title: High frequency of BRCA1 founder mutations in Polish women with nonfamilial breast cancer.
abstract: Possession of a BRCA1/2 mutation increases risk of contralateral breast and ovarian cancer recurrence and may have an impact on health management decisions, such as imaging screening, preventive surgical interventions and systemic therapies. A hospital-based study was conducted to assess the frequency and spectrum of pathogenic germline BRCA1 and BRCA2 mutations in Polish women with familial and nonfamilial breast cancer. Genomic DNA was extracted from 1581 women with breast cancer and from 2225 healthy individuals. For genotyping BRCA1 (5382insC, T300G, 3819del5, 185delAG, C5370T, 3875del4, 3896delT, 4153delA, 4184del4, 4160delAG, G5332A) mutations and BRCA2 (G1408T, 5467insT, 6174delT, 6192delAT, 6675delTA, 8138del5, 9152delT, C9610T, 9630delC) mutations, a Custom TaqMan (Applied Biosystems) PCR-based technology was adopted. A BRCA1 mutation was found in 26 and 12.5 % of women with familial breast cancer and in 13 and 8.3 % nonfamilial (sporadic) breast cancer, diagnosed before or after 50 years of age, respectively. A much lower frequency of BRCA2 mutation was observed. The predominance of seven BRCA1 mutations (5382insC, T300G, 3819del5, 185delAG, C5370T, 3875del4, 4153delA) studied in the Masovian voivodeship population confirmed a strong founder effect for BRCA1 mutations in the Polish population, and the results of BRCA2 testing confirmed a high diversity in the studied pathogenic mutations in BRCA2 gene. We propose offering inexpensive testing for the presence of BRCA1 founder mutations to all Polish women at the time of initial breast cancer diagnosis, regardless of the patient's family history or age of disease onset.
authors.affiliation: Department of Gastroenterology and Hepatology, Medical Center for Postgraduate Education, Warsaw, Poland.
authors.forename: Pawel
authors.initials: P
authors.lastname: Gaj
authors.forename: Anna
authors.initials: A
authors.lastname: Kluska
authors.forename: Dorota
authors.initials: D
authors.lastname: Nowakowska
authors.forename: Aneta
authors.initials: A
authors.lastname: Bałabas
authors.forename: Magdalena
authors.initials: M
authors.lastname: Piątkowska
authors.forename: Michalina
authors.initials: M
authors.lastname: Dabrowska
authors.forename: Anna
authors.initials: A
authors.lastname: Niwińska
authors.forename: Jerzy
authors.initials: J
authors.lastname: Ostrowski
mesh_terms: D000328:Adult; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D004247:DNA / Q000032:analysis / Q000235:genetics; D005260:Female; D018703:Founder Effect; D005820:Genetic Testing; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D011044:Poland / Q000453:epidemiology; D016133:Polymerase Chain Reaction; D011379:Prognosis
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D004247:DNA