Senologie - Zeitschrift für Mammadiagnostik und -therapie 2019; 16(02): e43-e44
DOI: 10.1055/s-0039-1688068
Abstracts
Georg Thieme Verlag KG Stuttgart · New York

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

N Weber-Lassalle
1   Faculty of Medicine and University Hospital Cologne, Center for Hereditary Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), Cologne, Deutschland
,
J Borde
1   Faculty of Medicine and University Hospital Cologne, Center for Hereditary Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), Cologne, Deutschland
,
K Weber-Lassalle
1   Faculty of Medicine and University Hospital Cologne, Center for Hereditary Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), Cologne, Deutschland
,
J Horváth
2   University Hospital Muenster, Institute for Human Genetics, Münster, Deutschland
,
D Niederacher
3   Heinrich-Heine University Duesseldorf, Department of Gynaecology and Obstetrics, Düsseldorf, Deutschland
,
N Arnold
4   Christian-Albrechts University Kiel, Institute of Clinical Molecular Biology, Department of Gynaecology and Obstetrics, Kiel, Deutschland
,
S Kaulfuß
5   Georg August University, University Medical Center, Institute of Human Genetics, Goettingen, Deutschland
,
C Ernst
1   Faculty of Medicine and University Hospital Cologne, Center for Hereditary Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), Cologne, Deutschland
,
VG Paul
2   University Hospital Muenster, Institute for Human Genetics, Münster, Deutschland
,
E Honisch
3   Heinrich-Heine University Duesseldorf, Department of Gynaecology and Obstetrics, Düsseldorf, Deutschland
,
K Klaschik
1   Faculty of Medicine and University Hospital Cologne, Center for Hereditary Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), Cologne, Deutschland
,
AE Volk
6   University Medical Center Hamburg-Eppendorf, Institute of Human Genetics, Hamburg, Deutschland
,
C Kubisch
6   University Medical Center Hamburg-Eppendorf, Institute of Human Genetics, Hamburg, Deutschland
,
S Rapp
7   University Medical Center of the Johannes Gutenberg-University Mainz, Preventive Cardiology and Preventive Medicine, Mainz, Deutschland
,
N Lichey
2   University Hospital Muenster, Institute for Human Genetics, Münster, Deutschland
,
J Altmüller
8   University of Cologne, Cologne Center for Genomics, Cologne, Deutschland
9   University of Cologne, Center for Molecular Medicine Cologne (CMMC), Cologne, Deutschland
,
L Lepkes
1   Faculty of Medicine and University Hospital Cologne, Center for Hereditary Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), Cologne, Deutschland
,
E Pohl-Rescigno
1   Faculty of Medicine and University Hospital Cologne, Center for Hereditary Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), Cologne, Deutschland
,
H Thiele
8   University of Cologne, Cologne Center for Genomics, Cologne, Deutschland
,
P Nürnberg
8   University of Cologne, Cologne Center for Genomics, Cologne, Deutschland
9   University of Cologne, Center for Molecular Medicine Cologne (CMMC), Cologne, Deutschland
,
M Larsen
1   Faculty of Medicine and University Hospital Cologne, Center for Hereditary Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), Cologne, Deutschland
,
L Richters
1   Faculty of Medicine and University Hospital Cologne, Center for Hereditary Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), Cologne, Deutschland
,
K Rhiem
1   Faculty of Medicine and University Hospital Cologne, Center for Hereditary Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), Cologne, Deutschland
,
B Wappenschmidt
1   Faculty of Medicine and University Hospital Cologne, Center for Hereditary Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), Cologne, Deutschland
,
C Engel
10   University of Leipzig, Institute for Medical Informatics, Statistics and Epidemiology, Leipzig, Deutschland
11   University of Leipzig, LIFE, Leipzig Research Centre for Civilization Diseases, Leipzig, Deutschland
,
A Meindl
12   University of Munich, Department of Gynaecology and Obstetrics, Munich, Deutschland
,
RK Schmutzler
1   Faculty of Medicine and University Hospital Cologne, Center for Hereditary Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), Cologne, Deutschland
,
E Hahnen
1   Faculty of Medicine and University Hospital Cologne, Center for Hereditary Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), Cologne, Deutschland
,
J Hauke
1   Faculty of Medicine and University Hospital Cologne, Center for Hereditary Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), Cologne, Deutschland
› Author Affiliations
Further Information

Publication History

Publication Date:
28 May 2019 (online)

Also available at
 

The role of BARD1 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. A total of 4,469 BRCA1/2-negative female index patients with BC, 451 BRCA1/2-negative index patients with OC, and 2,767 geographically-matched female controls were screened for loss-of-function (LoF) mutations and potentially damaging rare missense variants in BARD1. All patients met the inclusion criteria of the German Consortium for Hereditary Breast and Ovarian Cancer for germline testing and reported at least one relative with BC or OC. Additional control datasets (ExAC, FLOSSIES) were included for the calculation of odds ratios (ORs). We identified LoF variants in 23 of 4,469 BC index patients (0.51%) and in 36 of 37,265 controls (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 (42.3 years, range: 24 – 60 years) compared with the overall study sample (48.6 years, range: 17 – 92 years; P = 0.00347). Overall, rare and predicted damaging (SIFT, MutationTaster) BARD1 missense variants were significantly more prevalent in BC index patients compared with controls (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. Due to the significant association of germline LoF-variants in BARD1 with early-onset BC, we suggest that intensified surveillance programs should be considered for women carrying pathogenic BARD1 gene variants.