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The Average Cumulative Risks of Breast and Ovarian Cancer for Carriers of Mutations in BRCA1 and BRCA2 Attending Genetic Counseling Units in Spain

Authors' Affiliations: ¹ Unidad de Genotipación-CEGEN and ² Grupo de Genética Humana, Programa de Genética del Cáncer Humano, Centro Nacional de Investigaciones Oncológicas; ³ Laboratrio de Oncología Molecular, Hospital Clínico San Carlos; ⁴ Servicio de Genética Médica, Hospital Universitario Ramón y Cajal; ⁵ Centro de Investigación Biomédica En Red de Enfermedades Raras (CIBERER), Madrid, Spain; ⁶ Servicio de Oncología Médica and ⁷ Servei de Genètica, Hospital de la Santa Creu i Sant Pau; ⁸ Unitat de Consell Genètic, Servei de Prevenció i Control del Càncer, Institut Català d'Oncologia, Hospital Duran i Reynals; ⁹ Programa de Medicina Molecular i Genètica, Laboratori de Genética del Cáncer Hereditari, Hospital Universitari Vall d'Hebrón; ¹⁰ Programa de Diagnóstico Molecular de Cáncer Hereditario, Laboratori de Recerca Tranlacional, Institut Català d'Oncologia, Barcelona, Spain; ¹¹ Unidade de Medicina Molecular, Fundación Pública Galega de Medicina Xenómica-SERGAS and Grupo de Medicina Xenómica-CIBERER and ¹² Servicio de Oncología Médica, Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain; ¹³ Unitat d'Avaluació del Risc de Cancer i Consell Genetic-Institut Català d'Oncologia, Hospital Dr. Josep Trueta, Girona, Spain; ¹⁴ Laboratorio de Genética del Cáncer, Instituto de Biología y Genética Molecular, Universidad de Valladolid, Valladolid, Spain; ¹⁵ Unidad de Consejo Genético en Cáncer, Hospital Clínico Universitario de Valencia, ¹⁶ Laboratorio de Biología Molecular del Servicio de Análisis Clínicos, Hospital Universitario La Fe, ¹⁷ Unidad de Consejo Genético en Cáncer, Servicio de Oncología Médica, Hospital Provincial de Castellón, and ¹⁸ Unidad de Consejo Genético, Hospital General Universitario de Elche, Grupo de Cáncer Hereditario de la Comunidad Valenciana, Valencia, Spain; ¹⁹ Laboratorio de Genética Molecular, Hospital de Cruces, Barakaldo-Bizkaia, Spain; ²⁰ Sección de Genética Médica, Servicio de Bioquímica Clínica, Hospital Universitario Miguel Server, Zaragoza, Spain; ²¹ Centro de Investigación del Cáncer, Universidad de Salamanca, Salamanca, Spain; and ²² Cancer Research UK Genetic Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom

Requests for reprints: Roger Milne, Centro Nacional de Investigaciones Oncológicas, C/Melchor Fernández Almagro, 3, E-28029 Madrid, Spain. Phone: 34-91-224-6974; Fax: 34-91-224-6923; E-mail: rmilne{at}cnio.es.

Purpose: 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.

Experimental Design: 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.