Multiple founder effects and geographical clustering of BRCA1 and BRCA2 families in Finland

In the Finnish breast and ovarian cancer families six BRCA1 and five BRCA2 mutations have been found recurrently. Some of these recurrent mutations ha ve also been seen elsewhere in the world, while others are exclusively of F innish origin. A haplotype analysis of 26 Finnish families carrying a BRCA1 mutation and 20 families with a BRCA2 mutation indicated that the carriers of each recurrent mutation have common ancestors. The common ancestors wer e estimated to trace back to 7-36 generations (150-800 years). The time est imates and the geographical clustering of these founder mutations in Finlan d are in concordance with the population history of this country. Analysis of the cancer phenotypes showed differential ovarian cancer expression in f amilies carrying mutations in the 5' and 3' ends of the BRCA1 gene, and ear lier age of ovarian cancer onset in families with BRCA1 mutations compared with families with BRCA2 mutations. The identification of prominent and reg ional BRCA1 and BRCA2 founder mutations in Finland will have significant im pact on diagnostics in Finnish breast and ovarian cancer families. An isola ted population with known history and multiple local founder effects in mul tigenic disease may offer distinct advantages also for mapping novel predis posing genes.