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Grant support

Contract grant sponsor: Supported by the Carlos III National Health Institute funded by FEDER funds-a way to build Europe-(PI19/00553; PI16/00563; PI16/01898; PI16/11363; PI15/00355; PI12/02585; SAF2015-68016-R and CIBERONC); the Government of Catalonia (Pla estrategic de recerca i innovacio en salut (PERIS_MedPerCan and URDCat projects), 2017SGR1282 and 2017SGR496); and CERCA Programa/Generalitat de Catalunya for institutional support. GCAT is supported by Accion de Dinamizacion del ISCIII-MINECO (ADE 10/00026), by the Ministry of Health of the Generalitat of Catalunya and by Agencia de Gestio d'Ajuts Universitaris i de Recerca (AGAUR) (2017-SGR 529) and GCAT Cession Research Project PI-2018-09 GCAT_CM.

Analysis of institutional authors

Rofes PAuthorDel Valle JAuthorFeliubadalo LAuthorStradella AAuthorLopez-Doriga AAuthorMunté EAuthorLazaro CCorresponding AuthorTeule AAuthorCapella GAuthorBrunet JAuthor

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February 7, 2021
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Article

BARD1 Pathogenic Variants are Associated with Triple-Negative Breast Cancer in a Spanish Hereditary Breast and Ovarian Cancer Cohort

Publicated to:Genes. 12 (2): 1-11 - 2021-02-01 12(2), DOI: 10.3390/genes12020150

Authors: Rofes, P; Del Valle, J; Torres-Esquius, S; Feliubadaló, L; Stradella, A; Moreno-Cabrera, JM; López-Doriga, A; Munté, E; De Cid, R; Campos, O; Cuesta, R; Teulé, A; Grau, E; Sanz, J; Capellá, G; Díez, O; Brunet, J; Balmaña, J; Lázaro, C

Affiliations

Althaia Xarxa Assistencial de Manresa - Author
Centro de Investigacion Biomedica en Red de Cancer (CIBERONC) - Author
Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP) - Author
Hospital Universitari de Bellvitge - Author
Hospital Universitari Vall d'Hebron - Author
IGTP - Author
Institut d'investigació biomèdica de bellvitge - Author
Institute Catala Oncologia - Author
Universitat de Girona - Author
Vall d’Hebron Institute of Oncology (VHIO) - Author
‎ Althaia Xarxa Assistencial Univ Manresa, Med Oncol Dept, Genet Counselling Unit, Manresa 08243, Spain - Author
‎ Catalan Inst Oncol, IDIBELL, Hereditary Canc Program, Lhospitalet De Llobregat 08908, Spain - Author
‎ Catalan Inst Oncol, IDIBELL, Med Oncol Dept, Lhospitalet De Llobregat 08908, Spain - Author
‎ Catalan Inst Oncol, IDIBGI, Hereditary Canc Program, Girona 17007, Spain - Author
‎ Catalan Inst Oncol, IGTP, Hereditary Canc Program, Badalona 08916, Spain - Author
‎ Catalan Inst Oncol, Oncol Data Analyt Program ODAP, Lhospitalet De Llobregat 08908, Spain - Author
‎ Consortium Biomed Res Epidemiol & Publ Hlth CIBER, Madrid 28029, Spain - Author
‎ Ctr Invest Biomed Red Canc CIBERONC, Madrid 28929, Spain - Author
‎ IDIBELL, Program Mol Mech & Expt Therapy Oncol Oncobell, Lhospitalet De Llobregat 08908, Spain - Author
‎ Inst Germans Trias & Pujol IGTP, IGTP, Genomes Life GCAT Lab Grp, Badalona 08916, Spain - Author
‎ Univ Autonoma Barcelona, Univ Hosp Vall dHebron, Med Oncol Dept, Hereditary Canc Genet Grp,Vall dHebron Inst Oncol, Barcelona 08035, Spain - Author
‎ Univ Girona, Sch Med, Med Sci Dept, Girona 17007, Spain - Author
‎ Vall dHebron Hosp Univ, Catalan Hlth Inst, Barcelona 08035, Spain - Author
‎ Vall dHebron Inst Oncol VHIO, Hereditary Canc Genet Grp, Barcelona 08035, Spain - Author
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Abstract

© 2021 by the authors. Licensee MDPI, Basel, Switzerland. Only a small fraction of hereditary breast and/or ovarian cancer (HBOC) cases are caused by germline variants in the high-penetrance breast cancer 1 and 2 genes (BRCA1 and BRCA2). BRCA1-associated ring domain 1 (BARD1), nuclear partner of BRCA1, has been suggested as a potential HBOC risk gene, although its prevalence and penetrance are variable according to populations and type of tumor. We aimed to investigate the prevalence of BARD1 truncating variants in a cohort of patients with clinical suspicion of HBOC. A comprehensive BARD1 screening by multigene panel analysis was performed in 4015 unrelated patients according to our regional guidelines for genetic testing in hereditary cancer. In addition, 51,202 Genome Aggregation Database (gnomAD) non-Finnish, non-cancer European individuals were used as a control population. In our patient cohort, we identified 19 patients with heterozygous BARD1 truncating variants (0.47%), whereas the frequency observed in the gnomAD controls was 0.12%. We found a statistically significant association of truncating BARD1 variants with overall risk (odds ratio (OR) = 3.78; CI = 2.10–6.48; p = 1.16 × 10−5). This association remained significant in the hereditary breast cancer (HBC) group (OR = 4.18; CI = 2.10–7.70; p = 5.45 × 10−5). Furthermore, deleterious BARD1 variants were enriched among triple-negative BC patients (OR = 5.40; CI = 1.77–18.15; p = 0.001) compared to other BC subtypes. Our results support the role of BARD1 as a moderate penetrance BC predisposing gene and highlight a stronger association with triple-negative tumors.

Keywords

AdultAlleleAllelesArticleBard1Bard1 protein, humanBiomarkers, tumorBrca1 associated ring domain protein 1Breast cancerCancer riskCohort analysisCohort studiesControlled studyDisease associationEndometrioid carcinomaExonFemaleGene deletionGenetic association studiesGenetic association studyGenetic predispositionGenetic predisposition to diseaseGenetic screeningGenetic testingGenetic variationGeneticsGenotypeGerm-line mutationGermline mutationHealth surveyHereditary breast and ovarian cancerHereditary breast and ovarian cancer syndromeHeterozygosityHomologous recombinationHumanHumansMajor clinical studyMaleModerate cancer riskOvarian cancerOvary cancerPhenotypePopulation surveillancePrevalenceProtein analysisProtein domainSpainTriple negative breast cancerTriple negative breast neoplasmsTriple-negative breast cancerTumor markerTumor suppressor geneTumor suppressor proteinTumor suppressor proteinsUbiquitin protein ligaseUbiquitin-protein ligases

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Genes due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2021, it was in position 72/175, thus managing to position itself as a Q2 (Segundo Cuartil), in the category Genetics & Heredity. Notably, the journal is positioned en el Cuartil Q2 para la agencia Scopus (SJR) en la categoría Genetics.

From a relative perspective, and based on the normalized impact indicator calculated from the Field Citation Ratio (FCR) of the Dimensions source, it yields a value of: 2.77, which indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: Dimensions Jul 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-07-16, the following number of citations:

  • WoS: 10
  • Scopus: 9
  • Europe PMC: 9

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-07-16:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 37.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 38 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 1.
  • The number of mentions on the social network X (formerly Twitter): 3 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.

Leadership analysis of institutional authors

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (ROFES TORRES, PAULA) and Last Author (De Cid R).

the authors responsible for correspondence tasks have been Lazaro Garcia, Concepcion and De Cid R.