BRCA1 and BRCA2 mutations in Scotland and Northern Ireland

BRCA1 and BRCA2 mutations have been identified in 107 families in Scotland and Northern Ireland. Ninety-seven of these families had been referred to regional cancer genetics centres and a further 10 were identified from a sequential series of male breast cancers treated in Edinburgh. Fifty-nine of the families had a mutation in BRCA1 and 46 in BRCA2. Two families had both. Family trees were extended and cancer diagnoses verified by means of the unusually complete and accessible Scottish and Northern Irish records. Ten specific recurring mutations (five in each gene) accounted for almost half of the total detected, and almost one-quarter were accounted for by just two (BRCA1 2800 delAA and BRCA2 6503 delTT). The prevalence of breast cancer is similar for BRCA1 and BRCA2 mutation families (average 3.7 and 3.6 per family), but the former have a much greater risk of ovarian cancer (average 1.5 and 0.6 per family, respectively). For breast cancer, age of onset tended to be younger in BRCA1 mutation carriers but, for ovarian cancer, there was no difference between BRCA1 and BRCA2 families in mean age at diagnosis. Mutations within the 5′ two-thirds of BRCA1 carry a significantly higher relative risk of ovarian cancer and the same is true for mutations within the central portion of BRCA2 (the ‘OCCR’). In the former case, this appears to be because of differences in absolute risk for both ovarian and breast cancer, while, in the latter, only ovarian cancer risk varies significantly. The findings confirm that founder mutations are present within the Scottish/Northern Irish population and have implications for the organisation of molecular screening services.