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Record W2998134184 · doi:10.1093/ije/dyz242

A Mendelian randomization analysis of circulating lipid traits and breast cancer risk

2019· article· en· W2998134184 on OpenAlexafffund
Alicia Beeghly‐Fadiel, Nikhil K. Khankari, Ryan Delahanty, Xiao‐Ou Shu, Yingchang Lu, Marjanka K. Schmidt, Manjeet K. Bolla, Kyriaki Michailidou, Qin Wang, Joe Dennis, Drakoulis Yannoukakos, Alison M. Dunning, Paul D.P. Pharoah, Georgia Chenevix‐Trench, Roger L. Milne, David J. Hunter, Hall Per, Peter Kraft, Jacques Simard, Douglas F. Easton, Wei Zheng

Bibliographic record

VenueInternational Journal of Epidemiology · 2019
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCancer, Lipids, and Metabolism
Canadian institutionsUniversité LavalCentre hospitalier universitaire de Québec
FundersNiilo Helanderin SäätiöNational Cancer InstituteUniversitätsklinikum Hamburg-EppendorfCancer Council VictoriaMedical Research CouncilNational Institutes of HealthRheinische Friedrich-Wilhelms-Universität BonnFondazione Italiana per la Ricerca sul CancroNational Health and Medical Research CouncilOulun YliopistoDeutsche KrebshilfeNorges ForskningsrådLeids Universitair Medisch CentrumStockholms Läns LandstingKuopion Yliopistollinen SairaalaKarolinska InstitutetOvarian Cancer Research FundBundesministerium für Bildung und ForschungMinisterio de Economía y CompetitividadDeutsche Gesetzliche UnfallversicherungNederlandse Organisatie voor Wetenschappelijk OnderzoekFonds Wetenschappelijk OnderzoekCancerfondenAcademy of FinlandNational Breast Cancer FoundationEuropean CommissionKWF KankerbestrijdingUniversity of Southern CaliforniaFondation du cancer du sein du QuébecWellcome TrustAssociazione Italiana per la Ricerca sul CancroBeckman Research Institute, City of HopeU.S. Department of DefenseCancer Research UKNational Institute for Health and Care ResearchEuropean Social FundAgency for Science, Technology and ResearchMinistère du Développement Économique, de l’Innovation et de l’ExportationCanadian Institutes of Health ResearchGeneral Secretariat for Research and TechnologyMcGill University Health CentreSusan G. KomenNational Heart, Lung, and Blood InstituteItä-Suomen YliopistoGenome CanadaDeutsches KrebsforschungszentrumNIHR Biomedical Research Centre, Royal Marsden NHS Foundation Trust/Institute of Cancer ResearchUniversity of CambridgeGovernment of CanadaHelsingin ja Uudenmaan SairaanhoitopiiriUniversity of California, IrvineDavid F. and Margaret T. Grohne Family FoundationMinistero dello Sviluppo EconomicoVicHealthVanderbilt UniversityU.S. Department of Health and Human ServicesCancer AustraliaBreast Cancer Research FoundationMcGill University
KeywordsMendelian randomizationBreast cancerGenome-wide association studyOdds ratioMedicineOncologyInternal medicineConfidence intervalCancerGenetic associationGeneticsBiologyGenotypeSingle-nucleotide polymorphismGenetic variantsGene

Abstract

fetched live from OpenAlex

BACKGROUND: Conventional epidemiologic studies have evaluated associations between circulating lipid levels and breast cancer risk, but results have been inconsistent. As Mendelian randomization analyses may provide evidence for causal inference, we sought to evaluate potentially unbiased associations between breast cancer risk and four genetically predicted lipid traits. METHODS: Previous genome-wide association studies (GWAS) have identified 164 discrete variants associated with high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), triglycerides and total cholesterol. We used 162 of these unique variants to construct weighted genetic scores (wGSs) for a total of 101 424 breast cancer cases and 80 253 controls of European ancestry from the Breast Cancer Association Consortium (BCAC). Unconditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for associations between per standard deviation increase in genetically predicted lipid traits and breast cancer risk. Additional Mendelian randomization analysis approaches and sensitivity analyses were conducted to assess pleiotropy and instrument validity. RESULTS: Corresponding to approximately 15 mg/dL, one standard deviation increase in genetically predicted HDL-C was associated with a 12% increased breast cancer risk (OR: 1.12, 95% CI: 1.08-1.16). Findings were consistent after adjustment for breast cancer risk factors and were robust in several sensitivity analyses. Associations with genetically predicted triglycerides and total cholesterol were inconsistent, and no association for genetically predicted LDL-C was observed. CONCLUSIONS: This study provides strong evidence that circulating HDL-C may be associated with an increased risk of breast cancer, whereas LDL-C may not be related to breast cancer risk.

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)0.042
metaresearch head score (Gemma)0.109
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: none
Teacher disagreement score0.042
Threshold uncertainty score0.223

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0420.109
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0020.003
Bibliometrics0.0020.002
Science and technology studies0.0010.002
Scholarly communication0.0010.001
Open science0.0010.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0050.000

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 head0.310
Teacher spread0.297 · 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

Citations100
Published2019
Admission routes2
Has abstractyes

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