title: Screening for BRCA1 and BRCA2 mutations in Eastern Finnish breast/ovarian cancer families.
abstract: Familial aggregation is thought to account for 5-10% of all breast cancer cases, and high penetrance breast and ovarian cancer susceptibility genes BRCA1 and BRCA2 explain < or =20% of these. Hundreds of mutations among breast/ovarian cancer families have been found in these two genes. The mutation spectrum and prevalence, however, varies widely among populations. Thirty-six breast/ovarian cancer families were identified from a population sample of breast and ovarian cancer cases among a relatively isolated population in Eastern Finland, and the frequency of BRCA1/BRCA2 germline mutations were screened using heteroduplex analysis, protein truncation test and sequencing. Five different mutations were detected in seven families (19.4%). Two mutations were found in BRCA1 and three in BRCA2. One of the mutations (BRCA2 4088insA) has not been detected elsewhere in Finland while the other four, 4216-2nt A-->G and 5370 C-->T in BRCA1 and 999del5 and 6503delTT in BRCA2, are recurrent Finnish founder mutations. These results add to the evidence of the geographical differences in distribution of Finnish BRCA1/BRCA2 mutations. This screen also provides further evidence for the presumption that the majority of Finnish BRCA1/BRCA2 founder mutations have been found and that the proportion of BRCA1/BRCA2 mutations in Finnish breast/ovarian cancer families is around 20%.
authors.affiliation: Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Kuopio, Kuopio, Finland. jaana.hartikainen@uku.fi
authors.forename: J M
authors.initials: JM
authors.lastname: Hartikainen
authors.forename: V
authors.initials: V
authors.lastname: Kataja
authors.forename: M
authors.initials: M
authors.lastname: Pirskanen
authors.forename: A
authors.initials: A
authors.lastname: Arffman
authors.forename: U
authors.initials: U
authors.lastname: Ristonmaa
authors.forename: P
authors.initials: P
authors.lastname: Vahteristo
authors.forename: M
authors.initials: M
authors.lastname: Ryynänen
authors.forename: S
authors.initials: S
authors.lastname: Heinonen
authors.forename: V-M
authors.initials: VM
authors.lastname: Kosma
authors.forename: A
authors.initials: A
authors.lastname: Mannermaa
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005387:Finland; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008403:Mass Screening / Q000379:methods; D018895:Microsatellite Repeats; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics*; D011110:Polymorphism, Genetic; D015995:Prevalence