Founder effect of the BRCA1 5382insC mutation in Brazilian patients with hereditary breast ovary cancer syndrome.

The 5382insC mutation in BRCA1 is a frequently reported mutation, being very prevalent in Central and Eastern Europe. This mutation was recurrently reported in Brazil and one case was reported Portugal, but not in Spain and other South-American countries,. We analyzed the haplotypic profile of seven Brazilian carriers of 5382insC to characterize a possible founder effect. The analyses indicated that mutation carriers shared an identical haplotype. The absence of this mutation in Spain, other South American countries, and sub-Saharan populations, as well as the patients' own ancestry, point to a significant Central or Eastern European contribution to the present genetic background of Brazilian population, different from the population structuring of remaining South American countries.

Genomic variation at the MDR1 promoter and P-glycoprotein expression and activity in AML patients.

Sequence variation at the proximal MDR1 promoter of 72 patients with acute myeloid leukemia (AML) was investigated and its association with P-glycoprotein (Pgp) expression and activity using flow cytometry were analyzed. Two variants were found: -129T/C and a non-described A/T substitution at position +68 of intron 1 in one patient. Three different genotypes were identified for single nucleotide polymorphism (SNP) -129T/C: 60 patients TT, 11 individuals TC, and 1 CC. No significant association was found between SNP variants and Pgp activity and expression, at protein level. Our data also suggested that an evaluation of MDR1 promoter polymorphisms is of uncertain prognostic value.