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Record W3042240604 · doi:10.1002/ijc.33206

Mendelian randomization analyses suggest a role for cholesterol in the development of endometrial cancer

2020· article· en· W3042240604 on OpenAlexafffund
Pik Fang Kho, Frédéric Amant, Daniela Annibali, Katie A. Ashton, John Attia, Paul L. Auer, Matthias W. Beckmann, Amanda Black, Louise A. Brinton, Daniel D. Buchanan, Stephen J. Chanock, Chu Chen, Maxine Chen, Timothy Cheng, Linda S. Cook, Marta Crous‐Bou, Kamila Czene, Immaculata De Vivo, Joe Dennis, Thilo Dörk, Sean C. Dowdy, Alison M. Dunning, Matthias Dürst, Douglas F. Easton, Arif B. Ekici, Peter A. Fasching, Brooke L. Fridley, Christine M. Friedenreich, Montserrat García‐Closas, Mia M. Gaudet, Graham G. Giles, Ellen L. Goode, Maggie Gorman, Christopher A. Haiman, Per Hall, Susan E. Hankinson, Alexander Hein, Peter Hillemanns, Shirley Hodgson, Erling A. Høivik, Elizabeth Holliday, David J. Hunter, Angela Jones, Peter Kraft, Camilla Krakstad, Diether Lambrechts, Loı̈c Le Marchand, Xiaolin Liang, Annika Lindblom, Jolanta Lissowska, Jirong Long, Lingeng Lu, Anthony M. Magliocco, Lynn Martin, Mark McEvoy, Roger L. Milne, Miriam Mints, Rami Nassir, Geoffrey Otton, Claire Palles, Loreall Pooler, Tony Proietto, Timothy R. Rebbeck, Stefan P. Renner, Harvey A. Risch, 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, Emma Tham, Ian Tomlinson, Jone Trovik, Constance Turman, Jonathan P. Tyrer, David Van Den Berg, Zhaoming Wang, Nicolas Wentzensen, Lucy Xia, Yong‐Bing Xiang, Hannah Yang, Herbert Yu, Wei Zheng, Penelope M. Webb, Deborah J. Thompson, Amanda B. Spurdle, Dylan M. Glubb, Tracy A. O’Mara

Bibliographic record

VenueInternational Journal of Cancer · 2020
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCancer, Lipids, and Metabolism
Canadian institutionsAlberta Health Services
FundersNational Cancer InstituteNational Institute on AgingCancer Council VictoriaNational Health and Medical Research CouncilNational Center for Advancing Translational SciencesMedical Research CouncilNational Institutes of HealthVincent Fairfax Family FoundationHaukeland UniversitetssjukehusNorges ForskningsrådUniversitetet i BergenEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentKarolinska InstitutetCancer Council QueenslandMinisterio de Economía y CompetitividadCanadian Institutes of Health ResearchDepartment of Defence, Australian GovernmentCancerfondenHunter Medical Research InstituteAgency for Science, Technology and ResearchNational Heart, Lung, and Blood InstituteFred C. and Katherine B. Andersen FoundationFred Hutchinson Cancer Research CenterAustralian GovernmentCancer Research UKWellcome TrustMayo Foundation for Medical Education and ResearchU.S. Public Health ServiceGenome CanadaStockholms Läns LandstingQIMR Berghofer Medical Research InstituteSusan G. KomenFoundation for the National Institutes of HealthKreftforeningenHelse VestCancer Council TasmaniaBrigham and Women's HospitalEuropean CommissionBreast Cancer Research FoundationOvarian Cancer Research FundU.S. Department of Health and Human Services
KeywordsMendelian randomizationEndometrial cancerRandomizationBiologyMedicineOncologyMendelian inheritanceCancerGeneticsInternal medicineEndocrinologyBioinformaticsGynecologyClinical trialGene

Abstract

fetched live from OpenAlex

Abstract Blood lipids have been associated with the development of a range of cancers, including breast, lung and colorectal cancer. For endometrial cancer, observational studies have reported inconsistent associations between blood lipids and cancer risk. To reduce biases from unmeasured confounding, we performed a bidirectional, two‐sample Mendelian randomization analysis to investigate the relationship between levels of three blood lipids (low‐density lipoprotein [LDL] and high‐density lipoprotein [HDL] cholesterol, and triglycerides) and endometrial cancer risk. Genetic variants associated with each of these blood lipid levels ( P < 5 × 10 −8 ) were identified as instrumental variables, and assessed using genome‐wide association study data from the Endometrial Cancer Association Consortium (12 906 cases and 108 979 controls) and the Global Lipids Genetic Consortium (n = 188 578). Mendelian randomization analyses found genetically raised LDL cholesterol levels to be associated with lower risks of endometrial cancer of all histologies combined, and of endometrioid and non‐endometrioid subtypes. Conversely, higher genetically predicted HDL cholesterol levels were associated with increased risk of non‐endometrioid endometrial cancer. After accounting for the potential confounding role of obesity (as measured by genetic variants associated with body mass index), the association between genetically predicted increased LDL cholesterol levels and lower endometrial cancer risk remained significant, especially for non‐endometrioid endometrial cancer. There was no evidence to support a role for triglycerides in endometrial cancer development. Our study supports a role for LDL and HDL cholesterol in the development of non‐endometrioid endometrial cancer. Further studies are required to understand the mechanisms underlying these findings.

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 score0.708
Threshold uncertainty score0.219

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 head0.040
GPT teacher head0.373
Teacher spread0.333 · 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

Citations73
Published2020
Admission routes2
Has abstractyes

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