title: Multiple founder effects and geographical clustering of BRCA1 and BRCA2 families in Finland.
abstract: In the Finnish breast and ovarian cancer families six BRCA1 and five BRCA2 mutations have been found recurrently. Some of these recurrent mutations have also been seen elsewhere in the world, while others are exclusively of Finnish origin. A haplotype analysis of 26 Finnish families carrying a BRCA1 mutation and 20 families with a BRCA2 mutation indicated that the carriers of each recurrent mutation have common ancestors. The common ancestors were estimated to trace back to 7-36 generations (150-800 years). The time estimates and the geographical clustering of these founder mutations in Finland are in concordance with the population history of this country. Analysis of the cancer phenotypes showed differential ovarian cancer expression in families carrying mutations in the 5' and 3' ends of the BRCA1 gene, and earlier age of ovarian cancer onset in families with BRCA1 mutations compared with families with BRCA2 mutations. The identification of prominent and regional BRCA1 and BRCA2 founder mutations in Finland will have significant impact on diagnostics in Finnish breast and ovarian cancer families. An isolated population with known history and multiple local founder effects in multigenic disease may offer distinct advantages also for mapping novel predisposing genes.
authors.affiliation: Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Finland.
authors.forename: L
authors.initials: L
authors.lastname: Sarantaus
authors.forename: P
authors.initials: P
authors.lastname: Huusko
authors.forename: H
authors.initials: H
authors.lastname: Eerola
authors.forename: V
authors.initials: V
authors.lastname: Launonen
authors.forename: P
authors.initials: P
authors.lastname: Vehmanen
authors.forename: K
authors.initials: K
authors.lastname: Rapakko
authors.forename: E
authors.initials: E
authors.lastname: Gillanders
authors.forename: K
authors.initials: K
authors.lastname: Syrjäkoski
authors.forename: T
authors.initials: T
authors.lastname: Kainu
authors.forename: P
authors.initials: P
authors.lastname: Vahteristo
authors.forename: R
authors.initials: R
authors.lastname: Krahe
authors.forename: K
authors.initials: K
authors.lastname: Pääkkönen
authors.forename: J
authors.initials: J
authors.lastname: Hartikainen
authors.forename: C
authors.initials: C
authors.lastname: Blomqvist
authors.forename: T
authors.initials: T
authors.lastname: Löppönen
authors.forename: K
authors.initials: K
authors.lastname: Holli
authors.forename: M
authors.initials: M
authors.lastname: Ryynänen
authors.forename: R
authors.initials: R
authors.lastname: Bützow
authors.forename: A
authors.initials: A
authors.lastname: Borg
authors.forename: B
authors.initials: B
authors.lastname: Wasteson Arver
authors.forename: E
authors.initials: E
authors.lastname: Holmberg
authors.forename: A
authors.initials: A
authors.lastname: Mannermaa
authors.forename: J
authors.initials: J
authors.lastname: Kere
authors.forename: O P
authors.initials: OP
authors.lastname: Kallioniemi
authors.forename: R
authors.initials: R
authors.lastname: Winqvist
authors.forename: H
authors.initials: H
authors.lastname: Nevanlinna
mesh_terms: D000328:Adult; D000368:Aged; D024682:BRCA2 Protein; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D005190:Family; D005260:Female; D005387:Finland / Q000453:epidemiology; D018703:Founder Effect; D019398:Genes, BRCA1 / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D024682:BRCA2 Protein; D009363:Neoplasm Proteins; D014157:Transcription Factors