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Breast and ovarian cancer risk evaluation in families with a disease-causing mutation in BRCA1/2

Journal of Community Genetics volume 1, pages 91–99 (2010)Cite this article

Abstract

Germline mutations in BRCA1 and BRCA2 confer high risks of breast and ovarian cancer, and their identification allows genetic testing of at-risk relatives. However, estimates of these risks illustrate controversies, depending on the published series. The penetrance, the earlier onset of the disease and the effect of mutations on the risk of developing breast and ovarian cancer were evaluated in 344 females belonging to 34 families from the Basque Country in Spain, in which BRCA1 or BRCA2 mutations were transmitted. Kaplan–Meier survival curves were used to derive cumulative probability curves for breast and ovarian cancer by mutation status, birth cohort and mutation position, and significance of the differences was assessed using the log-rank test. The estimated probability for breast cancer by age 70 is about 64% in BRCA1 and 69% in BRCA2, whereas the probability of developing ovarian cancer is about 37% and 25% for BRCA1 and BRCA2, respectively. There is a marginally significant higher risk of developing ovarian cancer in BRCA1 families than in BRCA2 families. The effect of birth cohort on breast cancer cumulative incidence presents an increased risk for females born after 1966 and a decreased risk for those born before 1940. There is no association between mutation position and breast cancer; however, ovarian cancer is associated to BRCA1, presenting exon 11 as an ovarian cluster. These results are important for the breast and ovarian cancer diagnosis and prevention in at-risk families.

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Acknowledgements

We would like to thank the Health Department of the Basque Country Government, the BIOEF foundation (BIO07/CA/006) and the KATXALIN patients’ association (BIOEF08/015), for their financial support for this work. Furthermore, we thank the families and the clinicians involved in this study for their enthusiastic help in this research.

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Affiliations

  1. Molecular Genetics Laboratory, Biochemistry Department, Hospital de Cruces, Plaza de Cruces s/n, 48903, Barakaldo, Bizkaia, Spain

    Elena Beristain, Cristina Martínez-Bouzas & Maria Isabel Tejada

  2. Basque Foundation for Health Innovation & Research (BIOEF), Plaza de Asua s/n, 48150, Sondika, Spain

    Berta Ibáñez & Itziar Vergara

  3. Anatomy and Pathology Department, Hospital de Txagorritxu, Jose Atxotegi s/n, 01006, Vitoria-Gasteiz, Spain

    Isabel Guerra

Authors
  1. Elena Beristain
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  2. Berta Ibáñez
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  3. Itziar Vergara
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  4. Cristina Martínez-Bouzas
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  5. Isabel Guerra
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  6. Maria Isabel Tejada
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Correspondence to Maria Isabel Tejada.

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Beristain, E., Ibáñez, B., Vergara, I. et al. Breast and ovarian cancer risk evaluation in families with a disease-causing mutation in BRCA1/2. J Community Genet 1, 91–99 (2010). https://doi.org/10.1007/s12687-010-0014-0

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  • DOI: https://doi.org/10.1007/s12687-010-0014-0

Keywords

  • Breast cancer
  • Ovarian cancer
  • Penetrance
  • Cumulative risk