title: Novel germline BRCA1 mutations detected in women in singapore who developed breast carcinoma before the age of 36 years.
abstract: BACKGROUND
  In recent years, although BRCA1 has been extensively investigated, the contribution of inherited BRCA1 mutations to breast carcinoma in Asian populations is largely unknown. The authors undertook this study to determine the prevalence and spectrum of germline BRCA1 mutations among women in Singapore with early onset breast carcinoma.
  
  
  METHODS
  Forty-three of 72 eligible patients whose breast carcinoma was diagnosed before the age of 36 years were studied, independent of family history. DNA samples from 50 unrelated individuals randomly selected from the National Thalassemia Registry served as controls. Mutational screening was performed by single-strand conformation polymorphism analysis and protein truncation test, and alterations were confirmed by sequencing. First-degree relatives of patients with definite BRCA1 mutations were offered screening.
  
  
  RESULTS
  A total of 6 novel alterations in BRCA1 were identified, including 2 frameshift mutations in exon 11 (2846insA and 2885delA), 3 rare sequence variants, and 1 polymorphism. Three women (7%) carried deleterious mutations, and the mutation was present in at least 1 unaffected first-degree relative of the proband. The same mutation (2846insA) was identified in 2 of the 7 unrelated subjects of Malay ethnicity. One mutation and three rare variants were identified in four women with no family history of breast or ovarian carcinoma whereas all women with affected first-degree relatives did not harbor BRCA1 mutations. No mutation was identified in the controls.
  
  
  CONCLUSIONS
  The spectrum of germline BRCA1 mutations among the patients in this study was distinct from that in Caucasian populations although a similar prevalence was observed. Larger studies are necessary to clarify the significance of the mutation 2846insA in the Malay community and the penetrance of specific mutations in the Singapore population.
authors.affiliation: Department of Surgery, Singapore General Hospital, Singapore.
authors.forename: G H
authors.initials: GH
authors.lastname: Ho
authors.forename: B H
authors.initials: BH
authors.lastname: Phang
authors.forename: I S
authors.initials: IS
authors.lastname: Ng
authors.forename: H Y
authors.initials: HY
authors.lastname: Law
authors.forename: K C
authors.initials: KC
authors.lastname: Soo
authors.forename: E H
authors.initials: EH
authors.lastname: Ng
mesh_terms: D000328:Adult; D017668:Age of Onset; D019313:BRCA1 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers; D014644:Genetic Variation; D018095:Germ-Line Mutation; D006801:Humans; D010375:Pedigree; D011110:Polymorphism, Genetic; D012846:Singapore / Q000453:epidemiology
chemical_list: D019313:BRCA1 Protein; D005819:Genetic Markers