title: The importance of p53 pathway genetics in inherited and somatic cancer genomes.
abstract: 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.
authors.affiliation: Ludwig Institute for Cancer Research, University of Oxford, Nuffield Department of Clinical Medicine, Old Road Campus Research Building, Oxford OX3 7DQ, UK.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Stracquadanio
authors.affiliation: Environmental Genomics Group, Genome Integrity and Structural Biology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA.
authors.forename: Xuting
authors.initials: X
authors.lastname: Wang
authors.affiliation: Ludwig Institute for Cancer Research, University of Oxford, Nuffield Department of Clinical Medicine, Old Road Campus Research Building, Oxford OX3 7DQ, UK.
authors.forename: Marsha D
authors.initials: MD
authors.lastname: Wallace
authors.affiliation: Ludwig Institute for Cancer Research, University of Oxford, Nuffield Department of Clinical Medicine, Old Road Campus Research Building, Oxford OX3 7DQ, UK.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Grawenda
authors.affiliation: Ludwig Institute for Cancer Research, University of Oxford, Nuffield Department of Clinical Medicine, Old Road Campus Research Building, Oxford OX3 7DQ, UK.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Ludwig Institute for Cancer Research, University of Oxford, Nuffield Department of Clinical Medicine, Old Road Campus Research Building, Oxford OX3 7DQ, UK.
authors.forename: Juliet
authors.initials: J
authors.lastname: Hewitt
authors.affiliation: Vall d'Hebron University Hospital, Oncology Department, Passeig de la Vall D'Hebron 119, 08035 Barcelona, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: Zeron-Medina
authors.affiliation: Molecular and Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
authors.forename: Francesc
authors.initials: F
authors.lastname: Castro-Giner
authors.affiliation: Molecular and Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
authors.forename: Ian P
authors.initials: IP
authors.lastname: Tomlinson
authors.affiliation: Ludwig Institute for Cancer Research, University of Oxford, Nuffield Department of Clinical Medicine, Old Road Campus Research Building, Oxford OX3 7DQ, UK.
authors.forename: Colin R
authors.initials: CR
authors.lastname: Goding
authors.affiliation: Center for Computational Molecular Biology, Brown University, 115 Waterman Street, Providence, Rhode Island 02912, USA.|Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, 70 Ship Street, Providence, Rhode Island 02903, USA.
authors.forename: Kamil J
authors.initials: KJ
authors.lastname: Cygan
authors.affiliation: Center for Computational Molecular Biology, Brown University, 115 Waterman Street, Providence, Rhode Island 02912, USA.|Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, 70 Ship Street, Providence, Rhode Island 02903, USA.
authors.forename: William G
authors.initials: WG
authors.lastname: Fairbrother
authors.affiliation: Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, NO-7491 Trondheim, Norway.
authors.forename: Laurent F
authors.initials: LF
authors.lastname: Thomas
authors.affiliation: Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, NO-7491 Trondheim, Norway.|Department of Computer and Information Science, Norwegian University of Science and Technology, NO-7491 Trondheim, Norway.
authors.forename: Pål
authors.initials: P
authors.lastname: Sætrom
authors.affiliation: Genetics, Department of Biology, University of Pisa, Via Derna 1, 56126 Pisa, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Gemignani
authors.affiliation: Genetics, Department of Biology, University of Pisa, Via Derna 1, 56126 Pisa, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Landi
authors.affiliation: Ludwig Institute for Cancer Research, University of Oxford, Nuffield Department of Clinical Medicine, Old Road Campus Research Building, Oxford OX3 7DQ, UK.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Schuster-Böckler
authors.affiliation: Environmental Genomics Group, Genome Integrity and Structural Biology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA.
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Bell
authors.affiliation: Ludwig Institute for Cancer Research, University of Oxford, Nuffield Department of Clinical Medicine, Old Road Campus Research Building, Oxford OX3 7DQ, UK.
authors.forename: Gareth L
authors.initials: GL
authors.lastname: Bond
mesh_terms: D020022:Genetic Predisposition to Disease / Q000235:genetics*; D015894:Genome, Human; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53