System size and centrality dependence of the balance function in A + A collisions at sqrt s NN = 17.2 GeV

Electric charge correlations were studied for p+p, C+C, Si+Si and centrality selected Pb+Pb collisions at sqrt s_NN = 17.2$ GeV with the NA49 large acceptance detector at the CERN-SPS. In particular, long range pseudo-rapidity correlations of oppositely charged particles were measured using the Balance Function method. The width of the Balance Function decreases with increasing system size and centrality of the reactions. This decrease could be related to an increasing delay of hadronization in central Pb+Pb collisions

System size and centrality dependence of the balance function in A+A collisions at sqrt[sNN]=17.2 GeV

Electric charge correlations were studied for p+p, C+C, Si+Si, and centrality selected Pb+Pb collisions at sqrt[sNN]=17.2 GeV with the NA49 large acceptance detector at the CERN SPS. In particular, long-range pseudorapidity correlations of oppositely charged particles were measured using the balance function method. The width of the balance function decreases with increasing system size and centrality of the reactions. This decrease could be related to an increasing delay of hadronization in central Pb+Pb collisions

Ikonosfera hierofanii. Dom a sacrum. Transmisja kulturowa artefaktów sztuki ludowej w rejestracji fotograficznej i antropologicznym opracowaniu tekstowym.

Andrzej Białkowski Wprowadzenie do Ikonosfery hierofanii W tekście przedstawiono główne założenia merytoryczne „Dom a sacrum. Transmisja kulturowa artefaktów sztuki ludowej w rejestracji fotograficznej i antropologicznym opracowaniu tekstowym”. We wstępie autor nawiązuje do definicji sacrum i znaczenia świętości w kulturze. To także indywidualistyczna refleksja na temat hierofanii, religijności, tradycji i estetyki. Artykuł stanowi również analizę spostrzeżeń dotyczących współczesnego postrzegania sacrum w odniesieniu do fotografii dokumentujących funkcjonujące do dziś domowe ołtarze oraz wprowadzenie do tekstów przygotowanych przez grono antropologów zaproszonych do realizacji tego projektu Piotr Wypych Święty kąt... Artykuł przedstawia opis ołtarza domowego z domu dziadków autora, który znajdował się w części pokoju zwanej „świętym kątem”. We wstępie przedstawiono nazewnictwo, genezę i zarys historyczny tego zjawiska na przestrzeni lat, następnie autor kontynuuje opis wyglądu i programu obiektów ikonograficznych wchodzących w skład tej „kapliczki”. Jarosław Eichstaedt Ikonosfera i współczesna religijność Współczesna kultura wizualna w konfrontacji z religijnością ujawnia szereg nowych zjawisk. Kultura popularna, również w środowiskach wiejskich, podąża za trendami transkulturalizmu, zmierzając nie w stronę kultury ludowej, ale konglomeratu i hybrydy. Sacrum może pojawić się wszędzie: w mediach, polityce, sporcie, biznesie, sztuce i we wnętrzach domu. Sacrum wkracza w sferę profanum i przełamuje dychotomię tych dwóch sfer i owocuje sacrofanum. Współczesny człowiek żyje w sacrofanum, sakralizacja i sekularyzacja przenikają się wzajemnie, tworząc dwa aspekty jednej rzeczywistości. W ikonosferze religijnej od dawna podejmowana jest wielka próbę oswojenia nowej estetyki. Dla tej estetyki ważne wydaje się być takie przedstawienie, które koniecznie winno mieć status autentycznego doświadczenia. Mamy więc do czynienia z podmianą wartości, kategorie estetyczne zastępowane są etycznymi. Autentyczność doświadczenia zaświadcza prawdę, legitymizuje, nadaje wartość pozytywną i przekonuje. Krystyna Piątkowska Domowe miejsca sacrum - wrażenia ze świata, którego już prawie nie ma oraz antropologicznych zdarzeń. Esej. Przedstawiam opis projektu Andrzeja Białkowskiego i Piotra Wypycha Ikonosfera Hierofanii. Dom a sacrum. Transmisja kulturowa artefaktów sztuki ludowej w rejestracji fotograficznej i antropologicznym opracowaniu tekstowym. We wstępie autorzy informują, że głównym tematem koncepcji jest zapis, foto-repozytorium, dokumentujący przemiany współczesnej religijności domowej na przykładzie analizy domowych ołtarzy. W tym momencie dwie najważniejsze dla mnie kwestie okazały się założeniami, którymi zajmuję się fotografia i „zapis foto-antropologiczny”. Jakie refleksje wywołują te informacje? Fotografia, podobnie jak nauka i filozofia, konfrontuje nas z różnymi, czasem zaskakującymi przedstawieniami czasu, śmierci, rzeczywistości, istnienia i bytu. Zresztą zobowiązuje nas to nie zapominać o tych, często niewidocznych, rzeczach. Odwołajmy te krótko przedstawione współczesne wypowiedzi o fotografii do dwóch zasadniczo antropologicznych zjawisk - zapytania znanej i cenionej nie tylko w Polsce fotografki Zofii Rydet, a zwłaszcza jej monumentalnej pracy: „Zapis socjologiczny” oraz projektu Andrzeja Białkowskiego i Piotra Wypych, którą nazwałbym „Zapisem antropologicznym AD 2019/2020. Kontynuacja. Świat, który utrwalili i kontynuują A.Białkowski i P.Wypych, ma zupełnie inną fakturę i strukturę aksjologiczną niż u Rydeta - jest rozproszony, fragmentaryczny, zestawiony bez żadnej troski i świadomości semantycznej, na zasadzie połączenia ładne lub ważne artefakty, stanowiące wyspę w gęstej ikonosferze życia codziennego. Nie dość, że kultura przeżywa metamorfozę - ten zawsze dynamiczny proces stał się na tyle intensywny, że być może to, co pozostało badaczom - ratowanie kontekstów i proroctw - w najlepszy możliwy sposób, jest realizowane właśnie przez tego typu procedury i działania etnologiczne. Damian Kasprzyk Natura - kultura - transcendencja. Wokół kompozycji domowego sacrum Przedstawiony komentarz na temat materiału ikonograficznego pozyskanego w Polsce centralnej koncentruje się na zauważonej prawidłowości. W zdecydowanej większości przykłady takie jak malarstwo, krzyż, kapliczka, figurka cygańska, rzeźba drewniana zyskują oprawę i dopełnienie w postaci naturalizmu. Zwykle jest to flora sztuczna, żywa lub suszona. Kompozycje te - z perspektywy ich twórców - stanowią estetyczną i ideologiczną całość, z drugiej strony, choć mamy do czynienia z dwoma odrębnymi składnikami. Wszakże święte obrazy uzyskuje się bez naturalistycznych ozdób, które pojawiają się tylko w domach, w nurcie jakiejś indywidualnej lub środowiskowej potrzeby. Tekst jest próbą odpowiedzi na pytanie, na czym polega istota tej potrzeby, a przede wszystkim skąd ta konsekwencja w budowaniu kontekstu religijnych przedstawień z elementów naturalnych (roślin) czy naśladowania natury. Autor posługuje się koncepcjami estetycznymi, religijnymi i antropologicznymi. W tym ostatnim sięga po opozycję natura - kultura. Katarzyna Orszulak-Dudkowska Dom i sacrum w kulturze polskiej wsi. Tradycja i współczesność. Artykuł przedstawia refleksje nad obecnością i znaczeniem elementów sakralnych w przestrzeni domowej człowieka religijnego w odniesieniu do tradycyjnej polskiej kultury wiejskiej, a także kultury współczesnej. Autorka przedstawia przede wszystkim wiedzę etnograficzną dotyczącą sposobów organizacji przestrzeni życiowej w wiejskim domu, ze szczególnym uwzględnieniem sakralnej funkcji stołu oraz wyglądu i roli tzw. Świętego narożnika i domowego ołtarza. W opisie zawartym w tekście autorka stara się uwzględnić zmiany, jakie zaszły w aranżacji wyposażenia wnętrza domu oraz organizacji przestrzeni sakralnej domu i jego walorów estetycznych. Następnie autorka odwołuje się do dokumentacji fotograficznej ołtarzy znalezionych we współczesnych polskich domach, zgromadzonej w ramach projektu Ikonosfera hierofanii. Dom a sacrum. Transmisja kulturowa artefaktów sztuki ludowej w rejestracji fotograficznej i antropologicznym opracowaniu tekstowym, realizowany w 2019 roku na terenie województwa łódzkiego. Autorka zauważa, że niezależnie od powszechnych przemian kulturowych zachodzących w otaczającym świecie, we współczesnym polskim domu, jako przestrzeni głęboko naznaczonej prywatnością, wielofunkcyjnej, związanej ze stylem życia i indywidualną tożsamością jego mieszkańców, wnętrze nadal pozostaje miejscem zaspokajania potrzeb duchowych i religijnych, a zmieniać mogą się tylko sposoby eksponowania i estetyzowania sacrum. Alicja Woźniak Domowe sacrum w etnograficznym zapisie muzealnika. Tradycja/kontynuacja/innowacja. Moja refleksja jako etnografa - muzealnika na temat współczesnej ikonografii przedstawionej w projekcie Dom i sacrum opiera się na tym, co było, a punktem odniesienia są muzealne materiały archiwalne. Odnosząc się do badań empirycznych, za źródło porównawcze przyjmuję projekt wnętrza na osi czasu, zestawiając go z aktualnymi obrazami prezentowanymi w projekcie. Przedstawię zmiany dotyczące umiejscowienia sacrum w domu, jego estetyki i estetyzacji, czyli „upiększenia” domowego ołtarza. Rozważania dotyczą zarówno strony materialnej, jak i mentalnej, nie oddzielając tego, co wizualne, od indywidualistycznego sposobu myślenia i postrzegania rzeczywistości - jedno jest odbiciem drugiego. Zmieniający się wymiar religijności i potrzeb estetycznych sprawia, że prezentowane w projekcie artefakty, które wypełniają obecne domowe ołtarze, jutro mogą stać się kolekcją muzealną, która będzie stanowić materiał do przyszłych interpretacji. Robert Dzięcielski Domowa ikonosfera sacrum Autor artykułu przedstawia refleksję antropologiczną dotyczącą stanu i przemian tradycyjnie rozumianej domowej ikonosfery sacrum. Transformacja kultury tradycyjnej wpłynęła na zmianę dawnego stosunku do sfery sakralnej. Niepewność i narastające poczucie straty, rozpad dawnych autorytetów, subiektywne podejście do wartości i norm kulturowych, komercjalizacja, rosnące znaczenie wirtualnej rzeczywistości - to tylko niektóre z przyczyn obecnego upadku relacji z ikonosferą religijną. Autor, odwołując się do koncepcji Eliadego, wskazuje, że ludzka potrzeba odbudowy porządku i harmonii metafizycznej, a także pamięć kulturowa, którą można odzyskać i zaktualizować o tradycyjne wartości, są nadal korzystnymi elementami wspierającymi istnienie świętej ikonosfery w przestrzeni domowej. . Potencjał doświadczenia sacrum we współczesnym świecie kryje się w sakralnej postawie człowieka oraz w hierofanicznej sile miejsca i podmiotów. Barnaba Bonati Domowe sacrum - kulinaria pomiędzy domem we Włoszech, a w Polsce Barnaba Bonati, wychowany we Włoszech, a obecnie mieszkający w Polsce, mówi o znaczeniu domowej sfery sakralnej, która rozciąga się między doświadczeniami dwóch kultur. W domu rodzinnym tradycja kulinarna rodziny odgrywała świętą rolę. Obrazy wspólnej celebracji przy stole, utrwalone w pamięci uczestnika, pozwalają autorowi na powrót do tego „świętego czasu” i nieustanne podążanie za nim do dziś. Podstawą siły oddziaływania mentalnych obrazów na tradycje kulinarne są trzy elementy - rodzinny stół, naczynia i wszelkie akcesoria, a przede wszystkim uczestnicy wspólnie spędzający czas i jednocześnie wprowadzający się w doświadczenie sacrum. Autor bardzo osobiście zwraca uwagę, że to ojciec wprowadził go w doświadczenie domowego kulinarnego sacrum. Dzięki temu dziedzictwu wizualna sfera pamięci jest ściśle związana z całą gamą zapamiętanych gustów. Michał Żerkowski Uwagi na temat transmisji kulturowej Zagadnienie transmisji kulturowej ma w historii antropologii kulturowej długą i złożoną historię, sięgającą samych początków dyscypliny, a ukształtowaną w XIX i XX wieku przez kolejne szkoły i podejścia antropologiczne: klasyczny ewolucjonizm, dyfuzjonizm, konfiguracjonizm i studia nad charakterem narodowym w ramach szkoły kultury i osobowości, neoewolucjonizmu i materializmu kulturowego. Współcześnie odnowione zainteresowanie problemem transmisji kulturowej nastąpiło za sprawą interdyscyplinarnych badań nad jego mechanizmami w ramach teorii ewolucji kulturowej, które paradygmatycznie pozostają w kontraście z podejściami konstruktywistycznymi i kulturowymi, które pod koniec XX wieku zdominowały sfera nauk społecznych. Ewolucja kulturowa, rozumiana jako nauka, jest ujednolicona przez zastosowanie logiki ewolucyjnej do opisu społecznie dystrybuowanych i przekazywanych elementów kulturowych (a także materialistycznych), ale jest podzielona przesłankami i zastosowanymi metodologiami.Andrzej Białkowski An introduction to the Iconosphere of Hierophany The text presents the main substantive premises of “Home and Sacrum. Cultural Transmission of Folk Art Artifacts in Photographical Registration and Anthropological Text Study”. In the introduction, the author refers to the definition of the sacred and meaning of holiness in culture. It is also an individualistic reflection on the topic of hierophany, religiosity, tradition and aesthetics. This article is also an analysis of the observations of the contemporary perception of the sacred in reference to photographs documenting the home altars, functioning until today, and an introduction to the texts prepared by a body of anthropologists invited to implement this project. Piotr Wypych Holy corner... The article presents a description of the home altar from the author’s grandparents’ house, which was located in the part of the room called “holy corner”. An introduction includes nomenclature, genesis and historical outline of this phenomenon over the years, whilst the author continues to describe appearance and program of iconographical objects constituting on this “little shrine”. Jarosław Eichstaedt Iconosphere and the contemporary religiosity The contemporary visual culture, when confronted with religiosity, reveals a number of new phenomena. Popular culture, also in rural environments, follows the trends of transculturalism, moving not towards folk culture, but towards a conglomerate and a hybrid. The sacred can appear anywhere: in the media, politics, sports, business, art and in the home interior. The sacred enters sphere of the profane and breaks the dichotomy of these two spheres, the sacrophane bears fruit. Contemporary man lives in the sacrophane, sacralization and secularization interpenetrate each other, constituting two aspects of one reality. In the religious iconosphere, we have long had a great attempt to tame the new aesthetics. What seems important for this aesthetics is such a presentation which must necessarily have the status of an authentic experience. Thus, we are dealing with a substitution of values, aesthetic categories are replaced with ethical ones. The authenticity of experience assures of the truth and reality, authenticity legitimizes, gives positive value and convinces. Krystyna Piątkowska Home places of the sacred - impressions from a world that is almost gone and anthropological experiences. An essay. I present the description of a project created by Andrzej Białkowski and Piotr Wypych, titled Iconosphere of Hierophany. Home and sacrum. Cultural Transmission of Folk Art Artifacts in Photographic Recording and Anthropological Text Study. In the introduction the authors inform that the main theme of the concept is a photo-anthropological record (photo – repository) documenting changes in the contemporary domestic religiousness, based on the example of the analysis of “home sacrum” – home altars constructed in traditional culture on the basis of the artifacts of folk art. At this moment, the two most significant issues for me turned out to be the assumptions I am dealing with photography and a “photo – anthropological record”. What reflections do these information evoke? Photography, similarly to science and philosophy, confronts us with various, sometimes surprising representations of time, death, reality, existence and being. Anyway, it obliges us not to forget about these, often invisible, things. Let’s refer these briefly presented contemporary statements about photography to two essentially anthropological phenomena – a query by the photographer Zofia Rydet, known and valued not only in Poland, and especially to her monumental work: “Sociological Record” and a project by Andrzej Białkowski and Piotr Wypych, which I would title “Anthropological Record AD 2019/2020. The Continuation.. The world that A. Białkowski and P. Wypych have recorded, and continue to, has a completely different texture and axiological structure than in Rydet’s presentation – it is scattered, fragmentary, put together without any care and semantic awareness, on the basis of combining pretty or personally important artifacts, constituting an island in the dense iconosphere of everyday life. Not only does the culture experience metamorphosis – this always dynamic process have become intensive enough, that perhaps what is left for researchers – saving contexts and prophetism – in the best way possible is carried out by exactly this type of procedures and ethnological activities. Damian Kasprzyk Nature – culture – transcendence. Around the composition of home sacrum Presented comment on the subject of iconographic material obtained in Central Poland concentrates on noticed regularity. In vast majority, examples such as painting, cross, shrine, gypseous figurine, wooden sculpture gain the setting and complement in the form of a naturalism. Usually, it is artificial, live or dried flora. These compositions – from their creators’ perspective – constitute the aesthetic and ideological entirety, on the other side though we are palpably dealing with two individual components. After all, the holy images are obtained without naturalistic ornaments, which appear only in houses, in the current of some individual or environmental need. The text is an attempt to answer the question of what is the essence of this need, and above all, where does this consistency come from in building the context for religious representations from natural elements (plants) or imitating nature. The author uses aesthetic, religious and anthropological concepts. Within the latter, he reaches for the nature – culture opposition. Katarzyna Orszulak-Dudkowska Summary: Home and sacrum in Polish rural culture. Tradition and the contemporary times. The article presents reflections on the presence and meaning of sacred elements in the home space of a religious man, in reference to the traditional Polish rural culture, as well as to the contemporary culture. The author first of all presents the ethnographic knowledge concerning the ways of organizing the living space in a country house, with particular emphasis on the sacred function of a table and the appearance and role of the so-called sacred corner and the home altar. In the description included in the text, the author tries to take into account the changes that took place in arrangement of equipment in home interior and the organization of the sacred space of a house and its aesthetic values. Next, the author refers to the photographic documentation of altars found in the contemporary Polish houses, collected as part of the project: Iconosphere of Hierophany. Home and Sacrum. Cultural transmission of Folk Art Artifacts in Photographic Registration and Anthropological Text Study, carried out in 2019 in the Łódź voivodeship. The author notices that, regardless of the common cultural changes taking place in the surrounding world, in the contemporary Polish home, as a space deeply marked by privacy, multifunctional, connected with the way of life and individual identity of its inhabitants, there still has to be a place to satisfy spiritual and religious needs, and only the ways of exposing and aestheticising the sacrum can change. Alicja Woźniak Home sacrum in the ethnographic record of the museologist. Tradition/continuation/innovation. My reflection as an ethnographer – museologist on the contemporary iconography presented in the Home and sacrum project is based on what was, and the museum archival material is the reference point. Referring to empirical research I take the interior design on the timeline as a comparative source, juxtaposing it with the current images presented in the project. I will present the changes regarding the location of the sacrum in a house, its aesthetics and aestheticization, that is, “embellishing” of home altar. The considerations concern both the material and mental side, not separating the visual from the individualistic way of thinking and perceiving reality – one is a reflection of the other. The changing dimension of religiosity and aesthetic needs means that the artifacts presented in the project that fill current home altars, tomorrow may become a museum collection, which will then pose as a material for future interpretations. Robert Dzięcielski Home iconosphere of the sacred The author of this article presents anthropological reflection concerning the state and changes of traditionally understood home iconosphere of the sacred. The transformation of the traditional culture influenced the change of past attitude towards the sacral sphere. The uncertainty and increasing sense of loss, decay of the old authorities, subjective attitude towards the values and cultural norms, commercialization, increasing importance of virtual reality – these are some of the reasons for the current decline in relations to the religious iconosphere. The author, referring to Eliade’s anthropology, indicates that human needs to rebuild the order and metaphysical harmony, as well as cultural memory that can be recovered and updated on traditional values, are still favourable elements supporting the existence of the sacred iconosphere in the home space. The potential of the sacrum experience in the contemporary world is hidden in the sacral attitude of a person as well as in hierophanic power of place and subjects. Barnaba Bonati Home sacrum – cuisine between a home in Italy and in Poland Barnaba Bonati, raised in Italy, now living in Poland, talks about the importance of the domestic sacred sphere that stretches between the experience of two cultures. In the family home, the family culinary tradition played a sacred role. The images of a joint celebration at the table, recorded in the memory of the participant, allow the author to regain this “sacred time” and constantly follow them today. The basis of the strength of the impact of mental images regarding culinary traditions are three elements – the family table, dishes and all accessories, and above all, participants spending time together and at the same time introducing each other to the experience of sacrum. The author points out in a very personal way that it was his father who introduced him into the experience of home culinary sacrum. Due to this heritage, the visual sphere of memory is closely linked with the whole range of remembered tastes. Michał Żerkowski Remarks on the topic of cultural transmission The issue of cultural transmission has a long and complex history in the history of cultural anthropology, going back to the very beginnings of the discipline, and formed in 19th and 20th century by the successive schools and anthropological approaches: classical evolutionism, diffusionism, configurationism and studies on the national character within the school of culture and personality, neoevolutionism and cultural materialism. Contemporarily renewed interest in the problem of cultural message has occurred due to the interdisciplinary studies on its mechanisms under the umbrella of cultural evolution theories, which paradigmatically remains in the cont

Polygenic score distribution differences across European ancestry populations:implications for breast cancer risk prediction

Background: The 313-variant polygenic risk score (PRS313) provides a promising tool for clinical breast cancer risk prediction. However, evaluation of the PRS313 across different European populations which could influence risk estimation has not been performed. Methods: We explored the distribution of PRS313 across European populations using genotype data from 94,072 females without breast cancer diagnosis, of European-ancestry from 21 countries participating in the Breast Cancer Association Consortium (BCAC) and 223,316 females without breast cancer diagnosis from the UK Biobank. The mean PRS was calculated by country in the BCAC dataset and by country of birth in the UK Biobank. We explored different approaches to reduce the observed heterogeneity in the mean PRS across the countries, and investigated the implications of the distribution variability in risk prediction. Results: The mean PRS313 differed markedly across European countries, being highest in individuals from Greece and Italy and lowest in individuals from Ireland. Using the overall European PRS313 distribution to define risk categories, leads to overestimation and underestimation of risk in some individuals from these countries. Adjustment for principal components explained most of the observed heterogeneity in the mean PRS. The mean estimates derived when using an empirical Bayes approach were similar to the predicted means after principal component adjustment. Conclusions: Our results demonstrate that PRS distribution differs even within European ancestry populations leading to underestimation or overestimation of risk in specific European countries, which could potentially influence clinical management of some individuals if is not appropriately accounted for. Population-specific PRS distributions may be used in breast cancer risk estimation to ensure predicted risks are correctly calibrated across risk categories.</p

A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers

Peer reviewedPublisher PD

Mendelian randomisation study of height and body mass index as modifiers of ovarian cancer risk in 22,588 BRCA1 and BRCA2 mutation carriers

Funder: CIMBA: The CIMBA data management and data analysis were supported by Cancer Research – UK grants C12292/A20861, C12292/A11174. ACA is a Cancer Research -UK Senior Cancer Research Fellow. GCT and ABS are NHMRC Research Fellows. iCOGS: the European Community's Seventh Framework Programme under grant agreement No. 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK (C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692, C8197/A16565), the National Institutes of Health (CA128978) and Post-Cancer GWAS initiative (1U19 CA148537, 1U19 CA148065 and 1U19 CA148112 - the GAME-ON initiative), the Department of Defence (W81XWH-10-1-0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer (CRN-87521), and the Ministry of Economic Development, Innovation and Export Trade (PSR-SIIRI-701), Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund. The PERSPECTIVE project was supported by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research, the Ministry of Economy, Science and Innovation through Genome Québec, and The Quebec Breast Cancer Foundation. BCFR: UM1 CA164920 from the National Cancer Institute. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the BCFR. BFBOCC: Lithuania (BFBOCC-LT): Research Council of Lithuania grant SEN-18/2015. BIDMC: Breast Cancer Research Foundation. BMBSA: Cancer Association of South Africa (PI Elizabeth J. van Rensburg). CNIO: Spanish Ministry of Health PI16/00440 supported by FEDER funds, the Spanish Ministry of Economy and Competitiveness (MINECO) SAF2014-57680-R and the Spanish Research Network on Rare diseases (CIBERER). COH-CCGCRN: Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under grant number R25CA112486, and RC4CA153828 (PI: J. Weitzel) from the National Cancer Institute and the Office of the Director, National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. CONSIT: Associazione Italiana Ricerca sul Cancro (AIRC; IG2014 no.15547) to P. Radice. Italian Association for Cancer Research (AIRC; grant no.16933) to L. Ottini. Associazione Italiana Ricerca sul Cancro (AIRC; IG2015 no.16732) to P. Peterlongo. Jacopo Azzollini is supported by funds from Italian citizens who allocated the 5x1000 share of their tax payment in support of the Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws (INT-Institutional strategic projects ‘5x1000’). DEMOKRITOS: European Union (European Social Fund – ESF) and Greek national funds through the Operational Program "Education and Lifelong Learning" of the National Strategic Reference Framework (NSRF) - Research Funding Program of the General Secretariat for Research & Technology: SYN11_10_19 NBCA. Investing in knowledge society through the European Social Fund. DFKZ: German Cancer Research Center. EMBRACE: Cancer Research UK Grants C1287/A10118 and C1287/A11990. D. Gareth Evans and Fiona Lalloo are supported by an NIHR grant to the Biomedical Research Centre, Manchester. The Investigators at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust are supported by an NIHR grant to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. Ros Eeles and Elizabeth Bancroft are supported by Cancer Research UK Grant C5047/A8385. Ros Eeles is also supported by NIHR support to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. FCCC: The University of Kansas Cancer Center (P30 CA168524) and the Kansas Bioscience Authority Eminent Scholar Program. A.K.G. was funded by R0 1CA140323, R01 CA214545, and by the Chancellors Distinguished Chair in Biomedical Sciences Professorship. FPGMX: FISPI05/2275 and Mutua Madrileña Foundation (FMMA). GC-HBOC: German Cancer Aid (grant no 110837, Rita K. Schmutzler) and the European Regional Development Fund and Free State of Saxony, Germany (LIFE - Leipzig Research Centre for Civilization Diseases, project numbers 713-241202, 713-241202, 14505/2470, 14575/2470). GEMO: Ligue Nationale Contre le Cancer; the Association “Le cancer du sein, parlons-en!” Award, the Canadian Institutes of Health Research for the "CIHR Team in Familial Risks of Breast Cancer" program and the French National Institute of Cancer (INCa grants 2013-1-BCB-01-ICH-1 and SHS-E-SP 18-015). GEORGETOWN: the Non-Therapeutic Subject Registry Shared Resource at Georgetown University (NIH/NCI grant P30-CA051008), the Fisher Center for Hereditary Cancer and Clinical Genomics Research, and Swing Fore the Cure. G-FAST: Bruce Poppe is a senior clinical investigator of FWO. Mattias Van Heetvelde obtained funding from IWT. HCSC: Spanish Ministry of Health PI15/00059, PI16/01292, and CB-161200301 CIBERONC from ISCIII (Spain), partially supported by European Regional Development FEDER funds. HEBCS: Helsinki University Hospital Research Fund, Academy of Finland (266528), the Finnish Cancer Society and the Sigrid Juselius Foundation. HEBON: the Dutch Cancer Society grants NKI1998-1854, NKI2004-3088, NKI2007-3756, the Netherlands Organisation of Scientific Research grant NWO 91109024, the Pink Ribbon grants 110005 and 2014-187.WO76, the BBMRI grant NWO 184.021.007/CP46 and the Transcan grant JTC 2012 Cancer 12-054. HRBCP: Hong Kong Sanatorium and Hospital, Dr Ellen Li Charitable Foundation, The Kerry Group Kuok Foundation, National Institute of Health1R 03CA130065, and North California Cancer Center. HUNBOCS: Hungarian Research Grants KTIA-OTKA CK-80745 and OTKA K-112228. ICO: The authors would like to particularly acknowledge the support of the Asociación Española Contra el Cáncer (AECC), the Instituto de Salud Carlos III (organismo adscrito al Ministerio de Economía y Competitividad) and “Fondo Europeo de Desarrollo Regional (FEDER), una manera de hacer Europa” (PI10/01422, PI13/00285, PIE13/00022, PI15/00854, PI16/00563 and CIBERONC) and the Institut Català de la Salut and Autonomous Government of Catalonia (2009SGR290, 2014SGR338 and PERIS Project MedPerCan). IHCC: PBZ_KBN_122/P05/2004. ILUH: Icelandic Association “Walking for Breast Cancer Research” and by the Landspitali University Hospital Research Fund. INHERIT: Canadian Institutes of Health Research for the “CIHR Team in Familial Risks of Breast Cancer” program – grant # CRN-87521 and the Ministry of Economic Development, Innovation and Export Trade – grant # PSR-SIIRI-701. IOVHBOCS: Ministero della Salute and “5x1000” Istituto Oncologico Veneto grant. IPOBCS: Liga Portuguesa Contra o Cancro. kConFab: The National Breast Cancer Foundation, and previously by the National Health and Medical Research Council (NHMRC), the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. MAYO: NIH grants CA116167, CA192393 and CA176785, an NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201),and a grant from the Breast Cancer Research Foundation. MCGILL: Jewish General Hospital Weekend to End Breast Cancer, Quebec Ministry of Economic Development, Innovation and Export Trade. Marc Tischkowitz is supported by the funded by the European Union Seventh Framework Program (2007Y2013)/European Research Council (Grant No. 310018). MODSQUAD: MH CZ - DRO (MMCI, 00209805), MEYS - NPS I - LO1413 to LF and by the European Regional Development Fund and the State Budget of the Czech Republic (RECAMO, CZ.1.05/2.1.00/03.0101) to LF, and by Charles University in Prague project UNCE204024 (MZ). MSKCC: the Breast Cancer Research Foundation, the Robert and Kate Niehaus Clinical Cancer Genetics Initiative, the Andrew Sabin Research Fund and a Cancer Center Support Grant/Core Grant (P30 CA008748). NAROD: 1R01 CA149429-01. NCI: the Intramural Research Program of the US National Cancer Institute, NIH, and by support services contracts NO2-CP-11019-50, N02-CP-21013-63 and N02-CP-65504 with Westat, Inc, Rockville, MD. NICCC: Clalit Health Services in Israel, the Israel Cancer Association and the Breast Cancer Research Foundation (BCRF), NY. NNPIO: the Russian Foundation for Basic Research (grants 17-54-12007, 17-00-00171 and 18-515-12007). NRG Oncology: U10 CA180868, NRG SDMC grant U10 CA180822, NRG Administrative Office and the NRG Tissue Bank (CA 27469), the NRG Statistical and Data Center (CA 37517) and the Intramural Research Program, NCI. OSUCCG: Ohio State University Comprehensive Cancer Center. PBCS: Italian Association of Cancer Research (AIRC) [IG 2013 N.14477] and Tuscany Institute for Tumors (ITT) grant 2014-2015-2016. SEABASS: Ministry of Science, Technology and Innovation, Ministry of Higher Education (UM.C/HlR/MOHE/06) and Cancer Research Initiatives Foundation. SMC: the Israeli Cancer Association. SWE-BRCA: the Swedish Cancer Society. UCHICAGO: NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA125183), R01 CA142996, 1U01CA161032, P20CA233307, American Cancer Society (MRSG-13-063-01-TBG, CRP-10-119-01-CCE), Breast Cancer Research Foundation, Susan G. Komen Foundation (SAC110026), and Ralph and Marion Falk Medical Research Trust, the Entertainment Industry Fund National Women's Cancer Research Alliance. Mr. Qian was supported by the Alpha Omega Alpha Carolyn L. Cuckein Student Research Fellowship. UCLA: Jonsson Comprehensive Cancer Center Foundation; Breast Cancer Research Foundation. UCSF: UCSF Cancer Risk Program and Helen Diller Family Comprehensive Cancer Center. UKFOCR: Cancer Research UK. UPENN: Breast Cancer Research Foundation; Susan G. Komen Foundation for the cure, Basser Center for BRCA. UPITT/MWH: Hackers for Hope Pittsburgh. VFCTG: Victorian Cancer Agency, Cancer Australia, National Breast Cancer Foundation. WCP: Dr Karlan is funded by the American Cancer Society Early Detection Professorship (SIOP-06-258-01-COUN) and the National Center for Advancing Translational Sciences (NCATS), Grant UL1TR000124.Abstract: Background: Height and body mass index (BMI) are associated with higher ovarian cancer risk in the general population, but whether such associations exist among BRCA1/2 mutation carriers is unknown. Methods: We applied a Mendelian randomisation approach to examine height/BMI with ovarian cancer risk using the Consortium of Investigators for the Modifiers of BRCA1/2 (CIMBA) data set, comprising 14,676 BRCA1 and 7912 BRCA2 mutation carriers, with 2923 ovarian cancer cases. We created a height genetic score (height-GS) using 586 height-associated variants and a BMI genetic score (BMI-GS) using 93 BMI-associated variants. Associations were assessed using weighted Cox models. Results: Observed height was not associated with ovarian cancer risk (hazard ratio [HR]: 1.07 per 10-cm increase in height, 95% confidence interval [CI]: 0.94–1.23). Height-GS showed similar results (HR = 1.02, 95% CI: 0.85–1.23). Higher BMI was significantly associated with increased risk in premenopausal women with HR = 1.25 (95% CI: 1.06–1.48) and HR = 1.59 (95% CI: 1.08–2.33) per 5-kg/m2 increase in observed and genetically determined BMI, respectively. No association was found for postmenopausal women. Interaction between menopausal status and BMI was significant (Pinteraction < 0.05). Conclusion: Our observation of a positive association between BMI and ovarian cancer risk in premenopausal BRCA1/2 mutation carriers is consistent with findings in the general population

Polygenic risk scores and breast and epithelial ovarian cancer risks for carriers of BRCA1 and BRCA2 pathogenic variants

Purpose We assessed the associations between population-based polygenic risk scores (PRS) for breast (BC) or epithelial ovarian cancer (EOC) with cancer risks forBRCA1andBRCA2pathogenic variant carriers. Methods Retrospective cohort data on 18,935BRCA1and 12,339BRCA2female pathogenic variant carriers of European ancestry were available. Three versions of a 313 single-nucleotide polymorphism (SNP) BC PRS were evaluated based on whether they predict overall, estrogen receptor (ER)-negative, or ER-positive BC, and two PRS for overall or high-grade serous EOC. Associations were validated in a prospective cohort. Results The ER-negative PRS showed the strongest association with BC risk forBRCA1carriers (hazard ratio [HR] per standard deviation = 1.29 [95% CI 1.25-1.33],P = 3x10(-72)). ForBRCA2, the strongest association was with overall BC PRS (HR = 1.31 [95% CI 1.27-1.36],P = 7x10(-50)). HR estimates decreased significantly with age and there was evidence for differences in associations by predicted variant effects on protein expression. The HR estimates were smaller than general population estimates. The high-grade serous PRS yielded the strongest associations with EOC risk forBRCA1(HR = 1.32 [95% CI 1.25-1.40],P = 3x10(-22)) andBRCA2(HR = 1.44 [95% CI 1.30-1.60],P = 4x10(-12)) carriers. The associations in the prospective cohort were similar. Conclusion Population-based PRS are strongly associated with BC and EOC risks forBRCA1/2carriers and predict substantial absolute risk differences for women at PRS distribution extremes.Peer reviewe

A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers.

Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10-8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers

Transcriptome-wide association study of breast cancer risk by estrogen-receptor status

Previous transcriptome-wide association studies (TWAS) have identified breast cancer risk genes by integrating data from expression quantitative loci and genome-wide association studies (GWAS), but analyses of breast cancer subtype-specific associations have been limited. In this study, we conducted a TWAS using gene expression data from GTEx and summary statistics from the hitherto largest GWAS meta-analysis conducted for breast cancer overall, and by estrogen receptor subtypes (ER+ and ER-). We further compared associations with ER+ and ER- subtypes, using a case-only TWAS approach. We also conducted multigene conditional analyses in regions with multiple TWAS associations. Two genes, STXBP4 and HIST2H2BA, were specifically associated with ER+ but not with ER- breast cancer. We further identified 30 TWAS-significant genes associated with overall breast cancer risk, including four that were not identified in previous studies. Conditional analyses identified single independent breast-cancer gene in three of six regions harboring multiple TWAS-significant genes. Our study provides new information on breast cancer genetics and biology, particularly about genomic differences between ER+ and ER- breast cancer.Peer reviewe