Founder mutations in the BRCA1 gene in polish families with breast-ovariancancer

We have undertaken a hospital-based study, to identify possible BRCA1 and B RCA2 founder mutations in the Polish population. The study group consisted of 66 Polish families with cancer who have at least three related females a ffected with breast or ovarian cancer and who had cancer diagnosed, in at l east one of the three affected females, at age <50 years. A total of 26 fam ilies had both breast and ovarian cancers, 4 families had ovarian cancers o nly, and 36 families had breast cancers only. Genomic DNA was prepared from the peripheral blood leukocytes of at least one affected woman from each f amily. The entire coding region of BRCA1 and BRCA2 was screened for the pre sence of germline mutations, by use of SSCP followed by direct sequencing o f observed variants. Mutations were found in 35 (53 %) of the 66 families s tudied. All but one of the mutations were detected within the BRCA1 gene. B RCA1 abnormalities were identified in all four families with ovarian cancer only, in 67% of 27 families with both breast and ovarian cancer, and in 34 % of 35 families with breast cancer only. The single family with a BRCA2 mu tation had the breast-ovarian cancer syndrome. Seven distinct mutations wer e identified; five of these occurred in two or more families. In total, rec urrent mutations were found in 33 (94%) of the 35 families with detected mu tations. Three BRCA1 abnormalities-5382insC, C61G, and 4153delA-accountcd f or 51%, 20%, and 11% of the identified mutations, respectively.