High frequency of BRCA1 founder mutations in Polish women with nonfamilial breast cancer

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.