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Record W2788540749 · doi:10.1038/s41467-018-02942-5

Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer

2018· review· en· W2788540749 on OpenAlexaff
Alison P. Klein, Brian M. Wolpin, Harvey A. Risch, Rachael Z. Stolzenberg‐Solomon, Evelina Mocci, Mingfeng Zhang, Federico Canzian, Erica J. Childs, Jason W. Hoskins, Ashley Jermusyk, Jun Zhong, Fei Chen, Demetrius Albanes, Gabriella Andreotti, Alan A. Arslan, Ana Babić, William R. Bamlet, Laura E. Beane Freeman, Sonja I. Berndt, Amanda L. Blackford, Michael Borges, Ayelet Borgida, Paige M. Bracci, Lauren K. Brais, Paul Brennan, Hermann Brenner, Bas Bueno‐de‐Mesquita, Julie E. Buring, Daniele Campa, Gabriele Capurso, Giulia Martina Cavestro, Kari G. Chaffee, Charles C. Chung, Sean P. Cleary, Michelle Cotterchio, Frederike Dijk, Eric J. Duell, Lenka Foretová, Charles S. Fuchs, Niccola Funel, Steven Gallinger, J. Michael Gaziano, Maria Gazouli, Graham G. Giles, Edward Giovannucci, Michael Goggins, Gary E. Goodman, Phyllis J. Goodman, Thilo Hackert, Christopher A. Haiman, Patricia Hartge, Manal Hasan, Péter Hegyi, Kathy J. Helzlsouer, Joseph M. Herman, Ivana Holcátová, Elizabeth A. Holly, Robert N. Hoover, Eric J. Jacobs, Krzysztof Jamroziak, Vladimí­r Janout, Rudolf Kaaks, Kay‐Tee Khaw, Eric A. Klein, Manolis Kogevinas, Charles Kooperberg, Matthew H. Kulke, Juozas Kupčinskas, Robert J. Kurtz, Daniel A. Laheru, Stefano Landi, Rita T. Lawlor, I.-Min Lee, Loı̈c Le Marchand, Lingeng Lu, Núria Malats, Andrea Mambrini, Satu Männistö, Roger L. Milne, Beatrice Mohelníková-Duchoňová, Rachel Ε. Neale, John P. Neoptolemos, Ann L. Oberg, Sara H. Olson, Irene Orlow, Claudio Pasquali, Alpa V. Patel, Ulrike Peters, Raffaele Pezzilli, Miquel Porta, Francisco X. Real, Nathaniel Rothman, Ghislaine Scélo, Howard D. Sesso, Gianluca Severi, Xiao‐Ou Shu, Debra T. Silverman, Jill P. Smith, Pavel Souček, Malin Sund, Renata Talar‐Wojnarowska, Francesca Tavano, Mark Thornquist, Geoffrey S. Tobias, Stephen K. Van Den Eeden, Yogesh K. Vashist, Kala Visvanathan, Pavel Vodička, Jean Wactawski‐Wende, Zhaoming Wang, Nicolas Wentzensen, Emily White, Herbert Yu, Kai Yu, Anne Zeleniuch‐Jacquotte, Wei Zheng, Peter Kraft, Donghui Li, Stephen J. Chanock, Ofure Obazee, Gloria M. Petersen, Laufey T. Ámundadóttir

Bibliographic record

VenueNature Communications · 2018
Typereview
Languageen
FieldMedicine
TopicPancreatic and Hepatic Oncology Research
Canadian institutionsPublic Health OntarioUniversity of TorontoLunenfeld-Tanenbaum Research InstituteCancer Care OntarioMount Sinai Hospital
FundersCommon FundNational Institute of Environmental Health SciencesNational Institute of Neurological Disorders and StrokeNational Cancer InstituteNational Human Genome Research InstituteNational Institute on Drug AbuseNational Institute of Mental HealthNational Center for Chronic Disease Prevention and Health PromotionNational Heart, Lung, and Blood InstituteInstituto de Salud Carlos IIINational Health and Medical Research CouncilCenters for Disease Control and PreventionNational Institutes of HealthUniversity of California, San FranciscoMinistero della SaluteGrantová Agentura České RepublikyCalifornia Department of Public HealthGeneralitat de CatalunyaBundesministerium für Bildung und ForschungNew York City Department of Health and Mental HygieneNational Institute for Health and Care ResearchMemorial Sloan-Kettering Cancer CenterUniversity of WashingtonFondazione Italiana per la ricerca sulle Malattie del PancreasJohns Hopkins UniversityKaiser PermanenteState of Connecticut Department of Public HealthU.S. Department of DefenseAssociazione Italiana per la Ricerca sul CancroNational Center for Advancing Translational SciencesMedical Research CouncilPancreatic Cancer Action NetworkCancer Research UKWorld Health OrganizationMinisterstvo Zdravotnictví Ceské RepublikyAmerican Cancer SocietyMinisterio de Ciencia y TecnologíaNIH Office of the DirectorCancer Council VictoriaYale UniversityU.S. Department of Health and Human Services
KeywordsPancreatic cancerGenome-wide association studyLocus (genetics)BiologyAlleleGenomeInternal medicineCancerGeneticsGeneOncologyBioinformaticsMedicineGenotypeSingle-nucleotide polymorphism

Abstract

fetched live from OpenAlex

Abstract In 2020, 146,063 deaths due to pancreatic cancer are estimated to occur in Europe and the United States combined. To identify common susceptibility alleles, we performed the largest pancreatic cancer GWAS to date, including 9040 patients and 12,496 controls of European ancestry from the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4). Here, we find significant evidence of a novel association at rs78417682 (7p12/ TNS3 , P = 4.35 × 10 −8 ). Replication of 10 promising signals in up to 2737 patients and 4752 controls from the PANcreatic Disease ReseArch (PANDoRA) consortium yields new genome-wide significant loci: rs13303010 at 1p36.33 ( NOC2L , P = 8.36 × 10 −14 ), rs2941471 at 8q21.11 ( HNF4G , P = 6.60 × 10 −10 ), rs4795218 at 17q12 ( HNF1B , P = 1.32 × 10 −8 ), and rs1517037 at 18q21.32 ( GRP , P = 3.28 × 10 −8 ). rs78417682 is not statistically significantly associated with pancreatic cancer in PANDoRA. Expression quantitative trait locus analysis in three independent pancreatic data sets provides molecular support of NOC2L as a pancreatic cancer susceptibility gene.

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)0.004
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: Meta-analysis · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: none
Teacher disagreement score0.004
Threshold uncertainty score0.020

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0040.006
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0020.012
Bibliometrics0.0030.004
Science and technology studies0.0010.000
Scholarly communication0.0020.001
Open science0.0010.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0030.000

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 head0.228
GPT teacher head0.492
Teacher spread0.264 · 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 designMeta-analysis
Domainnot available
GenreReview

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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Citations280
Published2018
Admission routes1
Has abstractyes

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