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Record W2899376484 · doi:10.1038/s41467-018-06863-1

Germline variation at 8q24 and prostate cancer risk in men of European ancestry

2018· article· en· W2899376484 on OpenAlexaff
Marco Matejcic, Edward J. Saunders, Tokhir Dadaev, Mark N. Brook, Kan Wang, Xin Sheng, Ali Amin Al Olama, Fredrick R. Schumacher, Sue A. Ingles, Koveela Govindasami, Sara Benlloch, Sonja I. Berndt, Demetrius Albanes, Stella Koutros, Kenneth Muir, Victoria L. Stevens, Susan M. Gapstur, Catherine M. Tangen, Jyotsna Batra, Judith A. Clements, Henrik Grönberg, Nora Pashayan, Johanna Schleutker, Alicja Wolk, Catharine West, Lorelei A. Mucci, Peter Kraft, Géraldine Cancel‐Tassin, Karina D. Sørensen, Lovise Mæhle, Eli Marie Grindedal, Sara S. Strom, David E. Neal, Freddie C. Hamdy, Jenny Donovan, Ruth C. Travis, Robert J. Hamilton, Barry S. Rosenstein, Yong‐Jie Lu, Graham G. Giles, Adam S. Kibel, Ana Vega, J.T. Bensen, Manolis Kogevinas, Kathryn L. Penney, Jong Y. Park, Janet L. Stanford, Cezary Cybulski, Børge G. Nordestgaard, Hermann Brenner, Christiane Maier, Jeri Kim, Manuel R. Teixeira, Susan L. Neuhausen, Kim De Ruyck, Azad Hassan Abdul Razack, Lisa F. Newcomb, Davor Lessel, Radka Kaneva, Nawaid Usmani, Frank Claessens, Paul A. Townsend, Manuela Gago-Domínguez, Monique J. Roobol, F. Ménégaux, Kay‐Tee Khaw, Lisa Cannon‐Albright, Hardev Pandha, Stephen N. Thibodeau, Daniel J. Schaid, B. E. Henderson, Mariana C. Stern, Alison Thwaites, Michelle Guy, Ian Whitmore, Angela Morgan, Cyril Fisher, Steve Hazel, Naomi Livni, Margaret Cook, Laura Fachal, Stephanie J. Weinstein, Laura E. Beane Freeman, Robert N. Hoover, Mitchell J. Machiela, Artitaya Lophatananon, Brian D. Carter, Phyllis J. Goodman, Leire Moya, Srilakshmi Srinivasan, Mary‐Anne Kedda, Trina Yeadon, Allison Eckert, Martin Eklund, Carin Cavalli-Bjoerkman, Alison M. Dunning, Csilla Sipeky, Niclas Håkansson, Rebecca Elliott, Hardeep Ranu, Edward L. Giovannucci, Constance Turman, David J. Hunter, Olivier Cussenot, Torben F. Ørntoft, J. Athene Lane, Sarah J. Lewis, Michael S. Davis, Tim Key, Paul Brown, Girish S. Kulkarni, Alexandre R. Zlotta, Neil E. Fleshner, Antonio Finelli, Xueying Mao, Jacek Marzec, Robert J. MacInnis, Roger Milne, John L. Hopper, Miguel Aguado, Mariona Bustamante, Gemma Castaño‐Vinyals, Esther Gràcia‐Lavedan, Lluís Cecchini, Meir J. Stampfer, Jing Ma, Thomas A. Sellers, Milan S. Geybels, Hyun Jung Park, Babu Zachariah, Suzanne Kolb, Dominika Wokołorczyk, Jan Lubiński, Wojciech Kluźniak, Sune F. Nielsen, Maren Weisher, Katarina Ćuk, Walther Vogel, Manuel Luedeke, Christopher J. Logothetis, Paula Paulo, Marta Cardoso, Sofia Maia, María P. Silva, Linda Steele, Yuan Chun Ding, Gert De Meerleer, Sofie De Langhe, Hubert Thierens, Jasmine Lim, Meng H. Tan, Aik T. Ong, Darina Kachakova, A. Mitkova, Vanio Mitev, Matthew Parliament, Guido Jenster, Christopher Bangma, Fritz H. Schröder, Thérèse Truong, Yves Akoli Koudou, Agnieszka Michael, Andrzej Kierzek, Ami Karlsson, Michael Broms, Huihai Wu, Claire Aukim-Hastie, Lori S. Tillmans, Shaun M. Riska, Shannon K. McDonnell, David Dearnaley, Amanda B. Spurdle, Robert A. Gardiner, Vanessa M. Hayes, Lisa M. Butler, Renea A. Taylor, Melissa Papargiris, Pâmela Saunders, Paula Kujala, Kirsi Talala, Kimmo Taari, Søren M. Bentzen, Belynda Hicks, Aurélie Vogt, Amy Hutchinson, Angela Cox, Anne George, Ants Toi, Andrew Evans, Theodorus van der Kwast, Takashi Imai, Shiro Saito, Shan‐Chao Zhao, Guoping Ren, Yangling Zhang, Yongwei Yu, Yudong Wu, Ji Wu, Bo Zhou, John Pedersen, Ramón Lobato-Busto, José Manuel Ruiz-Dominguez, Lourdes Mengual, Antonio Alcaraz, Julio M. Pow‐Sang, Kathleen Herkommer, Tihomir Dikov, S. Christova, Ángel Carracedo, Brigitte Trétarre, Xavier Rébillard, Claire Mulot, Jan Adolfsson, Pär Stattin, Jan-Erik Johansson, Richard M. Martin, Ian M. Thompson, Suzanne K. Chambers, Joanne F. Aitken, Lisa Horvath, Anne‐Maree Haynes, Wayne D. Tilley, Gail P. Risbridger, Markus Aly, Tobias Nordström, Paul D.P. Pharoah, Teuvo L.J. Tammela, Teemu J. Murtola, Anssi Auvinen, Neil Burnet, Gill Barnett, Gerald L. Andriole, Aleksandra Klim, Bettina F. Drake, Michael Borre, Harry Ostrer, Hong-Wei Zhang, Guangwen Cao, Ji Lin, Jin Ling, Meiling Li, Ninghan Feng, Jie Li, Weiyang He, Xin Guo, Zan Sun, Guomin Wang, Jianming Guo, Melissa C. Southey, Liesel M. FitzGerald, Gemma Marsden, Antonio Gómez‐Caamaño, Ana M. Carballo, Paula Peleteiro, Patricia Calvo, Robert Szulkin, Javier Llorca, Trinidad Dierssen-Sotos, Inés Gómez‐Acebo, Hui‐Yi Lin, Elaine A. Ostrander, Rasmus Bisbjerg, Peter Klarskov, Martin Andreas Røder, Peter Kr. Iversen, Bernd Holleczek, Christa Stegmaier, Thomas Schnoeller, Philipp Bohnert, Esther M. John, Piet Ost, Soo‐Hwang Teo, Marija Gamulin, Tomislav Kuliš, Zeljko Kastelan, Chavdar Slavov, Elenko Popov, Thomas Van den Broeck, Steven Joniau, Samantha Larkin, Jose E. Castelao, Marı́a Elena Martı́nez, Ron H. N. van Schaik, Jianfeng Xu, Sara Lindström, Elio Ríboli, Clare Berry, Afshan Siddiq, Federico Canzian, Laurence N. Kolonel, Loïc Le Marchand, Matthew L. Freedman, Sylvie Cénée, Fredrik Wiklund, Stephen J. Chanock, Douglas F. Easton, Rosalind A. Eeles, Zsofia Kote-Jarai, David V. Conti, Christopher A. Haiman

Bibliographic record

VenueNature Communications · 2018
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsUniversity Health NetworkUniversity of AlbertaPrincess Margaret Cancer Centre
FundersNational Heart, Lung, and Blood InstituteNational Cancer InstituteNational Institutes of HealthCancer Research UKEuropean CommissionRoyal Marsden NHS Foundation TrustNational Institute of Environmental Health SciencesNational Institute for Health and Care ResearchNational Cancer Research InstituteMedical Research CouncilCancer Research Institute
KeywordsGermlineProstate cancerVariation (astronomy)BiologyMedicineCancerOncologyGeneticsGenePhysics

Abstract

fetched live from OpenAlex

Abstract Chromosome 8q24 is a susceptibility locus for multiple cancers, including prostate cancer. Here we combine genetic data across the 8q24 susceptibility region from 71,535 prostate cancer cases and 52,935 controls of European ancestry to define the overall contribution of germline variation at 8q24 to prostate cancer risk. We identify 12 independent risk signals for prostate cancer (p < 4.28 × 10−15), including three risk variants that have yet to be reported. From a polygenic risk score (PRS) model, derived to assess the cumulative effect of risk variants at 8q24, men in the top 1% of the PRS have a 4-fold (95%CI = 3.62–4.40) greater risk compared to the population average. These 12 variants account for ~25% of what can be currently explained of the familial risk of prostate cancer by known genetic risk factors. These findings highlight the overwhelming contribution of germline variation at 8q24 on prostate cancer risk which has implications for population risk stratification.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.008

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.001
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.001
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0030.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.016
GPT teacher head0.319
Teacher spread0.303 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

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Citations59
Published2018
Admission routes1
Has abstractyes

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Same venueNature CommunicationsSame topicGenetic Associations and EpidemiologyFrench-language works237,207