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

Genes

Judit Sanz¹  Rafael de Cid²  Judith Balmaña³  Sara Torres-Esquius³  Lídia Feliubadaló⁴  Olga Campos⁴  Joan Brunet⁴  Gabriel Capellá⁴  Èlia Grau⁴  Jesús del Valle⁴  Paula Rofes⁴  Agostina Stradella⁴  JoséMarcos Moreno-Cabrera⁴  Raquel Cuesta⁴  Conxi Lázaro⁴  Elisabet Munté⁴  Àlex Teulé⁴  Adriana López-Doriga⁵  Orland Díez⁶ 

[1] Genetic Counselling Unit, Medical Oncology Department, Althaia Xarxa Assistencial Universitària de Manresa, 08243 Manresa, Spain;Genomes for Life-GCAT Lab Group, IGTP, Institut Germans Trias i Pujol (IGTP), 08916 Badalona, Spain;Hereditary Cancer Genetics Group, Vall d’Hebron Institute of Oncology (VHIO), Medical Oncology Department, University Hospital Vall d’Hebron, Universitat Autònoma de Barcelona, 08035 Barcelona, Spain;Hereditary Cancer Program, Catalan Institute of Oncology, IDIBELL-IGTP-IDIBGI, 08916 Badalona, Spain;Oncology Data Analytics Program (ODAP), Catalan Institute of Oncology, 08916 Barcelona, Spain;Vall d’Hebron Hospital Universitari, Catalan Health Institute, 08035 Barcelona, Spain;

关键词: BARD1;    breast cancer;    triple-negative breast cancer;    ovarian cancer;    hereditary breast and ovarian cancer;    moderate cancer risk;   

DOI  :  10.3390/genes12020150

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown