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Surveying germline genomic landscape of breast cancer

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Abstract

The recent large genotyping studies have identified a new repertoire of breast cancer susceptibility genes and loci which are characterized by common risk alleles and low relative risks. Because of these properties, these loci explain a much larger proportion of the etiology of the particular cancers, described by the population attributable fraction (PAF), than of their familial risks. PAF is particularly suitable for ‘genomic landscaping’ because it defines the proportion of breast cancer explained by the variant under study. The joint PAF for the previously described high-penetrance alleles is about 1%, for moderate-penetrance alleles it is 1.5% and for low-penetrance susceptibility alleles it is 58%. The evidence appears compelling in pointing to the remarkably high population impacts of the recently described heritable loci compared to the ‘classical’ high-penetrance genes.

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Acknowledgements

The study was supported by the Deutsche Krebshilfe, the BMBF for NGNF+, the Swedish Cancer Society, the Swedish Council for Working Life and Social Research, the EU, LSHC-LT-2004-503465 and EU Food-CT-2005-016320.

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Authors and Affiliations

  1. Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, 69120, Heidelberg, Germany

    Kari Hemminki, Asta Försti & Justo Lorenzo Bermejo

  2. Center for Family and Community Medicine, Karolinska Institute, 141 83, Huddinge, Sweden

    Kari Hemminki & Asta Försti

Authors
  1. Kari Hemminki
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  2. Asta Försti
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  3. Justo Lorenzo Bermejo
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Correspondence to Kari Hemminki.

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Hemminki, K., Försti, A. & Lorenzo Bermejo, J. Surveying germline genomic landscape of breast cancer. Breast Cancer Res Treat 113, 601–603 (2009). https://doi.org/10.1007/s10549-008-9946-z

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