المؤلفون: K. D. Williams, C. M. Harris, A. Bodas-Salcedo, J. Camp, R. E. Comer, D. Copsey, D. Fereday, T. Graham, R. Hill, T. Hinton, P. Hyder, S. Ineson, G. Masato, S. F. Milton, M. J. Roberts, D. P. Rowell, C. Sanchez, A. Shelly, B. Sinha, D. N. Walters, A. West, T. Woollings, P. K. Xavier

المصدر: Geoscientific Model Development, Vol 8, Iss 5, Pp 1509-1524 (2015)

مصطلحات موضوعية: Geology, QE1-996.5

الوصف: The latest coupled configuration of the Met Office Unified Model (Global Coupled configuration 2, GC2) is presented. This paper documents the model components which make up the configuration (although the scientific description of these components is detailed elsewhere) and provides a description of the coupling between the components. The performance of GC2 in terms of its systematic errors is assessed using a variety of diagnostic techniques. The configuration is intended to be used by the Met Office and collaborating institutes across a range of timescales, with the seasonal forecast system (GloSea5) and climate projection system (HadGEM) being the initial users. In this paper GC2 is compared against the model currently used operationally in those two systems. Overall GC2 is shown to be an improvement on the configurations used currently, particularly in terms of modes of variability (e.g. mid-latitude and tropical cyclone intensities, the Madden–Julian Oscillation and El Niño Southern Oscillation). A number of outstanding errors are identified with the most significant being a considerable warm bias over the Southern Ocean and a dry precipitation bias in the Indian and West African summer monsoons. Research to address these is ongoing.

وصف الملف: electronic resource

العلاقة: http://www.geosci-model-dev.net/8/1509/2015/gmd-8-1509-2015.pdfTest; https://doaj.org/toc/1991-959XTest; https://doaj.org/toc/1991-9603Test

الوصول الحر: https://doaj.org/article/93166d9105d543d199e90711d63a474fTest

المؤلفون: Oswaldo C. Villena, Katherine M. McClure, Richard J. Camp, Dennis A. LaPointe, Carter T. Atkinson, Helen R. Sofaer, Lucas Berio Fortini

المصدر: Scientific Reports, Vol 14, Iss 1, Pp 1-14 (2024)

مصطلحات موضوعية: Medicine, Science

الوصف: Hawaiian honeycreepers, a group of endemic Hawaiian forest birds, are being threatened by avian malaria, a non-native disease that is driving honeycreepers populations to extinction. Avian malaria is caused by the parasite Plasmodium relictum, which is transmitted by the invasive mosquito Culex quinquefasciatus. Environmental and geographical factors play an important role in shaping mosquito-borne disease transmission dynamics through their influence on the distribution and abundance of mosquitoes. We assessed the effects of environmental (temperature, precipitation), geographic (site, elevation, distance to anthropogenic features), and trap type (CDC light trap, CDC gravid trap) factors on mosquito occurrence and abundance. Occurrence was analyzed using classification and regression tree models (CART) and generalized linear models (GLM); abundance (count data) was analyzed using generalized linear mixed models (GLMMs). Models predicted highest mosquito occurrence at mid-elevation sites and between July and November. Occurrence increased with temperature and precipitation up to 580 mm. For abundance, the best model was a zero-inflated negative-binomial model that indicated higher abundance of mosquitoes at mid-elevation sites and peak abundance between August and October. Estimation of occurrence and abundance as well as understanding the factors that influence them are key for mosquito control, which may reduce the risk of forest bird extinction.

العلاقة: https://doi.org/10.1038/s41598-023-49793-9Test; https://doaj.org/toc/2045-2322Test; https://doaj.org/article/13e0c5f6026243a99b9f674d7e2f0810Test

الإتاحة: https://doi.org/10.1038/s41598-023-49793-9Test
https://doaj.org/article/13e0c5f6026243a99b9f674d7e2f0810Test

المؤلفون: Euan Jenkinson, Andrew J. Alexander, Philip J. Camp

مصطلحات موضوعية: Biophysics, Biomaterials, polarization, optical rotatory dispersion, mackerel

الوصف: Collagen is the most prevalent of Nature’s structural proteins, and is found in the extracellular matrices of animals. The structures of collagen molecules and aggregates are chiral, which leads to the rotation of transmitted, plane-polarized light. Here, it is shown that the concentrations of chiral molecules and aggregates in the optically transparent, adipose eyelid of Atlantic mackerel ( Scomber scombrus ) can be so high, that plane-polarized light in the visible spectrum is rotated by 10–100 s of degrees, depending on wavelength (the optical rotatory dispersion (ORD)). This gives rise to intensely coloured images of eyelid samples when illuminated with white light and viewed between crossed polarizers. The ORD in the visible spectrum is measured with monochromatic light sources, and using this dispersion, the variation of optical thickness within a sample (proportional to collagen concentration and path length) is determined. The agreement between observed and simulated white-light images is almost perfect. While collagen provides vital mechanical rigidity to animal tissue, it might also possess optical properties that are useful for vision and camouflage.

العلاقة: https://figshare.com/articles/journal_contribution/Figure_S1_Schematic_experimental_setup_Figure_S2_Dependence_of_the_photodiode_detector_voltage_on_polarizer_angle_for_samples_1_and_2_Figure_S3_Color_images_of_sample_1_demonstrating_ORD_Figure_S4_Color_images_of_sample_2_demonstrating_ORD_/22284729Test

الإتاحة: https://doi.org/10.6084/m9.figshare.22284729.v1Test
https://figshare.com/articles/journal_contribution/Figure_S1_Schematic_experimental_setup_Figure_S2_Dependence_of_the_photodiode_detector_voltage_on_polarizer_angle_for_samples_1_and_2_Figure_S3_Color_images_of_sample_1_demonstrating_ORD_Figure_S4_Color_images_of_sample_2_demonstrating_ORD_/22284729Test

المؤلفون: Gisella Figlioli, Amandine Billaud, Qin Wang, Manjeet K. Bolla, Joe Dennis, Michael Lush, Anders Kvist, Muriel A. Adank, Thomas U. Ahearn, Natalia N. Antonenkova, Päivi Auvinen, Sabine Behrens, Marina Bermisheva, Natalia V. Bogdanova, Stig E. Bojesen, Bernardo Bonanni, Thomas Brüning, Nicola J. Camp, Archie Campbell, Jose E. Castelao, Melissa H. Cessna, NBCS Collaborators NBCS Collaborators, Kamila Czene, Peter Devilee, Thilo Dörk, Mikael Eriksson, Peter A. Fasching, Henrik Flyger, Marike Gabrielson, Manuela Gago-Dominguez, Montserrat García-Closas, Gord Glendon, Encarna B. Gómez Garcia, Anna González-Neira, Felix Grassmann, Pascal Guénel, Eric Hahnen, Ute Hamann, Peter Hillemanns, Maartje J. Hooning, Reiner Hoppe, Anthony Howell, Keith Humphreys, kConFab Investigators kConFab Investigators, Anna Jakubowska, Elza K. Khusnutdinova, Vessela N. Kristensen, Annika Lindblom, Maria A. Loizidou, Jan Lubiński, Arto Mannermaa, Tabea Maurer, Dimitrios Mavroudis, William G. Newman, Nadia Obi, Mihalis I. Panayiotidis, Paolo Radice, Muhammad U. Rashid, Valerie Rhenius, Matthias Ruebner, Emmanouil Saloustros, Elinor J. Sawyer, Marjanka K. Schmidt, Rita K. Schmutzler, Mitul Shah, Melissa C. Southey, Ian Tomlinson, Thérèse Truong, Elke M. van Veen, Camilla Wendt, Xiaohong R. Yang, Kyriaki Michailidou, Alison M. Dunning, Paul D. P. Pharoah, Douglas F. Easton, Irene L. Andrulis, D. Gareth Evans, Antoinette Hollestelle, Jenny Chang-Claude, Roger L. Milne, Paolo Peterlongo

المصدر: Cancers ; Volume 15 ; Issue 13 ; Pages: 3313

مصطلحات موضوعية: breast cancer predisposition, breast cancer risk factors, FANCM PTVs spectrum, protein truncating variants, PTVs

الوصف: FANCM germline protein truncating variants (PTVs) are moderate-risk factors for ER-negative breast cancer. We previously described the spectrum of FANCM PTVs in 114 European breast cancer cases. In the present, larger cohort, we report the spectrum and frequency of four common and 62 rare FANCM PTVs found in 274 carriers detected among 44,803 breast cancer cases. We confirmed that p.Gln1701* was the most common PTV in Northern Europe with lower frequencies in Southern Europe. In contrast, p.Gly1906Alafs*12 was the most common PTV in Southern Europe with decreasing frequencies in Central and Northern Europe. We verified that p.Arg658* was prevalent in Central Europe and had highest frequencies in Eastern Europe. We also confirmed that the fourth most common PTV, p.Gln498Thrfs*7, might be a founder variant from Lithuania. Based on the frequency distribution of the carriers of rare PTVs, we showed that the FANCM PTVs spectra in Southwestern and Central Europe were much more heterogeneous than those from Northeastern Europe. These findings will inform the development of more efficient FANCM genetic testing strategies for breast cancer cases from specific European populations.

وصف الملف: application/pdf

العلاقة: Cancer Epidemiology and Prevention; https://dx.doi.org/10.3390/cancers15133313Test

الإتاحة: https://doi.org/10.3390/cancers15133313Test

المؤلفون: Esther Clavero, José Manuel Sanchez-Maldonado, Angelica Macauda, Rob Ter Horst, Belém Sampaio-Marques, Artur Jurczyszyn, Alyssa Clay-Gilmour, Angelika Stein, Michelle A. T. Hildebrandt, Niels Weinhold, Gabriele Buda, Ramón García-Sanz, Waldemar Tomczak, Ulla Vogel, Andrés Jerez, Daria Zawirska, Marzena Wątek, Jonathan N. Hofmann, Stefano Landi, John J. Spinelli, Aleksandra Butrym, Abhishek Kumar, Joaquín Martínez-López, Sara Galimberti, María Eugenia Sarasquete, Edyta Subocz, Elzbieta Iskierka-Jażdżewska, Graham G. Giles, Malwina Rybicka-Ramos, Marcin Kruszewski, Niels Abildgaard, Francisco García Verdejo, Pedro Sánchez Rovira, Miguel Inacio da Silva Filho, Katalin Kadar, Małgorzata Razny, Wendy Cozen, Matteo Pelosini, Manuel Jurado, Parveen Bhatti, Marek Dudzinski, Agnieszka Druzd-Sitek, Enrico Orciuolo, Yang Li, Aaron D. Norman, Jan Maciej Zaucha, Rui Manuel Reis, Miroslaw Markiewicz, Juan José Rodríguez Sevilla, Vibeke Andersen, Krzysztof Jamroziak, Kari Hemminki, Sonja I. Berndt, Vicent Rajkumar, Grzegorz Mazur, Shaji K. Kumar, Paula Ludovico, Arnon Nagler, Stephen J. Chanock, Charles Dumontet, Mitchell J. Machiela, Judit Varkonyi, Nicola J. Camp, Elad Ziv, Annette Juul Vangsted, Elizabeth E. Brown, Daniele Campa, Celine M. Vachon, Mihai G. Netea, Federico Canzian, Asta Försti, Juan Sainz

المصدر: International Journal of Molecular Sciences; Volume 24; Issue 10; Pages: 8500

مصطلحات موضوعية: multiple myeloma, autophagy, genetic variants, genetic susceptibility

جغرافية الموضوع: agris

الوصف: Multiple myeloma (MM) arises following malignant proliferation of plasma cells in the bone marrow, that secrete high amounts of specific monoclonal immunoglobulins or light chains, resulting in the massive production of unfolded or misfolded proteins. Autophagy can have a dual role in tumorigenesis, by eliminating these abnormal proteins to avoid cancer development, but also ensuring MM cell survival and promoting resistance to treatments. To date no studies have determined the impact of genetic variation in autophagy-related genes on MM risk. We performed meta-analysis of germline genetic data on 234 autophagy-related genes from three independent study populations including 13,387 subjects of European ancestry (6863 MM patients and 6524 controls) and examined correlations of statistically significant single nucleotide polymorphisms (SNPs; p < 1 × 10−9) with immune responses in whole blood, peripheral blood mononuclear cells (PBMCs), and monocyte-derived macrophages (MDM) from a large population of healthy donors from the Human Functional Genomic Project (HFGP). We identified SNPs in six loci, CD46, IKBKE, PARK2, ULK4, ATG5, and CDKN2A associated with MM risk (p = 4.47 × 10−4−5.79 × 10−14). Mechanistically, we found that the ULK4rs6599175 SNP correlated with circulating concentrations of vitamin D3 (p = 4.0 × 10−4), whereas the IKBKErs17433804 SNP correlated with the number of transitional CD24+CD38+ B cells (p = 4.8 × 10−4) and circulating serum concentrations of Monocyte Chemoattractant Protein (MCP)-2 (p = 3.6 × 10−4). We also found that the CD46rs1142469 SNP correlated with numbers of CD19+ B cells, CD19+CD3− B cells, CD5+IgD− cells, IgM− cells, IgD−IgM− cells, and CD4−CD8− PBMCs (p = 4.9 × 10−4−8.6 × 10−4) and circulating concentrations of interleukin (IL)-20 (p = 0.00082). Finally, we observed that the CDKN2Ars2811710 SNP correlated with levels of CD4+EMCD45RO+CD27− cells (p = 9.3 × 10−4). These results suggest that genetic variants within these six loci influence MM risk through the modulation of ...

وصف الملف: application/pdf

العلاقة: Molecular Pathology, Diagnostics, and Therapeutics; https://dx.doi.org/10.3390/ijms24108500Test

الإتاحة: https://doi.org/10.3390/ijms24108500Test

المؤلفون: Anna Morra, Maartje A. C. Schreurs, Irene L. Andrulis, Hoda Anton‐Culver, Annelie Augustinsson, Matthias W. Beckmann, Sabine Behrens, Stig E. Bojesen, Manjeet K. Bolla, Hiltrud Brauch, Annegien Broeks, Saundra S. Buys, Nicola J. Camp, Jose E. Castelao, Melissa H. Cessna, Jenny Chang‐Claude, Wendy K. Chung, NBCS Collaborators, Sarah V. Colonna, Fergus J. Couch, Angela Cox, Simon S. Cross, Kamila Czene, Mary B. Daly, Joe Dennis, Peter Devilee, Thilo Dörk, Alison M. Dunning, Miriam Dwek, Douglas F. Easton, Diana M. Eccles, Mikael Eriksson, D. Gareth Evans, Peter A. Fasching, Tanja N. Fehm, Jonine D. Figueroa, Henrik Flyger, Marike Gabrielson, Manuela Gago‐Dominguez, Montserrat García‐Closas, José A. García‐Sáenz, Jeanine Genkinger, Felix Grassmann, Melanie Gündert, Eric Hahnen, Christopher A. Haiman, Ute Hamann, Patricia A. Harrington, Jaana M. Hartikainen, Reiner Hoppe, John L. Hopper, Richard S. Houlston, Anthony Howell, ABCTB Investigators, kConFab Investigators, Anna Jakubowska, Wolfgang Janni, Helena Jernström, Esther M. John, Nichola Johnson, Michael E. Jones, Vessela N. Kristensen, Allison W. Kurian, Diether Lambrechts, Loic Le Marchand, Annika Lindblom, Jan Lubiński, Michael P. Lux, Arto Mannermaa, Dimitrios Mavroudis, Anna Marie Mulligan, Taru A. Muranen, Heli Nevanlinna, Ines Nevelsteen, Patrick Neven, William G. Newman, Nadia Obi, Kenneth Offit, Andrew F. Olshan, Tjoung‐Won Park‐Simon, Alpa V. Patel, Paolo Peterlongo, Kelly‐Anne Phillips, Dijana Plaseska‐Karanfilska, Eric C. Polley, Nadege Presneau, Katri Pylkäs, Brigitte Rack, Paolo Radice, Muhammad U. Rashid, Valerie Rhenius, Mark Robson, Atocha Romero, Emmanouil Saloustros, Elinor J. Sawyer, Rita K. Schmutzler, Sabine Schuetze, Christopher Scott, Mitul Shah, Snezhana Smichkoska, Melissa C. Southey, William J. Tapper, Lauren R. Teras, Rob A. E. M. Tollenaar, Katarzyna Tomczyk, Ian Tomlinson, Melissa A. Troester, Celine M. Vachon, Elke M. vanVeen, Qin Wang, Camilla Wendt, Hans Wildiers, Robert Winqvist, Argyrios Ziogas, Per Hall, Paul D. P. Pharoah, Muriel A. Adank, Antoinette Hollestelle, Marjanka K. Schmidt, Maartje J. Hooning

المصدر: Cancer Medicine, Vol 12, Iss 15, Pp 16142-16162 (2023)

مصطلحات موضوعية: CHEK2 c.1100delC germline genetic variant, contralateral breast cancer risk, radiotherapy, survival, systemic treatment, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Background Breast cancer (BC) patients with a germline CHEK2 c.1100delC variant have an increased risk of contralateral BC (CBC) and worse BC‐specific survival (BCSS) compared to non‐carriers. Aim To assessed the associations of CHEK2 c.1100delC, radiotherapy, and systemic treatment with CBC risk and BCSS. Methods Analyses were based on 82,701 women diagnosed with a first primary invasive BC including 963 CHEK2 c.1100delC carriers; median follow‐up was 9.1 years. Differential associations with treatment by CHEK2 c.1100delC status were tested by including interaction terms in a multivariable Cox regression model. A multi‐state model was used for further insight into the relation between CHEK2 c.1100delC status, treatment, CBC risk and death. Results There was no evidence for differential associations of therapy with CBC risk by CHEK2 c.1100delC status. The strongest association with reduced CBC risk was observed for the combination of chemotherapy and endocrine therapy [HR (95% CI): 0.66 (0.55–0.78)]. No association was observed with radiotherapy. Results from the multi‐state model showed shorter BCSS for CHEK2 c.1100delC carriers versus non‐carriers also after accounting for CBC occurrence [HR (95% CI): 1.30 (1.09–1.56)]. Conclusion Systemic therapy was associated with reduced CBC risk irrespective of CHEK2 c.1100delC status. Moreover, CHEK2 c.1100delC carriers had shorter BCSS, which appears not to be fully explained by their CBC risk.

العلاقة: https://doi.org/10.1002/cam4.6272Test; https://doaj.org/toc/2045-7634Test; https://doaj.org/article/cc3bc48accce42618076136563685d7bTest

الإتاحة: https://doi.org/10.1002/cam4.6272Test
https://doaj.org/article/cc3bc48accce42618076136563685d7bTest

المؤلفون: Trevor M. Bak, Richard J. Camp, Noel A. Heim, Douglas J. McCauley, Jonathan L. Payne, Matthew L. Knope

المصدر: Cambridge Prisms: Extinction, Vol 1 (2023)

مصطلحات موضوعية: IUCN Red List, biodiversity threats, body size, marine ray-finned fishes, extinction risk, Evolution, QH359-425

الوصف: Many marine fish species are experiencing population declines, but their extinction risk profiles are largely understudied in comparison to their terrestrial vertebrate counterparts. Selective extinction of marine fish species may result in rapid alteration of the structure and function of ocean ecosystems. In this study, we compiled an ecological trait dataset for 8,185 species of marine ray-finned fishes (class Actinopterygii) from FishBase and used phylogenetic generalized linear models to examine which ecological traits are associated with increased extinction risk, based on the International Union for the Conservation of Nature Red List. We also assessed which threat types may be driving these species toward greater extinction risk and whether threatened species face a greater average number of threat types than non-threatened species. We found that larger body size and/or fishes with life histories involving movement between marine, brackish, and freshwater environments are associated with elevated extinction risk. Commercial harvesting threatens the greatest number of species, followed by pollution, development, and then climate change. We also found that threatened species, on average, face a significantly greater number of threat types than non-threatened species. These results can be used by resource managers to help address the heightened extinction risk patterns we found.

العلاقة: https://www.cambridge.org/core/product/identifier/S2755095823000232/type/journal_articleTest; https://doaj.org/toc/2755-0958Test; https://doaj.org/article/b73af5cfc6df448c920fc18dc600afd5Test

الإتاحة: https://doi.org/10.1017/ext.2023.23Test
https://doaj.org/article/b73af5cfc6df448c920fc18dc600afd5Test

المؤلفون: Richard J. Camp, David L. Miller, Stephen T. Buckland, Steve J. Kendall

المصدر: PeerJ, Vol 11, p e15558 (2023)

مصطلحات موضوعية: Density estimation, Loxops coccineus, Point-transect distance sampling, Soap film smoother, Spatial modelling, Medicine, Biology (General), QH301-705.5

الوصف: Birds are often obligate to specific habitats which can result in study areas with complex boundaries due to sudden changes in vegetation or other features. This can result in study areas with concave arcs or that include holes of unsuitable habitat such as lakes or agricultural fields. Spatial models used to produce species’ distribution and density estimates need to respect such boundaries to make informed decisions for species conservation and management. The soap film smoother is one model for complex study regions which controls the boundary behaviour, ensuring realistic values at the edges of the region. We apply the soap film smoother to account for boundary effects and compare it with thin plate regression spline (TPRS) smooth and design-based conventional distance sampling methods to produce abundance estimates from point-transect distance sampling collected data on Hawai‘i ‘Ākepa Loxops coccineus in the Hakalau Forest Unit of the Big Island National Wildlife Refuge Complex, Hawai‘i Island, USA. The soap film smoother predicted zero or near zero densities in the northern part of the domain and two hotspots (in the southern and central parts of the domain). Along the boundary the soap film model predicted relatively high densities where ‘Ākepa occur in the adjacent forest and near zero elsewhere. The design-based and soap film abundance estimates were nearly identical. The width of the soap film confidence interval was 16.5% and 0.8% wider than the width of the TPRS smooth and design-based confidence intervals, respectively. The peaks in predicted densities along the boundary indicates leakage by the TPRS smooth. We provide a discussion of the statistical methods, biological findings and management implications of applying soap film smoothers to estimate forest bird population status.

العلاقة: https://peerj.com/articles/15558.pdfTest; https://peerj.com/articles/15558Test/; https://doaj.org/toc/2167-8359Test; https://doaj.org/article/829670b3e6b44bbe9d4592b7db73ec94Test

الإتاحة: https://doi.org/10.7717/peerj.15558Test
https://doaj.org/article/829670b3e6b44bbe9d4592b7db73ec94Test

المؤلفون: Richard J. Camp, Chauncey K. Asing, Paul C. Banko, Lainie Berry, Kevin W. Brinck, Chris Farmer, Ayesha S. Genz

المصدر: Wildlife Society Bulletin, Vol 47, Iss 3, Pp n/a-n/a (2023)

مصطلحات موضوعية: Hawai‘i Island, hierarchical generalized additive model, Loxioides bailleui, palila, replicate sampling, sampling effort, General. Including nature conservation, geographical distribution, QH1-199.5

الوصف: Effective species management and conservation benefit from knowledge of species distribution and status. Surveys to obtain that information often involve replicate sampling, which increases survey effort and costs. We simultaneously modeled species distribution, abundance and spatial correlation, and compared the uncertainty in replicate abundance estimates of the endangered palila (Loxioides bailleui) using hierarchical generalized additive models with a soap film smoother that incorporated random effects for visit. Based on survey coverage and detections, we selected the 2017 point‐transect distance sampling survey on Mauna Kea, Hawai‘i Island, for our modeling. Our modeling approach allowed us to account for imperfect detections, control the effects of boundary features, and generate visit‐specific density surface maps. We found that visit‐specific smooths were nearly identical, indicating that little information was gained from a subsequent visit, and that most of the estimator uncertainty was derived from within‐visit variability. Scaling back the palila survey to a single visit would halve the survey effort and logistical costs and increase efficiencies in data management and processing. Changing the sampling protocol warrants careful consideration and our findings may help management and regulatory agencies by maximizing efficiency and minimizing costs of surveying protocols, while providing guidelines on how to best collect information critical to species' conservation.

العلاقة: https://doi.org/10.1002/wsb.1471Test; https://doaj.org/toc/2328-5540Test; https://doaj.org/article/d935ba0122d844c2bab15b38c915a255Test

الإتاحة: https://doi.org/10.1002/wsb.1471Test
https://doaj.org/article/d935ba0122d844c2bab15b38c915a255Test

المؤلفون: Taru A. Muranen, Anna Morra, Sofia Khan, Daniel R. Barnes, Manjeet K. Bolla, Joe Dennis, Renske Keeman, Goska Leslie, Michael T. Parsons, Qin Wang, Thomas U. Ahearn, Kristiina Aittomäki, Irene L. Andrulis, Banu K. Arun, Sabine Behrens, Katarzyna Bialkowska, Stig E. Bojesen, Nicola J. Camp, Jenny Chang-Claude, Kamila Czene, Peter Devilee, HEBON investigators, Susan M. Domchek, Alison M. Dunning, Christoph Engel, D. Gareth Evans, Manuela Gago-Dominguez, Montserrat García-Closas, Anne-Marie Gerdes, Gord Glendon, Pascal Guénel, Eric Hahnen, Ute Hamann, Helen Hanson, Maartje J. Hooning, Reiner Hoppe, Louise Izatt, Anna Jakubowska, Paul A. James, Vessela N. Kristensen, Fiona Lalloo, Geoffrey J. Lindeman, Arto Mannermaa, Sara Margolin, Susan L. Neuhausen, William G. Newman, Paolo Peterlongo, Kelly-Anne Phillips, Miquel Angel Pujana, Johanna Rantala, Karina Rønlund, Emmanouil Saloustros, Rita K. Schmutzler, Andreas Schneeweiss, Christian F. Singer, Maija Suvanto, Yen Yen Tan, Manuel R. Teixeira, Mads Thomassen, Marc Tischkowitz, Vishakha Tripathi, Barbara Wappenschmidt, Emily Zhao, Douglas F. Easton, Antonis C. Antoniou, Georgia Chenevix-Trench, Paul D. P. Pharoah, Marjanka K. Schmidt, Carl Blomqvist, Heli Nevanlinna

المصدر: npj Breast Cancer, Vol 9, Iss 1, Pp 1-15 (2023)

مصطلحات موضوعية: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: We assessed the PREDICT v 2.2 for prognosis of breast cancer patients with pathogenic germline BRCA1 and BRCA2 variants, using follow-up data from 5453 BRCA1/2 carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) and the Breast Cancer Association Consortium (BCAC). PREDICT for estrogen receptor (ER)-negative breast cancer had modest discrimination for BRCA1 carrier patients overall (Gönen & Heller unbiased concordance 0.65 in CIMBA, 0.64 in BCAC), but it distinguished clearly the high-mortality group from lower risk categories. In an analysis of low to high risk categories by PREDICT score percentiles, the observed mortality was consistently lower than the expected mortality, but the confidence intervals always included the calibration slope. Altogether, our results encourage the use of the PREDICT ER-negative model in management of breast cancer patients with germline BRCA1 variants. For the PREDICT ER-positive model, the discrimination was slightly lower in BRCA2 variant carriers (concordance 0.60 in CIMBA, 0.65 in BCAC). Especially, inclusion of the tumor grade distorted the prognostic estimates. The breast cancer mortality of BRCA2 carriers was underestimated at the low end of the PREDICT score distribution, whereas at the high end, the mortality was overestimated. These data suggest that BRCA2 status should also be taken into consideration with tumor characteristics, when estimating the prognosis of ER-positive breast cancer patients.

العلاقة: https://doi.org/10.1038/s41523-023-00546-xTest; https://doaj.org/toc/2374-4677Test; https://doaj.org/article/b25ef8c428ef4ff4ab3dccc937dc88a5Test

الإتاحة: https://doi.org/10.1038/s41523-023-00546-xTest
https://doaj.org/article/b25ef8c428ef4ff4ab3dccc937dc88a5Test