PREDICTIVE TESTING PROGRAM FOR P53 MUTATIONS IN LFS

患有遗传性癌症综合征的家庭提供了重要的 信息与影响更常见的零星形式的 一般人群中的恶性肿瘤。生殖系鉴定 在一些罕见的家族中的肿瘤抑制基因突变 癌症综合征为分子改变提供了重要线索 涉及多种肿瘤类型。越来越多的肿瘤抑制因子 基因，以及识别其中突变的能力增加， 癌症易感性的分子标志物 很快就会对医疗保健产生重大影响。充分利用这些 这些能力可能会对个人产生重大影响 和社会p53肿瘤生殖系突变的鉴定 Li-Fraumeni癌家族成员中的抑制基因 综合征及其变体提供了一个定义的人群， 探讨了许多重要的问题，以预测癌症基因的测试。 在这个试点项目中，我们将邀请经典和变体的成年成员 Li-Fraumeni家族携带改变的p53基因的风险为50%， 参加一个项目，让他们知道他们的p53 status.我们将评估处于危险中的成年人的期望和动机 和他们的合作伙伴参加一个预测性测试项目。 我们将探讨他们参与的心理准备， 结果披露后，将评估知识的影响， 他们的p53状态对他们的心理健康和家庭 关系。我们将评估他们对遗传信息的理解， 并将提供广泛的遗传咨询有关的选择 及其在整个过程中的影响。我们将与他们一起探索 作为父母和准父母的受试者是否准备好进入 他们有风险的孩子进入一个预测性测试项目， 以及这样一个项目的哪些特点对家庭可能很重要。 我们 还将评估民众对以下建议的接受程度： 疾病监测和风险规避。我们将开展这项计划， 充分认识到复杂的道德和社会问题， 与这项工作密不可分。 该项目已提交给伦理法律的和社会 人类基因组计划的影响。

Families with inherited cancer syndromes have provided important information with implications for the more common sporadic forms of malignancies in the general population. The identification of germ line mutations in tumor suppressor genes in some rare families with unusual cancer syndromes have provided important clues to molecular alterations involved in diverse tumor types. The growing list of tumor suppressor genes, and the increasing ability to identify mutations therein, increase the likelihood that molecular markers of susceptibility to cancer will soon have a significant impact on medical care. Full exploitation of these capabilities are likely to have substantial ramifications for individuals and society. The identification of germ line mutations in the p53 tumor suppressor gene in members of families with the Li-Fraumeni cancer syndrome and its variants provides a defined population in which to approach many issues of importance to predictive testing for cancer genes. In this pilot project, we will invite adult members of classic and variant Li-Fraumeni families at 50% risk of carrying an altered p53 gene to participate in a program in which they could be made aware of their p53 status. We will assess the expectations and motivations of at-risk adults and their partners for participation in a program of predictive testing. We will explore their psychological preparedness to participate, and, after disclosure of results, will evaluate the impact of the knowledge of their p53 status on their psychological well-being and family relationships. We will assess their understanding of genetic information, and will provide extensive genetic counseling regarding relevant choices and their implications throughout the process. We will explore with them the readiness of subjects who are parents and prospective parents to enter their at-risk children into a predictive testing program were it to exist, and what features of such a program might be important to families. We will also assess the receptiveness of the population to advice regarding disease surveillance and risk avoidance. We will conduct this program with full cognizance of the complex ethical and social issues which are inextricable from this work. This project is submitted to the attention of the Ethical Legal and Social Implications program of the Human Genome Initiative.