Evidence map›Paper›PMID 31036035›Full record

ArticleBreast cancer research : BCR2019

Germline loss-of-function variants in the BARD1 gene are associated with early-onset familial breast cancer but not ovarian cancer.

Nana Weber-Lassalle, Julika Borde, Konstantin Weber-Lassalle, Judit Horváth, Dieter Niederacher, Norbert Arnold, Silke Kaulfuß, Corinna Ernst, Victoria G Paul, Ellen Honisch and 19 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Breast cancer research : BCR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed, 2 pooled it
6.1field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

39 citing papers in PubMed, 2 syntheses or guidelines pooled it, 64 citations in OpenAlex.

  1. Pooled it
  2. Summary ofGenes · 2020
    Pooled it
  3. Article
  4. Article
  5. Review
  6. BARD1: A Friend or Foe in Pancreatic Ductal Adenocarcinoma?International journal of molecular sciences · 2025
    Review
  7. GermlineCancers · 2025
    Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Review
  16. bioRxiv : the preprint server for biology · 2023
    Article
  17. Article
  18. Article
  19. Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

29 authors at 9 institutions in 1 country.

Nana Weber-LassalleCenter for Hereditary Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), University of Cologne, Faculty of Medicine and University Hospital Cologne, Kerpener Str. 34, 50931, Cologne, Germany.
Julika BordeCenter for Hereditary Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), University of Cologne, Faculty of Medicine and University Hospital Cologne, Kerpener Str. 34, 50931, Cologne, Germany.
Konstantin Weber-LassalleCenter for Hereditary Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), University of Cologne, Faculty of Medicine and University Hospital Cologne, Kerpener Str. 34, 50931, Cologne, Germany.
Judit HorváthInstitute for Human Genetics, University Hospital Muenster, Muenster, Germany.
Dieter NiederacherDepartment of Gynaecology and Obstetrics, University Hospital Duesseldorf, Heinrich-Heine University Duesseldorf, Duesseldorf, Germany.
Norbert ArnoldInstitute of Clinical Molecular Biology, Department of Gynaecology and Obstetrics, University Hospital of Schleswig-Holstein, Campus Kiel, Christian-Albrechts University Kiel, Kiel, Germany.
Silke KaulfußInstitute of Human Genetics, University Medical Center, Georg August University, Goettingen, Germany.
Corinna ErnstCenter for Hereditary Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), University of Cologne, Faculty of Medicine and University Hospital Cologne, Kerpener Str. 34, 50931, Cologne, Germany.
Victoria G PaulInstitute for Human Genetics, University Hospital Muenster, Muenster, Germany.
Ellen HonischDepartment of Gynaecology and Obstetrics, University Hospital Duesseldorf, Heinrich-Heine University Duesseldorf, Duesseldorf, Germany.
Kristina KlaschikCenter for Hereditary Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), University of Cologne, Faculty of Medicine and University Hospital Cologne, Kerpener Str. 34, 50931, Cologne, Germany.
Alexander E VolkInstitute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Christian KubischInstitute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Steffen RappPreventive Cardiology and Preventive Medicine, Center for Cardiology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.
Nadine LicheyInstitute for Human Genetics, University Hospital Muenster, Muenster, Germany.
Janine AltmüllerCologne Center for Genomics, University of Cologne, Cologne, Germany.
Louisa LepkesCenter for Hereditary Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), University of Cologne, Faculty of Medicine and University Hospital Cologne, Kerpener Str. 34, 50931, Cologne, Germany.
Esther Pohl-RescignoCenter for Hereditary Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), University of Cologne, Faculty of Medicine and University Hospital Cologne, Kerpener Str. 34, 50931, Cologne, Germany.
Holger ThieleCologne Center for Genomics, University of Cologne, Cologne, Germany.
Peter NürnbergCologne Center for Genomics, University of Cologne, Cologne, Germany.
Mirjam LarsenCenter for Hereditary Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), University of Cologne, Faculty of Medicine and University Hospital Cologne, Kerpener Str. 34, 50931, Cologne, Germany.
Lisa RichtersCenter for Hereditary Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), University of Cologne, Faculty of Medicine and University Hospital Cologne, Kerpener Str. 34, 50931, Cologne, Germany.
Kerstin RhiemCenter for Hereditary Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), University of Cologne, Faculty of Medicine and University Hospital Cologne, Kerpener Str. 34, 50931, Cologne, Germany.
Barbara WappenschmidtCenter for Hereditary Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), University of Cologne, Faculty of Medicine and University Hospital Cologne, Kerpener Str. 34, 50931, Cologne, Germany.
Christoph EngelInstitute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.
Alfons MeindlDepartment of Gynaecology and Obstetrics, University of Munich, Campus Großhadern, Munich, Germany.
Rita K SchmutzlerCenter for Hereditary Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), University of Cologne, Faculty of Medicine and University Hospital Cologne, Kerpener Str. 34, 50931, Cologne, Germany.
Eric HahnenCenter for Hereditary Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), University of Cologne, Faculty of Medicine and University Hospital Cologne, Kerpener Str. 34, 50931, Cologne, Germany. eric.hahnen@uk-koeln.de.ORCID 0000-0002-1152-8367
Jan HaukeCenter for Hereditary Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), University of Cologne, Faculty of Medicine and University Hospital Cologne, Kerpener Str. 34, 50931, Cologne, Germany.
University of Cologne · DEUniversity Hospital Münster · DEDüsseldorf University Hospital · DEUniversität Hamburg · DEChristian-Albrechts-Universität zu Kiel · DEJohannes Gutenberg University Mainz · DELeipzig University · DELudwig-Maximilians-Universität München · DEUniversity of Göttingen · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe role of the BARD1 gene in breast cancer (BC) and ovarian cancer (OC) predisposition remains elusive, as published case-control investigations have revealed controversial results. We aimed to assess the role of deleterious BARD1 germline variants in BC/OC predisposition in a sample of 4920 BRCA1/2-negative female BC/OC index patients of the German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC).

methodsA total of 4469 female index patients with BC, 451 index patients with OC, and 2767 geographically matched female control individuals were screened for loss-of-function (LoF) mutations and potentially damaging rare missense variants in BARD1. All patients met the inclusion criteria of the GC-HBOC for germline testing and reported at least one relative with BC or OC. Additional control datasets (Exome Aggregation Consortium, ExAC; Fabulous Ladies Over Seventy, FLOSSIES) were included for the calculation of odds ratios (ORs).

resultsWe identified LoF variants in 23 of 4469 BC index patients (0.51%) and in 36 of 37,265 control individuals (0.10%), resulting in an OR of 5.35 (95% confidence interval [CI] = 3.17-9.04; P < 0.00001). BARD1-mutated BC index patients showed a significantly younger mean age at first diagnosis (AAD; 42.3 years, range 24-60 years) compared with the overall study sample (48.6 years, range 17-92 years; P = 0.00347). In the subgroup of BC index patients with an AAD < 40 years, an OR of 12.04 (95% CI = 5.78-25.08; P < 0.00001) was observed. An OR of 7.43 (95% CI = 4.26-12.98; P < 0.00001) was observed when stratified for an AAD < 50 years. LoF variants in BARD1 were not significantly associated with BC in the subgroup of index patients with an AAD ≥ 50 years (OR = 2.29; 95% CI = 0.82-6.45; P = 0.11217). Overall, rare and predicted damaging BARD1 missense variants were significantly more prevalent in BC index patients compared with control individuals (OR = 2.15; 95% CI = 1.26-3.67; P = 0.00723). Neither LoF variants nor predicted damaging rare missense variants in BARD1 were identified in 451 familial index patients with OC.

conclusionsDue to the significant association of germline LoF variants in BARD1 with early-onset BC, we suggest that intensified BC surveillance programs should be offered to women carrying pathogenic BARD1 gene variants.

Indexed as

Genetic Predisposition to DiseaseGerm-Line MutationLoss of Function MutationAdolescentAdultAgedAged, 80 and overAge of OnsetBreast NeoplasmsFemaleGenetic Association StudiesHigh-Throughput Nucleotide SequencingHumansMiddle AgedOdds RatioOvarian NeoplasmsBARD1 protein, humanTumor Suppressor ProteinsUbiquitin-Protein LigasesBARD1Early onset breast cancerGermline mutationsOvarian cancer

Identifiers

PMID31036035
PMCPMC6489184
OpenAlexW2943029247

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.