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The Inheritance of p53

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p53 in the Clinics

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Abstract

The p53 pathway constitutes a major cellular gene network that is crucial in directing the suppression of cancer formation, mediating the response to commonly used cancer therapies, as well as the regulation of germline maintenance, fertility, and reproduction. It has been demonstrated that various cancer predisposition syndromes are caused by low-frequency, highly penetrant inherited mutations in the p53 network, the knowledge of which is already positively affecting patient survival. Mounting evidence from studies utilizing human material, patient cohorts, and mouse models suggests that higher frequency, lesser penetrant genetic variants can also affect p53 signaling, resulting in differences in cancer risk, prognosis, response to therapies, and/or natural selection. Indeed, multiple genes in the p53 network have been shown to harbor functional single nucleotide polymorphisms (SNPs). Comprehensive analyses of two SNPs have demonstrated that their effects on cancer can be modified by factors such as gender, estrogen, and other p53 pathway SNPs. Together these insights suggest that genetic variants in the p53 network could present an excellent opportunity to further define individuals in their abilities to react to stress, suppress tumor formation, and respond to therapies.

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Authors and Affiliations

  1. The Ludwig Institute for Cancer Research, ORCRB, University of Oxford, Old Road Campus, Off Roosevelt Drive, Oxford, OX3 7DQ, UK

    Lukasz F. Grochola, Jorge Zeron-Medina, Emmanouela Repapi, Alexander E. Finlayson & Gareth L. Bond

  2. Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, NY, USA

    Ying Cai & Gurinder Singh Atwal

Authors
  1. Lukasz F. Grochola
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  2. Jorge Zeron-Medina
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  3. Emmanouela Repapi
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  4. Alexander E. Finlayson
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  5. Ying Cai
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  6. Gurinder Singh Atwal
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  7. Gareth L. Bond
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Corresponding author

Correspondence to Gareth L. Bond .

Editor information

Editors and Affiliations

  1. International Prevention Research Instit, 95 cours Lafayette, Lyon, 69006, France

    Pierre Hainaut

  2. International Agency for Cancer Research, 150 Cours Albert-Thomas, Lyon, 69372, France

    Magali Olivier

  3. Cancer Center Karolinska (CCK), Dept. Oncology and Pathology, Karolinska Institute, Karolinska Institutet, Stockholm, 171 76, Sweden

    Klas G. Wiman

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© 2013 Springer Science+Business Media New York

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Grochola, L.F. et al. (2013). The Inheritance of p53. In: Hainaut, P., Olivier, M., Wiman, K. (eds) p53 in the Clinics. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3676-8_2

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