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Record W4396887285 · doi:10.1016/j.ebiom.2024.105146

Genome-wide interaction study of dietary intake of fibre, fruits, and vegetables with risk of colorectal cancer

2024· article· en· W4396887285 on OpenAlexafffund
Nikos Papadimitriou, Andre Kim, Eric S. Kawaguchi, John L. Morrison, Virginia Díez‐Obrero, Demetrius Albanes, Sonja I. Berndt, Stéphane Bezieau, Stephanie A. Bien, D. Timothy Bishop, Emmanouil Bouras, Hermann Brenner, Daniel D. Buchanan, Peter T. Campbell, Robert Carreras‐Torres, Andrew T. Chan, Jenny Chang‐Claude, David V. Conti, Matthew A.M. Devall, Niki Dimou, David A. Drew, Stephen B. Gruber, Tabitha A. Harrison, Michael Hoffmeister, Jeroen R. Huyghe, Amit D. Joshi, Temitope O. Keku, Anshul Kundaje, Sébastien Küry, Loı̈c Le Marchand, Juan Pablo Lewinger, Li Li, Brigid M. Lynch, Vı́ctor Moreno, Christina C. Newton, Mireia Obón‐Santacana, Jennifer Ose, Andrew J. Pellatt, Anita R. Peoples, Elizabeth A. Platz, Conghui Qu, Gad Rennert, Edward Ruiz-Narváez, Anna Shcherbina, Mariana C. Stern, Yu‐Ru Su, Duncan C. Thomas, Claire E. Thomas, Yu Tian, Konstantinos K. Tsilidis, Cornelia M. Ulrich, Caroline Y. Um, Kala Visvanathan, Jun Wang, Emily White, Michael O. Woods, Stephanie L. Schmit, Finlay Macrae, John D. Potter, John L. Hopper, Ulrike Peters, Neil Murphy, Li Hsu, Marc J. Gunter, W. James Gauderman

Bibliographic record

VenueEBioMedicine · 2024
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsMemorial University of Newfoundland
FundersOffice of Research Infrastructure Programs, National Institutes of HealthNational Institute of Environmental Health SciencesNational Cancer InstituteCancer Council VictoriaNational Human Genome Research InstituteNational Heart, Lung, and Blood InstituteDeutsche KrebshilfeSchool of Public Health, Imperial College LondonNIHR Imperial Biomedical Research CentreNational Institute for Health and Care ResearchAgència de Gestió d'Ajuts Universitaris i de RecercaNational Health and Medical Research CouncilMedical Research CouncilCenters for Disease Control and PreventionNational Institutes of HealthInstituto de Salud Carlos IIIWorld Health OrganizationXarxa de Bancs de Tumors de CatalunyaJunta de Castilla y LeónInstitut Gustave-RoussyAssociazione Italiana per la Ricerca sul CancroVetenskapsrådetMutuelle Générale de l'Education NationaleBundesministerium für Bildung und ForschungMinisterio de Economía y CompetitividadCanadian Institutes of Health ResearchCancerfondenKarolinska InstitutetCanadian Cancer Society Research InstituteMarshfield Clinic Research FoundationInstitut National de la Santé et de la Recherche MédicaleFood Standards AgencyImperial College LondonGeneralitat de CatalunyaSwedish Cancer FoundationNational Institute on AgingDivision of Cancer Prevention, National Cancer InstituteCancer Research UKCentres de Recerca de CatalunyaGénome QuébecNational Institute of Diabetes and Digestive and Kidney DiseasesWorld Cancer Research FundJohns Hopkins UniversityMcGill UniversityFred Hutchinson Cancer Research CenterLigue Contre le CancerDeutsches KrebsforschungszentrumDamon Runyon Cancer Research FoundationEmory UniversityU.S. Department of Health and Human Services
KeywordsQuartileColorectal cancerGenotypeMedicineGenome-wide association studyInternal medicineGenetic associationBiologyCancerGeneGeneticsSingle-nucleotide polymorphismConfidence interval

Abstract

fetched live from OpenAlex

Background Consumption of fibre, fruits and vegetables have been linked with lower colorectal cancer (CRC) risk. A genome-wide gene-environment (G × E) analysis was performed to test whether genetic variants modify these associations. Methods A pooled sample of 45 studies including up to 69,734 participants (cases: 29,896; controls: 39,838) of European ancestry were included. To identify G × E interactions, we used the traditional 1--degree-of-freedom (DF) G × E test and to improve power a 2-step procedure and a 3DF joint test that investigates the association between a genetic variant and dietary exposure, CRC risk and G × E interaction simultaneously. Findings The 3-DF joint test revealed two significant loci with p-value <5 × 10 −8 . Rs4730274 close to the SLC26A3 gene showed an association with fibre (p-value: 2.4 × 10 −3 ) and G × fibre interaction with CRC (OR per quartile of fibre increase = 0.87, 0.80, and 0.75 for CC, TC, and TT genotype, respectively; G × E p-value: 1.8 × 10 −7 ). Rs1620977 in the NEGR1 gene showed an association with fruit intake (p-value: 1.0 × 10 −8 ) and G × fruit interaction with CRC (OR per quartile of fruit increase = 0.75, 0.65, and 0.56 for AA, AG, and GG genotype, respectively; G × E -p-value: 0.029). Interpretation We identified 2 loci associated with fibre and fruit intake that also modify the association of these dietary factors with CRC risk. Potential mechanisms include chronic inflammatory intestinal disorders, and gut function. However, further studies are needed for mechanistic validation and replication of findings. Funding National Institutes of Health, National Cancer Institute. Full funding details for the individual consortia are provided in acknowledgments.

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: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.306
Threshold uncertainty score0.234

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 head0.010
GPT teacher head0.275
Teacher spread0.265 · 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

Citations12
Published2024
Admission routes2
Has abstractyes

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