Susceptibility genes in an Iranian breast cancer population: BRCA1, BRCA2, ATM and AR

Introduction: A-breast tumor has a complex nature and concerns as a leading cause of death from cancer in most countries. Epidemiologic studies of familial aggregation have long been provided promising evidences that a family history is a principal risk factor for the disease. Germline mutations in either BRCA1 or BRCA2 are responsible for the majority of hereditary breast and ovarian cancers. Over 800 distinct BRCA1 and over 900 BRCA2 mutations have been identified. To date, within the Iranian population only a small number of germline mutations in BRCA1 and BRCA2 have been identified in wemon with early-onset breast. B-Ataxia-telangiectasia (A-T) is a pleiotropic inherited disease, involved in a wide range of solid tumors and may play a role in sporadic breast cancer and leukemia. Is ATM gene considered as a risk factor for breast cancer? Heterozygosity, LOH, truncated protein, and germline ATM sequence variants in AT families have been reported, but the evaluation of increased risk is still unclear. Regarding the exposure to ionizing radiation, the cellular events seem to be ATM-dependent functions. C-Androgen receptor gene (AR) has a polymorphic CAG-repeat in exon 1 and is considered as a susceptibility allele & phenotypic modifier in BRCA1-associated breast cancer (BC). AR-CAG allele size is associated with BC penetrance in BRCA1 mutation carriers. Wemon were at significant increased risk of BC if they carried at least one AR allele with >27 CAG repeats. The association for the longer two AR alleles is found to be 5% increase in BC-risk. Materials and methods: Blood samples of 300 probands affected with breast cancer were collected. DNAs were extracted by standard procedure, and the informative aspects, regarding the family histories in order to draw the pedigrees, and clinical were gathered. The BRCA gene has been analysed by using the Applied Biosystem ABI sequencer. Results and discussion: Polymorphism 441A>G BRCA2 in exon 11 of BRCA2 in 5 out of 300 probands affected with BC. BRCA2 4643del4 and BRCA1-53C>T IVS17 were also found. As a matter of fact, BRCA2 mutations are more involved in inherited breast cancer in the Iranian population or to the existence of mutations in unknown breast cancer susceptibility genes leading to the disease remains to be investigated in larger studies. Regarding the ATM gene, we found a heterozygotic polymorphism of exon 16 in 3 of 50 probands affected with BC. An association was found between a longer CAG-repeat of AR gene and metastasis in patients of BC who had a positive family history of BC. Longer survival was attained significantly in patients of BC who have higher repeats of CAG (Lower: 69.2±2.1 vs. higher: 76.0±2.9, P