title: The average cumulative risks of breast and ovarian cancer for carriers of mutations in BRCA1 and BRCA2 attending genetic counseling units in Spain.
abstract: OBJECTIVE
  It is not clear that the published estimates of the breast and ovarian cancer penetrances of mutations in BRCA1 and BRCA2 can be used in genetic counseling in countries such as Spain, where the incidence of breast cancer in the general population is considerably lower, the prevalence of BRCA2 mutations seems to be higher, and a distinct spectrum of recurrent mutations exists for both genes. We aimed to estimate these penetrances for women attending genetic counseling units in Spain.
  
  
  METHODS
  We collected phenotype and genotype data on 155 BRCA1 and 164 BRCA2 mutation carrier families from 12 centers across the country. Average age-specific cumulative risks of breast cancer and ovarian cancer were estimated using a modified segregation analysis method.
  
  
  RESULTS
  The estimated average cumulative risk of breast cancer to age 70 years was estimated to be 52% [95% confidence interval (95% CI), 26-69%] for BRCA1 mutation carriers and 47% (95% CI, 29-60%) for BRCA2 mutation carriers. The corresponding estimates for ovarian cancer were 22% (95% CI, 0-40%) and 18% (95% CI, 0-35%), respectively. There was some evidence (two-sided P = 0.09) that 330A>G (R71G) in BRCA1 may have lower breast cancer penetrance.
  
  
  CONCLUSIONS
  These results are consistent with those from a recent meta-analysis of practically all previous penetrance studies, suggesting that women with BRCA1 and BRCA2 mutations attending genetic counseling services in Spain have similar risks of breast and ovarian cancer to those published for other Caucasian populations. Carriers should be fully informed of their mutation- and age-specific risks to make appropriate decisions regarding prophylactic interventions such as oophorectomy.
authors.affiliation: Unidad de Genotipación-CEGEN and Grupo de Genética Humana, Programa de Genética del Cáncer Humano, Centro Nacional de Investigaciones Oncológicas, Madrid, Spain. rmilne@cnio.es
authors.forename: Roger L
authors.initials: RL
authors.lastname: Milne
authors.forename: Ana
authors.initials: A
authors.lastname: Osorio
authors.forename: Teresa Ramón Y
authors.initials: TR
authors.lastname: Cajal
authors.forename: Ana
authors.initials: A
authors.lastname: Vega
authors.forename: Gemma
authors.initials: G
authors.lastname: Llort
authors.forename: Miguel
authors.initials: M
authors.lastname: de la Hoya
authors.forename: Orland
authors.initials: O
authors.lastname: Díez
authors.forename: M Carmen
authors.initials: MC
authors.lastname: Alonso
authors.forename: Conxi
authors.initials: C
authors.lastname: Lazaro
authors.forename: Ignacio
authors.initials: I
authors.lastname: Blanco
authors.forename: Ana
authors.initials: A
authors.lastname: Sánchez-de-Abajo
authors.forename: Trinidad
authors.initials: T
authors.lastname: Caldés
authors.forename: Ana
authors.initials: A
authors.lastname: Blanco
authors.forename: Begoña
authors.initials: B
authors.lastname: Graña
authors.forename: Mercedes
authors.initials: M
authors.lastname: Durán
authors.forename: Eladio
authors.initials: E
authors.lastname: Velasco
authors.forename: Isabel
authors.initials: I
authors.lastname: Chirivella
authors.forename: Eva Esteban
authors.initials: EE
authors.lastname: Cardeñosa
authors.forename: María-Isabel
authors.initials: MI
authors.lastname: Tejada
authors.forename: Elena
authors.initials: E
authors.lastname: Beristain
authors.forename: María-Dolores
authors.initials: MD
authors.lastname: Miramar
authors.forename: María-Teresa
authors.initials: MT
authors.lastname: Calvo
authors.forename: Eduardo
authors.initials: E
authors.lastname: Martínez
authors.forename: Carmen
authors.initials: C
authors.lastname: Guillén
authors.forename: Raquel
authors.initials: R
authors.lastname: Salazar
authors.forename: Carlos
authors.initials: C
authors.lastname: San Román
authors.forename: Antonis C
authors.initials: AC
authors.lastname: Antoniou
authors.forename: Miguel
authors.initials: M
authors.lastname: Urioste
authors.forename: Javier
authors.initials: J
authors.lastname: Benítez
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics*; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D005817:Genetic Counseling; D020022:Genetic Predisposition to Disease; D006801:Humans; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics*; D019683:Penetrance; D012307:Risk Factors; D013030:Spain