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arXiv 2024年

作者： Ding, Tong Wagner, Sophia J. Song, Andrew H. Chen, Richard J. Lu, Ming Y. Zhang, Andrew Vaidya, Anurag J. Jaume, Guillaume Shaban, Muhammad Kim, Ahrong Williamson, Drew F.K. Chen, Bowen Almagro-Perez, Cristina Doucet, Paul Sahai, Sharifa Chen, Chengkuan Komura, Daisuke Kawabe, Akihiro Ishikawa, Shumpei Gerber, Georg Peng, Tingying Le, Long Phi Mahmood, Faisal Department of Pathology Mass General Brigham Harvard Medical School BostonMA United States Data Science Program Dana-Farber Cancer Institute BostonMA United States Cancer Program Broad Institute of Harvard and MIT CambridgeMA United States John A. Paulson School of Engineering and Applied Sciences Harvard University CambridgeMA United States Helmholtz Munich German Research Center for Environment and Health Munich Germany School of Computation Information and Technology Technical University of Munich Munich Germany Department of Electrical Engineering and Computer Science Massachusetts Institute of Technology CambridgeMA United States Harvard-MIT Division of Health Sciences and Technology Massachusetts Institute of Technology CambridgeMA United States Department of Pathology Pusan National University Busan Korea Republic of Department of Pathology and Laboratory Medicine Emory University School of Medicine AtlantaGA United States Harvard Data Science Initiative Harvard University CambridgeMA United States Department of Systems Biology Harvard Medical School BostonMA United States Department of Preventive Medicine Graduate School of Medicine The University of Tokyo Tokyo Japan Division of Pathology National Cancer Center Exploratory Oncology Research & Clinical Trial Center Chiba Japan

The field of computational pathology has been transformed with recent advances in foundation models that encode histopathology region-of-interests (ROIs) into versatile and transferable feature representations via self-supervised learning (SSL). However, translating these advancements to address complex clinical challenges at the patient and slide level remains constrained by limited clinical data in disease-specific cohorts, especially for rare clinical conditions. We propose TITAN, a multimodal whole slide foundation model pretrained using 335,645 WSIs via visual self-supervised learning and vision-language alignment with corresponding pathology reports and 423,122 synthetic captions generated from a multimodal generative AI copilot for pathology. Without any finetuning or requiring clinical labels, TITAN can extract general-purpose slide representations and generate pathology reports that generalize to resource-limited clinical scenarios such as rare disease retrieval and cancer prognosis. We evaluate TITAN on diverse clinical tasks and find that TITAN outperforms both ROI and slide foundation models across machine learning settings such as linear probing, few-shot and zero-shot classification, rare cancer retrieval and cross-modal retrieval, and pathology report generation. The model is publicly accessible at https://***/mahmoodlab/TITAN © 2024, CC BY-NC-ND.

关键词： Self-supervised learning

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A-336 Comparison Between the Immune Profile of Pregnant and Postpartum Women with and without COVID-19 by Flow Cytometry

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Clinical Chemistry 2023年第SUPPLEMENT_1期69卷

作者： Machado, M L de Souza, A T Silva, S E Fonseca, A L Camargo, J D Vale, A J Azevedo, E P Oliveira, G H Luchessi, A D Junior, G B Silbiger, V N Cobucci, R N Post-Graduate Program in Sciences Applied to Women's Health Maternidade Escola Januário Cicco (MEJC/EBSERH) Federal University of Rio Grande do Norte Natal Brazil Department of Pharmacy Health Sciences Center Federal University of Rio Grande do Norte Natal Brazil Biosciences Center Federal University of Rio Grande do Norte Natal Brazil Department of Medicine Health Sciences Center Federal University of Rio Grande do Norte Natal Brazil Maternidade Escola Januário Cicco (MEJC/EBSERH) Federal University of Rio Grande do Norte Natal Brazil Biotechnology Graduate Program Potiguar University Natal Brazil Flow Cytometry Laboratory Hemocentro do Rio Grande do Norte Dalton Cunha (Hemonorte) Natal Brazil Department of Clinical and Toxicological Analyses Federal University of Rio Grande do Norte Natal Brazil Laboratory of Immunology Department of Clinical and Toxicological Analysis Center for Health Sciences Universidade Federal do Rio Grande do Norte Natal Brazil

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Theranostic doxorubicin encapsulated FeAu alloy@metal-organic framework nanostructures enable magnetic hyperthermia and medical imaging in oral carcinoma

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Nanomedicine: Nanotechnology, Biology, and Medicine 2023年 48卷 102652-102652页

作者： Dhawan, Udesh Tseng, Ching-Li Wu, Ping-Hsuan Liao, Mei-Yi Wang, Huey-Yuan Wu, Kevin C.-W. Chung, Ren-Jei Centre for the Cellular Microenvironment Division of Biomedical Engineering School of Engineering University of Glasgow GlasgowG12 8LT United Kingdom Graduate Institute of Biomedical Materials and Tissue Engineering College of Biomedical Engineering Taipei Medical University Taipei City110 Taiwan International Ph. D. Program in Biomedical Engineering College of Biomedical Engineering Taipei Medical University Taipei City110 Taiwan Research Center of Biomedical Device College of Biomedical Engineering Taipei Medical University Taipei City110 Taiwan International Ph. D. Program in Cell Therapy and Regenerative Medicine College of Medicine Taipei Medical University Taipei City110 Taiwan Taipei106344 Taiwan Department of Applied Chemistry National Pingtung University Pingtung 90003 Taiwan Department of Stomatology MacKay Memorial Hospital Taipei104217 Taiwan Department of Chemical Engineering National Taiwan University Taipei10617 Taiwan Institute of Biomedical Engineering & Nanomedicine National Health Research Institute Keyan Road Zhunan Miaoli City350 Taiwan National Taiwan University Taipei106216 Taiwan

Metal-organic frameworks (MOFs) have emerged as attractive candidates in cancer theranostics due to their ability to envelop magnetic nanoparticles, resulting in reduced cytotoxicity and high porosity, enabling chemodrug encapsulation. Here, FeAu alloy nanoparticles (FeAu NPs) are synthesized and coated with MIL-100(Fe) MOFs to fabricate FeAu@MOF nanostructures. We encapsulated Doxorubicin within the nanostructures and evaluated the suitability of this platform for medical imaging and cancer theranostics. FeAu@MOF nanostructures (FeAu@MIL-100(Fe)) exhibited superparamagnetism, magnetic hyperthermia behavior and displayed DOX encapsulation and release efficiency of 69.95 % and 97.19 %, respectively, when stimulated with alternating magnetic field (AMF). In-vitro experiments showed that AMF-induced hyperthermia resulted in 90 % HSC-3 oral squamous carcinoma cell death, indicating application in cancer theranostics. Finally, in an in-vivo mouse model, FeAu@MOF nanostructures improved image contrast, reduced tumor volume by 30-fold and tumor weight by 10-fold, which translated to enhancement in cumulative survival, highlighting the prospect of this platform for oral cancer treatment. © 2023

关键词： Metal nanoparticles

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Association between periodontitis and anti-cardiolipin antibodies in Buerger disease

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Journal of Clinical Periodontology 2009年第10期36卷 830-835页

作者： Chen, Yi-Wen Nagasawa, Toshiyuki Wara-Aswapati, Nawarat Ushida, Yuka Wang, Dongqing Takeuchi, Yasuo Kobayashi, Hiroaki Umeda, Makoto Inoue, Yoshinori Iwai, Takehisa Ishikawa, Isao Izumi, Yuichi Department of Hard Tissue Engineering Graduate School Tokyo Medical and Dental University Tokyo Japan National Taiwan University Hospital National Taiwan University Taipei Taiwan Department of Periodontology Faculty of Dentistry Khon Kaen University Khon Kaen Thailand Department of Periodontics and Oral Medicine Beijing Stomatological Hospital Capital Medical University Beijing China Department of Vascular and Applied Surgery Graduate School Tokyo Medical and Dental University Tokyo Japan Tsukuba Vascular Center Buerger Disease Research Institute Ibaragi Japan Institute of Advanced Biomedical Engineering and Science Tokyo Women's Medical University Tokyo Japan Global Center of Excellence Program International Research Center for Molecular Science in Tooth and Bone Diseases Tokyo Medical and Dental University Tokyo Japan Department of Periodontology and Endodontology Health Science University of Hokkaido Ishikari-gun Hokkaido 061-0293 1757 Kanazawa Tobetsu-cho Japan

Aim: Anti-cardiolipin (CL) antibodies can be induced in Buerger disease (BD), an inflammatory occlusive disorder affecting peripheral blood vessels, in response to bacteria bearing homology to the TLRVYK peptide of a phospholipid-binding plasma protein β-2-glycoprotein I. TLRVYK homologies are present in Porphyromonas gingivalis (TLRIYT) and Treponema denticola (TLALYK). This study investigated the association between periodontal infection and anti-CL antibodies in BD patients. Material and Methods: Periodontal conditions were examined in 19 BD patients and 25 systemically healthy control subjects. All subjects were heavy smokers. Serum anti-CL, anti-TLRVYK, anti-TLRIYT, and anti-TLALYK antibodies were assessed using the enzyme-linked immunosorbent assay. Results: BD patients had a significantly higher prevalence of periodontitis, more severe periodontal destruction and increased titres of serum anti-CL, anti-TLRVYK, anti-TLRIYT, and anti-TLALYK antibodies compared with healthy subjects. The levels of anti-CL antibodies positively correlated with those of the three anti-peptide antibodies. Anti-CL antibody titres were significantly associated with the percentage of sites with clinical attachment level ≥4 mm in BD patients. Conclusion: Elevated anti-CL antibody levels were associated with periodontal destruction in BD patients. Periodontopathic bacteria may serve as exogenous antigens that stimulate the anti-CL antibody production through molecular mimicry between the bacterial peptides and a host plasma protein. © 2009 John Wiley & Sons A/S.

关键词： β-2-glycoprotein I Anti-cardiolipin antibody Buerger disease Molecular mimicry Periodontitis

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Corrigendum to "Immediate effect of basic body awareness therapy on heart rate variability" [Complement. Ther. Clin. Pract. 22 (2016) 8-11]

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Complementary therapies in clinical practice 2018年 31卷 388页

作者： Alessandra Madia Mantovani Cristina Elena Prado Teles Fregonesi Roselene Modolo Regueiro Lorençoni Nathalia Ulices Savian Mariana Romanholi Palma Afonso Shiguemi Inoue Salgado Luís Vicente Franco de Oliveira Rodolfo Borges Parreira PhD Student in Science Motricity Institute of Biosciences Universidade Estadual Paulista Rio Claro SP 19060-900 Brazil. Department of Post Graduate Program of Physical Therapy Universidade Estadual Paulista Presidente Prudente 19060-900 Brazil. School of Postural and Manual Therapy Salgado Institute of Integral Health Londrina 86055-240 PR Brazil. Rehabilitation Sciences Master and Doctoral Degree Program - Nove de Julho University UNINOVE Sao Paulo SP 01504-000 Brazil. School of Postural and Manual Therapy Salgado Institute of Integral Health Londrina 86055-240 PR Brazil. Electronic address: dolfo23@***.

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The overlapping burden of the three leading causes of disability and death in sub-Saharan African children

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Nature Communications 2022年第1期13卷 1-14页

作者： Reiner, Robert C. Welgan, Catherine A. Troeger, Christopher E. Baumann, Mathew M. Weiss, Daniel J. Deshpande, Aniruddha Blacker, Brigette F. Miller-Petrie, Molly K. Earl, Lucas Bhatt, Samir Abolhassani, Hassan Abosetugn, Akine Eshete Abu-Gharbieh, Eman Adekanmbi, Victor Adetokunboh, Olatunji O. Aghaali, Mohammad Aji, Budi Alahdab, Fares Al-Aly, Ziyad Alhassan, Robert Kaba Ali, Saqib Alizade, Hesam Aljunid, Syed Mohamed Almasi-Hashiani, Amir Al-Mekhlafi, Hesham M. Altirkawi, Khalid A. Alvis-Guzman, Nelson Amare, Azmeraw T. Amini, Saeed Amugsi, Dickson A. Ancuceanu, Robert Andrei, Catalina Liliana Ansari, Fereshteh Anvari, Davood Appiah, Seth Christopher Yaw Arabloo, Jalal Aremu, Olatunde Atout, Maha Moh’d Wahbi Ausloos, Marcel Ausloos, Floriane Ayanore, Martin Amogre Aynalem, Yared Asmare Azene, Zelalem Nigussie Badawi, Alaa Baig, Atif Amin Banach, Maciej Bedi, Neeraj Bhagavathula, Akshaya Srikanth Bhandari, Dinesh Bhardwaj, Nikha Bhardwaj, Pankaj Bhattacharyya, Krittika Bhutta, Zulfiqar A. Bijani, Ali Birhanu, Tesega Tesega Mengistu Bitew, Zebenay Workneh Boloor, Archith Brady, Oliver J. Butt, Zahid A. Car, Josip Carvalho, Felix Casey, Daniel C. Chattu, Vijay Kumar Chowdhury, Mohiuddin Ahsanul Kabir Chu, Dinh-Toi Coelho, Camila H. Cook, Aubrey J. Damiani, Giovanni Daoud, Farah Gela, Jiregna Darega Darwish, Amira Hamed Daryani, Ahmad Das, Jai K. Davis Weaver, Nicole Deribe, Kebede Desalew, Assefa Dharmaratne, Samath Dhamminda Dianatinasab, Mostafa Diaz, Daniel Djalalinia, Shirin Dorostkar, Fariba Dubljanin, Eleonora Duko, Bereket Dwyer-Lindgren, Laura Effiong, Andem El Sayed Zaki, Maysaa El Tantawi, Maha Enany, Shymaa Fattahi, Nazir Feigin, Valery L. Fernandes, Eduarda Ferrara, Pietro Fischer, Florian Foigt, Nataliya A. Folayan, Morenike Oluwatoyin Foroutan, Masoud Frostad, Joseph Jon Fukumoto, Takeshi Gaidhane, Abhay Motiramji Gebrekrstos, Hailemikael Gebrekidan G. K. Gebremeskel, Leake Gebreslassie, Assefa Ayalew Gething, Peter W. Gezae, Kebede Embaye Ghadiri, Keyghobad Ghashghaee, Ahmad Golechha, Mahaveer Gubar Institute for Health Metrics and Evaluation University of Washington Seattle WA United States Department of Health Metrics Sciences School of Medicine University of Washington Seattle WA United States Malaria Atlas Project University of Oxford Oxford United Kingdom Imperial College London London United Kingdom Department of Laboratory Medicine Karolinska University Hospital Huddinge Sweden Research Center for Immunodeficiencies Tehran University of Medical Sciences Tehran Iran Department of Public Health Debre Berhan University Debre Berhan Ethiopia Department of Clinical Sciences University of Sharjah Sharjah United Arab Emirates Population Health Sciences King’s College London London United Kingdom Centre of Excellence for Epidemiological Modelling and Analysis Stellenbosch University Stellenbosch South Africa Department of Global Health Stellenbosch University Cape Town South Africa Department of Epidemiology and Biostatistics Qom University of Medical Sciences Qom Iran Faculty of Medicine and Public Health Jenderal Soedirman University Purwokerto Indonesia Mayo Evidence-based Practice Center Mayo Clinic Foundation for Medical Education and Research Rochester MN United States John T. Milliken Department of Internal Medicine Washington University in St. Louis St. Louis MO United States Clinical Epidemiology Center Department of Veterans Affairs St Louis MO United States Institute of Health Research University of Health and Allied Sciences Ho Ghana Department of Information Systems College of Economics and Political Science Sultan Qaboos University Muscat Oman Infectious and Tropical Disease Research Center Hormozgan University of Medical Sciences Bandar Abbas Iran Department of Health Policy and Management Kuwait University Safat Kuwait International Centre for Casemix and Clinical Coding National University of Malaysia Bandar Tun Razak Malaysia Department of Epidemiology Arak University of Medical Sciences Arak Iran Medical Research Center

Despite substantial declines since 2000, lower respiratory infections (LRIs), diarrhoeal diseases, and malaria remain among the leading causes of nonfatal and fatal disease burden for children under 5 years of age (under 5), primarily in sub-Saharan Africa (SSA). The spatial burden of each of these diseases has been estimated subnationally across SSA, yet no prior analyses have examined the pattern of their combined burden. Here we synthesise subnational estimates of the burden of LRIs, diarrhoea, and malaria in children under-5 from 2000 to 2017 for 43 sub-Saharan countries. Some units faced a relatively equal burden from each of the three diseases, while others had one or two dominant sources of unit-level burden, with no consistent pattern geographically across the entire subcontinent. Using a subnational counterfactual analysis, we show that nearly 300 million DALYs could have been averted since 2000 by raising all units to their national average. Our findings are directly relevant for decision-makers in determining which and targeting where the most appropriate interventions are for increasing child survival. © 2022, The Author(s).

关键词： Biogeography Epidemiology Infectious diseases Malaria

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44. Cohabitation with a sick-cage mate exacerbates allergic lung inflammatory response in mice

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Brain, Behavior, and Immunity 2014年 40卷 e13-e14页

作者： Hamasato, E.K. Nascimento de Lima, A. Ligeiro de Oliveira, A. Lino dos Santos Franco, A. Tavares de Lima, W. Palermo-Neto, J. Neuroimmunomodulation Research Group Department of Pathology School of Veterinary Medicine University of São Paulo São Paulo Brazil Post Graduate Program in Biophotonics Applied to Health Sciences Nove de Julho University UNINOVE Brazil Department of Clinical and Toxicological Analyses Faculty of Pharmaceutical Sciences University of São Paulo Brazil Department of Pharmacology University of São Paulo Brazil

The objective of this study was analyze the effects of cohabitation with sick partner on allergic lung inflammatory response in ovalbumin (OVA) sensitized and challenged mice. Pairs of mice were divided into control and experimental groups. Within each group, one mouse from each pairs was immunized with a solution containing (OVA). The remaining mouse from the experimental group was injected with Ehrlich tumor cells being designated as “companion of sick partner” (CSP); the remaining mouse of the control group was injected with PBS being designated as “companion of healthy partner” (CHP). CSP mice presented in relation to CHP mice: increased number of eosinophils and neutrophils in the BAL; increased IL-4 and IL-5 levels and decreased IL-10 and INF-γ in the BAL supernatant; increased IgG1-OVA and decrease IgG2a-OVA levels on peripheral blood; increased expression of L-selectin in the BAL granulocytes; decreased in vitro tracheal reactivity to metacholine; no changes on plasma corticosterone levels and increased levels of plasmatic noradrenaline. The results suggest that the exacerbation of the allergic lung inflammatory response in CSP mice is a consequence of the psychological stress induced by forced long-term cohabitation with sick the partner, a fact that might ultimately depend on the changes induced by catecholamines on Th1/Th2 balance, toward a Th2 cytokine profile and finally the recruitment and activation of eosinophils in the airways. FAPESP: 2012/03372-3; 2009/51886-3.

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Bioprospecting culturable and unculturable microbial consortia through metagenomics for bioremediation

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Cleaner Chemical Engineering 2022年 2卷

作者： Atif Khurshid Wani Nahid Akhtar Nafiaah Naqash Chirag Chopra Reena Singh Vineet Kumar Sunil Kumar Sikandar I. Mulla Juliana Heloisa Pinê Américo-Pinheiro School of Bioengineering and Biosciences Lovely Professional University Phagwara Punjab 144411 India Waste Re-processing Division CSIR-National Environmental Engineering Research Institute (CSIR-NEERI) Nehru Marg Nagpur 440020 Maharashtra India Department of Biochemistry School of Applied Sciences REVA University Bangalore 560 064 India Post-graduate Program in Environmental Sciences Brazil University Street Carolina Fonseca 584 São Paulo SP 08230-030 Brazil

With the enormous increase in population and industrial network, the harmful pollutants affecting biota have also escalated. The pollutants are consumed by living organisms directly or indirectly reducing animal and economic wellbeing. The degradation of contaminants is imperative owing to the prolonged persistence of contaminants like plastics, heavy metals, pesticides, dyes, pharmaceuticals, and hydrocarbons. Remediation of such pollutants requires efficient methods to prevent mobilizing-contaminants leaching into soil and finally to human beings. In this regard, metagenomics (MGs), a non-culturable technique, involving the direct recovery of the genetic material from environmental samples is an effective tool for understanding the remediation process mediated by microorganisms and their gene products like enzymes. MGs offers a gateway to previously hidden microbial communities grown in the normal and extreme environment through sequence-based or function-based approaches. The culture-independent MGs approach in combination with other meta-omics approaches involves an easy and rapid method for the selection of remediation-efficient microbes. This paper elucidates the negative implications of several contaminants on terrestrial and aquatic biota besides highlighting the role of MGs and associated meta-omics approaches in characterizing contaminant degrading microbes. The MGs research related to bioremediation can help to generate information that will improve the bioremediation process and aid in deciphering the complete microbe-mediated bioremediation mechanism pathways. In future MGs can be helpful to comprehensively understand the mechanisms involved in efficient bioremediation, develop new strategies and models for application in rapid, accurate and efficient bioremediation process and optimize the bioremediation technique. Furthermore, the application of metagenomics to determine microbial diversity and specific genes can act as pollution biomarkers.

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Correction: SNCA genetic lowering reveals differential cognitive function of alpha-synuclein dependent on sex

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Acta neuropathologica communications 2024年第1期12卷 92页

作者： Jennifer L Brown Damyan W Hart Gabriel E Boyle Taylor G Brown Michael LaCroix Andrés M Baraibar Ross Pelzel Minwoo Kim Mathew A Sherman Samuel Boes Michelle Sung Tracy Cole Michael K Lee Alfonso Araque Sylvain E Lesné Graduate Program in Neuroscience University of Minnesota Minneapolis MN USA. Department of Neuroscience University of Minnesota Minneapolis MN USA. Institute for Translational Neuroscience University of Minnesota Wallin Medical Biosciences Building (Room 4-114) 2101 Sixth Street SE CDC 2641 Minneapolis MN 55414 USA. Graduate Program in Molecular and Cellular Biology University of Washington Seattle WA 98195 USA. Medical Scientist Training Program University of Minnesota Minneapolis MN USA. Medical Scientist Training Program University of Texas Southwestern Medical School Dallas TX 75390 USA. Department of Neurosciences University of the Basque Country UPV/EHU Leioa Spain. Bloomberg School of Public Health Johns Hopkins University Baltimore MD 21218 USA. Ionis Pharmaceuticals Inc. Carlsbad CA USA. n-Lorem Foundation Carlsbad CA 92010 USA. Graduate Program in Neuroscience University of Minnesota Minneapolis MN USA. lesne002@umn.edu. Department of Neuroscience University of Minnesota Minneapolis MN USA. lesne002@umn.edu. Institute for Translational Neuroscience University of Minnesota Wallin Medical Biosciences Building (Room 4-114) 2101 Sixth Street SE CDC 2641 Minneapolis MN 55414 USA. lesne002@umn.edu.

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Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction (vol 53, pg 65, 2021)

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NATURE GENETICS 2021年第3期53卷 413-413页

作者： Conti, David V. Darst, Burcu F. Moss, Lilit C. Saunders, Edward J. Sheng, Xin Chou, Alisha Schumacher, Fredrick R. Al Olama, Ali Amin Benlloch, Sara Dadaev, Tokhir Brook, Mark N. Sahimi, Ali Hoffmann, Thomas J. Takahashi, Atushi Matsuda, Koichi Momozawa, Yukihide Fujita, Masashi Muir, Kenneth Lophatananon, Artitaya Wan, Peggy Le Marchand, Loic Wilkens, Lynne R. Stevens, Victoria L. Gapstur, Susan M. Carter, Brian D. Schleutker, Johanna Tammela, Teuvo L. J. Sipeky, Csilla Auvinen, Anssi Giles, Graham G. Southey, Melissa C. MacInnis, Robert J. Cybulski, Cezary Wokolorczyk, Dominika Lubinski, Jan Neal, David E. Donovan, Jenny L. Hamdy, Freddie C. Martin, Richard M. Nordestgaard, Borge G. Nielsen, Sune F. Weischer, Maren Bojesen, Stig E. Roder, Martin Andreas Iversen, Peter Batra, Jyotsna Chambers, Suzanne Moya, Leire Horvath, Lisa Clements, Judith A. Tilley, Wayne Risbridger, Gail P. Gronberg, Henrik Aly, Markus Szulkin, Robert Eklund, Martin Nordstrom, Tobias Pashayan, Nora Dunning, Alison M. Ghoussaini, Maya Travis, Ruth C. Key, Tim J. Riboli, Elio Park, Jong Y. Sellers, Thomas A. Lin, Hui-Yi Albanes, Demetrius Weinstein, Stephanie J. Mucci, Lorelei A. Giovannucci, Edward Lindstrom, Sara Kraft, Peter Hunter, David J. Penney, Kathryn L. Turman, Constance Tangen, Catherine M. Goodman, Phyllis J. Thompson, Ian M., Jr. Hamilton, Robert J. Fleshner, Neil E. Finelli, Antonio Parent, Marie-Elise Stanford, Janet L. Ostrander, Elaine A. Geybels, Milan S. Koutros, Stella Freeman, Laura E. Beane Stampfer, Meir Wolk, Alicja Hakansson, Niclas Andriole, Gerald L. Hoover, Robert N. Machiela, Mitchell J. Sorensen, Karina Dalsgaard Borre, Michael Blot, William J. Zheng, Wei Yeboah, Edward D. Mensah, James E. Lu, Yong-Jie Zhang, Hong-Wei Feng, Ninghan Mao, Xueying Wu, Yudong Zhao, Shan-Chao Sun, Zan Thibodeau, Stephen N. McDonnell, Shannon K. Schaid, Daniel J. West, Catharine M. L. Burnet, Neil Barnett, Gill Maier, Christiane Schnoeller, Thomas Luedeke, Manuel Kibel, Adam S. Drake, Bettina F. Cussenot, Olivier Cancel-Tassin, Gerald Center for Genetic Epidemiology Department of Preventive Medicine Keck School of Medicine University of Southern California/Norris Comprehensive Cancer Center Los Angeles CA USA The Institute of Cancer Research London UK Department of Population and Quantitative Health Sciences Case Western Reserve University Cleveland OH USA Seidman Cancer Center University Hospitals Cleveland OH USA Centre for Cancer Genetic Epidemiology Department of Public Health and Primary Care University of Cambridge Strangeways Research Laboratory Cambridge UK Stroke Research Group Department of Clinical Neurosciences University of Cambridge Cambridge UK Department of Epidemiology and Biostatistics University of California San Francisco CA USA Institute for Human Genetics University of California San Francisco CA USA Laboratory for Statistical Analysis RIKEN Center for Integrative Medical Sciences Yokohama Japan Department of Genomic Medicine National Cerebral and Cardiovascular Center Research Institute Suita Japan Laboratory of Clinical Genome Sequencing Department of Computational Biology and Medical Sciences Graduate School of Frontier Sciences The University of Tokyo Tokyo Japan Biobank Tokyo Japan Laboratory for Genotyping Development RIKEN Center of Integrative Medical Sciences Yokohama Japan Laboratory for Cancer Genomics RIKEN Center of Integrative Medical Sciences Yokohama Japan Division of Population Health Health Services Research and Primary Care School of Health Sciences Faculty of Biology Medicine and Health University of Manchester Manchester UK Warwick Medical School University of Warwick Coventry UK Epidemiology Program University of Hawaii Cancer Center Honolulu HI USA Behavioral and Epidemiology Research Group Research Program American Cancer Society Atlanta GA USA Institute of Biomedicine University of Turku Turku Finland Department of Medical Genetics Genomics Laboratory Division Turku University Hospital Turku Finland Department of Urolog

Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction.

关键词： Epidemiology Genome-wide association studies Personalized medicine Prostate cancer

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