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Record W4385460735 · doi:10.1158/0008-5472.c.6769316

Data from A Genetic Locus within the FMN1/GREM1 Gene Region Interacts with Body Mass Index in Colorectal Cancer Risk

2023· preprint· en· W4385460735 on OpenAlexafffund
Elom K. Aglago, Andre E. Kim, Yi Lin, Conghui Qu, Marina Evangelou, Ren Yu, John L. Morrison, Demetrius Albanes, Volker Arndt, Elizabeth L. Barry, James W. Baurley, Sonja I. Berndt, Stephanie A. Bien, D. Timothy Bishop, Emmanouil Bouras, Hermann Brenner, Daniel D. Buchanan, Arif Budiarto, Robert Carreras‐Torres, Graham Casey, Tjeng Wawan Cenggoro, Andrew T. Chan, Jenny Chang‐Claude, Xuechen Chen, David V. Conti, Matthew A.M. Devall, Virginia Díez‐Obrero, Niki Dimou, David A. Drew, Jane C. Figueiredo, Steven Gallinger, Graham G. Giles, Stephen B. Gruber, Andrea Gsur, Marc J. Gunter, Heather Hampel, Sophia Harlid, Akihisa Hidaka, Tabitha A. Harrison, Michael Hoffmeister, Jeroen R. Huyghe, Mark A. Jenkins, Kristina M. Jordahl, Amit D. Joshi, Eric S. Kawaguchi, Temitope O. Keku, Anshul Kundaje, Susanna C. Larsson, Loı̈c Le Marchand, Juan Pablo Lewinger, Li Li, Brigid M. Lynch, Bharuno Mahesworo, Marko Mandic, Mireia Obón‐Santacana, Vı́ctor Moreno, Neil Murphy, Hongmei Nan, Rami Nassir, Polly A. Newcomb, Shuji Ogino, Jennifer Ose, Rish K. Pai, Julie R. Palmer, Nikos Papadimitriou, Bens Pardamean, Anita R. Peoples, Elizabeth A. Platz, John D. Potter, Ross L. Prentice, Gad Rennert, Edward Ruiz-Narváez, Lori C. Sakoda, Peter C. Scacheri, Stephanie L. Schmit, Robert E. Schoen, Anna Shcherbina, Martha L. Slattery, Mariana C. Stern, Yu‐Ru Su, Catherine M. Tangen, Stephen N. Thibodeau, Duncan C. Thomas, Yu Tian, Cornelia M. Ulrich, Fränzel J.B. van Duijnhoven, Bethany Van Guelpen, Kala Visvanathan, Pavel Vodička, Jun Wang, Emily White, Alicja Wolk, Michael O. Woods, Anna H. Wu, Natalia Zemlianskaia, Li Hsu, W. James Gauderman, Ulrike Peters, Konstantinos K. Tsilidis, Peter T. Campbell

Bibliographic record

Venuenot available
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicDigestive system and related health
Canadian institutionsLunenfeld-Tanenbaum Research InstituteUniversity of TorontoMount Sinai Hospital
FundersNational Cancer InstituteSchool of Public Health, Imperial College LondonAgència de Gestió d'Ajuts Universitaris i de RecercaNational Health and Medical Research CouncilWorld Cancer Research FundMedical Research CouncilCenters for Disease Control and PreventionNational Institutes of HealthInstituto de Salud Carlos IIIXarxa de Bancs de Tumors de CatalunyaOffice of Research Infrastructure Programs, National Institutes of HealthJunta de Castilla y LeónInstitut Gustave-RoussyCancer Council VictoriaDeutsche KrebshilfeAssociazione Italiana per la Ricerca sul CancroVetenskapsrådetHerzfelder'sche FamilienstiftungCanadian Institutes of Health ResearchCancerfondenNIHR Imperial Biomedical Research CentreCentre International de Recherche sur le CancerGrantová Agentura České RepublikyInstitut National de la Santé et de la Recherche MédicaleFood Standards AgencyBundesministerium für Bildung und ForschungHarvard T.H. Chan School of Public HealthNational Institute for Health and Care ResearchMinisterstvo Zdravotnictví Ceské RepublikyWorld Health OrganizationCancer Research UKGénome QuébecMutuelle Générale de l'Education NationaleMinisterio de Economía y CompetitividadUniversity of PittsburghJohns Hopkins UniversityOntario Ministry of Research and InnovationLigue Contre le CancerDeutsches KrebsforschungszentrumUniverzita Karlova v PrazeCanadian Cancer Society Research InstituteMcGill UniversityBrigham and Women's HospitalFred Hutchinson Cancer Research CenterImperial College LondonDamon Runyon Cancer Research FoundationU.S. Department of Health and Human Services
KeywordsLocus (genetics)Colorectal cancerBody mass indexGeneGeneticsIndex (typography)BiologyComputational biologyCancerComputer scienceEndocrinologyWorld Wide Web

Abstract

fetched live from OpenAlex

<div>Abstract<p>Colorectal cancer risk can be impacted by genetic, environmental, and lifestyle factors, including diet and obesity. Gene-environment interactions (G × E) can provide biological insights into the effects of obesity on colorectal cancer risk. Here, we assessed potential genome-wide G × E interactions between body mass index (BMI) and common SNPs for colorectal cancer risk using data from 36,415 colorectal cancer cases and 48,451 controls from three international colorectal cancer consortia (CCFR, CORECT, and GECCO). The G × E tests included the conventional logistic regression using multiplicative terms (one degree of freedom, 1DF test), the two-step EDGE method, and the joint 3DF test, each of which is powerful for detecting G × E interactions under specific conditions. BMI was associated with higher colorectal cancer risk. The two-step approach revealed a statistically significant G×BMI interaction located within the Formin 1/Gremlin 1 (<i>FMN1/GREM1</i>) gene region (rs58349661). This SNP was also identified by the 3DF test, with a suggestive statistical significance in the 1DF test. Among participants with the CC genotype of rs58349661, overweight and obesity categories were associated with higher colorectal cancer risk, whereas null associations were observed across BMI categories in those with the TT genotype. Using data from three large international consortia, this study discovered a locus in the <i>FMN1/GREM1</i> gene region that interacts with BMI on the association with colorectal cancer risk. Further studies should examine the potential mechanisms through which this locus modifies the etiologic link between obesity and colorectal cancer.</p>Significance:<p>This gene-environment interaction analysis revealed a genetic locus in FMN1/GREM1 that interacts with body mass index in colorectal cancer risk, suggesting potential implications for precision prevention strategies.</p></div>

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 categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.069
Threshold uncertainty score1.000

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 science0.0010.001
Research integrity0.0010.001
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 head0.031
GPT teacher head0.300
Teacher spread0.268 · 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.

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".

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Citations0
Published2023
Admission routes2
Has abstractyes

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