The majority of 22 Dutch high-risk breast cancer families are due to either BRCA1 or BRCA2.
We have analyzed, by a combination of mutation and linkage analysis, the genetic basis of 22 breast cancer families in which at least 4 cases of either breast cancer diagnosed under the age of 60 or ovarian cancer had occurred. Chain-terminating mutations in BRCA1 were evidenced in 6 families, and posterior probabilities of > 0.90 of being linked to BRCA1 in 3. The breast versus ovarian cancer ratio in these 9 families was approximately 2:1. Among the remaining 13 families, significant linkage to markers flanking BRCA2 was established in the admixture test with a maximum multipoint lod score of 3.38, but there was no statistical evidence for genetic heterogeneity. The breast:ovarian cancer ratio in these families was 7:1, suggesting BRCA2 confers a much lower risk for ovarian cancer than does BRCA1. These results suggest that BRCA2 will explain a significant proportion of hereditary breast cancer in the Netherlands, and, together with BRCA1, account for the majority of all high-risk families.
Peelen
T
T
Department of Human Genetics, University of Leiden, The Netherlands.
Cornelis
R S
RS
van Vliet
M
M
Petrij-Bosch
A
A
Cleton-Jansen
A M
AM
Meijers-Heijboer
H
H
Klijn
J G
JG
Vasen
H F
HF
Cornelisse
C J
CJ
Devilee
P
P
D024682:BRCA2 Protein; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D019398:Genes, BRCA1; D005819:Genetic Markers; D006801:Humans; D008126:Lod Score; D008957:Models, Genetic; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D009426:Netherlands / Q000453:epidemiology; D010051:Ovarian Neoplasms / Q000453:epidemiology / Q000235:genetics*; D012307:Risk Factors; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000235:genetics*
D024682:BRCA2 Protein; D005819:Genetic Markers; D009363:Neoplasm Proteins; D014157:Transcription Factors