The inheritance of p53

Lukasz F. Grochola, Jorge Zeron-Medina, Emmanouela Repapi, Alexander E. Finlayson, Ying Cai, Gurinder Singh Atwal, Gareth L. Bond*

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingChapter

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.

Original languageEnglish
Title of host publicationp53 in the Clinics
PublisherSpringer
Pages25-46
Number of pages22
Volume9781461436768
ISBN (Electronic)9781461436768
ISBN (Print)1461436753, 9781461436751
DOIs
Publication statusPublished - 1 May 2013

ASJC Scopus subject areas

  • General Medicine

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