title: Low proportion of BRCA1 and BRCA2 mutations in Finnish breast cancer families: evidence for additional susceptibility genes.
abstract: One hundred breast and breast-ovarian cancer families identified at the Helsinki University Central Hospital in southern Finland and previously screened for mutations in the BRCA2 gene were now analyzed for mutations in the BRCA1 gene. The coding region and splice boundaries of BRCA1 were analyzed by protein truncation test (PTT) and heteroduplex analysis (HA)/SSCP in all 100 families, and 70 were also screened by direct sequencing. Contrary to expectations based on Finnish population history and strong founder effects in several monogenic diseases in Finland, a wide spectrum of BRCA1 and BRCA2 mutations was found. In the BRCA1 gene, 10 different protein truncating mutations were found each in one family. Six of these are novel Finnish mutations and four have been previously found in other European populations. Six different BRCA2 mutations were found in 11 families. Altogether only 21% of the breast cancer families were accounted for by mutations in these two genes. Linkage to both chromosome 17q21 (BRCA1) and 13q12 (BRCA2) was also excluded in a subset of seven mutation-negative families with four or more cases of breast or ovarian cancer. These data indicate that additional breast and breast-ovarian cancer susceptibility genes are likely to be important in Finland.
authors.affiliation: Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Haartmaninkatu 2, 00290 Helsinki, Finland.
authors.forename: P
authors.initials: P
authors.lastname: Vehmanen
authors.forename: L S
authors.initials: LS
authors.lastname: Friedman
authors.forename: H
authors.initials: H
authors.lastname: Eerola
authors.forename: M
authors.initials: M
authors.lastname: McClure
authors.forename: B
authors.initials: B
authors.lastname: Ward
authors.forename: L
authors.initials: L
authors.lastname: Sarantaus
authors.forename: T
authors.initials: T
authors.lastname: Kainu
authors.forename: K
authors.initials: K
authors.lastname: Syrjäkoski
authors.forename: S
authors.initials: S
authors.lastname: Pyrhönen
authors.forename: O P
authors.initials: OP
authors.lastname: Kallioniemi
authors.forename: T
authors.initials: T
authors.lastname: Muhonen
authors.forename: M
authors.initials: M
authors.lastname: Luce
authors.forename: T S
authors.initials: TS
authors.lastname: Frank
authors.forename: H
authors.initials: H
authors.lastname: Nevanlinna
mesh_terms: D000328:Adult; D000368:Aged; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein; D001943:Breast Neoplasms / Q000208:ethnology / Q000235:genetics*; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D004198:Disease Susceptibility; D005006:Ethnicity / Q000235:genetics; D005060:Europe / Q000208:ethnology; D005091:Exons / Q000235:genetics; D005260:Female; D005387:Finland / Q000453:epidemiology; D018703:Founder Effect; D019398:Genes, BRCA1; D006801:Humans; D007585:Jews / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D009386:Neoplastic Syndromes, Hereditary / Q000208:ethnology / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000208:ethnology / Q000235:genetics; D010641:Phenotype; D012307:Risk Factors; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D019313:BRCA1 Protein; D024682:BRCA2 Protein; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D014157:Transcription Factors