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Record W1901788189 · doi:10.1002/ijc.29590

<scp><i>TERT</i></scp> gene harbors multiple variants associated with pancreatic cancer susceptibility

2015· article· en· W1901788189 on OpenAlexaff
Daniele Campa, Cosmeri Rizzato, Rachael Z. Stolzenberg‐Solomon, Paola Pacetti, Pavel Vodička, Sean P. Cleary, Gabriele Capurso, H. Bas Bueno‐de‐Mesquita, Jens Werner, Maria Gazouli, Katja Butterbach, Audrius Ivanauskas, Nathalia A. Giese, Gloria M. Petersen, Paola Fogar, Zhaoming Wang, Claudio Bassi, Miroslav Ryska, George Theodoropoulos, Charles Kooperberg, Donghui Li, William Greenhalf, Claudio Pasquali, Thilo Hackert, Charles S. Fuchs, Beatrice Mohelníková-Duchoňová, Cosimo Sperti, Niccola Funel, Aida Karina Dieffenbach, Nicholas J. Wareham, Julie E. Buring, Ivana Holcátová, Eithne Costello, Carlo‐Federico Zambon, Juozas Kupčinskas, Harvey A. Risch, Peter Kraft, Paige M. Bracci, Raffaele Pezzilli, Sara H. Olson, Howard D. Sesso, Patricia Hartge, Oliver Strobel, Ewa Małecka‐Panas, Kala Visvanathan, Alan A. Arslan, Sergio Pedrazzoli, Pavel Souček, Domenica Gioffreda, Timothy J. Key, Renata Talar‐Wojnarowska, Aldo Scarpa, Andrea Mambrini, Eric J. Jacobs, Krzysztof Jamroziak, Alison P. Klein, Francesca Tavano, Franco Bambi, Stefano Landi, Melissa A. Austin, Ludmila Vodičková, Hermann Brenner, Stephen J. Chanock, Gianfranco Delle Fave, Ada Piepoli, Maurizio Cantore, Wei Zheng, Brian M. Wolpin, Laufey T. Ámundadóttir, Federico Canzian

Bibliographic record

VenueInternational Journal of Cancer · 2015
Typearticle
Languageen
FieldMedicine
TopicTelomeres, Telomerase, and Senescence
Canadian institutionsUniversity of TorontoUniversity Health Network
FundersNational Institute of Diabetes and Digestive and Kidney DiseasesNational Heart, Lung, and Blood InstituteMedical Research CouncilMinistero della SaluteGrantová Agentura České RepublikyNational Institute for Health and Care ResearchNational Cancer InstituteCancer Research UKPancreatic Cancer UK
KeywordsPancreatic cancerLinkage disequilibriumSingle-nucleotide polymorphismOdds ratioLocus (genetics)BiologyTelomerase RNA componentGeneticsGenotypeCancerInternal medicineTelomerase reverse transcriptaseOncologyGeneTelomeraseMedicine

Abstract

fetched live from OpenAlex

A small number of common susceptibility loci have been identified for pancreatic cancer, one of which is marked by rs401681 in the TERT-CLPTM1L gene region on chromosome 5p15.33. Because this region is characterized by low linkage disequilibrium, we sought to identify whether additional single nucleotide polymorphisms (SNPs) could be related to pancreatic cancer risk, independently of rs401681. We performed an in-depth analysis of genetic variability of the telomerase reverse transcriptase (TERT) and the telomerase RNA component (TERC) genes, in 5,550 subjects with pancreatic cancer and 7,585 controls from the PANcreatic Disease ReseArch (PANDoRA) and the PanScan consortia. We identified a significant association between a variant in TERT and pancreatic cancer risk (rs2853677, odds ratio = 0.85; 95% confidence interval = 0.80-0.90, p = 8.3 × 10(-8)). Additional analysis adjusting rs2853677 for rs401681 indicated that the two SNPs are independently associated with pancreatic cancer risk, as suggested by the low linkage disequilibrium between them (r(2) = 0.07, D' = 0.28). Three additional SNPs in TERT reached statistical significance after correction for multiple testing: rs2736100 (p = 3.0 × 10(-5) ), rs4583925 (p = 4.0 × 10(-5) ) and rs2735948 (p = 5.0 × 10(-5) ). In conclusion, we confirmed that the TERT locus is associated with pancreatic cancer risk, possibly through several independent variants.

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)0.001
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 score0.011
Threshold uncertainty score0.621

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.001
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 science0.0000.000
Research integrity0.0000.000
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 head0.033
GPT teacher head0.313
Teacher spread0.280 · 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

Citations77
Published2015
Admission routes1
Has abstractyes

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