sequence variants of brca1 and brca2 genes in four iranian families with breast and ovarian cancer

background: brca1 and brca2 genes have been recognized to be responsible for 20-30% of hereditary breast can­cers and approximately 50% of familial breast and ovarian cancers. therefore, the demand for brca1 and brca2 muta­tion screening is rapidly increasing as their identification will affect medical management of people at increased risk. because of high costs involved in analysis of brca1 and 2 genes, contribution of different mutation types in brca1 and 2 and not knowing who should be tested has hampered wide spread use of molecular testing of high -risk fami­lies. there is a need to identify the genes and types of mutations involved in breast or ovarian cancers at different age of onsets and polymorphism and polymorphic variations in our population. methods: twenty-seven patients with either early onset breast cancer (at age≤ 35 years) or a personal and/or family his­tory of breast or ovarian cancer and 50 control subjects participated in this study. after collecting blood samples and extract­ing dna, brca1 and brca2 genes were fully sequenced. results: thirteen missense substitutions in brca1 and brca2 (9 and 4, respectively) were revealed. two nucleotide substitu­tions were novel (gly1140ser in brca1 and glu1391gly in brca2). the glu1038pro and gly1140ser were found in large series of breast and ovarian cancer and matched controls. conclusion: some nucleotide substitutions were seen only in single families and other in several. in other cases, muta­tions were seen in both brca1 and brca2 genes. clinical significance of these mutations was evaluated comparing with normal controls.