title: Relationship of BRCA1 and BRCA2 mutations with cancer burden in the family and tumor incidence.
abstract: The aim of the present study is to analyze the relationship of the incidence of mutations in the two major genes BRCA1 and BRCA2 conferring risk of breast cancer (BC) and ovarian cancer (OC) with the cancer burden in families and with the presence and age of onset of BC/OC. We included 704 index patients (IP) and 668 family members of the IP who tested positive for BRCA1/BRCA2 who were studied in the Program of Genetic Counselling in Cancer of the Valencia Community (Spain). We found 129 IPs with deleterious mutations (18.3%), 59 in BRCA1 and 70 in BRCA2, detecting 396 mutations in this kindred. The incidence of mutations and their distribution between BRCA1 and BRCA2 showed a significantly uneven incidence among the family groups (P < 0.001). We found 179 tumors in the 396 mutation carriers (45%) and detected only 11 cancers among the 272 non-mutation carriers (P < 0.001). No differences in the tumor prevalence or the age of onset of cancer between the genes among the mutation carriers were found. The mutation carriers showed a 50% probability of having BC/OC at a median age of 49 years (95% CI 46-52 years) and 78% at the age of 70 years (95% CI: 71-85%). In conclusion the family burden of BC and OC is strongly associated with the incidence of BRCAs mutations and could foretell which of the two BRCAs genes is more likely to have mutations. Mutation carriers have a 50% risk of having BC/OC by the age of 50 years.
authors: Laboratory of Molecular Biology. Service of Clinical Analysis, University Hospital La Fe, Avda. Campanar 21, 46009, Valencia, Spain. esteban_eva@gva.es
authors: Eva
authors: E
authors: Esteban Cardeñosa
authors: Pascual
authors: P
authors: Bolufer Gilabert
authors: Inmaculada
authors: I
authors: de Juan Jiménez
authors: Sarai
authors: S
authors: Palanca Suela
authors: Eva
authors: E
authors: Barragán González
authors: Virginia
authors: V
authors: González Anguix
authors: Enrique
authors: E
authors: Lerma Alejos
authors: Isabel
authors: I
authors: Chirivella González
authors: Angel
authors: A
authors: Segura Huerta
authors: Carmen
authors: C
authors: Guillén Ponce
authors: Eduardo
authors: E
authors: Martínez de Dueñas
authors: Dolores
authors: D
authors: Cuevas Cuerda
authors: Dolores
authors: D
authors: Salas Trejo
mesh_terms: D017668:Age of Onset; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D018567:Breast Neoplasms, Male / Q000453:epidemiology / Q000235:genetics; D005190:Family; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006579:Heterozygote; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010051:Ovarian Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D010375:Pedigree; D016133:Polymerase Chain Reaction