Engel, Christoph

[["dc.bibliographiccitation.artnumber","55"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Breast Cancer Research"],["dc.bibliographiccitation.volume","21"],["dc.contributor.author","Weber-Lassalle, Nana"],["dc.contributor.author","Borde, Julika"],["dc.contributor.author","Weber-Lassalle, Konstantin"],["dc.contributor.author","Horváth, Judit"],["dc.contributor.author","Niederacher, Dieter"],["dc.contributor.author","Arnold, Norbert"],["dc.contributor.author","Kaulfuß, Silke"],["dc.contributor.author","Ernst, Corinna"],["dc.contributor.author","Paul, Victoria G."],["dc.contributor.author","Honisch, Ellen"],["dc.contributor.author","Klaschik, Kristina"],["dc.contributor.author","Volk, Alexander E."],["dc.contributor.author","Kubisch, Christian"],["dc.contributor.author","Rapp, Steffen"],["dc.contributor.author","Lichey, Nadine"],["dc.contributor.author","Altmüller, Janine"],["dc.contributor.author","Lepkes, Louisa"],["dc.contributor.author","Pohl-Rescigno, Esther"],["dc.contributor.author","Thiele, Holger"],["dc.contributor.author","Nürnberg, Peter"],["dc.contributor.author","Larsen, Mirjam"],["dc.contributor.author","Richters, Lisa"],["dc.contributor.author","Rhiem, Kerstin"],["dc.contributor.author","Wappenschmidt, Barbara"],["dc.contributor.author","Engel, Christoph"],["dc.contributor.author","Meindl, Alfons"],["dc.contributor.author","Schmutzler, Rita K."],["dc.contributor.author","Hahnen, Eric"],["dc.contributor.author","Hauke, Jan"],["dc.date.accessioned","2019-07-09T11:51:25Z"],["dc.date.available","2019-07-09T11:51:25Z"],["dc.date.issued","2019"],["dc.description.abstract","BACKGROUND: The 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). METHODS: A 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). RESULTS: We 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. CONCLUSIONS: Due 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."],["dc.identifier.doi","10.1186/s13058-019-1137-9"],["dc.identifier.pmid","31036035"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16123"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59944"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","Germline loss-of-function variants in the BARD1 gene are associated with early-onset familial breast cancer but not ovarian cancer"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]