KEY POINTS * Inherited cancer predisposition syndromes are increasingly diagnosed due to greater public awareness of germline genetic testing, and also as an incidental finding when somatic

mutation testing for 'druggable targets' * Some inherited cancer syndromes predispose to cancers at multiple sites, such as Li-Fraumeni syndrome (LFS) caused by germline _TP53_

mutations, requiring a whole-body approach to cancer risk management * The 5-year, 10-year and lifetime cancer risk of many the LFS-associated cancers remains unclear and further study is

required to provide such data, which can guide cancer risk management * At present, a limited number of validated screening tests for LFS-associated cancers exist, and no validated screening

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. Access through

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CONTENT BEING VIEWED BY OTHERS CANCER IN COSTELLO SYNDROME: A SYSTEMATIC REVIEW AND META-ANALYSIS Article 25 March 2023 EXTENDED SPECTRUM OF CANCERS IN PTEN HAMARTOMA TUMOR SYNDROME Article

Open access 06 March 2025 GERMLINE MUTATIONS IN PROSTATE CANCER: A SYSTEMATIC REVIEW OF THE EVIDENCE FOR PERSONALIZED MEDICINE Article 24 November 2022 REFERENCES * Pruthi, S., Gostout, B.

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Cancer Screening version 2_ [online], (2013). Download references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * The Familial Cancer Service, Crown Princess Mary Cancer Centre, Sydney Medical

School, Westmead Millennium Institute, Westmead, 2145, NSW, Australia Kate A. McBride & Judy Kirk * Research Division, Sir Peter MacCallum Department of Oncology, University of

Melbourne, Peter MacCallum Cancer Centre, East Melbourne, 3002, VIC, Australia Mandy L. Ballinger * Sir Peter MacCallum Department of Oncology, The Familial Cancer Centre, University of

Melbourne, Peter MacCallum Cancer Centre, East Melbourne, 3002, VIC, Australia Gillian Mitchell * Medical Oncology Unit, University Hospital Southampton NHS Foundation Trust, Southampton,

SO16 6YD, UK Emma Killick * Department of Cancer Medicine, Sydney Medical School, Royal Prince Alfred Hospital, Camperdown, 2040, NSW, Australia Martin H. N. Tattersall * Oncogenetics Team,

The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Sutton, SM2 5PT, Surrey, UK Rosalind A. Eeles * The Kinghorn Cancer Centre and Garvan Institute, Darlinghurst, 2010,

NSW, Australia David M. Thomas Authors * Kate A. McBride View author publications You can also search for this author inPubMed Google Scholar * Mandy L. Ballinger View author publications

You can also search for this author inPubMed Google Scholar * Emma Killick View author publications You can also search for this author inPubMed Google Scholar * Judy Kirk View author

publications You can also search for this author inPubMed Google Scholar * Martin H. N. Tattersall View author publications You can also search for this author inPubMed Google Scholar *

Rosalind A. Eeles View author publications You can also search for this author inPubMed Google Scholar * David M. Thomas View author publications You can also search for this author inPubMed

 Google Scholar * Gillian Mitchell View author publications You can also search for this author inPubMed Google Scholar CONTRIBUTIONS D.M.T. and G.M. contributed equally to this Review.

K.A.M. researched the data for the article. All authors contributed substantially to discussion of content, the writing of the article review and/or editing of the manuscript before

submission. CORRESPONDING AUTHOR Correspondence to Gillian Mitchell. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no competing financial interests. POWERPOINT SLIDES

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al._ Li-Fraumeni syndrome: cancer risk assessment and clinical management. _Nat Rev Clin Oncol_ 11, 260–271 (2014). https://doi.org/10.1038/nrclinonc.2014.41 Download citation * Published:

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