• Roger L Milne, Ana Osorio, CajalTeresa Ramón YTR, Ana Vega, Gemma Llort, Miguel de la Hoya, Orland Díez, M Carmen Alonso, Conxi Lazaro, Ignacio Blanco, Ana Sánchez-de-Abajo, Trinidad Caldés, Ana Blanco, Begoña Graña, Mercedes Durán, Eladio Velasco, Isabel Chirivella, CardeñosaEva EstebanEE, María-Isabel Tejada, Elena Beristain, María-Dolores Miramar, María-Teresa Calvo, Eduardo Martínez, Carmen Guillén, Raquel Salazar, Carlos San Román, Antonis C Antoniou, Miguel Urioste, and Javier Benítez.
• 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
• Clin Cancer Res. 2008 May 1; 14 (9): 2861-9.

PurposeIt 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.Experimental DesignWe 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.ResultsThe 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.ConclusionsThese 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.

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