title: Low prevalence of BRCA1 and BRCA2 mutations in the sporadic breast cancer of Spanish population.
abstract: The true prevalence of BRCA1/BRCA2 (BRCAs) germline mutations in sporadic breast or ovarian cancer (SBC/SOC) in Caucasian population is not well established. The aim of the study is to establish the prevalence of BRCAs mutations in SBC to ponder its relevance in the programs of genetic counseling in cancer and to explore the genotype-phenotype relationship of these particular breast cancers. The study was performed in 495 SBC. We sought 46 BRCA1 and 53 BRCA2 pathogenic mutations reported in the Spanish population. We followed a high resolution melting method performed in the LightCycler 480 (Roche Diagnostics) for the screening of these Spanish mutations using 49 primer pairs. Eight different deleterious mutations, one of them novel, were detected in nine patients, five without family history of BC/OC, what yields a true prevalence of 1.05% for BRCAs mutations in SBC. Furthermore, we found 18 unknown variants. Larger tumour size (T > 1) and earlier presentation are the independent parameters associated with the presence of BRCAs pathogenic mutations in SBC (P < 0.01) and the BRCA1 mutations carriers develop steroid-receptors negative tumors. Our results indicate that the true prevalence of BRCAs germline deleterious mutations in SBC of Spaniards is low. However, this does not lessens its relevance since the presence of BRCAs mutations in SBC could represent circa 16% of total BRCAs mutations detected in BC. SBCs of BRCAs mutation carriers have phenotype more aggressiveness than SBC without BRCAs mutation.
authors.affiliation: Laboratory of Molecular Biology, Clinical Analysis Service, Escuela de Enfermería 7ª planta, Hospital Universitario La Fe, Avd. Campanar, 21, 46009, Valencia, Spain.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: de Juan Jiménez
authors.forename: Eva
authors.initials: E
authors.lastname: Esteban Cardeñosa
authors.forename: Sarai
authors.initials: S
authors.lastname: Palanca Suela
authors.forename: Eva
authors.initials: E
authors.lastname: Barragán González
authors.forename: Ismael
authors.initials: I
authors.lastname: Aznar Carretero
authors.forename: Blanca
authors.initials: B
authors.lastname: Munárriz Gandía
authors.forename: Ana
authors.initials: A
authors.lastname: Santaballa Bertran
authors.forename: María Dolores
authors.initials: MD
authors.lastname: Torregrosa Maicas
authors.forename: Carmen
authors.initials: C
authors.lastname: Guillén Ponce
authors.forename: Ana Beatriz
authors.initials: AB
authors.lastname: Sánchez Heras
authors.forename: Ana
authors.initials: A
authors.lastname: Bayón Lara
authors.forename: Oscar
authors.initials: O
authors.lastname: Fuster Lluch
authors.forename: Pascual
authors.initials: P
authors.lastname: Bolufer Gilabert
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000453:epidemiology / Q000235:genetics / Q000556:secondary; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000453:epidemiology / Q000235:genetics / Q000556:secondary; D018275:Carcinoma, Lobular / Q000453:epidemiology / Q000235:genetics / Q000556:secondary; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D010375:Pedigree; D013030:Spain / Q000453:epidemiology; D044465:White People / Q000235:genetics*
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human