title: Differences in the frequency and distribution of BRCA1 and BRCA2 mutations in breast/ovarian cancer cases from the Basque country with respect to the Spanish population: implications for genetic counselling.
abstract: The prevalence of unique and recurrent BRCA1 and BRCA2 pathogenic mutations and unclassified variants varies among different populations. Two hundred and thirty-six breast and/or ovarian cancer patients were analysed to clarify the role of these genes in the Basque Country. We also studied 130 healthy women from the general population from the same region. Fifteen different pathological mutations were found in 16 index cases: 10 truncating mutations, 4 missense mutations and 1 splicing mutation. c.3002_3003insT and c.5788_5789delGT, both in exon 11 of BRCA2 have not previously been described. No pathological mutations were found in cases of sporadic juvenile breast cancer. There are no recurrent mutations in our population; apart from the mutation c.9254_9258del5, which appears in only two index cases. We have also found a lot of variants whose effect is unknown. From these variants, 17 have not previously been described: 6 missenses, 6 synonymous and 5 alterations in intronic regions. We would like to highlight the fact that 14.3% of patients with 3 or more cases of breast cancer in the family, and 16.7% of patients with family history of breast and ovarian cancer, present a pathological mutation in BRCA1 or BRCA2. This manuscript demonstrates that each population can have different mutations and due to this, Genetic Counselling and selection criteria must be different for each population. Furthermore, this article describes for the first time some new mutations and unclassified variants found in our population.
authors.affiliation: Laboratorio de Genética Molecular, Hospital de Cruces, Pza. de Cruces s/n, 48903 Barakaldo, Bizkaia, Spain. eberistain@ikasle.ehu.es
authors.forename: E
authors.initials: E
authors.lastname: Beristain
authors.forename: C
authors.initials: C
authors.lastname: Martínez-Bouzas
authors.forename: I
authors.initials: I
authors.lastname: Guerra
authors.forename: N
authors.initials: N
authors.lastname: Viguera
authors.forename: J
authors.initials: J
authors.lastname: Moreno
authors.forename: E
authors.initials: E
authors.lastname: Ibañez
authors.forename: J
authors.initials: J
authors.lastname: Díez
authors.forename: F
authors.initials: F
authors.lastname: Rodríguez
authors.forename: G
authors.initials: G
authors.lastname: Mallabiabarrena
authors.forename: S
authors.initials: S
authors.lastname: Luján
authors.forename: J
authors.initials: J
authors.lastname: Gorostiaga
authors.forename: J L
authors.initials: JL
authors.lastname: De Pablo
authors.forename: J L
authors.initials: JL
authors.lastname: Mendizabal
authors.forename: M I
authors.initials: MI
authors.lastname: Tejada
mesh_terms: D000328:Adult; D017398:Alternative Splicing / Q000235:genetics; D051017:Apoptosis Regulatory Proteins; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000523:psychology; D018389:Codon, Nonsense / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D005260:Female; D016368:Frameshift Mutation; D005817:Genetic Counseling; D005820:Genetic Testing; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D008297:Male; D010051:Ovarian Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000523:psychology; D011159:Population Surveillance; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D013030:Spain / Q000453:epidemiology
chemical_list: D051017:Apoptosis Regulatory Proteins; C118024:BLID protein, human; D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D018389:Codon, Nonsense; D004273:DNA, Neoplasm; D012333:RNA, Messenger; D012334:RNA, Neoplasm