UICC World Cancer Congress 2006

Objective:The mutations in two breast cancer susceptibility genes, including, BRCA1 and BRCA2, are frequently associated with familial breast cancer. There are a few identical of founder mutations BRCA1 and BRCA2 appears to predispose a substantial proportion of high-risk families. Therefore, we aimed to investigate the probable founder mutations in 400 Iranian affected patients with primary breast cancer. Methods:Totally 400 patients affected with primary breast cancer included in this study. Mutation detection was carried out on the basis of a PCR-based amplification and two founder mutations for BRCA1 (185delAG, 5382insC) and one for BRCA2 (6174delT) were screened by considering pedigree analysis. Results: A positive family history of BC and other malignancies were recorded in 27.5% and 52% of patients' pedigrees, respectively. The most frequent occurrence of breast cancer across four generations revealed to be in 1st degree in 3rd generation 50%, in 2nd degree in 2nd generation 68.8% and in 3rd degree in 3rd generation 59.5%. The 185delAG mutation in the BRCA1 gene was found in 2/400 (0.5%) investigated pedigrees. The 185delAG mutation in the BRCA1 gene was found in 0.5% of Iranian participants, including two sisters of the same family. To our interest both sisters carry similar genetic alteration of the genes, which had a complete penetrance. However, the identical mutation was observed in two different organic targeting, at almost an early age of onset (Proband: 45y, her sister: 30y).