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Record W3041532210 · doi:10.1158/0008-5472.can-20-0447

Genome-Wide Association Study Data Reveal Genetic Susceptibility to Chronic Inflammatory Intestinal Diseases and Pancreatic Ductal Adenocarcinoma Risk

2020· article· en· W3041532210 on OpenAlexaff
Fangcheng Yuan, Rayjean J. Hung, Naomi Walsh, Han Zhang, Elizabeth A. Platz, William Wheeler, Lei Song, Alan A. Arslan, Laura E. Beane Freeman, Paige M. Bracci, Federico Canzian, Mengmeng Du, Steven Gallinger, Graham G. Giles, Phyllis J. Goodman, Charles Kooperberg, Loı̈c Le Marchand, Rachel Ε. Neale, Jonas Rosendahl, Ghislaine Scélo, Xiao‐Ou Shu, Kala Visvanathan, Emily White, Wei Zheng, Demetrius Albanes, Pilar Amiano, Gabriella Andreotti, Ana Babić, William R. Bamlet, Sonja I. Berndt, Paul Brennan, Bas Bueno‐de‐Mesquita, Julie E. Buring, Peter T. Campbell, Stephen J. Chanock, Charles S. Fuchs, J. Michael Gaziano, Michael Goggins, Thilo Hackert, Patricia Hartge, Manal M. Hassan, Elizabeth A. Holly, Robert N. Hoover, Verena Katzke, Holger Kirsten, Robert C. Kurtz, I‐Min Lee, Núria Malats, Roger L. Milne, Neil Murphy, Kimmie Ng, Ann L. Oberg, Miquel Porta, Kari G. Rabe, Francisco X. Real, Nathaniel Rothman, Howard D. Sesso, Debra T. Silverman, Ian M. Thompson, Jean Wactawski‐Wende, Xiaoliang Wang, Nicolas Wentzensen, Lynne R. Wilkens, Herbert Yu, Anne Zeleniuch‐Jacquotte, Jianxin Shi, Eric J. Duell, Laufey T. Ámundadóttir, Donghui Li, Gloria M. Petersen, Brian M. Wolpin, Harvey A. Risch, Kai Yu, Alison P. Klein, Rachael Z. Stolzenberg‐Solomon

Bibliographic record

VenueCancer Research · 2020
Typearticle
Languageen
FieldMedicine
TopicPancreatitis Pathology and Treatment
Canadian institutionsLunenfeld-Tanenbaum Research Institute
FundersNational Center for Chronic Disease Prevention and Health PromotionDivision of Cancer Epidemiology and Genetics, National Cancer InstituteNational Institute of Neurological Disorders and StrokeNational Cancer InstituteCancer Council VictoriaNational Institute of Environmental Health SciencesMinisterio de Ciencia y TecnologíaNational Institute of Mental HealthNational Heart, Lung, and Blood InstituteMinistero della SaluteGrantová Agentura České RepublikyEuropean Cooperation in Science and TechnologyMinisterstvo Zdravotnictví Ceské RepublikyCalifornia Department of Public HealthPancreatic Cancer Action NetworkU.S. Department of DefenseWorld Health OrganizationNational Institutes of HealthU.S. Department of Health and Human ServicesLustgarten FoundationNational Human Genome Research InstituteCentro de Investigación Biomédica en Red de Epidemiología y Salud Pública
KeywordsInflammatory bowel diseasePancreatitisUlcerative colitisGenome-wide association studyMedicineDiseaseGenetic predispositionGenetic associationPrimary sclerosing cholangitisInternal medicineGastroenterologyBiologyGenotypeSingle-nucleotide polymorphismGeneGenetics

Abstract

fetched live from OpenAlex

Abstract Registry-based epidemiologic studies suggest associations between chronic inflammatory intestinal diseases and pancreatic ductal adenocarcinoma (PDAC). As genetic susceptibility contributes to a large proportion of chronic inflammatory intestinal diseases, we hypothesize that the genomic regions surrounding established genome-wide associated variants for these chronic inflammatory diseases are associated with PDAC. We examined the association between PDAC and genomic regions (±500 kb) surrounding established common susceptibility variants for ulcerative colitis, Crohn's disease, inflammatory bowel disease, celiac disease, chronic pancreatitis, and primary sclerosing cholangitis. We analyzed summary statistics from genome-wide association studies data for 8,384 cases and 11,955 controls of European descent from two large consortium studies using the summary data-based adaptive rank truncated product method to examine the overall association of combined genomic regions for each inflammatory disease group. Combined genomic susceptibility regions for ulcerative colitis, Crohn disease, inflammatory bowel disease, and chronic pancreatitis were associated with PDAC at P values < 0.05 (0.0040, 0.0057, 0.011, and 3.4 × 10−6, respectively). After excluding the 20 PDAC susceptibility regions (±500 kb) previously identified by GWAS, the genomic regions for ulcerative colitis, Crohn disease, and inflammatory bowel disease remained associated with PDAC (P = 0.0029, 0.0057, and 0.0098, respectively). Genomic regions for celiac disease (P = 0.22) and primary sclerosing cholangitis (P = 0.078) were not associated with PDAC. Our results support the hypothesis that genomic regions surrounding variants associated with inflammatory intestinal diseases, particularly, ulcerative colitis, Crohn disease, inflammatory bowel disease, and chronic pancreatitis are associated with PDAC. Significance: The joint effects of common variants in genomic regions containing susceptibility loci for inflammatory bowel disease and chronic pancreatitis are associated with PDAC and may provide insights to understanding pancreatic cancer etiology.

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)0.001
metaresearch head score (Gemma)0.004
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 score0.009
Threshold uncertainty score0.602

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.004
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 science0.0000.001
Research integrity0.0000.001
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 head0.074
GPT teacher head0.377
Teacher spread0.302 · 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

Citations9
Published2020
Admission routes1
Has abstractyes

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