The average cumulative risks of breast and ovarian cancer for carriers of mutations in BRCA1 and BRCA2 attending genetic counseling units in Spain.
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.
Milne
Roger L
RL
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
Osorio
Ana
A
Cajal
Teresa Ramón Y
TR
Vega
Ana
A
Llort
Gemma
G
de la Hoya
Miguel
M
Díez
Orland
O
Alonso
M Carmen
MC
Lazaro
Conxi
C
Blanco
Ignacio
I
Sánchez-de-Abajo
Ana
A
Caldés
Trinidad
T
Blanco
Ana
A
Graña
Begoña
B
Durán
Mercedes
M
Velasco
Eladio
E
Chirivella
Isabel
I
Cardeñosa
Eva Esteban
EE
Tejada
María-Isabel
MI
Beristain
Elena
E
Miramar
María-Dolores
MD
Calvo
María-Teresa
MT
Martínez
Eduardo
E
Guillén
Carmen
C
Salazar
Raquel
R
San Román
Carlos
C
Antoniou
Antonis C
AC
Urioste
Miguel
M
Benítez
Javier
J
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