title: BRCA1 and BRCA2 mutations in ethnic Lebanese Arab women with high hereditary risk breast cancer.
abstract: OBJECTIVE
  Breast cancer is the most common malignancy among women in Lebanon and in Arab countries, with 50% of cases presenting before the age of 50 years.
  
  
  METHODS
  Between 2009 and 2012, 250 Lebanese women with breast cancer who were considered to be at high risk of carrying BRCA1 or BRCA2 mutations because of presentation at young age and/or positive family history (FH) of breast or ovarian cancer were recruited. Clinical data were analyzed statistically. Coding exons and intron-exon boundaries of BRCA1 and BRCA2 were sequenced from peripheral blood DNA. All patients were tested for BRCA1 rearrangements using multiplex ligation-dependent probe amplification (MLPA). BRCA2 MLPA was done in selected cases.
  
  
  RESULTS
  Overall, 14 of 250 patients (5.6%) carried a deleterious BRCA mutation (7 BRCA1, 7 BRCA2) and 31 (12.4%) carried a variant of uncertain significance. Eight of 74 patients (10.8%) aged ≤40 years with positive FH and only 1 of 74 patients (1.4%) aged ≤40 years without FH had a mutated BRCA. Four of 75 patients (5.3%) aged 41-50 years with FH had a deleterious mutation. Only 1 of 27 patients aged >50 years at diagnosis had a BRCA mutation. All seven patients with BRCA1 mutations had grade 3 infiltrating ductal carcinoma and triple-negative breast cancer. Nine BRCA1 and 17 BRCA2 common haplotypes were observed.
  
  
  CONCLUSIONS
  Prevalence of deleterious BRCA mutations is lower than expected and does not support the hypothesis that BRCA mutations alone cause the observed high percentage of breast cancer in young women of Lebanese and Arab descent. Studies to search for other genetic mutations are recommended.
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, and Departments of Pharmacology and Toxicology, Surgery, and Obstetrics and Gynecology, American University of Beirut, Lebanon; University of Auvergne and Laboratoire Diagnostique Génétique et Moléculaire, Centre Jean Perrin, Clermont-Ferrand, France; Sidney Kimmel Comprehensive Cancer Center and Department of Gynecology and Obstetrics, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA nagi.saghir@aub.edu.lb.
authors.forename: Nagi S
authors.initials: NS
authors.lastname: El Saghir
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, and Departments of Pharmacology and Toxicology, Surgery, and Obstetrics and Gynecology, American University of Beirut, Lebanon; University of Auvergne and Laboratoire Diagnostique Génétique et Moléculaire, Centre Jean Perrin, Clermont-Ferrand, France; Sidney Kimmel Comprehensive Cancer Center and Department of Gynecology and Obstetrics, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Nathalie K
authors.initials: NK
authors.lastname: Zgheib
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, and Departments of Pharmacology and Toxicology, Surgery, and Obstetrics and Gynecology, American University of Beirut, Lebanon; University of Auvergne and Laboratoire Diagnostique Génétique et Moléculaire, Centre Jean Perrin, Clermont-Ferrand, France; Sidney Kimmel Comprehensive Cancer Center and Department of Gynecology and Obstetrics, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Hussein A
authors.initials: HA
authors.lastname: Assi
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, and Departments of Pharmacology and Toxicology, Surgery, and Obstetrics and Gynecology, American University of Beirut, Lebanon; University of Auvergne and Laboratoire Diagnostique Génétique et Moléculaire, Centre Jean Perrin, Clermont-Ferrand, France; Sidney Kimmel Comprehensive Cancer Center and Department of Gynecology and Obstetrics, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Katia E
authors.initials: KE
authors.lastname: Khoury
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, and Departments of Pharmacology and Toxicology, Surgery, and Obstetrics and Gynecology, American University of Beirut, Lebanon; University of Auvergne and Laboratoire Diagnostique Génétique et Moléculaire, Centre Jean Perrin, Clermont-Ferrand, France; Sidney Kimmel Comprehensive Cancer Center and Department of Gynecology and Obstetrics, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Bidet
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, and Departments of Pharmacology and Toxicology, Surgery, and Obstetrics and Gynecology, American University of Beirut, Lebanon; University of Auvergne and Laboratoire Diagnostique Génétique et Moléculaire, Centre Jean Perrin, Clermont-Ferrand, France; Sidney Kimmel Comprehensive Cancer Center and Department of Gynecology and Obstetrics, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Sara M
authors.initials: SM
authors.lastname: Jaber
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, and Departments of Pharmacology and Toxicology, Surgery, and Obstetrics and Gynecology, American University of Beirut, Lebanon; University of Auvergne and Laboratoire Diagnostique Génétique et Moléculaire, Centre Jean Perrin, Clermont-Ferrand, France; Sidney Kimmel Comprehensive Cancer Center and Department of Gynecology and Obstetrics, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Raghid N
authors.initials: RN
authors.lastname: Charara
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, and Departments of Pharmacology and Toxicology, Surgery, and Obstetrics and Gynecology, American University of Beirut, Lebanon; University of Auvergne and Laboratoire Diagnostique Génétique et Moléculaire, Centre Jean Perrin, Clermont-Ferrand, France; Sidney Kimmel Comprehensive Cancer Center and Department of Gynecology and Obstetrics, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Rania A
authors.initials: RA
authors.lastname: Farhat
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, and Departments of Pharmacology and Toxicology, Surgery, and Obstetrics and Gynecology, American University of Beirut, Lebanon; University of Auvergne and Laboratoire Diagnostique Génétique et Moléculaire, Centre Jean Perrin, Clermont-Ferrand, France; Sidney Kimmel Comprehensive Cancer Center and Department of Gynecology and Obstetrics, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Firas Y
authors.initials: FY
authors.lastname: Kreidieh
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, and Departments of Pharmacology and Toxicology, Surgery, and Obstetrics and Gynecology, American University of Beirut, Lebanon; University of Auvergne and Laboratoire Diagnostique Génétique et Moléculaire, Centre Jean Perrin, Clermont-Ferrand, France; Sidney Kimmel Comprehensive Cancer Center and Department of Gynecology and Obstetrics, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Decousus
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, and Departments of Pharmacology and Toxicology, Surgery, and Obstetrics and Gynecology, American University of Beirut, Lebanon; University of Auvergne and Laboratoire Diagnostique Génétique et Moléculaire, Centre Jean Perrin, Clermont-Ferrand, France; Sidney Kimmel Comprehensive Cancer Center and Department of Gynecology and Obstetrics, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Pierre
authors.initials: P
authors.lastname: Romero
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, and Departments of Pharmacology and Toxicology, Surgery, and Obstetrics and Gynecology, American University of Beirut, Lebanon; University of Auvergne and Laboratoire Diagnostique Génétique et Moléculaire, Centre Jean Perrin, Clermont-Ferrand, France; Sidney Kimmel Comprehensive Cancer Center and Department of Gynecology and Obstetrics, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Georges M
authors.initials: GM
authors.lastname: Nemer
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, and Departments of Pharmacology and Toxicology, Surgery, and Obstetrics and Gynecology, American University of Beirut, Lebanon; University of Auvergne and Laboratoire Diagnostique Génétique et Moléculaire, Centre Jean Perrin, Clermont-Ferrand, France; Sidney Kimmel Comprehensive Cancer Center and Department of Gynecology and Obstetrics, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Ziad
authors.initials: Z
authors.lastname: Salem
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, and Departments of Pharmacology and Toxicology, Surgery, and Obstetrics and Gynecology, American University of Beirut, Lebanon; University of Auvergne and Laboratoire Diagnostique Génétique et Moléculaire, Centre Jean Perrin, Clermont-Ferrand, France; Sidney Kimmel Comprehensive Cancer Center and Department of Gynecology and Obstetrics, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Ali
authors.initials: A
authors.lastname: Shamseddine
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, and Departments of Pharmacology and Toxicology, Surgery, and Obstetrics and Gynecology, American University of Beirut, Lebanon; University of Auvergne and Laboratoire Diagnostique Génétique et Moléculaire, Centre Jean Perrin, Clermont-Ferrand, France; Sidney Kimmel Comprehensive Cancer Center and Department of Gynecology and Obstetrics, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Arafat
authors.initials: A
authors.lastname: Tfayli
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, and Departments of Pharmacology and Toxicology, Surgery, and Obstetrics and Gynecology, American University of Beirut, Lebanon; University of Auvergne and Laboratoire Diagnostique Génétique et Moléculaire, Centre Jean Perrin, Clermont-Ferrand, France; Sidney Kimmel Comprehensive Cancer Center and Department of Gynecology and Obstetrics, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Jaber
authors.initials: J
authors.lastname: Abbas
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, and Departments of Pharmacology and Toxicology, Surgery, and Obstetrics and Gynecology, American University of Beirut, Lebanon; University of Auvergne and Laboratoire Diagnostique Génétique et Moléculaire, Centre Jean Perrin, Clermont-Ferrand, France; Sidney Kimmel Comprehensive Cancer Center and Department of Gynecology and Obstetrics, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Faek
authors.initials: F
authors.lastname: Jamali
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, and Departments of Pharmacology and Toxicology, Surgery, and Obstetrics and Gynecology, American University of Beirut, Lebanon; University of Auvergne and Laboratoire Diagnostique Génétique et Moléculaire, Centre Jean Perrin, Clermont-Ferrand, France; Sidney Kimmel Comprehensive Cancer Center and Department of Gynecology and Obstetrics, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Muhieddine
authors.initials: M
authors.lastname: Seoud
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, and Departments of Pharmacology and Toxicology, Surgery, and Obstetrics and Gynecology, American University of Beirut, Lebanon; University of Auvergne and Laboratoire Diagnostique Génétique et Moléculaire, Centre Jean Perrin, Clermont-Ferrand, France; Sidney Kimmel Comprehensive Cancer Center and Department of Gynecology and Obstetrics, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Deborah K
authors.initials: DK
authors.lastname: Armstrong
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, and Departments of Pharmacology and Toxicology, Surgery, and Obstetrics and Gynecology, American University of Beirut, Lebanon; University of Auvergne and Laboratoire Diagnostique Génétique et Moléculaire, Centre Jean Perrin, Clermont-Ferrand, France; Sidney Kimmel Comprehensive Cancer Center and Department of Gynecology and Obstetrics, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Yves-Jean
authors.initials: YJ
authors.lastname: Bignon
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, and Departments of Pharmacology and Toxicology, Surgery, and Obstetrics and Gynecology, American University of Beirut, Lebanon; University of Auvergne and Laboratoire Diagnostique Génétique et Moléculaire, Centre Jean Perrin, Clermont-Ferrand, France; Sidney Kimmel Comprehensive Cancer Center and Department of Gynecology and Obstetrics, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Nancy
authors.initials: N
authors.lastname: Uhrhammer
mesh_terms: D000328:Adult; D018912:Arabs / Q000235:genetics*; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007861:Lebanon; D008875:Middle Aged; D009154:Mutation
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human
keywords: Arab countries; BRCA mutations; Breast cancer; Family history; Haplotype; Lebanon; Young age