title: The majority of 22 Dutch high-risk breast cancer families are due to either BRCA1 or BRCA2.
abstract: 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.
authors.affiliation: Department of Human Genetics, University of Leiden, The Netherlands.
authors.forename: T
authors.initials: T
authors.lastname: Peelen
authors.forename: R S
authors.initials: RS
authors.lastname: Cornelis
authors.forename: M
authors.initials: M
authors.lastname: van Vliet
authors.forename: A
authors.initials: A
authors.lastname: Petrij-Bosch
authors.forename: A M
authors.initials: AM
authors.lastname: Cleton-Jansen
authors.forename: H
authors.initials: H
authors.lastname: Meijers-Heijboer
authors.forename: J G
authors.initials: JG
authors.lastname: Klijn
authors.forename: H F
authors.initials: HF
authors.lastname: Vasen
authors.forename: C J
authors.initials: CJ
authors.lastname: Cornelisse
authors.forename: P
authors.initials: P
authors.lastname: Devilee
mesh_terms: 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*
chemical_list: D024682:BRCA2 Protein; D005819:Genetic Markers; D009363:Neoplasm Proteins; D014157:Transcription Factors