J Med Genet 1999;36:304-308
( April )
High frequency of BRCA1/2 germline mutations in 42 Belgian
families with a small number of symptomatic subjects
G Goelena, E Teugelsb d, M Bonduellec, B Neynsb d, J De Grèveb d
a Department of Cancer
Prevention, Vrije Universiteit Brussel, Laarbeeklaan 101, B-1090
Brussels, Belgium, b Laboratory of
Medical and Molecular Oncology, Vrije Universiteit Brussel,
Laarbeeklaan 101, B-1090 Brussels, Belgium, c Department of Medical
Genetics, Vrije Universiteit Brussel, Laarbeeklaan 101, B-1090
Brussels, Belgium, d Department
of Medical Oncology, Vrije Universiteit Brussel, Laarbeeklaan 101, B-1090 Brussels, Belgium
Correspondence to: Professor De Grève.
Received 15 April 1998;
Revised version accepted for publication 6 August 1998
AIM
The initial risk assessments
for BRCA1/2 mutation carriers and estimates of carrier frequencies were
based on extended pedigrees with a large number of symptomatic
subjects. When counselling based on BRCA gene mutation analysis was
initiated, we faced requests for counselling mostly from members of
small families with only two or three affected members. We report on
the likelihood of finding a BRCA mutation in such small families.
METHODSIn the first 100 families
that came for oncogenetic counselling since September 1994, a BRCA1/2
gene mutation screen was initiated if there were two or more
symptomatic first degree relatives, if one of them had ovarian cancer,
or if one breast cancer was diagnosed before the age of 50 years.
RESULTSBRCA gene mutations were
found and confirmed by sequencing in 14 out of 42 families (33%); 10 mutations were in the BRCA1 gene and four in the BRCA2 gene. Our
findings indicate an increased probability of detecting a BRCA gene
mutation when ovarian cancer occurred in the family. There is no
increased probability of detecting a mutation with increasing numbers
of breast cancers. Only 22% of the eligible presymptomatic family
members opted for testing. The presymptomatic female carriers currently
prefer breast surveillance rather than prophylactic surgery.
CONCLUSIONBRCA1/2 gene mutation
testing can be done with reasonable efficiency in the Belgian
population when there are two symptomatic family members. The
availability of testing does not lead to a high frequency of requests
for testing by presymptomatic family members.
Keywords:
BRCA genes;
breast cancer;
ovarian cancer;
predictive testing
© 1999 by J Med Genet
