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Record W4404024219 · doi:10.1007/s00439-024-02707-9

Germline copy number variants and endometrial cancer risk

2024· article· en· W4404024219 on OpenAlexfundno aff
Cassie E. Stylianou, George A. R. Wiggins, V. Lau, Joe Dennis, Andrew N. Shelling, Michelle Wilson, Peter Sykes, Frédéric Amant, Daniela Annibali, Wout De Wispelaere, Douglas F. Easton, Peter A. Fasching, Dylan M. Glubb, Ellen L. Goode, Diether Lambrechts, Paul D. P. Pharoah, Rodney J. Scott, Emma Tham, Ian Tomlinson, Manjeet K. Bolla, Fergus J. Couch, Kamila Czene, Thilo Dörk, Alison M. Dunning, Olivia Fletcher, Montserrat García‐Closas, Reiner Hoppe, Christine L. Clarke, Deborah J. Marsh, Rodney Scott, Robert Baxter, Desmond Yip, Jane Carpenter, Alison Davis, Nirmala Pathmanathan, Peter T. Simpson, J Dinny Graham, Mythily Sachchithananthan, Helena Jernström, Rudolf Kaaks, Kyriaki Michailidou, Nadia Obi, Melissa C. Southey, Jennifer Stone, Qin Wang, Amanda B. Spurdle, Tracy A. O’Mara, Logan C. Walker

Bibliographic record

VenueHuman Genetics · 2024
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenomic variations and chromosomal abnormalities
Canadian institutionsnot available
FundersNational Cancer InstituteDepartment of Health and Social CareMedical Research CouncilCancer Institute NSWFonds Wetenschappelijk OnderzoekCanadian Institutes of Health ResearchDeutsche Gesetzliche UnfallversicherungNational Institutes of HealthDeutsche KrebshilfeCancer Council Western AustraliaNIHR Cambridge Biomedical Research CentreEuropean CommissionNational Health and Medical Research CouncilWellcome TrustCancer Research UKDeutsche ForschungsgemeinschaftGovernment of CanadaNational Breast Cancer FoundationBundesministerium für Bildung und ForschungNational Institute for Health and Care ResearchHealth Research Council of New ZealandGenome CanadaFondation du cancer du sein du QuébecDeutsches Krebsforschungszentrum
KeywordsEndometrial cancerBiologyCopy-number variationGermlineGeneticsCancerGene duplicationCandidate geneHuman geneticsGermline mutationGeneGenome-wide association studyGene dosageGenomeSingle-nucleotide polymorphismGenotypeMutation

Abstract

fetched live from OpenAlex

Abstract Known risk loci for endometrial cancer explain approximately one third of familial endometrial cancer. However, the association of germline copy number variants (CNVs) with endometrial cancer risk remains relatively unknown. We conducted a genome-wide analysis of rare CNVs overlapping gene regions in 4115 endometrial cancer cases and 17,818 controls to identify functionally relevant variants associated with disease. We identified a 1.22-fold greater number of CNVs in DNA samples from cases compared to DNA samples from controls ( p = 4.4 × 10 –63 ). Under three models of putative CNV impact (deletion, duplication, and loss of function), genome-wide association studies identified 141 candidate gene loci associated ( p < 0.01) with endometrial cancer risk. Pathway analysis of the candidate loci revealed an enrichment of genes involved in the 16p11.2 proximal deletion syndrome, driven by a large recurrent deletion (chr16:29,595,483-30,159,693) identified in 0.15% of endometrial cancer cases and 0.02% of control participants. Together, these data provide evidence that rare copy number variants have a role in endometrial cancer susceptibility and that the proximal 16p11.2 BP4-BP5 region contains 25 candidate risk gene(s) that warrant further analysis to better understand their role in human disease.

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 distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.602
Threshold uncertainty score0.486

Codex and Gemma teacher scores by category

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

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 head0.013
GPT teacher head0.282
Teacher spread0.269 · 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 teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
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

Citations2
Published2024
Admission routes1
Has abstractyes

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