Screening for BRCA1 and BRCA2 mutations in Eastern Finnish breast/ovarian cancer families

• Published in: Clinical genetics 2007-10, Vol.72 (4), p.311-320
• Main Authors: Hartikainen, JM, Kataja, V, Pirskanen, M, Arffman, A, Ristonmaa, U, Vahteristo, P, Ryynänen, M, Heinonen, S, Kosma, V-M, Mannermaa, A
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; BRCA1; BRCA2; breast cancer; Breast Neoplasms - genetics; DNA Mutational Analysis; familial; Female; Finland; Fundamental and applied biological sciences. Psychology; General aspects. Genetic counseling; Genes, BRCA1; Genes, BRCA2; Genetics of eukaryotes. Biological and molecular evolution; Genotype; germline; Gynecology. Andrology. Obstetrics; Haplotypes; Humans; Mammary gland diseases; Mass Screening - methods; Medical genetics; Medical sciences; Microsatellite Repeats; Molecular and cellular biology; Mutation; ovarian cancer; Ovarian Neoplasms - genetics; Polymorphism, Genetic; Prevalence; Tumors
• ISSN: 0009-9163; 1399-0004
• DOI: 10.1111/j.1399-0004.2007.00866.x

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 ≤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%.