BRCA and BRCA Genetic Testing in Breast and/or Ovarian Cancer Families in Iran

Germline mutations in breast cancer susceptibility genes, breast cancer susceptibility gene (BRCA) and breast cancer susceptibility gene (BRCA) are responsible for a substantial proportion of high-risk breast and breast/ovarian cancer in families. Therefore, the aim of this study was to investigate BRCA/ mutations in five high risk Iranian families. Of the 0 breast/ovarian cancer families counselled in our center, five were selected for BRCA/ mutation screening according to our minimal criteria. The complete coding sequences in addition to each intron/exon boundary of the BRCA/ genes were screened by direct sequencing. Fourteen missense substitutions were identified, which were: Gly40Ser, Gly78Glu, Glu75Glu, leu87pro, Ser6Gly, ser040Asn, Glu08Gly, Leu77Leu and Ser46Ser in BRCA; and Gln7His, Glu9Gly, Leu5Leu, Val7Val and Glu05Glu in BRCA. In addition, the splice site mutations (IVS7+8(-TT) and so IVS8-70 (-CATT) were observed in two families. Three mutations were novel (Gly40Ser in BRCA and Glu9Gly, Gln7His in BRCA). The missense substitutions Glu08Pro and Gly40Ser were found in a large series of patients and in five controls. The missense substitution Gly78Glu in BRCA is pathogenic. In addition, these results showed that the probability genotype at the BRCA locus defined by alleles Leu87Pro, GLu08Gly, Ser6Gly, Gly40Ser has an effect pathogenic. In another family َseveral missense substitutions in BRCA gene such as Glu08Gly, Gly 40Ser were found as well as Glu9Gly and Gln7His in BRCA. The pathogenic effect yet has to be verified by more comprehensive populations studies. These results support this thinking that screening for BRCA and BRCA mutations may have the strongest impact on health-care when targeted to high-risk populations.