title: Prevalence of BRCA1 mutations in familial and sporadic greek ovarian cancer cases.
abstract: Germline mutations in the BRCA1 and BRCA2 genes contribute to approximately 18% of hereditary ovarian cancers conferring an estimated lifetime risk from 15% to 50%. A variable incidence of mutations has been reported for these genes in ovarian cancer cases from different populations. In Greece, six mutations in BRCA1 account for 63% of all mutations detected in both BRCA1 and BRCA2 genes. This study aimed to determine the prevalence of BRCA1 mutations in a Greek cohort of 106 familial ovarian cancer patients that had strong family history or metachronous breast cancer and 592 sporadic ovarian cancer cases. All 698 patients were screened for the six recurrent Greek mutations (including founder mutations c.5266dupC, p.G1738R and the three large deletions of exon 20, exons 23-24 and exon 24). In familial cases, the BRCA1 gene was consequently screened for exons 5, 11, 12, 20, 21, 22, 23, 24. A deleterious BRCA1 mutation was found in 43/106 (40.6%) of familial cancer cases and in 27/592 (4.6%) of sporadic cases. The variant of unknown clinical significance p.V1833M was identified in 9/698 patients (1.3%). The majority of BRCA1 carriers (71.2%) presented a high-grade serous phenotype. Identifying a mutation in the BRCA1 gene among breast and/or ovarian cancer families is important, as it enables carriers to take preventive measures. All ovarian cancer patients with a serous phenotype should be considered for genetic testing. Further studies are warranted to determine the prevalence of mutations in the rest of the BRCA1 gene, in the BRCA2 gene, and other novel predisposing genes for breast and ovarian cancer.
authors.affiliation: Molecular Diagnostics Laboratory, INRaSTES, National Center for Scientific Research Demokritos, Athens, Greece.
authors.forename: Alexandra V
authors.initials: AV
authors.lastname: Stavropoulou
authors.forename: Florentia
authors.initials: F
authors.lastname: Fostira
authors.forename: Maroulio
authors.initials: M
authors.lastname: Pertesi
authors.forename: Marianthi
authors.initials: M
authors.lastname: Tsitlaidou
authors.forename: Gerassimos E
authors.initials: GE
authors.lastname: Voutsinas
authors.forename: Olga
authors.initials: O
authors.lastname: Triantafyllidou
authors.forename: Aristotelis
authors.initials: A
authors.lastname: Bamias
authors.forename: Meletios A
authors.initials: MA
authors.lastname: Dimopoulos
authors.forename: Eleni
authors.initials: E
authors.lastname: Timotheadou
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Pectasides
authors.forename: Christos
authors.initials: C
authors.lastname: Christodoulou
authors.forename: George
authors.initials: G
authors.lastname: Klouvas
authors.forename: Christos
authors.initials: C
authors.lastname: Papadimitriou
authors.forename: Thomas
authors.initials: T
authors.lastname: Makatsoris
authors.forename: George
authors.initials: G
authors.lastname: Pentheroudakis
authors.forename: Gerasimos
authors.initials: G
authors.lastname: Aravantinos
authors.forename: Vassilis
authors.initials: V
authors.lastname: Karydakis
authors.forename: Drakoulis
authors.initials: D
authors.lastname: Yannoukakos
authors.forename: George
authors.initials: G
authors.lastname: Fountzilas
authors.forename: Irene
authors.initials: I
authors.lastname: Konstantopoulou
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D005091:Exons; D005190:Family; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006115:Greece / Q000453:epidemiology; D006579:Heterozygote; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D010051:Ovarian Neoplasms / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D010641:Phenotype; D015995:Prevalence; D055815:Young Adult
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