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Record W2345599686 · doi:10.1371/journal.pone.0153788

RAD51B in Familial Breast Cancer

2016· article· en· W2345599686 on OpenAlexafffund
Liisa M. Pelttari, Sofia Khan, Mikko Vuorela, Johanna I. Kiiski, Sara Vilske, Viivi Nevanlinna, Salla Ranta, Johanna Schleutker, Robert Winqvist, Anne Kallioniemi, Thilo Dörk, Natalia Bogdanova, Jonine D. Figueroa, Paul D.P. Pharoah, Marjanka K. Schmidt, Alison M. Dunning, Montserrat García‐Closas, Manjeet K. Bolla, Joe Dennis, Kyriaki Michailidou, John L. Hopper, Melissa C. Southey, Efraim H. Rosenberg, Peter A. Fasching, Matthias W. Beckmann, Julian Peto, Isabel dos‐Santos‐Silva, Elinor J. Sawyer, Ian Tomlinson, Barbara Burwinkel, Harald Surowy, Pascal Guénel, Thérèse Truong, Stig E. Bojesen, Børge G. Nordestgaard, Javier Benı́tez, Anna González‐Neira, Susan L. Neuhausen, Hoda Anton‐Culver, Hermann Brenner, Volker Arndt, Alfons Meindl, Rita K. Schmutzler, Hiltrud Brauch, Thomas Brüning, Annika Lindblom, Sara Margolin, Jaana M. Hartikainen, Georgia Chenevix‐Trench, Laurien Van Dyck, Hilde Janssen, Jenny Chang-Claude, Anja Rudolph, Paolo Radice, Paolo Peterlongo, Emily Hallberg, Janet E. Olson, Graham G. Giles, Roger L. Milne, Christopher A. Haiman, Fredrick R. Schumacher, Jacques Simard, Martine Dumont, Vessela Kristensen, Anne‐Lise Børresen‐Dale, Wei Zheng, Alicia Beeghly‐Fadiel, Mervi Grip, Irene L. Andrulis, Gord Glendon, Peter Devilee, Caroline Seynaeve, Maartje J. Hooning, Margriet Collée, Angela Cox, Simon S. Cross, Mitul Shah, Robert Luben, Ute Hamann, Diana Torres, Anna Jakubowska, Jan Lubiński, Fergus J. Couch, Drakoulis Yannoukakos, Nick Orr, Anthony J. Swerdlow, Hatef Darabi, Jingmei Li, Kamila Czene, Per Hall, Douglas F. Easton, Johanna Mattson, Carl Blomqvist, Kristiina Aittomäki, Heli Nevanlinna

Bibliographic record

VenuePLoS ONE · 2016
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicBRCA gene mutations in cancer
Canadian institutionsUniversity of TorontoMount Sinai HospitalUniversité LavalLunenfeld-Tanenbaum Research InstituteCentre hospitalier universitaire de Québec
FundersMedical Research and Materiel CommandNational Cancer InstituteCancer Council NSWNational Health and Medical Research CouncilMedical Research CouncilMinistero dello Sviluppo EconomicoDavid F. and Margaret T. Grohne Family FoundationNational Institutes of HealthCancer Council TasmaniaOrionin TutkimussäätiöCancer Institute NSWFonds Wetenschappelijk OnderzoekCanadian Institutes of Health ResearchAssociazione Italiana per la Ricerca sul CancroBiomedicum Helsinki-säätiöU.S. ArmyNorges ForskningsrådKreftforeningenCancer Research UKSuomen KulttuurirahastoFondation du cancer du sein du QuébecFrancis Crick InstituteCancer Council VictoriaDeutsche KrebshilfeMinisterio de Economía y CompetitividadAlfred Kordelinin SäätiöBundesministerium für Bildung und ForschungCancer Council South AustraliaDeutsches KrebsforschungszentrumEuropean CommissionBreast Cancer Research Foundation
KeywordsBreast cancerOdds ratioSingle-nucleotide polymorphismMedicineOncologyMale breast cancerHaplotypeCancerInternal medicineMissense mutationAlleleGeneticsMutationGenotypeBiologyGene

Abstract

fetched live from OpenAlex

Common variation on 14q24.1, close to RAD51B, has been associated with breast cancer: rs999737 and rs2588809 with the risk of female breast cancer and rs1314913 with the risk of male breast cancer. The aim of this study was to investigate the role of RAD51B variants in breast cancer predisposition, particularly in the context of familial breast cancer in Finland. We sequenced the coding region of RAD51B in 168 Finnish breast cancer patients from the Helsinki region for identification of possible recurrent founder mutations. In addition, we studied the known rs999737, rs2588809, and rs1314913 SNPs and RAD51B haplotypes in 44,791 breast cancer cases and 43,583 controls from 40 studies participating in the Breast Cancer Association Consortium (BCAC) that were genotyped on a custom chip (iCOGS). We identified one putatively pathogenic missense mutation c.541C>T among the Finnish cancer patients and subsequently genotyped the mutation in additional breast cancer cases (n = 5259) and population controls (n = 3586) from Finland and Belarus. No significant association with breast cancer risk was seen in the meta-analysis of the Finnish datasets or in the large BCAC dataset. The association with previously identified risk variants rs999737, rs2588809, and rs1314913 was replicated among all breast cancer cases and also among familial cases in the BCAC dataset. The most significant association was observed for the haplotype carrying the risk-alleles of all the three SNPs both among all cases (odds ratio (OR): 1.15, 95% confidence interval (CI): 1.11-1.19, P = 8.88 x 10-16) and among familial cases (OR: 1.24, 95% CI: 1.16-1.32, P = 6.19 x 10-11), compared to the haplotype with the respective protective alleles. Our results suggest that loss-of-function mutations in RAD51B are rare, but common variation at the RAD51B region is significantly associated with familial breast cancer risk.

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)0.001
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
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 score0.005
Threshold uncertainty score0.015

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.001
Bibliometrics0.0010.003
Science and technology studies0.0010.000
Scholarly communication0.0010.000
Open science0.0000.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0050.001

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 head0.022
GPT teacher head0.250
Teacher spread0.227 · 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 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".

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Citations670
Published2016
Admission routes2
Has abstractyes

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Same venuePLoS ONESame topicBRCA gene mutations in cancerFrench-language works237,207