Genetic epidemiology of BRCA1 mutations in Norway

Familial breast-ovarian cancer has been demonstrated to be frequent but une venly distributed in Norway. This was assumed to be caused by the reduced p opulation size created by the medieval Bubonic plague, 25 generations ago, and by the following rapid expansion. We have previously reported that four mutations account for 68% of the BRCA1 mutation carriers. Subsequent analy sis has resulted in a total of 100 separate families carrying one of these founder mutations. The four mutations occurred on one specific BRCA1 haplot ype each. The 1675delA, 816delGT and 3347detAG families originated from the South-West coast of Norway with a few Families in the north, while the tra ceable ancestors of the 1135insA families clustered along the historical in land road from the South-East to mid-Norway. The carriers of each of the fo ur mutations today are descendants of one or a few individuals surviving th e plagues. We may identify the majority of BRCA1 mutation carriers in Norwa y by screening for local founder mutations. (C) 2001 Elsevier Science Ltd. All rights reserved.