title: Involvement of BRCA1 and BRCA2 in breast cancer in a western Finnish sub-population.
abstract: To date, two major familial breast cancer predisposition genes, BRCA1 and BRCA2, have been identified with hundreds of germ-line mutations, accounting for 5--10% of all breast cancer and 40--60% of all inherited breast cancer. Unexpectedly elevated incidence of breast cancer, especially in the older age classes, was observed in a Western Finnish region representing a relatively homogeneous population. This study was designed to test the hypothesis that there are inherited BRCA1 or BRCA2 mutations, which confer variable and/or age-dependent penetrance on carriers. Expecting a founder effect, we searched for geographical clustering of breast cancer cases and searched for associations between the affected phenotype and shared genomic segments in the BRCA1 and BRCA2 genomic regions. Our haplotype association study did not reveal any founder effects for either BRCA1 or BRCA2. However, there were two mutations prevalent in this geographical area with minor founder effects, BRCA2 T8555G and 999del5. This is one of the few geographically ascertained, population-based studies that indicate an overall frequency of BRCA1 and BRCA2 mutations at about 2--3% in all breast cancer cases. The geographical clustering of breast cancer cases was not explained by BRCA1 or BRCA2 genes.
authors.affiliation: Department of Medical Genetics, Haartman Institute, University of Helsinki, Helsinki, Finland.
authors.forename: K
authors.initials: K
authors.lastname: Pääkkönen
authors.forename: S
authors.initials: S
authors.lastname: Sauramo
authors.forename: L
authors.initials: L
authors.lastname: Sarantaus
authors.forename: P
authors.initials: P
authors.lastname: Vahteristo
authors.forename: A
authors.initials: A
authors.lastname: Hartikainen
authors.forename: P
authors.initials: P
authors.lastname: Vehmanen
authors.forename: J
authors.initials: J
authors.lastname: Ignatius
authors.forename: V
authors.initials: V
authors.lastname: Ollikainen
authors.forename: H
authors.initials: H
authors.lastname: Kääriäinen
authors.forename: E
authors.initials: E
authors.lastname: Vauramo
authors.forename: H
authors.initials: H
authors.lastname: Nevanlinna
authors.forename: R
authors.initials: R
authors.lastname: Krahe
authors.forename: K
authors.initials: K
authors.lastname: Holli
authors.forename: J
authors.initials: J
authors.lastname: Kere
mesh_terms: D017668:Age of Onset; D024682:BRCA2 Protein; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D016021:Epidemiologic Studies; D005260:Female; D005387:Finland / Q000453:epidemiology; D018703:Founder Effect; D019398:Genes, BRCA1; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D015994:Incidence; D015810:Linkage Disequilibrium; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D019683:Penetrance; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D024682:BRCA2 Protein; D009363:Neoplasm Proteins; D014157:Transcription Factors