title: Novel mutations in the BRCA1 and BRCA2 genes in Iranian women with early-onset breast cancer.
abstract: BACKGROUND
  Breast cancer is the most common female malignancy and a major cause of death in middle-aged women. So far, germline mutations in the BRCA1 and BRCA2 genes in patients with early-onset breast and/or ovarian cancer have not been identified within the Iranian population.
  
  
  METHODS
  With the collaboration of two main centres for cancer in Iran, we obtained clinical information, family history and peripheral blood from 83 women under the age of 45 with early-onset breast cancer for scanning of germline mutations in the BRCA1 and BRCA2 genes. We analysed BRCA1 exons 11 and BRCA2 exons 10 and 11 by the protein truncation test, and BRCA1 exons 2, 3, 5, 13 and 20 and BRCA2 exons 9, 17, 18 and 23 with the single-strand conformation polymorphism assay on genomic DNA amplified by polymerase chain reaction.
  
  
  RESULTS
  Ten sequence variants were identified: five frameshifts (putative mutations - four novel); three missense changes of unknown significance and two polymorphisms, one seen commonly in both Iranian and British populations.
  
  
  CONCLUSIONS
  Identification of these novel mutations suggests that any given population should develop a mutation database for its programme of breast cancer screening. The pattern of mutations seen in the BRCA genes seems not to differ from other populations studied. Early-onset breast cancer (less than 45 years) and a limited family history is sufficient to justify mutation screening with a detection rate of over 25% in this group, whereas sporadic early-onset breast cancer (detection rate less than 5%) is unlikely to be cost-effective.
authors.affiliation: North Trent Molecular Genetics Laboratory, Sheffield Children's Hospital, Western Bank, Sheffield S10 2TH, UK.
authors.forename: Vahid R
authors.initials: VR
authors.lastname: Yassaee
authors.forename: Sirous
authors.initials: S
authors.lastname: Zeinali
authors.forename: Iraj
authors.initials: I
authors.lastname: Harirchi
authors.forename: Soghra
authors.initials: S
authors.lastname: Jarvandi
authors.forename: Mohammad A
authors.initials: MA
authors.lastname: Mohagheghi
authors.forename: David P
authors.initials: DP
authors.lastname: Hornby
authors.forename: Ann
authors.initials: A
authors.lastname: Dalton
mesh_terms: D000328:Adult; D017668:Age of Onset; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D016368:Frameshift Mutation; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D007492:Iran / Q000453:epidemiology; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D009386:Neoplastic Syndromes, Hereditary / Q000453:epidemiology / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D018389:Codon, Nonsense; D004273:DNA, Neoplasm