title: High frequency of recurrent mutations in BRCA1 and BRCA2 genes in Polish families with breast and ovarian cancer.
abstract: Germ-line mutations in BRCA1 and BRCA2 genes result in a significantly increased risk of breast and ovarian cancer. Other genes involved in an increased predisposition to breast cancer include the TP53 gene, mutated in Li-Fraumeni syndrome. To estimate the frequency of germ-line mutations in these three genes in Upper Silesia, we have analyzed 47 breast/ovarian cancer families from that region. We found five different disease predisposing mutations in 17 (36%) families. Twelve families (25.5%) carried known BRCA1 mutations (5382insC and C61G), four families (8.5%) carried novel BRCA2 mutations (9631delC and 6886delGAAAA), and one family (2%) harbored novel mutation 1095del8 in the TP53 gene, which is the largest germline deletion in coding sequence of this gene identified thus far. The 5382insC mutation in BRCA1 was found in 11 families and the 9631delC mutation in BRCA2 occurred in three families. These two mutations taken together contribute to 82% of all mutations found in this study, and 30% of the families investigated harbor one of these mutations. The very high frequency of common mutations observed in these families can only be compared to that reported for Ashkenazi Jewish, Icelandic, and Russian high-risk families. This frequency, however, may not be representative for the entire Polish population. The observed distribution of mutations will favor routine pre-screening of predisposed families using a simple and cost-effective test.
authors: Department of Tumor Biology, Centre of Oncology, Maria Sklodowska-Curie Memorial Institute, Gliwice, Poland. wlodkrzy@man.poznan.pl
authors: E
authors: E
authors: Grzybowska
authors: H
authors: H
authors: Zientek
authors: A
authors: A
authors: Jasinska
authors: M
authors: M
authors: Rusin
authors: P
authors: P
authors: Kozlowski
authors: K
authors: K
authors: Sobczak
authors: A
authors: A
authors: Sikorska
authors: E
authors: E
authors: Kwiatkowska
authors: L
authors: L
authors: Gorniak
authors: E
authors: E
authors: Kalinowska
authors: B
authors: B
authors: Utracka-Hutka
authors: J
authors: J
authors: Wloch
authors: E
authors: E
authors: Chmielik
authors: W J
authors: WJ
authors: Krzyzosiak
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D024682:BRCA2 Protein; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D019398:Genes, BRCA1 / Q000235:genetics*; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D010375:Pedigree; D011044:Poland / Q000453:epidemiology; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D024682:BRCA2 Protein; D005819:Genetic Markers; D009363:Neoplasm Proteins; D014157:Transcription Factors