It is a primary goal in clinical cancer genetics to identify in a population the full range of mutant alleles that predispose to breast cancer (or to another cancer) and then to offer a rapid and inexpensive genetic assay to test for these alleles in a single setting. Many challenges are raised by this approach. The genetic test must be accurate, rapid and cost effective. If a disease-associated mutation is found, presymptomatic testing of other family members for the specific mutation is possible.

Mutations in BRCA1 and BRCA2 genes confer a high lifetime risk for both breast and ovarian cancer. Many different BRCA1/2 mutations have been described in families with early-onset breast and ovarian cancer (1, 2). The presence of recurrent mutations in BRCA1 suggests the presence of founder effects. BRCA1 "de novo” mutations are very rare. 66 families were studied in Szczecin with strong aggregations of breast/ovarian cancers. Mutations were found in 35 (53%) of the 66 families. Three BRCA1 abnormalities – 5382insC, C61G, and 4153delA – accounted for 51%, 20%, and 11% of the identified mutations, respectively (3). Similar results were reported in Gliwice, Gdańsk and Poznań centres (4-6). Additional evaluation of 200 familiess originating from all regions of Poland (with at least 3 breast/ovarian cancers) revealed that, constitutional BRCA1 mutations can be detected in 64% (128/200) of these families, and 90% of all of them carried one of the 3 common founder mutations (5382insC, C61G and 4153delA) (7). Mutations in BRCA2 are relatively rare in Poland and no founder BRCA2 mutations have been identified. Several other rare mutations in the BRCA1/2 genes have been found in Polish families with occurrence of hereditary breast and ovarian cancers.Genetic testing for these common BRCA1 mutations is inexpensive and relatively simple in Poland (~100 Euro including genetic counseling). It is based on "multiplex PCR” method with almost 100% specificity in detection of three common Polish BRCA1 mutations. Application of Sequenom mutation detection platform, critically improved screening of broad Polish BRCA1/2 genes mutations spectrum. We have developed diagnostic test focused on 25 Polish recurrent BRCA1/2 genes mutations. Mutation detection method was based on automated MALDI-TOF mass spectrometry in Sequenom MassArray(tm) system using iPLEX GOLD assay reactions that ends after a Single Base Extension (8).

In 2006, 3500 unselected incident cases of early-onset breast cancers were screened for presence of the three common Polish BRCA1 mutations. The proportion of cases with identified mutation was 5.7% (9). In simillar study of 500 unselected ovarian cancers common BRCA1 mutations were detected in 13% of cases (10, 11). It is possible to increase women's awareness about hereditary cancer through the popular press. Genetic testing was offered to 5000 Polish women through an announcement placed in a popular women's magazine "Twój Styl”. A total of 5024 women who qualified received a free genetic test for three mutations in BRCA1 which are common in Poland. Out of these, 198 women (3.9%) were found to carry a BRCA1 mutation. Genetic testing for BRCA1 mutations in Poland should be recommended for adult females who:

– fulfil clinical criteria of hereditary breast/ovarian cancer,

– are affected by breast or ovarian cancer,

– are healthy but have at least one relative with breast/ovarian cancer (breast cancer diagnosed under age 60).

Genetic testing for presence of BRCA1 mutations should be preceded and followed by genetic counseling. So far nearly 5000 BRCA1 mutations carriers have been detected at the International Hereditary Cancer Centre in Szczecin (the world's largest registry of females diagnosed and under surveillance by single centre).

We believe that "Polish model” of solving the problem of BRCA1/BRCA2 testing can be valuable for many populations with relatively high level of genetic homogeneity.