Prevalence of the most frequent BRCA1 mutations in Polish population

Abstract

The purpose of our study was to establish the frequency and distribution of the four most common BRCA1 mutations in Polish general population and in a series of breast cancer patients. Analysis of the population frequency of 5382insC (c.5266dupC), 300T >G (p.181T >G), 185delAG (c.68_69delAG) and 3819del5 (c.3700_3704del5) mutations of the BRCA1 gene were performed on a group of respectively 16,849, 13,462, 12,485 and 3923 anonymous samples collected at birth in seven Polish provinces. The patient group consisted of 1845 consecutive female breast cancer cases. The most frequent BRCA1 mutation in the general population was 5382insC found in 29 out of 16,849 samples (0.17%). 300T >G and 3819del5 mutations were found in respectively 11 of 13,462 (0.08%) and four of 3923 (0.1%) samples. The population prevalence for combined Polish founder 5382insC and 300T >G mutations was 0.25% (1/400). The frequencies of 5382insC and 300T >G carriers among consecutive breast cancer cases were, respectively, 1.9% (35/1845) and 1.2% (18/1486). Comparing these data with the population frequency, we calculated the relative risk of breast cancer for 5382insC mutation at OR = 17 and for 300T >G mutation at OR = 26. Our results, based on large population studies, show high frequencies of founder 5382insC and 300T >G BRCA1 mutations in Polish general population. Carriage of one of these mutations is connected with a very high relative risk of breast cancer.

Fig. 1

The contributions the mutation detection methods made to analysis pathogenic allels and representative examples of detected mutations. a - representative gels showing PCR products, b - representative DHPLC chromatograms, c - representative sequencing results confirming the presence of the mutations, RFLP - restriction fragment length polymorphism, SSCP - single-strand conformation polymorphism, ASA-PCR - allele-specific PCR, DHPLC - denaturing high performance liquid chromatography

Fig. 2

Map of Poland with division into voivodeships showing geographical distribution and frequencies of BRCA1 5382insC, 300T >G, 185delAG, and 3819del5 mutations. * - only 5382insC mutation