The Two Sister Study

两姐妹研究

• 批准号: 7968236
• 负责人: Clarice Weinberg
• 金额: $ 8.06万
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7968236
• 关键词: Affect; Aftercare; Age; Archives; Award; Back; Breast Cancer Treatment; Cancer Survivor; Candidate Disease Gene; Clinical; Clinical Data; Computer Assisted; Computer software; Contract Services; Contracts; DNA; Data; Detection; Diagnosis; Disease; Enrollment; Environmental Risk Factor; Foundations; Funding; Future; Genes; Genetic; Genetic Variation; Genotype; Goals; Health; Interview; Joints; Letters; Life; Mails; Mediating; Mediation; Nuclear Family; Occupational Exposure; Paired Comparison; Parents; Participant; Publishing; Reproductive History; Research Ethics Committees; Research Infrastructure; Resources; Risk; Saliva; Secure; Sister; Statistical Methods; Telephone Interviews; Testing; Training; Woman; base; breast cancer diagnosis; cohort; cost; design; experience; family structure; follow up assessment; follow-up; genetic variant; genome wide association study; imprint; malignant breast neoplasm; novel; outcome forecast; response

This study is identifying and sending a letter of invitation to many motivated women with breast cancer and their parents, and can effectively combine their data with the DNA and environmental data now being collected from their unaffected sisters. The study gains enormous operational efficiency advantages, by taking advantage of the infrastructure that is already in place and functioning smoothly for the Sister Study (Dale Sandler, PI). Based on the first 10,000 Sister Study enrollees, more than 20% have an eligible sister and 80% of those have one or both parents living. Mail-back saliva kits will provide DNA from cases and parents. We will collect clinical data and attempt to validate the diagnoses for all 1,600 cases. Follow-up of these cases (through the Sister Study) will also allow us to identify environmental, clinical, and genetic factors that influence health after treatment. We plan to genotype 1,536 markers on some 150 candidate genes, including some expected to be related to risk and others expected to be related to prognosis. In addition, archived DNA will provide a resource for future tests of not-yet-known candidates identified in recently-published and ongoing genome-wide association studies. Case-parent analyses of gene variants are protected against bias due to confounding by genetic heritage, and also permit detection of both maternally-mediated genetic effects and parent-of-origin (imprinting) effects. In the proposed study, the participating affected sisters will complete a computer-assisted telephone interview like the one their sister will have completed, providing information about personal exposures, reproductive history, and past occupational exposures. Environmental effects will be identifiable through a paired comparison of affected and unaffected sisters. Gene-by-exposure interactions will be assessed with novel statistical methods. In summary, the proposed study leverages off the ongoing Sister Study to build a cost-effective, powerful, and statistically independent study of young-onset breast cancer. Findings related to combined effects of genetic variants and environmental factors can be replicated later in the Sister Study. This year we continued to develop the materials required, secured IRB approval for the study, and negotiated the contract required to be awarded foundation funding ($1.7M) to carry it out, through the Susan G. Komen for the Cure foundation. Interview staff was trained and software developed for the computer-assisted telephone interview. A new CATI interview had to be developed related to the breast cancer diagnosis. We have now put the study into the field, with assistance from the EB support services contract. Initial response to our letters of invitation mailed to the first 431 Sister Study participants has been encouraging, though it is too early to estimate the response rate.

这项研究是向许多有动力的乳腺癌及其父母的邀请信确定并发送邀请信，并且可以有效地将数据与目前从未受影响的姐妹那里收集的DNA和环境数据相结合。这项研究通过利用已经到位的基础设施并为姊妹研究平稳运行（Dale Sandler，PI），从而获得了巨大的运营效率优势。根据前10,000个姐妹研究的入学训练，超过20％的人有合格的姐妹，其中80％的父母有一个或两个父母的生活。 邮递的唾液套件将提供案件和父母的DNA。 我们将收集临床数据，并试图验证所有1,600例病例的诊断。 这些病例的随访（通过姐妹研究）还将使我们能够识别影响治疗后影响健康的环境，临床和遗传因素。 我们计划在约150个候选基因上为1,536个标记进行基因型，其中一些预计与风险有关，而另一些则与预后有关。 此外，存档的DNA将为将来的测试提供资源，以对最近出版和持续的全基因组关联研究中鉴定的尚未尚未著名的候选人进行测试。 由于遗传遗产的混淆，对基因变异的病例分析受到保护，还可以检测到母体介导的遗传效应和父母 - 源源物（印迹）效应。 在拟议的研究中，参与受影响的姐妹将完成计算机辅助的电话采访，就像他们的姐姐要完成的电话，提供有关个人暴露，生殖历史和过去职业曝光的信息。 通过对受影响和未受影响的姐妹的配对比较，可以识别环境影响。 逐个暴露基因的相互作用将通过新型统计方法进行评估。 总而言之，拟议的研究利用正在进行的姐妹研究来建立对年轻乳腺癌的成本效益，强大且统计上独立的研究。 在姊妹研究的稍后，可以复制与遗传变异和环境因素的综合作用相关的发现。 今年，我们继续开发所需的材料，获得了IRB的批准，并通过苏珊·科门（Susan G.采访人员接受了培训，并为计算机辅助的电话采访而开发了软件。 必须开发与乳腺癌诊断有关的新CATI访谈。 现在，在EB支持服务合同的协助下，我们已经将研究纳入了现场。邮寄给第一个431个姊妹研究参与者的邀请信的最初回应令人鼓舞，尽管现在估计响应率还为时过早。