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Record W4382046876 · doi:10.1038/s41416-023-02312-z

Probing the diabetes and colorectal cancer relationship using gene – environment interaction analyses

2023· article· en· W4382046876 on OpenAlexafffund
Niki Dimou, Andre E. Kim, Orlagh Flanagan, Neil Murphy, Virginia Díez‐Obrero, Anna Shcherbina, Elom K. Aglago, Emmanouil Bouras, Peter T. Campbell, Graham Casey, Steven Gallinger, Stephen B. Gruber, Mark A. Jenkins, Yi Lin, Vı́ctor Moreno, Edward Ruiz-Narváez, Mariana C. Stern, Yu Tian, Volker Arndt, Elizabeth L. Barry, James W. Baurley, Sonja I. Berndt, Stéphane Bezieau, Stephanie A. Bien, D. Timothy Bishop, Hermann Brenner, Arif Budiarto, Robert Carreras‐Torres, Tjeng Wawan Cenggoro, Andrew T. Chan, Jenny Chang‐Claude, Stephen J. Chanock, Xuechen Chen, David V. Conti, Christopher H. Dampier, Matthew A.M. Devall, David A. Drew, Jane C. Figueiredo, Graham G. Giles, Andrea Gsur, Tabitha A. Harrison, Akihisa Hidaka, Michael Hoffmeister, Jeroen R. Huyghe, Kristina M. Jordahl, Eric S. Kawaguchi, Temitope O. Keku, Susanna C. Larsson, Loı̈c Le Marchand, Juan Pablo Lewinger, Li Li, Bharuno Mahesworo, John L. Morrison, Polly A. Newcomb, Christina C. Newton, Mireia Obón‐Santacana, Jennifer Ose, Rish K. Pai, Julie R. Palmer, Nikos Papadimitriou, Bens Pardamean, Anita R. Peoples, Paul D.P. Pharoah, Elizabeth A. Platz, John D. Potter, Gad Rennert, Peter C. Scacheri, Robert E. Schoen, Yu‐Ru Su, Catherine M. Tangen, Stephen N. Thibodeau, Duncan C. Thomas, Cornelia M. Ulrich, Caroline Y. Um, Fränzel J.B. van Duijnhoven, Kala Visvanathan, Pavel Vodička, Ludmila Vodičková, Emily White, Alicja Wolk, Michael O. Woods, Conghui Qu, Anshul Kundaje, Li Hsu, W. James Gauderman, Marc J. Gunter, Ulrike Peters

Bibliographic record

VenueBritish Journal of Cancer · 2023
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicMetabolism, Diabetes, and Cancer
Canadian institutionsMemorial University of NewfoundlandLunenfeld-Tanenbaum Research InstituteUniversity of TorontoMount Sinai Hospital
FundersNational Center for Advancing Translational SciencesNational Institute of Environmental Health SciencesNational Cancer InstituteNational Human Genome Research InstituteNational Heart, Lung, and Blood InstituteOntario Ministry of Research and InnovationSchool of Public Health, Imperial College LondonAgència de Gestió d'Ajuts Universitaris i de RecercaCanadian Institutes of Health ResearchCenters for Disease Control and PreventionInstituto de Salud Carlos IIIXarxa de Bancs de Tumors de CatalunyaNational Institutes of HealthCentre Hospitalier Universitaire de NantesConseil Régional des Pays de la LoireNational Institute of Diabetes and Digestive and Kidney DiseasesHerzfelder'sche FamilienstiftungNIHR Imperial Biomedical Research CentreCentre International de Recherche sur le CancerGrantová Agentura České RepublikyMedizinische Universität GrazImperial College LondonGeneralitat de CatalunyaBundesministerium für Bildung und ForschungNational Institute on AgingHarvard T.H. Chan School of Public HealthNational Institute for Health and Care ResearchJohns Hopkins UniversityBrigham and Women's HospitalEmory UniversityFred Hutchinson Cancer Research CenterCentres de Recerca de CatalunyaMinisterstvo Zdravotnictví Ceské RepublikyWorld Health OrganizationCancer Research UKAmerican Cancer SocietyOffice of Research Infrastructure Programs, National Institutes of HealthJunta de Castilla y LeónKarl-Franzens-Universität GrazU.S. Department of Health and Human Services
KeywordsColorectal cancerDiabetes mellitusMedicineCancerInternal medicineOncologyBioinformaticsCancer researchComputational biologyBiologyEndocrinology

Abstract

fetched live from OpenAlex

Abstract Background Diabetes is an established risk factor for colorectal cancer. However, the mechanisms underlying this relationship still require investigation and it is not known if the association is modified by genetic variants. To address these questions, we undertook a genome-wide gene-environment interaction analysis. Methods We used data from 3 genetic consortia (CCFR, CORECT, GECCO; 31,318 colorectal cancer cases/41,499 controls) and undertook genome-wide gene-environment interaction analyses with colorectal cancer risk, including interaction tests of genetics(G)xdiabetes (1-degree of freedom; d.f.) and joint testing of Gxdiabetes, G-colorectal cancer association (2-d.f. joint test) and G-diabetes correlation (3-d.f. joint test). Results Based on the joint tests, we found that the association of diabetes with colorectal cancer risk is modified by loci on chromosomes 8q24.11 (rs3802177, SLC30A8 – OR AA : 1.62, 95% CI: 1.34–1.96; OR AG : 1.41, 95% CI: 1.30–1.54; OR GG : 1.22, 95% CI: 1.13–1.31; p -value 3-d.f. : 5.46 × 10 −11 ) and 13q14.13 (rs9526201, LRCH1 – OR GG : 2.11, 95% CI: 1.56–2.83; OR GA : 1.52, 95% CI: 1.38–1.68; OR AA : 1.13, 95% CI: 1.06–1.21; p -value 2-d.f. : 7.84 × 10 −09 ). Discussion These results suggest that variation in genes related to insulin signaling ( SLC30A8 ) and immune function ( LRCH1 ) may modify the association of diabetes with colorectal cancer risk and provide novel insights into the biology underlying the diabetes and colorectal cancer relationship.

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)0.007
metaresearch head score (Gemma)0.012
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 score0.008
Threshold uncertainty score0.036

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0070.012
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0010.005
Bibliometrics0.0040.004
Science and technology studies0.0010.001
Scholarly communication0.0010.001
Open science0.0010.002
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0040.000

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 head0.324
Teacher spread0.284 · 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

Citations14
Published2023
Admission routes2
Has abstractyes

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Same venueBritish Journal of CancerSame topicMetabolism, Diabetes, and CancerFrench-language works237,207