The Familial Cancer Service, Crown Princess Mary Cancer Centre, Sydney Medical School, Westmead Millennium Institute, Westmead, NSW 2145, Australia.
Research Division, Sir Peter MacCallum Department of Oncology, University of Melbourne, Peter MacCallum Cancer Centre, East Melbourne, VIC 3002, Australia.
Nat Rev Clin Oncol. 2014 May;11(5):260-71. doi: 10.1038/nrclinonc.2014.41. Epub 2014 Mar 18.
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.
携带有 TP53 基因突变的个体，其编码细胞周期调控因子和肿瘤抑制因子 p53，在儿童期和成年期都有明显增加的癌症相关发病率和死亡率的风险，因此需要进行适当和有效的癌症风险管理。然而，此类患者多器官肿瘤形成的倾向对癌症风险管理计划提出了特殊的挑战。在此，我们回顾了 TP53 种系突变的临床意义，以及携带这些突变的个体进行癌症筛查和预防策略的证据，同时还研究了终身管理普遍存在的癌症风险的潜在心理社会影响。此外，我们还提出了一种基于循证的 TP53 突变携带者的临床管理框架，并为解决可能影响多个器官的其他癌症易感性综合征的管理提供了一个平台。
