title: BRCA1 status in Pakistani breast cancer patients with moderate family history.
abstract: OBJECTIVE
  To determine BRCA1 status in breast carcinoma patients of Pakistani origin.
  
  
  METHODS
  Observational study.
  
  
  METHODS
  The Oncology Clinics of the Aga Khan University Hospital, Karachi, between May 2005 and December 2009.
  
  
  METHODS
  Fifty three breast cancer patients based on clinical and laboratory diagnosis were recruited for this study. Moderate family history was defined as having a close relative (mother, daughter, sister) diagnosed with breast cancer under 45 years. Peripheral blood samples were collected from each patient in a 5 ml tube containing EDTA as anticoagulant. Subsequent to DNA extraction, mutational analysis of BRCA1 exons 2, 5, 6, 16, 20 and 22 was carried out using single strand conformation polymorphism (SSCP) assay while protein truncation test (PTT) was used to examine mutations in exon 11. All BRCA1 sequence variants were confirmed by DNA sequencing.
  
  
  RESULTS
  Twenty-three patients were diagnosed with early onset breast cancer, 30 patients had moderate family history. At the time of diagnosis, the median age of enrolled patients was 39 years (range 24-65 years). Out of 53 patients, analyzed by SSCP assay, mobility shift was detected in exon 6, 16 and 20 of three patients, whereas one patient was tested positive for mutation in exon 11 by PTT assays. All patients with BRCA1 mutations were further confirmed by DNA sequencing analysis. In exon 16 c.4837A > G was confirmed, which is a common polymorphism reported in several populations including Asians. Moreover, mutations in exon 6 (c.271T > G), exon 20 (c.5231 delG) and exon 11 (c.1123 T > G) were reported first time in the Pakistani population.
  
  
  CONCLUSIONS
  Several BRCA1 mutations were observed in Pakistani breast cancer patients with moderate family history. Therefore, mutation-based genetic counselling for patients with moderate family history can facilitate management, if one first or second degree relative or early onset disease is apparent.
authors.affiliation: Department of Pathology and Microbiology, The Aga Khan University Hospital, Karachi.
authors.forename: Tariq
authors.initials: T
authors.lastname: Moatter
authors.forename: Muniba
authors.initials: M
authors.lastname: Aban
authors.forename: Shaista
authors.initials: S
authors.lastname: Khan
authors.forename: Iqbal
authors.initials: I
authors.lastname: Azam
authors.forename: Shahid
authors.initials: S
authors.lastname: Pervez
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics*; D005091:Exons; D005190:Family; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D010154:Pakistan / Q000453:epidemiology; D016133:Polymerase Chain Reaction; D015995:Prevalence; D012189:Retrospective Studies; D044767:Ubiquitin-Protein Ligases / Q000097:blood / Q000235:genetics*
chemical_list: D004273:DNA, Neoplasm; C111164:BRAP protein, human; D044767:Ubiquitin-Protein Ligases