Kesserwan Chimene, Friedman Ross Lainie, Bradbury Angela R, Nichols Kim E
From the Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN; Departments of Pediatrics, Medicine, and Surgery, MacLean Center for Clinical Medical Ethics, The University of Chicago, Chicago, IL; Department of Medicine, Department of Medical Ethics and Health Policy, Perelman School of Medicine of the University of Pennsylvania, Philadelphia, PA.
Am Soc Clin Oncol Educ Book. 2016;35:251-69. doi: 10.1200/EDBK_160621.
The increased application of germline genetic testing is expanding our understanding of the risk factors associated with childhood cancer development, and, in some cases, such testing is also informing clinical management. Nonetheless, the incorporation of genetic testing into the pediatric oncology setting is complex and associated with many ethical and practical challenges. The decision as to whether to pursue clinical genetic testing for hereditary cancer predisposition for children should always be guided by the best interest of the child. Despite this fundamental ethical principle, patients, parents, and health care providers may differ in their opinions. Clinical genetic testing to detect the presence of predisposition syndromes associated with childhood-onset cancers, particularly those for which surveillance and preventive measures have proven to enhance outcome, is currently well accepted. On the other hand, clinical genetic testing of children for syndromes associated with adult-onset cancers has raised many concerns about the potential for psychological harm and disrespect of patient autonomy. As a consequence, such testing is not encouraged. The challenges surrounding germline genetic testing are further complicated when testing is done in the research setting and/or when it involves whole-exome or whole-genome sequencing approaches, which can uncover genetic variants that may or may not be associated with the disease under study. Accordingly, there is great debate around these processes and the most appropriate approaches regarding the return of test results. Future research is needed to enhance knowledge about how best to incorporate genomic information into clinical practice.
生殖系基因检测应用的增加正在拓宽我们对儿童癌症发生相关风险因素的理解，并且在某些情况下，此类检测还为临床管理提供依据。尽管如此，将基因检测纳入儿科肿瘤治疗环境是复杂的，且伴随着许多伦理和实际挑战。关于是否对儿童进行遗传性癌症易感性的临床基因检测的决定，应以儿童的最大利益为始终的指导原则。尽管有这一基本伦理原则，但患者、家长和医疗服务提供者的观点可能存在差异。目前，用于检测与儿童期发病癌症相关的易感性综合征的临床基因检测已被广泛接受，尤其是那些已证明监测和预防措施可改善预后的癌症。另一方面，对儿童进行与成人期发病癌症相关综合征的临床基因检测引发了许多担忧，担心其可能造成心理伤害以及对患者自主权的不尊重。因此，不鼓励进行此类检测。当在研究环境中进行检测和/或涉及全外显子组或全基因组测序方法时，围绕生殖系基因检测的挑战会进一步复杂化，因为这些方法可能会发现与所研究疾病可能相关或不相关的基因变异。因此，围绕这些过程以及关于检测结果反馈的最合适方法存在很大争议。需要开展未来研究以增进对如何最好地将基因组信息纳入临床实践的认识。
