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Record W2886497950 · doi:10.1038/s41467-018-05427-7

Identification of nine new susceptibility loci for endometrial cancer

2018· article· en· W2886497950 on OpenAlexafffund
Tracy A. O’Mara, Dylan M. Glubb, Frédéric Amant, Daniela Annibali, Katie A. Ashton, John Attia, Paul L. Auer, Matthias W. Beckmann, Amanda Black, Manjeet K. Bolla, Hiltrud Brauch, Hermann Brenner, Louise A. Brinton, Daniel D. Buchanan, Barbara Burwinkel, Jenny Chang‐Claude, Stephen J. Chanock, Chu Chen, Maxine Chen, Timothy Cheng, Christine L. Clarke, Mark Clendenning, Linda S. Cook, Fergus J. Couch, Angela Cox, Marta Crous‐Bou, Kamila Czene, Felix R. Day, Joe Dennis, Jeroen Depreeuw, Jennifer A. Doherty, Thilo Dörk, Sean C. Dowdy, Matthias Dürst, Arif B. Ekici, Peter A. Fasching, Brooke L. Fridley, Christine M. Friedenreich, Lin Fritschi, Jenny N. Fung, Montserrat García‐Closas, Mia M. Gaudet, Graham G. Giles, Ellen L. Goode, Maggie Gorman, Christopher A. Haiman, Per Hall, Susan E. Hankison, Catherine S. Healey, Alexander Hein, Peter Hillemanns, Shirley Hodgson, Erling A. Høivik, Elizabeth Holliday, John L. Hopper, David J. Hunter, Angela Jones, Camilla Krakstad, Vessela N. Kristensen, Diether Lambrechts, Loı̈c Le Marchand, Xiaolin Liang, Annika Lindblom, Jolanta Lissowska, Jirong Long, Lingeng Lu, Anthony M. Magliocco, Lynn Martin, Mark McEvoy, Alfons Meindl, Kyriaki Michailidou, Roger L. Milne, Miriam Mints, Grant W. Montgomery, Rami Nassir, Håkan Olsson, Irene Orlow, Geoffrey Otton, Claire Palles, John R. B. Perry, Julian Peto, Loreall Pooler, Jennifer Prescott, Tony Proietto, Timothy R. Rebbeck, Harvey A. Risch, Peter A. W. Rogers, Matthias Rübner, Ingo B. Runnebaum, Carlotta Sacerdote, Gloria E. Sarto, Fredrick R. Schumacher, Rodney J. Scott, Veronica Wendy Setiawan, Mitul Shah, Xin Sheng, Xiao‐Ou Shu, Melissa C. Southey, Anthony J. Swerdlow, Emma Tham, Jone Trovik, Constance Turman, Jonathan P. Tyrer, Celine M. Vachon, David VanDen Berg, Adriaan Vanderstichele, Zhaoming Wang, Penelope M. Webb, Nicolas Wentzensen, Henrica M.J. Werner, Stacey J. Winham, Alicja Wolk, Lucy Xia, Yong‐Bing Xiang, Hannah Yang, Herbert Yu, Wei Zheng, Paul D.P. Pharoah, Alison M. Dunning, Peter Kraft, Immaculata De Vivo, Ian Tomlinson, Douglas F. Easton, Amanda B. Spurdle, Deborah J. Thompson

Bibliographic record

VenueNature Communications · 2018
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCancer-related molecular mechanisms research
Canadian institutionsAlberta Health Services
FundersNational Cancer InstituteNational Health and Medical Research CouncilMedical Research CouncilNational Institutes of HealthVincent Fairfax Family FoundationHaukeland UniversitetssjukehusNorges ForskningsrådUniversitetet i BergenHelse VestEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentKarolinska InstitutetCancer Council QueenslandMinisterio de Economía y CompetitividadCanadian Institutes of Health ResearchCancerfondenAgency for Science, Technology and ResearchHunter Medical Research InstituteNational Institute on AgingNational Institute for Health and Care ResearchNational Heart, Lung, and Blood InstituteFred C. and Katherine B. Andersen FoundationCancer Research UKWellcome TrustBreast Cancer Research FoundationUniversity of CambridgeKreftforeningenU.S. Public Health ServiceGenome CanadaMayo Foundation for Medical Education and ResearchCancer Council TasmaniaBrigham and Women's HospitalWomen's Health InitiativeRoswell Park Cancer InstituteFred Hutchinson Cancer Research CenterU.S. Department of Health and Human ServicesOvarian Cancer Research FundStockholms Läns LandstingQIMR Berghofer Medical Research InstituteEuropean CommissionSusan G. Komen for the Cure
KeywordsEndometrial cancerGenome-wide association studyExpression quantitative trait lociLocus (genetics)BiologyQuantitative trait locusGeneticsAlleleGenetic associationCandidate geneGeneGenotypeColorectal cancerCancerSingle-nucleotide polymorphism

Abstract

fetched live from OpenAlex

Endometrial cancer is the most commonly diagnosed cancer of the female reproductive tract in developed countries. Through genome-wide association studies (GWAS), we have previously identified eight risk loci for endometrial cancer. Here, we present an expanded meta-analysis of 12,906 endometrial cancer cases and 108,979 controls (including new genotype data for 5624 cases) and identify nine novel genome-wide significant loci, including a locus on 12q24.12 previously identified by meta-GWAS of endometrial and colorectal cancer. At five loci, expression quantitative trait locus (eQTL) analyses identify candidate causal genes; risk alleles at two of these loci associate with decreased expression of genes, which encode negative regulators of oncogenic signal transduction proteins (SH2B3 (12q24.12) and NF1 (17q11.2)). In summary, this study has doubled the number of known endometrial cancer risk loci and revealed candidate causal genes for future study.

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)0.002
metaresearch head score (Gemma)0.004
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 score0.012

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0020.004
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0010.003
Bibliometrics0.0020.002
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0010.001
Research integrity0.0010.001
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 head0.029
GPT teacher head0.382
Teacher spread0.353 · 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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Citations326
Published2018
Admission routes2
Has abstractyes

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