Age and Geographical Distribution in Families with BRCA1/BRCA2 Mutations in the Slovak Republic

Breast cancer is the most common malignancy affecting women in the Slovak Republic, accounting for 1,858 and 1,827 newly diagnosed breast cancer cases in years 2000 and 2001, respectively (World Standardized Rates 47.0/100,000 and 46.1/100,000). The complete data from NCRS show that it is also the leading cause of cancer-related mortality among Slovak women, the proportion being 15.1% of all cancer cases. NCRS was created as one of the first in Central and Eastern Europe and contains 30-year-old data about newly diagnosed cancer patients of all types. According to NCRS evidence, 414 and 449 newly diagnosed cases of ovarian cancer were reported in years 2000 and 2001 (World Standardized Rates: 10.9/100,000 and 11.4/100,000). They represent 4.3% of all cancer deaths, and ovarian cancer is therefore the most frequent cause of death of all gynaecological malignancies.A family history of breast and/or ovarian cancer is the most significant risk factor for developing the disease. An estimated 5-10% of all breast and ovarian cancer cases are hereditary in nature [1]. The search for genes associated with hereditary susceptibility to breast or ovarian cancer has been facilitated by the study of large kindreds with multiple affected individuals, and has led to the identification of several susceptibility genes, of which BRCA1 (MIM 113705) and BRCA2 (MIM 600185) are the most penetrant. Carriers of germline mutations in these genes have a 50-85% lifetime risk of breast cancer and a 15-45% risk of developing ovarian cancer during their lifetime [2,3]. It was estimated that the combination of BRCA1/BRCA2 mutations was responsible for approximately 80% of all HBOC families [4,5]. More recent estimates put this risk at about 30% and other low penetrance candidate genes involved in breast cancer susceptibility, CHEK2, ATM, TP53 and PTEN, have been identified [6,7].Here we aim to determine the frequency, age and geographical distribution of families carrying BRCA1/BRCA2 mutations wit