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| Home > Articles > Published articles > BARD1 Pathogenic Variants Are Associated with Triple-Negative Breast Cancer in a Spanish Hereditary Breast and Ovarian Cancer Cohort |
(Centro de Investigación Biomédica en Red de Cáncer) (Centro de Investigación Biomédica en Red de Cáncer) (Centro de Investigación Biomédica en Red de Cáncer) (Centro de Investigación Biomédica en Red de Cáncer) (Centro de Investigación Biomédica en Red de Cáncer) (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol) (Centro de Investigación Biomédica en Red de Cáncer) (Vall d'Hebron Institut d'Oncologia) (Universitat de Girona) (Vall d'Hebron Institut d'Oncologia) (Centro de Investigación Biomédica en Red de Cáncer)| Date: | 2021 |
| Abstract: | 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. |
| Grants: | Instituto de Salud Carlos III PI19/00553 Ministerio de Economía y Competitividad PI16/00563 Ministerio de Economía y Competitividad PI16/01898 Instituto de Salud Carlos III PI16/11363 Ministerio de Economía y Competitividad PI15/00355 Ministerio de Economía y Competitividad PI12/02585 Ministerio de Economía y Competitividad SAF2015-68016-R Ministerio de Ciencia e Innovación 2017SGR1282 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017SGR49 Ministerio de Ciencia e Innovación ADE 10/00026 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017-SGR 529 |
| Rights: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.  |
| Language: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Subject: | BARD1 ; Breast cancer ; Triple-negative breast cancer ; Ovarian cancer ; Hereditary breast and ovarian cancer ; Moderate cancer risk |
| Published in: | Genes, Vol. 12 (january 2021) , ISSN 2073-4425 |
