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Record W4306639137 · doi:10.1101/2022.10.16.22280490

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

2022· preprint· en· W4306639137 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, Nick Papadimitrou, 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 JB van Duijnhoven, Kala Visvanathan, Pavel Vodička, Ľudmila Vodičková, Emily White, Alicja Wolk, Michael O. Woods, Conghui Qu, Anshul Kundaje, Li Hsu, W. James Gauderman, Marc J. Gunter, Ulrike Peters

Bibliographic record

VenuemedRxiv · 2022
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicMetabolism, Diabetes, and Cancer
Canadian institutionsMemorial University of NewfoundlandLunenfeld-Tanenbaum Research InstituteUniversity of TorontoMount Sinai Hospital
FundersOffice of Research Infrastructure Programs, National Institutes of HealthNational Center for Advancing Translational SciencesNational Cancer InstituteNational Heart, Lung, and Blood InstituteOntario Ministry of Research and InnovationNIHR Imperial Biomedical Research CentreInstituto de Salud Carlos IIIWorld Cancer Research FundMedical Research CouncilCenters for Disease Control and PreventionWorld Health OrganizationXarxa de Bancs de Tumors de CatalunyaJunta de Castilla y LeónGénome QuébecConseil Régional des Pays de la LoireNational Institutes of HealthCentre Hospitalier Universitaire de NantesMedizinische Universität GrazGrantová Agentura České RepublikyHerzfelder'sche FamilienstiftungInstitut Gustave-RoussySchool of Public Health, Imperial College LondonDeutsche KrebshilfeAssociazione Italiana per la Ricerca sul CancroVetenskapsrådetStockholms Läns LandstingHarvard T.H. Chan School of Public HealthKarolinska InstitutetMutuelle Générale de l'Education NationaleBundesministerium für Bildung und ForschungMinisterio de Economía y CompetitividadMinisterstvo Zdravotnictví Ceské RepublikyCanadian Institutes of Health ResearchCancerfondenJohns Hopkins UniversityCentre International de Recherche sur le CancerCanadian Cancer Society Research InstituteInstitut National de la Santé et de la Recherche MédicaleDivision of Cancer Prevention, National Cancer InstituteAgència de Gestió d'Ajuts Universitaris i de RecercaNational Institute for Health and Care ResearchCentres de Recerca de CatalunyaImperial College LondonGeneralitat de CatalunyaFood Standards AgencySwedish Cancer FoundationDamon Runyon Cancer Research FoundationKarl-Franzens-Universität GrazUniverzita Karlova v PrazeMcGill UniversityLigue Contre le CancerDeutsches KrebsforschungszentrumFred Hutchinson Cancer Research CenterBrigham and Women's HospitalEmory UniversityCancer Research UKAmerican Cancer SocietyU.S. Department of Health and Human Services
KeywordsColorectal cancerDiabetes mellitusGenome-wide association studyCancerGeneOncologyType 2 diabetesImmune systemBiologyInternal medicineCancer researchMedicineBioinformaticsGeneticsEndocrinologySingle-nucleotide polymorphismGenotype

Abstract

fetched live from OpenAlex

Abstract Diabetes is an established risk factor for colorectal cancer; however, the mechanisms underlying this relationship are not fully understood and the role of genetic variation is unclear. 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 and joint testing of Gxdiabetes, G-colorectal cancer association and/or G-diabetes correlation (2,3-degrees of freedom joint tests; d.f.). Based on the joint tests, variant rs3802177 in SLC30A8 (p-value 3-d.f .:5.46×10 −11 ; regulates phosphorylation of the insulin receptor and phosphatidylinositol-3 kinase activity) and rs9526201 in LRCH1 (p-value 2-d.f .:7.84×10 −09 ; regulates T cell migration and Natural Killer Cell cytotoxicity) were associated with colorectal cancer. These results suggest that variation in genes related to insulin signalling and immune function may modify the association of diabetes with colorectal cancer 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)0.003
metaresearch head score (Gemma)0.006
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 score0.005
Threshold uncertainty score0.018

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0030.006
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.002
Bibliometrics0.0020.002
Science and technology studies0.0000.000
Scholarly communication0.0010.000
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 head0.058
GPT teacher head0.325
Teacher spread0.267 · 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

Citations0
Published2022
Admission routes2
Has abstractyes

Explore more

Same venuemedRxiv→Same topicMetabolism, Diabetes, and Cancer→French-language works237,207→