Involvement of BRCA1 and BRCA2 in breast cancer in a Western Finnish sub-population

To date, two major familial breast cancer predisposition genes, BRCA1 and B RCA2, have been identified with hundreds of germ-line mutations, accounting for 5-10% of all breast cancer and 40-60% of all inherited breast cancer. Unexpectedly elevated incidence of breast cancer, especially in the older a ge classes, was observed in a Western Finnish region representing a relativ ely homogeneous population. This study was designed to test the hypothesis that there are inherited BRCA1 or BRCA2 mutations, which confer variable an d/or age-dependent penetrance on carriers. Expecting a founder effect, we s earched for geographical clustering of breast cancer cases and searched for associations between the affected phenotype and shared genomic segments in the BRCA1 and BRCA2 genomic regions. Our haplotype association study did n ot reveal any founder effects for either BRCA1 or BRCA2. However, there wer e two mutations prevalent in this geographical area with minor founder effe cts,, BRCA2 T8555G and 999del5. This is one of the few geographically ascer tained, population-based studies that indicate an overall frequency of BRCA 1 and BRCA2 mutations at about 2-3% in all breast cancer cases. The geograp hical clustering of breast cancer cases was not explained by BRCA1 or BRCA2 genes. (C) 2001 Wiley-Liss, Inc.