Do Physicians Understand Uncertain Variants and Other Genetic Test Results?

医生了解不确定的变异和其他基因测试结果吗？

• 批准号: 7260064
• 负责人: Sharon E. Plon
• 金额: $ 33.75万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-10 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7260064
• 关键词: Area; BRCA1 gene; BRCA2 gene; Base Sequence; Breast; Cancer-Predisposing Gene; Categories; Clinical; Complex; Condition; Confusion; Control Groups; DNA; Decision Making; Development; Disease; Education; Educational Materials; Electronics; Evaluation; Family; Gene Chips; General Practitioners; Genes; Genetic; Genetic screening method; Genomics; Goals; Gynecologist; Health; Individual; Internist; Intervention Studies; Laboratories; Language; Licensing; Malignant Neoplasms; Malignant neoplasm of ovary; Measures; Medical; Medical Surveillance; Methods; Modality; Modeling; Mutation; Oncologist; Patients; Physicians; Predisposition; Prevention; Publishing; Questionnaires; RNA; Range; Recommendation; Relative (related person); Reporting; Research Design; Research Personnel; Risk; Risk Assessment; Risk Management; Surgeon; Surveys; Test Result; Testing; Texas; Variant; base; cancer genetics; cancer risk; design; experience; genetic pedigree; improved; medical specialties; member; programs; response

DESCRIPTION (provided by applicant): Testing for mutations in the BRCA1 and BRCA2 breast-ovarian cancer susceptibility genes has been performed in over 70,000 individuals. Like other sequence-based tests, the results can reveal a normal sequence, a clearly deleterious mutation or a sequence variant of uncertain significance (VUS), in which it is not known whether the VUS confers an increased cancer risk. VUS results are confusing and occur in approximately 12% of tests. Their adequate interpretation requires a basic understanding of genetic principles, the laboratory methods utilized and pedigree analysis. No studies, however, have been published that assess the interpretation and clinical recommendations of non-geneticist physicians receiving a VUS result for BRCA gene sequencing and our own clinical experience suggests that many physicians categorize all VUS results as deleterious mutations potentially leading to inappropriate management recommendations. Hypothesis: Non-geneticist physicians do not discriminate between a VUS and a deleterious mutation when making recommendations with regard to breast and ovarian cancer risk management. Study Design: We will optimize and administer to members of the Texas Medical Association (internists, family practitioners, obstetrician-gynecologists, general surgeons, and oncologists) an on-line questionnaire that presents case scenarios that include BRCA test results that are deleterious, negative or have one or more VUS. A control group of experts in cancer genetics will be included. Physicians will be queried on testing options for at-risk individuals in the family, impact of the test result on cancer risk and asked to choose among a range of management options. Statistical analysis will determine whether the "path" of responses to a VUS result is more similar to a clearly deleterious or negative result. These results will be used to develop appropriate CME-eligible educational materials and to design genetic testing report formats that decrease areas of confusion identified in the survey. Relevance: Consistent with the goals of the NHGRI to bring "Genomics to Health" it is imperative that we optimize the appropriate interpretation of sequence-based genetic tests by a variety of physician specialties for use in clinical decision making. With the increasing availability of complex testing modalities, e.g. DNA and RNA gene chips, for a variety of both rare and common diseases, appropriate reporting and physician education must accompany the development of these tests.

描述（由申请人提供）：对BRCA1和BRCA2乳腺癌癌易感性基因的突变测试已在70,000多名中进行。与其他基于序列的测试一样，结果可以揭示正常序列，明显有害的突变或具有不确定意义的序列变体（VUS），其中尚不知道VUS是否赋予癌症风险增加。 VUS结果令人困惑，大约12％的测试发生。他们的充分解释需要对遗传原理的基本理解，所利用的实验室方法和谱系分析。然而，尚无研究表明，评估非遗传学家医生的解释和临床建议，该医生接受了BRCA基因测序结果，而我们自己的临床经验表明，许多医生将所有VUS结果归类为有害突变，可能导致不适当的管理建议。 假设：在提出有关乳腺癌和卵巢癌风险管理的建议时，非遗传学家医生不会区分VU和有害突变。研究设计：我们将为德克萨斯医学协会（Internisters，家庭从业人员，产科医生，普通外科医生和肿瘤学家）优化和管理一份在线问卷，呈现包括有害，负面或有一个或更多vus的BRCA测试结果的案例场景，其中包括BRCA测试结果。将包括一个癌症遗传学专家的对照组。医师将在家庭中高危个人的测试选择中询问，测试对癌症风险的影响，并要求在一系列管理方案中进行选择。统计分析将确定对VUS结果的响应的“路径”是否与明显有害或负面结果更相似。这些结果将用于开发合适的CME符合条件的教育材料，并设计基因测试报告格式，以减少调查中发现的混乱区域。相关性：与NHGRI的目标一致，将“基因组学到健康”的目标是，我们必须通过各种用于临床决策的医师专业来优化对基于序列的基因检测的适当解释。随着复杂测试方式的可用性的增加，例如DNA和RNA基因芯片，对于各种稀有疾病和常见疾病，适当的报告和医师教育都必须伴随这些测试的发展。