title: BRCA2 gene mutations in Greek patients with familial breast cancer.
abstract: Family history is a well-recognized risk factor for the development of breast cancer. The isolation of BRCA1 and BRCA2 genes, the two major predisposing genes in familial and to early onset breast and ovarian cancer, has resulted to the identification of a large number of families with mutations in these two genes. Despite the large number of distinct mutations detected in both genes, several mutations have been found to recur in unrelated families of diverse geographical origin. We have analyzed 27 Greek patients with familial breast cancer the majority of those having one first and one second degree relatives affected and 28 patients with sporadic breast cancer for BRCA2 germline mutations. The techniques used were single-strand conformation polymorphism analysis (SSCP) followed by sequencing. Furthermore, the clinical presentation and prognosis of BRCA2 associated breast cancer cases was compared to 20 adequately matched for age and date of diagnosis (within one year) sporadic breast cancer patients. We identified three novel BRCA2 mutations (3058delA, 6024delTA, and 4147delG) in the ovarian cancer cluster region (OCCR) and one already known (2024del5) germline BRCA2 gene mutation in five different breast cancer families. The 4147delG mutation was detected in two unrelated patients. BRCA2 germline mutations were correlated with early-onset breast cancer RR=4.77 (95% CI: 0.666-34.463). Although patients with BRCA2 germline mutations did not have a distinct histological phenotype they had an improved overall survival (100% vs 65%). Our findings suggest that there is a cluster of novel mutations in exons 10 and 11 in Greek patients with familial breast cancer. These mutations appear to have a milder clinical phenotype when compared to the rest of the study group.
authors.affiliation: Laboratory of Surgical Research, A' Propaedeutic Surgical Clinic, Athens Medical School, Hippokrateion Hospital, Athens, Greece.
authors.forename: Athanasios
authors.initials: A
authors.lastname: Armakolas
authors.forename: Angela
authors.initials: A
authors.lastname: Ladopoulou
authors.forename: Irene
authors.initials: I
authors.lastname: Konstantopoulou
authors.forename: B
authors.initials: B
authors.lastname: Pararas
authors.forename: Ilias P
authors.initials: IP
authors.lastname: Gomatos
authors.forename: Agapi
authors.initials: A
authors.lastname: Kataki
authors.forename: Manoussos M
authors.initials: MM
authors.lastname: Konstadoulakis
authors.forename: George P
authors.initials: GP
authors.lastname: Stathopoulos
authors.forename: Christopher
authors.initials: C
authors.lastname: Markopoulos
authors.forename: Emmanouil
authors.initials: E
authors.lastname: Leandros
authors.forename: Ioannis
authors.initials: I
authors.lastname: Gogas
authors.forename: Drakoulis
authors.initials: D
authors.lastname: Yannoukakos
authors.forename: George
authors.initials: G
authors.lastname: Androulakis
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics*; D005260:Female; D024522:Genes, BRCA2; D005838:Genotype; D006115:Greece; D006801:Humans; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010641:Phenotype