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Decades of research have shown that mutations in the p53 stress response pathway affect the incidence of diverse cancers more than mutations in other pathways. However, most evidence is limited to somatic mutations and rare inherited mutations. Using newly abundant genomic data, we demonstrate that commonly inherited genetic variants in the p53 pathway also affect the incidence of a broad range of cancers more than variants in other pathways. The cancer-associated single nucleotide polymorphisms (SNPs) of the p53 pathway have strikingly similar genetic characteristics to well-studied p53 pathway cancer-causing somatic mutations. Our results enable insights into p53-mediated tumour suppression in humans and into p53 pathway-based cancer surveillance and treatment strategies.

Original publication




Journal article


Nature reviews. Cancer

Publication Date





251 - 265


Ludwig Institute for Cancer Research, University of Oxford, Nuffield Department of Clinical Medicine, Old Road Campus Research Building, Oxford OX3 7DQ, UK.


Humans, Neoplasms, Genetic Predisposition to Disease, Mutation, Polymorphism, Single Nucleotide, Genome, Human, Tumor Suppressor Protein p53