The implementation of informative BRCA1 testing programs is aided by acquisition of population-specific genetic data. From this it emerges that a number of mutations have been found repeatedly, and specific mutations are common in defined populations. This can be referred to a founder effect that in human genetics refers to the presence of genetic disorders that are either endemic to an isolated population or are very rare elsewhere. In a previous population-based study we described the first example of a founder BRCA1 mutation in Italy, with a strong recurrence of the 5083del19 in high-risk patients all of Calabrian origin selected for family history of the disease 1. The same mutation accounts in Canada for a significant percentage of women of Italian ancestry with breast–ovarian cancer 2.

The aim of this study was to investigate the extent to which the 5083del19 mutation contributed to breast–ovarian cancer incidence in Calabria, and to perform some genotype–phenotype correlations.

We tested 70 paraffin-embedded tissue specimens from a consecutive series of breast or ovarian cancer cases. It is estimated that our tissue archive collects more than 90% of incident cancers in the Catanzaro area. Archival tissue samples were genotyped only for the 5083del19 founder mutation. Immunohistochemical staining of several markers (i.e. ER, PR, Ki67, p53, HER2, CK5/6) as well as some pathological features (i.e. histology, grade) were evaluated.

Seven out of the 70 samples screened for this BRCA mutation had mutations. Haplotype analysis revealed a common ancestor. All cases aged in premenopausal years. The phenotype of the 5083del19 BRCA1-associated breast tumours appears characterized by a lack of expression of hormone receptors and is generally associated with high proliferation markers and poorly differentiated aspects. All cases were ductal invasive carcinomas and showed a 'basal-like' portrait according to expression profiling studies 3. The median age at diagnosis of the ovarian cancer carriers was 49 years and the histological type was serous adenocarcinoma.

A predominant BRCA1 gene founder mutation associated with a high risk of early onset breast cancer and ovarian cancer and unfavourable immunophenotype features has been identified and found to occur in a restricted geographical area, thereby allowing timely and cost-effective mutation screening using blood samples or archival histological material.