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Record W3022636907 · doi:10.1101/2020.04.29.20084095

Cross-cancer genome-wide association study of endometrial cancer and epithelial ovarian cancer identifies genetic risk regions associated with risk of both cancers

2020· preprint· en· W3022636907 on OpenAlexaff
Dylan M. Glubb, Deborah J. Thompson, Katja K.H. Aben, Ahmad Alsulimani, Frédéric Amant, Daniela Annibali, John Attia, Aurelio Barricarte, Matthias W. Beckmann, Andrew Berchuck, Marina Bermisheva, Marcus Q. Bernardini, Katharina Bischof, Line Bjørge, Clara Bodelón, Alison H. Brand, James D. Brenton, Louise A. Brinton, Fiona Bruinsma, Daniel D. Buchanan, Stefanie Burghaus, Ralf Bützow, Hui Cai, Michael E. Carney, Stephen J. Chanock, Chu Chen, Zhihua Chen, Linda S. Cook, Julie M. Cunningham, Immaculata De Vivo, Anna DeFazio, Jennifer A. Doherty, Thilo Dörk, Andreas du Bois, Alison M. Dunning, Matthias Dürst, Todd Edwards, Robert P. Edwards, Arif B. Ekici, Ailith Ewing, Peter A. Fasching, Sarah Ferguson, James M. Flanagan, Florentia Fostira, George Fountzilas, Christine M. Friedenreich, Bo Gao, Mia M. Gaudet, Jan Gawełko, Aleksandra Gentry‐Maharaj, Graham G. Giles, Rosalind Glasspool, Marc T. Goodman, Jacek Gronwald, Holly R. Harris, Philipp Harter, Alexander Hein, Florian Heitz, Michelle A.T. Hildebrandt, Peter Hillemanns, Estrid Høgdall, Claus Høgdall, Elizabeth Holliday, David G. Huntsman, Tomasz Huzarski, Anna Jakubowska, Allan Jensen, Michael E. Jones, Beth Y. Karlan, Anthony N. Karnezis, Joseph L. Kelley, Э. К. Хуснутдинова, Jeffrey Killeen, Susanne K. Kjær, Rüdiger Klapdor, Martin Köbel, Bożena Konopka, Irene Konstantopoulou, Reidun Kristin Kopperud, Madhuri Koti, Peter Kraft, Jolanta Kupryjańczyk, Diether Lambrechts, Melissa C. Larson, Loı̈c Le Marchand, Shashikant B. Lele, Jenny Lester, Andrew J. Li, Dong Liang, Clemens Liebrich, Loren Lipworth, Jolanta Lissowska, Lingeng Lu, Karen H. Lu, Alessandra Macciotta, Amalia Mattiello, Taymaa May, Jessica N. McAlpine, Valerie McGuire, Iain A. McNeish, Usha Menon, Francesmary Modugno, Kirsten B. Moysich, Heli Nevanlinna, Kunle Odunsi, Håkan Olsson, Sandra Oršulić, Ana Osório, Domenico Palli, Tjoung‐Won Park‐Simon, Celeste Leigh Pearce, Tanja Pejović, Jennifer B. Permuth, Agnieszka Podgórska, Susan J. Ramus, Timothy R. Rebbeck, Marjorie J. Riggan, Harvey A. Risch, Joseph H. Rothstein, Ingo B. Runnebaum, Rodney J. Scott, Thomas A. Sellers, Janine Senz, Veronica Wendy Setiawan, Nadeem Siddiqui, Weiva Sieh, Beata Śpiewankiewicz, Rebecca Sutphen, Anthony J. Swerdlow, Lukasz M. Szafron, Soo‐Hwang Teo, Pamela J. Thompson, Liv Cecilie Vestrheim Thomsen, Linda Titus, Alicia Tone, ­Rosario ­Tumino, Constance Turman, Adriaan Vanderstichele, Digna Velez Edwards, Ignace Vergote, Robert A. Vierkant, Zhaoming Wang, Shan Wang‐Gohrke, Penelope M. Webb, Emily White, Alice S. Whittemore, Stacey J. Winham, Xifeng Wu, Anna H. Wu, Drakoulis Yannoukakos, Amanda B. Spurdle, Tracy A. O’Mara

Bibliographic record

VenuemedRxiv · 2020
Typepreprint
Languageen
FieldMedicine
TopicOvarian cancer diagnosis and treatment
Canadian institutionsUniversity of CalgaryVancouver General HospitalFoothills Medical CentreBC Cancer AgencyPrincess Margaret Cancer CentreUniversity of British ColumbiaQueen's UniversityAlberta Health ServicesUniversity Health Network
FundersMedical Research Council
KeywordsEndometrial cancerOvarian cancerGenome-wide association studySerous fluidBiologyCancerOncologyGenetic associationInternal medicineGeneticsSingle-nucleotide polymorphismGeneMedicineGenotype

Abstract

fetched live from OpenAlex

Abstract Accumulating evidence suggests a relationship between endometrial cancer and epithelial ovarian cancer. For example, endometrial cancer and epithelial ovarian cancer share epidemiological risk factors and molecular features observed across histotypes are held in common (e.g. serous, endometrioid and clear cell). Independent genome-wide association studies (GWAS) for endometrial cancer and epithelial ovarian cancer have identified 16 and 27 risk regions, respectively, four of which overlap between the two cancers. Using GWAS summary statistics, we explored the shared genetic etiology between endometrial cancer and epithelial ovarian cancer. Genetic correlation analysis using LD Score regression revealed significant genetic correlation between the two cancers ( r G = 0.43, P = 2.66 × 10 −5 ). To identify loci associated with the risk of both cancers, we implemented a pipeline of statistical genetic analyses (i.e. inverse-variance meta-analysis, co-localization, and M-values), and performed analyses by stratified by subtype. We found seven loci associated with risk for both cancers (P Bonferroni < 2.4 × 10 −9 ). In addition, four novel regions at 7p22.2, 7q22.1, 9p12 and 11q13.3 were identified at a sub-genome wide threshold (P < 5 × 10 −7 ). Integration with promoter-associated HiChIP chromatin loops from immortalized endometrium and epithelial ovarian cell lines, and expression quantitative trait loci (eQTL) data highlighted candidate target genes for further investigation.

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)0.003
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 score0.004
Threshold uncertainty score0.014

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0030.004
Meta-epidemiology (narrow)0.0010.000
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)0.0040.000

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 head0.307
Teacher spread0.278 · 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".

Quick stats

Citations1
Published2020
Admission routes1
Has abstractyes

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