The Two Sister Study

两姐妹研究

• 批准号: 8149105
• 负责人: Clarice Weinberg
• 金额: $ 11.21万
• 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/8149105
• 关键词: Sister

This Komen-funded study is identifying and sending a letter of invitation to women with young-onset breast cancer and with their help to their parents. We will effectively combine their data with the DNA and environmental data now being collected from their unaffected sisters (who have joined the Sister Study) and DNA being collected from their parents. We will use this nuclear-family-based approach to study genetic and environmental factors involved in young-onset breast cancer. 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). Mail-back saliva kits are providing DNA from cases and parents. We will collect clinical data and attempt to validate the diagnoses for all the anticipated 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. 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 are each completing a computer-assisted telephone interview like the one their sister completed for the Sister Study, 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. We have now recruited a total of 1,517 breast cancer survivors, more than 1,000 of whom have completed all baseline activities. Some 900 are still pending, but we will need to end new enrollments of breast cancer survivor sisters at the end of September. We have also enrolled 1,292 of their parents, collecting 1,260 saliva samples from them. This work was accomplished with assistance from the EB support services contract. We have hired a postdoc, Chunyuan Fei, who will be writing papers based on the initial data set, using the case-control sibling sets based on the first 1,107 enrollees, who have provided questionnaire data that has been through the rigorous Westat quality control cleaning. This should provide good power for case-control analyses of environmental factors related to risk. Genotyping based on the available DNA is being deferred to provide time for recruitment of the parents into the study.

这项由Komen资助的研究是在识别并向患有年轻乳腺癌的妇女及其父母的帮助。我们将有效地将他们的数据与目前从未受影响的姐妹（加入姐妹研究的姐妹）中收集的DNA和环境数据相结合，并从父母那里收集DNA。 我们将使用这种基于核家庭的方法来研究涉及年轻乳腺癌的遗传和环境因素。 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。 邮寄唾液套件正在提供病例和父母的DNA。 我们将收集临床数据，并试图验证所有预期的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。 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，参与的受影响的姐妹分别完成了计算机辅助的电话采访，就像他们的姐姐完成姐妹学习的那样，提供了有关个人暴露，生殖历史和过去职业接触的信息。 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。 现在，我们总共招募了1,517名乳腺癌幸存者，其中1,000多名已经完成了所有基线活动。 大约900人仍在待处理中，但我们需要在9月底结束乳腺癌幸存者姐妹的新入学率。我们还注册了1,292个父母，从他们那里收集了1,260个唾液样本。 这项工作是在EB支持服务合同的协助下完成的。 我们聘请了博士后Chunyuan FEI，他将根据初始数据集撰写论文，并使用基于第一个1,107名参与者的案例对照兄弟姐妹集，他们通过严格的WestAt质量控制清洁提供了调查表数据。 这应该为与风险有关的环境因素的病例对照分析提供良好的功能。基于可用DNA的基因分型被延期，以提供将父母招募到研究中的时间。