2009 Vienna - European Society of Human Genetics

Cancer genetics
P06.130
spectrum and incidence of BRcA1 and BRcA2 mutations in the
Republic of ireland - An Audit
T. M. McDevitt 1,2 , M. Higgins 1,2 , A. Crowley 1,2 , N. Cody 1,2 , M. Meany 1,2 , C. de
Baroid 1,2 , M. Adams 1,2 , C. Nolan 3 , M. Farrell 3 , E. Berkeley 3 , R. Clarke 3 , P. A.
Daly 3 , A. J. Green 1,2 , D. E. Barton 1,2 ;
1 National Centre for Medical Genetics, Dublin, Ireland, 2 University College Dublin
School of Medicine and Medical Sciences, Dublin, Ireland, 3 HOPE Directorate,
Haematology, Oncology and Palliative Care Service, St James’s Hospital,
Dublin, Ireland.
Comprehensive mutation screening of BRCA1 and BRCA2 has been
available to Irish breast cancer families since 2005 via our Centre. We
present an audit of the data generated following bi-directional sequencing
and MLPA of BRCA1 and BRCA2 in 462 breast/ovarian cancer
patients to date. In total, pathogenic mutations have been identified in
154 families (33%). The spectrum of these mutations comprises nonsense
(BRCA1: 21, BRCA2: 3), frameshift (BRCA1: 30, BRCA2: 56),
splice-site (BRCA1: 7, BRCA2: 2), substitution (BRCA1: 5, BRCA2: 6)
and large deletions (BRCA1: 22, BRCA2: 2). Overall, the incidence of
large deletions was found to be approximately 5% in the patient group
screened to date, accounting for approximately 15% of the total mutation
incidence. Variants of unknown significance were identified in 28
families and of these, 6 were present with a pathogenic mutation. Eight
mutations have been identified in more than 3 apparently unrelated
families: BRCA1: p.E143X (19), c.1294_1333del40 (7), exon 3 deletion
(4), exon 21-24 deletion (4); BRCA2: c.8525delC (9), c.983del4
(6), c.2117delC (7). In addition, a large deletion encompassing exons
1-23 of BRCA1 has been identified in 4 families. Haplotype analysis
for a possible founder effect is underway for some of these recurrent
mutations.
Results to date indicate that a significant proportion of hereditary
breast/ovarian cancer in Ireland are attributable to mutations in BRCA1
and BRCA2 and that large deletions in BRCA1 occur in approximately
5% of Irish breast cancer families, an incidence that is in line with that
observed in other populations (2-10%).
P06.131
Prevention or surveillance - a study among BRcA1/2 mutation
carriers
E. Dagan 1,2 , R. Gershoni-Baruch 1,3 ;
1 Rambam Health Care Campus, Institute of Human Genetics, Haifa, Israel,
2 University of Haifa, Department of Nursing, Haifa, Israel, 3 Technion-Institute of
Technology, Ruth and Bruce Rappaport Faculty of Medicine, Haifa, Israel.
This study aimed to investigate the socio-demographic and clinical
characteristics of BRCA1/2 carriers opting for preventive surgeries. Of
148 BRCA1/2 carriers, 111 (75%) had unilateral breast cancer (BC) and
37 (25%) were asymptomatic women. The study protocol integrated
socio-demographic and clinical follow-up; and psychological questionnaires.
Prophylactic oophorectomy was reported by 84 (75.7%) and 25
(67.6%) unilateral BC patients and asymptomatic women, respectively.
Comparable mean ages at oophorectomy (47±9 years) were noted for
both BC patients and asymptomatic women. However, different mean
ages of 44±10 and 33±9 years recorded for BC and asymptomatic surveillance
groups, respectively (p