BRCA1 testing

Mutations in BRCA1 confer a high lifetime risk for both breast and ovarian cancer. Many different BRCA1 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 families 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]. Genetic testing for these BRCA1 mutations is inexpensive and relatively simple in Poland (~100 Euro including genetic counselling). It is based on the "multiplex PCR" method with almost 100% specificity in detection of three common Polish BRCA1 mutations. 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 an identified mutation was 5.7% [8]. In a similar study of 500 unselected ovarian cancers, common BRCA1 mutations were detected in 13% of cases [9, 10]. 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 with breast or ovarian cancer,

• are healthy but have at least one relative with breast/ovarian cancer (breast cancer diagnosed under age 50).

Genetic testing for presence of BRCA1 mutations should be preceded and followed by genetic counselling. So far nearly 4500 BRCA1 mutation carriers have been detected at the International Hereditary Cancer Centre in Szczecin (the world's largest registry of females diagnosed and under surveillance by a single centre).

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