhuysen, ElsVan, van Rensburg, Elizabeth J., Vega, Ana, Edwards, Digna Velez, Vierkant, Robert A., Wang, Frances, Wappenschmidt, Barbara, Webb, Penelope M., Weinberg, Clarice R., Weitzel, Jeffrey N., Wentzensen, Nicolas, White, Emily, Whittemore, Alice S., Winham, Stacey J., Wolk, Alicja, Woo, Yin-Ling, Wu, Anna H., Yan, Li, Yannoukakos, Drakoulis, Zavaglia, Katia M., Zheng, Wei, Ziogas, Argyrios, Zorn, Kristin K., Kleibl, Zdenek, Easton, Douglas, Lawrenson, Kate, DeFazio, Anna, Sellers, Thomas A., Ramus, Susan J., Pearce, Celeste L., Monteiro, Alvaro N., Cunningham, Julie, Goode, Ellen L., Schildkraut, Joellen M., Berchuck, Andrew, Chenevix-Trench, Georgia, Gayther, Simon A., Antoniou, Antonis C., and Pharoah, Paul D. P.
Abstract: Polygenic risk scores (PRS) for epithelial ovarian cancer (EOC) have the potential to improve risk stratification. Joint estimation of Single Nucleotide Polymorphism (SNP) effects in models could improve predictive performance over standard approaches of PRS construction. Here, we implemented computationally efficient, penalized, logistic regression models (lasso, elastic net, stepwise) to individual level genotype data and a Bayesian framework with continuous shrinkage, "select and shrink for summary statistics" (S4), to summary level data for epithelial non-mucinous ovarian cancer risk prediction. We developed the models in a dataset consisting of 23,564 non-mucinous EOC cases and 40,138 controls participating in the Ovarian Cancer Association Consortium (OCAC) and validated the best models in three populations of different ancestries: prospective data from 198,101 women of European ancestries; 7,669 women of East Asian ancestries; 1,072 women of African ancestries, and in 18,915 BRCA1 and 12,337 BRCA2 pathogenic variant carriers of European ancestries. In the external validation data, the model with the strongest association for non-mucinous EOC risk derived from the OCAC model development data was the S4 model (27,240 SNPs) with odds ratios (OR) of 1.38 (95% CI: 1.28-1.48, AUC: 0.588) per unit standard deviation, in women of European ancestries; 1.14 (95% CI: 1.08-1.19, AUC: 0.538) in women of East Asian ancestries; 1.38 (95% CI: 1.21-1.58, AUC: 0.593) in women of African ancestries; hazard ratios of 1.36 (95% CI: 1.29-1.43, AUC: 0.592) in BRCA1 pathogenic variant carriers and 1.49 (95% CI: 1.35-1.64, AUC: 0.624) in BRCA2 pathogenic variant carriers. Incorporation of the S4 PRS in risk prediction models for ovarian cancer may have clinical utility in ovarian cancer prevention programs.
Published: 2022
Full Text: View/download PDF

49. Prevalencia de patologías fonoaudiológicas en el Centro de Desarrollo Infantil de la Universidad de Cuenca, CEDIUC. 2016- 2019

Author: Ortega Mosquera, Paola Gabriela, Riera Riera, Pamela Michelle, Tapia Torres, Diana Carolina, Ortega Mosquera, Paola Gabriela, Riera Riera, Pamela Michelle, and Tapia Torres, Diana Carolina
Abstract: BACKGROUND: Phonoaudiological pathologies are alterations in one or more of the areas of phonoaudiology, such as: language, speech, voice, swallowing and hearing. Among the most relevant are: late language onset, language development disorder, speech sounds disorder, dysphonia, dysphagia and hypoacusis. To achieve this research, clinical histories and phonoaudiological reports of children between the ages of 3 years 11 months to 5 years 11 months, who attended the phonoaudiology area during the period 2016 - 2019, were reviewed. OBJECTIVE: To determine the prevalence of phonoaudiological pathologies in the CEDIUC 2016-2019 phonoaudiology area. METHOD: The analysis of the results was performed using Microsoft Excel program version 2010 and SPSS; for quantitative variables through statistical analysis of measures of central tendency. For qualitative variables, frequencies and percentages were used. RESULTS: The present study registered a sample of 117 participants, including clinical histories and speech therapy reports of CEDIUC assistants in the period 2016-2019. The prevalent sex was male with 65.81%, the age range with the highest rate of phonoaudiological pathologies was from 3 years to 3 years 11 months with 46.15%. The most prevalent phonoaudiological pathologies are: late onset of language (24.80%) and phonetic speech sounds disorder (25.65%), followed by dysphagia without specification (0.85%) and oral dysphagia (0.85%), in addition to transmission hypoacusis and without specification (0.85%) and additionally dysphonia (1.70%).
Published: 2022

50. Prevalencia de patologías fonoaudiológicas en el Centro de Desarrollo Infantil de la Universidad de Cuenca, CEDIUC. 2016- 2019

Author: Ortega Mosquera, Paola Gabriela, Riera Riera, Pamela Michelle, Tapia Torres, Diana Carolina, Ortega Mosquera, Paola Gabriela, Riera Riera, Pamela Michelle, and Tapia Torres, Diana Carolina
Abstract: BACKGROUND: Phonoaudiological pathologies are alterations in one or more of the areas of phonoaudiology, such as: language, speech, voice, swallowing and hearing. Among the most relevant are: late language onset, language development disorder, speech sounds disorder, dysphonia, dysphagia and hypoacusis. To achieve this research, clinical histories and phonoaudiological reports of children between the ages of 3 years 11 months to 5 years 11 months, who attended the phonoaudiology area during the period 2016 - 2019, were reviewed. OBJECTIVE: To determine the prevalence of phonoaudiological pathologies in the CEDIUC 2016-2019 phonoaudiology area. METHOD: The analysis of the results was performed using Microsoft Excel program version 2010 and SPSS; for quantitative variables through statistical analysis of measures of central tendency. For qualitative variables, frequencies and percentages were used. RESULTS: The present study registered a sample of 117 participants, including clinical histories and speech therapy reports of CEDIUC assistants in the period 2016-2019. The prevalent sex was male with 65.81%, the age range with the highest rate of phonoaudiological pathologies was from 3 years to 3 years 11 months with 46.15%. The most prevalent phonoaudiological pathologies are: late onset of language (24.80%) and phonetic speech sounds disorder (25.65%), followed by dysphagia without specification (0.85%) and oral dysphagia (0.85%), in addition to transmission hypoacusis and without specification (0.85%) and additionally dysphonia (1.70%).
Published: 2022

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Publication Year Range

Publication Type

Journal

Database

Publisher

397 results on '"Torres, Diana"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources