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

Eur J Hum Genet. 2000 Oct;8(10):757-63. doi: 10.1038/sj.ejhg.5200529.

Abstract

In the Finnish breast and ovarian cancer families six BRCA1 and five BRCA2 mutations have been found recurrently. Some of these recurrent mutations have also been seen elsewhere in the world, while others are exclusively of Finnish 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 were estimated to trace back to 7-36 generations (150-800 years). The time estimates and the geographical clustering of these founder mutations in Finland are in concordance with the population history of this country. Analysis of the cancer phenotypes showed differential ovarian cancer expression in families carrying mutations in the 5' and 3' ends of the BRCA1 gene, and earlier age of ovarian cancer onset in families with BRCA1 mutations compared with families with BRCA2 mutations. The identification of prominent and regional BRCA1 and BRCA2 founder mutations in Finland will have significant impact on diagnostics in Finnish breast and ovarian cancer families. An isolated population with known history and multiple local founder effects in multigenic disease may offer distinct advantages also for mapping novel predisposing genes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • BRCA2 Protein
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Family
  • Female
  • Finland / epidemiology
  • Founder Effect*
  • Genes, BRCA1 / genetics*
  • Genotype
  • Haplotypes
  • Humans
  • Middle Aged
  • Mutation / genetics*
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / pathology
  • Phenotype
  • Time Factors
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism

Substances

  • BRCA2 Protein
  • Neoplasm Proteins
  • Transcription Factors