BRCA1 and BRCA2 Genetic Testing in Breast and/or Ovarian Cancer Families in Iran

Objective: germline mutations in breast cancer susceptibility genes, breast cancer susceptibility gene 1 (brca1) and breast cancer susceptibility gene1 (brca2) 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 brca1/2 mutations in five high risk iranian families. materials and methods: of the 20 breast/ovarian cancer families counselled in our center, five were selected for brca1/2 mutation screening according to our minimal criteria. the complete coding sequences in addition to each intron/exon boundary of the brca1/2 genes were screened by direct sequencing. results: fourteen missense substitutions were identified, which were: gly1140ser, gly1738glu, glu1735glu, leu871pro, ser1613gly, ser1040asn, glu1038gly, leu771leu and ser1436ser in brca1; and gln373his, glu1391gly, leu1521leu, val2171val and glu1035glu in brca2. in addition, the splice site mutations (ivs7+83(-tt) and so ivs8- 70(-catt) were observed in two families. three mutations were novel (gly1140ser in brca1 and glu1391gly, gln373his in brca2).the missense substitutions glu1038pro and gly1140ser were found in a large series of patients and in five controls. conclusion: the missense substitution gly1738glu in brca1 is pathogenic. in addition, these results showed that the probability genotype at the brca1 locus defined by alleles leu871pro, glu1038gly, ser1613gly, gly1140ser has an effect pathogenic. in another family sَeveral missense substitutions in brca1 gene such as glu1038gly, gly 1140ser were found as well as glu1391gly and gln373his in brca2. the pathogenic effect yet has to be verified by more comprehensive populations studies. these results support this thinking that screening for brca1 and brca2 mutations may have the strongest impact on health-care when targeted to high-risk populations.