title: Li-Fraumeni syndrome: cancer risk assessment and clinical management.
abstract: Carriers of germline mutations in the TP53 gene, encoding the cell-cycle regulator and tumour suppressor p53, have a markedly increased risk of cancer-related morbidity and mortality during both childhood and adulthood, and thus require appropriate and effective cancer risk management. However, the predisposition of such patients to multiorgan tumorigenesis presents a specific challenge for cancer risk management programmes. Herein, we review the clinical implications of germline mutations in TP53 and the evidence for cancer screening and prevention strategies in individuals carrying such mutations, as well as examining the potential psychosocial implications of lifelong management for a ubiquitous cancer risk. In addition, we propose an evidence-based framework for the clinical management of TP53 mutation carriers and provide a platform for addressing the management of other cancer predisposition syndromes that can affect multiple organs.
authors.affiliation: The Familial Cancer Service, Crown Princess Mary Cancer Centre, Sydney Medical School, Westmead Millennium Institute, Westmead, NSW 2145, Australia.
authors.forename: Kate A
authors.initials: KA
authors.lastname: McBride
authors.affiliation: Research Division, Sir Peter MacCallum Department of Oncology, University of Melbourne, Peter MacCallum Cancer Centre, East Melbourne, VIC 3002, Australia.
authors.forename: Mandy L
authors.initials: ML
authors.lastname: Ballinger
authors.affiliation: Medical Oncology Unit, University Hospital Southampton NHS Foundation Trust, Southampton SO16 6YD, UK.
authors.forename: Emma
authors.initials: E
authors.lastname: Killick
authors.affiliation: The Familial Cancer Service, Crown Princess Mary Cancer Centre, Sydney Medical School, Westmead Millennium Institute, Westmead, NSW 2145, Australia.
authors.forename: Judy
authors.initials: J
authors.lastname: Kirk
authors.affiliation: Department of Cancer Medicine, Sydney Medical School, Royal Prince Alfred Hospital, Camperdown, NSW 2040, Australia.
authors.forename: Martin H N
authors.initials: MH
authors.lastname: Tattersall
authors.affiliation: Oncogenetics Team, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Sutton, Surrey SM2 5PT, UK.
authors.forename: Rosalind A
authors.initials: RA
authors.lastname: Eeles
authors.affiliation: The Kinghorn Cancer Centre and Garvan Institute, Darlinghurst, NSW 2010, Australia.
authors.forename: David M
authors.initials: DM
authors.lastname: Thomas
authors.affiliation: The Familial Cancer Centre, Sir Peter MacCallum Department of Oncology, University of Melbourne, Peter MacCallum Cancer Centre, East Melbourne, VIC 3002, Australia.
authors.forename: Gillian
authors.initials: G
authors.lastname: Mitchell
mesh_terms: D000328:Adult; D017668:Age of Onset; D002353:Carrier State; D002648:Child; D056915:DNA Copy Number Variations; D055088:Early Detection of Cancer / Q000379:methods / Q000523:psychology; D005260:Female; D016158:Genes, p53; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D053823:Hedgehog Proteins / Q000502:physiology; D006801:Humans; D016864:Li-Fraumeni Syndrome / Q000175:diagnosis / Q000235:genetics / Q000523:psychology / Q000628:therapy; D008297:Male; D009369:Neoplasms / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics; D012306:Risk; D059506:Telomere Shortening
chemical_list: D053823:Hedgehog Proteins; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2