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Record W3159733223 · doi:10.3390/cancers13092088

Associations between Genetically Predicted Circulating Protein Concentrations and Endometrial Cancer Risk

2021· article· en· W3159733223 on OpenAlexafffund
Jingjing Zhu, Tracy A. O’Mara, Duo Liu, Veronica Wendy Setiawan, Dylan M. Glubb, Amanda B. Spurdle, Peter A. Fasching, Diether Lambrechts, Daniel D. Buchanan, Pik Fang Kho, Linda S. Cook, Christine M. Friedenreich, James V. Lacey, Chu Chen, Nicolas Wentzensen, Immaculata De Vivo, Yan V. Sun, Jirong Long, Mengmeng Du, Xiao‐Ou Shu, Wei Zheng, Lang Wu, Herbert Yu

Bibliographic record

VenueCancers · 2021
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCancer-related molecular mechanisms research
Canadian institutionsAlberta Health Services
FundersEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNational Cancer InstituteNational Heart, Lung, and Blood InstituteNational Institute on AgingCancer Research UKUniversity of CambridgeNational Health and Medical Research CouncilCanadian Institutes of Health ResearchOvarian Cancer Research FundU.S. Department of Health and Human ServicesNational Institutes of HealthMinisterio de Economía y CompetitividadWellcome TrustRoswell Park Cancer Institute
KeywordsEndometrial cancerBiologyABO blood group systemGenome-wide association studyOdds ratioImmunologyInternal medicineCancerEndocrinologyGeneticsSingle-nucleotide polymorphismMedicineGeneGenotype

Abstract

fetched live from OpenAlex

Endometrial cancer (EC) is the leading female reproductive tract malignancy in developed countries. Currently, genome-wide association studies (GWAS) have identified 17 risk loci for EC. To identify novel EC-associated proteins, we used previously reported protein quantitative trait loci for 1434 plasma proteins as instruments to evaluate associations between genetically predicted circulating protein concentrations and EC risk. We studied 12,906 cases and 108,979 controls of European descent included in the Endometrial Cancer Association Consortium, the Epidemiology of Endometrial Cancer Consortium, and the UK Biobank. We observed associations between genetically predicted concentrations of nine proteins and EC risk at a false discovery rate of <0.05 (p-values range from 1.14 × 10−10 to 3.04 × 10−4). Except for vascular cell adhesion protein 1, all other identified proteins were independent from known EC risk variants identified in EC GWAS. The respective odds ratios (95% confidence intervals) per one standard deviation increase in genetically predicted circulating protein concentrations were 1.21 (1.13, 1.30) for DNA repair protein RAD51 homolog 4, 1.27 (1.14, 1.42) for desmoglein-2, 1.14 (1.07, 1.22) for MHC class I polypeptide-related sequence B, 1.05 (1.02, 1.08) for histo-blood group ABO system transferase, 0.77 (0.68, 0.89) for intestinal-type alkaline phosphatase, 0.82 (0.74, 0.91) for carbohydrate sulfotransferase 15, 1.07 (1.03, 1.11) for D-glucuronyl C5-epimerase, and 1.07 (1.03, 1.10) for CD209 antigen. In conclusion, we identified nine potential EC-associated proteins. If validated by additional studies, our findings may contribute to understanding the pathogenesis of endometrial tumor development and identifying women at high risk of EC along with other EC risk factors and biomarkers.

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)0.007
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 score0.001
Threshold uncertainty score0.007

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.007
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 integrity0.0010.001
Insufficient payload (model declined to judge)0.0010.000

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 head0.018
GPT teacher head0.295
Teacher spread0.277 · 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

Citations19
Published2021
Admission routes2
Has abstractyes

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