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Record W2147060099 · doi:10.1093/hmg/ddu300

Genetic variation in mitotic regulatory pathway genes is associated with breast tumor grade

2014· article· en· W2147060099 on OpenAlexafffund
Kristen S. Purrington, Seth W. Slettedahl, Manjeet K. Bolla, Kyriaki Michailidou, Kamila Czene, Heli Nevanlinna, Stig E. Bojesen, Irene L. Andrulis, Angela Cox, Per Hall, Jane Carpenter, Drakoulis Yannoukakos, Christopher A. Haiman, Peter A. Fasching, Robert Winqvist, Hermann Brenner, Annika Lindblom, Georgia Chenevix‐Trench, Javier Benı́tez, Anthony J. Swerdlow, Vessela Kristensen, Pascal Guénel, Alfons Meindl, Hatef Darabi, Mikael Eriksson, Rainer Fagerholm, Kristiina Aittomäki, Carl Blomqvist, Børge G. Nordestgaard, Sune F. Nielsen, Henrik Flyger, Xianshu Wang, Curtis Olswold, Janet E. Olson, Anna Marie Mulligan, Julia A. Knight, Sandrine Tchatchou, Malcolm Reed, Simon S. Cross, Jianjun Liu, Jingmei Li, Keith Humphreys, Christine L. Clarke, Rodney J. Scott, Florentia Fostira, George Fountzilas, Irene Konstantopoulou, Brian E. Henderson, Fredrick R. Schumacher, Loı̈c Le Marchand, Arif B. Ekici, Arndt Hartmann, Matthias W. Beckmann, Jaana M. Hartikainen, Veli‐Matti Kosma, Vesa Kataja, Arja Jukkola‐Vuorinen, Katri Pylkäs, Saila Kauppila, Aida Karina Dieffenbach, Christa Stegmaier, Volker Arndt, Sara Margolin, Rosemary L. Balleine, José Ignacio Arias Pérez, M. Pilar Zamora, Primitiva Menéndez, Alan Ashworth, Michael E. Jones, Nick Orr, Patrick Arveux, Pierre Kerbrat, Thérèse Truong, Peter Bugert, Amanda E. Toland, Christine B. Ambrosone, France Labrèche, Mark S. Goldberg, Martine Dumont, Argyrios Ziogas, Eunjung Lee, Gillian S. Dite, Carmel Apicella, Melissa C. Southey, Jirong Long, Martha J. Shrubsole, Sandra Deming-Halverson, Filomena Ficarazzi, Monica Barile, Paolo Peterlongo, Katarzyna Durda, Katarzyna Jaworska–Bieniek, Robert A.E.M. Tollenaar, Caroline Seynaeve, Thomas Brüning, Yon-Dschun Ko, Carolien H. M. van Deurzen, John W.M. Martens, Mieke Kriege, Jonine D. Figueroa, Stephen J. Chanock, Jolanta Lissowska, Ian Tomlinson, Michael J. Kerin, Nicola Miller, Andreas Schneeweiß, William Tapper, Susan M. Gerty, Lorraine Durcan, Catriona McLean, Roger L. Milne, Laura Baglietto, Isabel dos‐Santos‐Silva, Olivia Fletcher, Nichola Johnson, Laura J. van’t Veer, Sten Cornelissen, Asta Försti, Diana Torres, Thomas Rüdiger, Anja Rudolph, Dieter Flesch‐Janys, Stefan Nickels, Caroline Weltens, Giuseppe Floris, Matthieu Moisse, Joe Dennis, Qin Wang, Alison M. Dunning, Mitul Shah, Judith Brown, Jacques Simard, Hoda Anton‐Culver, Susan L. Neuhausen, John L. Hopper, Natalia Bogdanova, Thilo Dörk, Wei Zheng, Paolo Radice, Anna Jakubowska, Jan Lubiński, Peter Devillee, Hiltrud Brauch, Maartje J. Hooning, Montserrat García‐Closas, Elinor J. Sawyer, Barbara Burwinkel, Frederick Marmee, Graham G. Giles, Julian Peto, Marjanka K. Schmidt, Annegien Broeks, Ute Hamann, Jenny Chang‐Claude, Diether Lambrechts, Paul D.P. Pharoah, Douglas F. Easton, V. Shane Pankratz, Susan Slager, Celine M. Vachon, Fergus J. Couch

Bibliographic record

VenueHuman Molecular Genetics · 2014
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenomics and Chromatin Dynamics
Canadian institutionsUniversité LavalMcGill UniversityMcGill University Health CentreRoyal Victoria Regional Health CentreInstitute of AgingUniversité de MontréalPublic Health OntarioCentre hospitalier universitaire de QuébecRoyal Victoria HospitalUniversity of TorontoUniversity Health NetworkLunenfeld-Tanenbaum Research InstituteMount Sinai Hospital
FundersNational Center for Advancing Translational SciencesCanadian Institutes of Health ResearchNational Institute for Health and Care ResearchWellcome TrustNederlandse Organisatie voor Wetenschappelijk OnderzoekNational Cancer InstituteCancer Research UK
KeywordsBiologyGeneGeneticsGenetic variationMitosisVariation (astronomy)Breast cancerCancer researchCancer

Abstract

fetched live from OpenAlex

Mitotic index is an important component of histologic grade and has an etiologic role in breast tumorigenesis. Several small candidate gene studies have reported associations between variation in mitotic genes and breast cancer risk. We measured associations between 2156 single nucleotide polymorphisms (SNPs) from 194 mitotic genes and breast cancer risk, overall and by histologic grade, in the Breast Cancer Association Consortium (BCAC) iCOGS study (n = 39 067 cases; n = 42 106 controls). SNPs in TACC2 [rs17550038: odds ratio (OR) = 1.24, 95% confidence interval (CI) 1.16-1.33, P = 4.2 × 10(-10)) and EIF3H (rs799890: OR = 1.07, 95% CI 1.04-1.11, P = 8.7 × 10(-6)) were significantly associated with risk of low-grade breast cancer. The TACC2 signal was retained (rs17550038: OR = 1.15, 95% CI 1.07-1.23, P = 7.9 × 10(-5)) after adjustment for breast cancer risk SNPs in the nearby FGFR2 gene, suggesting that TACC2 is a novel, independent genome-wide significant genetic risk locus for low-grade breast cancer. While no SNPs were individually associated with high-grade disease, a pathway-level gene set analysis showed that variation across the 194 mitotic genes was associated with high-grade breast cancer risk (P = 2.1 × 10(-3)). These observations will provide insight into the contribution of mitotic defects to histological grade and the etiology of breast cancer.

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: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.908
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 science0.0000.000
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 head0.005
GPT teacher head0.189
Teacher spread0.185 · 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 designBench or experimental
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

Citations16
Published2014
Admission routes2
Has abstractyes

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