Population-Based Study of BRCA1 and BRCA2 Mutations in 1035 Unselected Finnish Breast Cancer Patients

Abstract

Two highly penetrant genes involved in hereditary breast and/or ovarian cancer syndromes, BRCA1 and BRCA2, have been identified (1,2). Mutations in these genes occur throughout their coding sequences, making large-scale testing for mutations challenging. It is, therefore, not surprising that only a few studies have reported estimates of the mutation frequencies among unselected breast cancer patients. Usually, only a few hundred patients have been analyzed in each study, with mutation frequencies ranging from 3.3% to 5.7% for BRCA1 (3–5). The largest studies of BRCA1 and BRCA2 mutations have been carried out in isolated populations, such as the Icelanders or Ashkenazi Jews (6), where individual, highly recurrent founder mutations account for the majority of all mutations (7,8). Results derived from such populations may, however, be biased by the specific nature of these mutations. In whole-gene mutation screening performed by two independent groups (9–11) on 188 breast and breast–ovarian cancer families in Finland, 11 mutations accounted for the vast majority (84%) of all detected BRCA1 and BRCA2 mutations. Besides these recurrent BRCA1 and BRCA2 founder mutations, eight other mutations have been identified only once in the Finnish population [(9–12); Vahteristo P, Eerola H, Tamminen A, Blomqvist C, Nevanlinna H: unpublished observations]. The 11 known mutations provide a unique, rapid way to analyze the impact of BRCA1 and BRCA2 mutations at the population level, without a bias toward any individual founder mutation.