title: BRCA1 and BRCA2 mutations in males with familial breast and ovarian cancer syndrome. Results of a Spanish multicenter study.
abstract: Male breast cancer (MBC) is a rare disease that represents <1% of all breast cancers (BCs). We analyze the results of a multicenter study performed in Spanish familial MBC including family history of hereditary breast and ovarian cancer syndrome (HBOCS) and clinicopathological features. We also study the relationship between BRCA1/BRCA2 mutational status in male relatives affected with cancer (MAC) and, family history and tumor types. The study included 312 men index cases with family history of HBOCS and 61 MAC BRCA1/2 mutation-carriers. Family history, histological grade (HG), clinicopathological and immunohistochemistry data were collected. BRCA1/2 mutation analyses were performed by direct sequencing or screening methods and the large rearrangements by multiplex ligation dependent probe amplification. We found 49 mutation-carriers (15.7%), 95.9% with BRCA2 mutations. BRCA2 mutation-carriers were associated with families with at least one MBC and one BC in female (type II; p = 0.05). Strong association were found between the presence of pathogenic mutations in MBCs and the advanced HG (p = 0.003). c.658_659delTG, c.2808_2811delACAA, c.6275_6276delTT and c.9026_9030delATCAT were the most prevalent mutations. In 61 MAC we found 20 mutations in BRCA1 and 41 in BRCA2. For MAC we show that mutational status was differentially associated with family history (p = 0.018) and tumor type, being BRCA2 mutations linked with BC and prostatic cancer (p = 0.018). MBC caused by BRCA1/2 mutations define two types of MBCs. The most frequent caused by BRCA2 mutation linked to type II families and the rarest one attributed to BRCA1 mutation. Tumor associated with MAC suggest that only BRCA2 mutations have to do with a specific type of cancer (BC and prostatic cancer); but the linkage to tumors is questionable for BRCA1 mutations .
authors.affiliation: Laboratory of Molecular Biology, Service of Clinical Analysis, University and Polytechnic Hospital La Fe, Escuela de Enfermería 7ª planta. Avd. Campanar 21, Valencia, 46009, Spain. dejuan_inm@gva.es.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: de Juan
authors.affiliation: Laboratory of Molecular Biology, Service of Clinical Analysis, University and Polytechnic Hospital La Fe, Escuela de Enfermería 7ª planta. Avd. Campanar 21, Valencia, 46009, Spain.
authors.forename: Sarai
authors.initials: S
authors.lastname: Palanca
authors.affiliation: Laboratory of Molecular Biology, Service of Clinical Analysis, University and Polytechnic Hospital La Fe, Escuela de Enfermería 7ª planta. Avd. Campanar 21, Valencia, 46009, Spain.
authors.forename: Asunción
authors.initials: A
authors.lastname: Domenech
authors.affiliation: Hereditary Cancer Program, Catalan Institute of Oncology (ICO), L'Hospitalet de Llobregat (Barcelona), Spain.
authors.forename: Lidia
authors.initials: L
authors.lastname: Feliubadaló
authors.affiliation: Unit of Genetic Counseling in Cancer, Hospital Universitario y Politécnico La Fe, Valencia, Spain.
authors.forename: Ángel
authors.initials: Á
authors.lastname: Segura
authors.affiliation: Human Genetics Group, Human Cancer Genetics Programme, Spanish National Cancer Research Centre and Spanish Network on Rare Diseases (CIBERER), Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Osorio
authors.affiliation: Unit of Genetic Counseling in Cancer, Hospital Clínico, Valencia, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Chirivella
authors.affiliation: Molecular Oncology Laboratory, IdISSC, Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: de la Hoya
authors.affiliation: Unit of Genetic Counseling in Cancer, Hospital General de Elche, Elche, Spain.
authors.forename: Ana Beatriz
authors.initials: AB
authors.lastname: Sánchez
authors.affiliation: Cancer Genetic Group, Institute of Genetics and Molecular Biology (UVa-CSIC), Valladolid, Spain.
authors.forename: Mar
authors.initials: M
authors.lastname: Infante
authors.affiliation: Unit of Genetic Counseling in Cancer, Hospital General de Castellón, Castellón, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Tena
authors.affiliation: Oncogenetics Laboratory, University Hospital Vall d'Hebron, Vall d'Hebron Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Orland
authors.initials: O
authors.lastname: Díez
authors.affiliation: Laboratory of Molecular Biology, Valencian Institute of Oncology (IVO), Valencia, Spain.
authors.forename: Zaida
authors.initials: Z
authors.lastname: Garcia-Casado
authors.affiliation: Fundación Pública Galega de Medicina Xenómica-SERGAS, Grupo de Medicina Xenómica-USC, IDIS, CIBERER, Santiago de Compostela, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Vega
authors.affiliation: Hereditary Cancer Program, Catalan Institute of Oncology (ICO), L'Hospitalet de Llobregat (Barcelona), Spain.
authors.forename: Àlex
authors.initials: À
authors.lastname: Teulé
authors.affiliation: Human Genetics Group, Human Cancer Genetics Programme, Spanish National Cancer Research Centre and Spanish Network on Rare Diseases (CIBERER), Madrid, Spain.
authors.forename: Alicia
authors.initials: A
authors.lastname: Barroso
authors.affiliation: Department of Oncology, IdISSC, Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Pérez
authors.affiliation: Cancer Genetic Group, Institute of Genetics and Molecular Biology (UVa-CSIC), Valladolid, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Durán
authors.affiliation: High Risk and Prevention Unit, University Hospital Vall d'Hebron, Barcelona, Spain.
authors.forename: Estela
authors.initials: E
authors.lastname: Carrasco
authors.affiliation: Unit of Genetic Counseling in Cancer, IVO, Valencia, Spain.
authors.forename: M José
authors.initials: MJ
authors.lastname: Juan-Fita
authors.affiliation: Laboratory of Molecular Biology, Service of Clinical Analysis, University and Polytechnic Hospital La Fe, Escuela de Enfermería 7ª planta. Avd. Campanar 21, Valencia, 46009, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Murria
authors.affiliation: Laboratory of Molecular Biology, Service of Clinical Analysis, University and Polytechnic Hospital La Fe, Escuela de Enfermería 7ª planta. Avd. Campanar 21, Valencia, 46009, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Llop
authors.affiliation: Laboratory of Molecular Biology, Service of Clinical Analysis, University and Polytechnic Hospital La Fe, Escuela de Enfermería 7ª planta. Avd. Campanar 21, Valencia, 46009, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Barragan
authors.affiliation: Hereditary Cancer Program, Catalan Institute of Oncology (ICO), L'Hospitalet de Llobregat (Barcelona), Spain.
authors.forename: Ángel
authors.initials: Á
authors.lastname: Izquierdo
authors.affiliation: Human Genetics Group and Genotyping Unit, Human Cancer Genetics Programme, Spanish National Cancer Research Centre and Spanish Network on Rare Diseases (CIBERER), Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Benítez
authors.affiliation: Molecular Oncology Laboratory, IdISSC, Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: Trinidad
authors.initials: T
authors.lastname: Caldés
authors.affiliation: General Directorate Public Health and Centre for Public Health Research (CSISP), Valencia Genetic Counseling in Cancer Programme, Valencia, Spain.
authors.forename: Dolores
authors.initials: D
authors.lastname: Salas
authors.affiliation: Laboratory of Molecular Biology, Service of Clinical Analysis, University and Polytechnic Hospital La Fe, Escuela de Enfermería 7ª planta. Avd. Campanar 21, Valencia, 46009, Spain. bolufer_pas@gva.es.
authors.forename: Pascual
authors.initials: P
authors.lastname: Bolufer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019313:BRCA1 Protein / Q000235:genetics* / Q000378:metabolism; D024682:BRCA2 Protein / Q000235:genetics* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D018567:Breast Neoplasms, Male / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D018275:Carcinoma, Lobular / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D013030:Spain / Q000453:epidemiology; D013577:Syndrome; D055815:Young Adult
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D014408:Biomarkers, Tumor
keywords: BRCA1; BRCA2 mutations; Familial male breast cancer; Hereditary breast and ovarian cancer syndrome