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Record W3022788208 · doi:10.1093/jnci/djaa056

Combined Associations of a Polygenic Risk Score and Classical Risk Factors With Breast Cancer Risk

2020· article· en· W3022788208 on OpenAlexafffund
Pooja Middha, Nasim Mavaddat, Parichoy Pal Choudhury, Amber N. Hurson, Sara Lindström, Sabine Behrens, Kyriaki Michailidou, Joe Dennis, Manjeet K. Bolla, Qin Wang, Audrey Jung, Zomoroda Abu‐Ful, Thomas U. Ahearn, Irene L. Andrulis, Hoda Anton‐Culver, Volker Arndt, Kristan J. Aronson, Paul L. Auer, Laura E. Beane Freeman, Heiko Becher, Matthias W. Beckmann, Alicia Beeghly‐Fadiel, Javier Benı́tez, Leslie Bernstein, Stig E. Bojesen, Hiltrud Brauch, Hermann Brenner, Thomas Brüning, Qiuyin Cai, Daniele Campa, Federico Canzian, Ángel Carracedo, Brian D. Carter, Jose E. Castelao, Stephen J. Chanock, Nilanjan Chatterjee, Georgia Chenevix‐Trench, Christine L. Clarke, Fergus J. Couch, Angela Cox, Simon S. Cross, Kamila Czene, James Y. Dai, H. Shelton Earp, Arif B. Ekici, A. Heather Eliassen, Mikael Eriksson, D. Gareth Evans, Peter A. Fasching, Jonine D. Figueroa, Lin Fritschi, Marike Gabrielson, Manuela Gago-Domínguez, Chi Gao, Susan M. Gapstur, Mia M. Gaudet, Graham G. Giles, Anna González‐Neira, Pascal Guénel, Lothar Haeberle, Christopher A. Haiman, Niclas Håkansson, Per Hall, Ute Hamann, Sigrid Hatse, Jane Heyworth, Bernd Holleczek, Robert N. Hoover, John L. Hopper, Anthony Howell, David J. Hunter, Esther M. John, Michael E. Jones, Rudolf Kaaks, Renske Keeman, Cari M. Kitahara, Yon-Dschun Ko, Stella Koutros, Allison W. Kurian, Diether Lambrechts, Loı̈c Le Marchand, Eunjung Lee, Flavio Lejbkowicz, Martha S. Linet, Jolanta Lissowska, Ana Llaneza, Robert J. MacInnis, Maria Elena Martinez, Tabea Maurer, Catriona McLean, Susan L. Neuhausen, Aaron D. Norman, Katie M. O’Brien, Andrew F. Olshan, Janet E. Olson, Håkan Olsson, Nick Orr, Charles M. Perou, Guillermo Pita, Eric C. Polley, Ross L. Prentice, Gad Rennert, Hedy S. Rennert, Kathryn J. Ruddy, Dale P. Sandler, Christobel Saunders, Minouk J. Schoemaker, Ben Schöttker, Fredrick R. Schumacher, Christopher G. Scott, Rodney J. Scott, Xiao‐Ou Shu, Ann Smeets, Melissa C. Southey, John J. Spinelli, Jennifer Stone, Anthony J. Swerdlow, Rulla M. Tamimi, Jack A. Taylor, Melissa A. Troester, Celine M. Vachon, Elke M. van Veen, Xiaoliang Wang, Clarice R. Weinberg, Caroline Weltens, Walter C. Willett, Stacey J. Winham, Alicja Wolk, Xiaohong R. Yang, Wei Zheng, Argyrios Ziogas, Alison M. Dunning, Paul D.P. Pharoah, Marjanka K. Schmidt, Peter Kraft, Douglas F. Easton, Roger L. Milne, Montserrat García‐Closas, Jenny Chang‐Claude

Bibliographic record

VenueJNCI Journal of the National Cancer Institute · 2020
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicBRCA gene mutations in cancer
Canadian institutionsUniversity of British ColumbiaQueen's UniversityLunenfeld-Tanenbaum Research InstituteUniversity of TorontoMount Sinai Hospital
FundersMedical Research and Materiel CommandNational Heart, Lung, and Blood InstituteServicio Gallego de SaludUniversitätsklinikum Hamburg-EppendorfProgramme Grants for Applied ResearchInstituto de Salud Carlos IIICancer Council TasmaniaNational Health and Medical Research CouncilWorld Cancer Research FundMedical Research CouncilCanadian Institutes of Health ResearchNational Institute of Environmental Health SciencesU.S. ArmyNational Institutes of HealthHellenic Health FoundationDeutschen Konsortium für Translationale KrebsforschungXunta de GaliciaInstitut Gustave-RoussyCenters for Disease Control and PreventionInstitut National Du CancerDeutsche KrebshilfeSwedish Cancer FoundationAgence Nationale de Sécurité Sanitaire de l’Alimentation, de l’Environnement et du TravailVetenskapsrådetKU LeuvenRheinische Friedrich-Wilhelms-Universität BonnGovernment of CanadaUniversity of CambridgeMinisterio de Sanidad, Servicios Sociales e IgualdadBundesministerium für Bildung und ForschungOvarian Cancer Research FundMinisterio de Economía y CompetitividadInstitut National de la Santé et de la Recherche MédicaleCancer AustraliaAgence Nationale de la RechercheAgency for Science, Technology and ResearchCancer Council South AustraliaFonds Wetenschappelijk OnderzoekCancerfondenNational Cancer InstituteCancer Institute NSWNational Breast Cancer FoundationMcGill UniversityBreast Cancer Research FoundationCancer Research UKFondation de FranceNIHR Biomedical Research Centre, Royal Marsden NHS Foundation Trust/Institute of Cancer ResearchDeutsche ForschungsgemeinschaftDeutsche Gesetzliche UnfallversicherungGentofte HospitalDivision of Cancer Prevention, National Cancer InstituteNational Institute for Health and Care ResearchAssociazione Italiana per la Ricerca sul CancroGenome CanadaLon V. Smith FoundationFondation du cancer du sein du QuébecDavid F. and Margaret T. Grohne Family FoundationLigue Contre le CancerDeutsches KrebsforschungszentrumSundhed og Sygdom, Det Frie ForskningsrådNational Human Genome Research InstituteCancer Council VictoriaCalifornia Department of Public HealthU.S. Department of Health and Human ServicesMayo ClinicCancer Council Western AustraliaEuropean CommissionStavros Niarchos FoundationCancer Council NSWSusan G. Komen for the Cure
KeywordsBreast cancerMedicineLogistic regressionOdds ratioDemographyRisk factorOncologyRisk factors for breast cancerFamily historyGynecologyInternal medicineCancerStatisticsMathematics

Abstract

fetched live from OpenAlex

We evaluated the joint associations between a new 313-variant PRS (PRS313) and questionnaire-based breast cancer risk factors for women of European ancestry, using 72 284 cases and 80 354 controls from the Breast Cancer Association Consortium. Interactions were evaluated using standard logistic regression and a newly developed case-only method for breast cancer risk overall and by estrogen receptor status. After accounting for multiple testing, we did not find evidence that per-standard deviation PRS313 odds ratio differed across strata defined by individual risk factors. Goodness-of-fit tests did not reject the assumption of a multiplicative model between PRS313 and each risk factor. Variation in projected absolute lifetime risk of breast cancer associated with classical risk factors was greater for women with higher genetic risk (PRS313 and family history) and, on average, 17.5% higher in the highest vs lowest deciles of genetic risk. These findings have implications for risk prevention for women at increased risk 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 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)0.002
metaresearch head score (Gemma)0.005
Version: metacan-v3-hybrid-931329e0061cValidation 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 score0.004
Threshold uncertainty score0.009

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0020.005
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.001
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.001
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

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 head0.032
GPT teacher head0.297
Teacher spread0.265 · 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 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

Citations74
Published2020
Admission routes2
Has abstractyes

Explore more

Same venueJNCI Journal of the National Cancer InstituteSame topicBRCA gene mutations in cancerFrench-language works237,207