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Record W3170603059 · doi:10.1038/s41467-021-24334-y

Identification of 22 susceptibility loci associated with testicular germ cell tumors

2021· article· en· W3170603059 on OpenAlexafffund
John Pluta, Louise C. Pyle, Kevin T. Nead, Rona Wilf, Mingyao Li, Nandita Mitra, Benita Weathers, Kurt D’Andrea, Kristian Almstrup, Lynn Anson‐Cartwright, Javier Benı́tez, Christopher D. Brown, Stephen J. Chanock, Chu Chen, Victoria K. Cortessis, Alberto Ferlin, Carlo Foresta, Marija Gamulin, Jourik A. Gietema, Chiara Grasso, Mark H. Greene, Tom Grotmol, Robert J. Hamilton, Trine B. Haugen, Russ Hauser, Michelle A.T. Hildebrandt, Matthew E. Johnson, Robert Karlsson, Lambertus A. Kiemeney, Davor Lessel, Ragnhild A. Lothe, Jennifer T. Loud, Chey Loveday, Paloma Martín, Coby Meijer, Jérémie Nsengimana, David I. Quinn, Þórunn Rafnar, Shweta Ramdas, Lorenzo Richiardi, Rolf I. Skotheim, Kāri Stefánsson, Clare Turnbull, David J. Vaughn, Fredrik Wiklund, Xifeng Wu, Daphne Yang, Tongzhang Zheng, Andrew D. Wells, Struan F.A. Grant, Ewa Rajpert‐De Meyts, Stephen M. Schwartz, D. Timothy Bishop, Katherine A. McGlynn, Peter A. Kanetsky, Katherine L. Nathanson, Christian Kubisch

Bibliographic record

VenueNature Communications · 2021
Typearticle
Languageen
FieldMedicine
TopicTesticular diseases and treatments
Canadian institutionsPrincess Margaret Cancer CentreUniversity of Toronto
FundersNational Center for Advancing Translational SciencesNational Institute of Environmental Health SciencesNational Cancer InstituteNational Human Genome Research InstituteStrategic Research CouncilHelse Sør-Øst RHFNational Institutes of HealthYale UniversityDeutsche KrebshilfeBørnecancerfondenFondazione Umberto VeronesiUniversity of PennsylvaniaAbramson Cancer CenterNovo NordiskMinistero dell’Istruzione, dell’Università e della RicercaCancerfondenRegione PiemonteDipartimenti di EccellenzaUniversity of Texas MD Anderson Cancer CenterYale Cancer CenterPrincess Margaret Cancer FoundationNovo Nordisk FondenWellcome TrustCancer Research UKState of Connecticut Department of Public HealthKreftforeningenHorizon 2020 Framework ProgrammeKræftens BekæmpelseNational Institute of General Medical SciencesMovember FoundationCancer Prevention and Research Institute of Texas
KeywordsTesticular Germ Cell TumorTesticular cancerGenome-wide association studyHeritabilitySeminomaBiologySomatic cellDiseaseGeneticsCancerGenetic associationOncologyInternal medicineMedicineGeneGenotypeSingle-nucleotide polymorphism

Abstract

fetched live from OpenAlex

Abstract Testicular germ cell tumors (TGCT) are the most common tumor in young white men and have a high heritability. In this study, the international Testicular Cancer Consortium assemble 10,156 and 179,683 men with and without TGCT, respectively, for a genome-wide association study. This meta-analysis identifies 22 TGCT susceptibility loci, bringing the total to 78, which account for 44% of disease heritability. Men with a polygenic risk score (PRS) in the 95 th percentile have a 6.8-fold increased risk of TGCT compared to men with median scores. Among men with independent TGCT risk factors such as cryptorchidism, the PRS may guide screening decisions with the goal of reducing treatment-related complications causing long-term morbidity in survivors. These findings emphasize the interconnected nature of two known pathways that promote TGCT susceptibility: male germ cell development within its somatic niche and regulation of chromosomal division and structure, and implicate an additional biological pathway, mRNA translation.

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)0.001
Version: codex-gemma-dda1882f352aValidation 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 score0.018
Threshold uncertainty score0.366

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.001
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 head0.014
GPT teacher head0.294
Teacher spread0.280 · 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 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

Citations73
Published2021
Admission routes2
Has abstractyes

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