The Two Sister Study

这项研究正在确定并向许多有动力的乳腺癌妇女及其父母发出邀请信，并能有效地将她们的数据与现在从她们未受影响的姐妹篇那里收集的DNA和环境数据联合收割机结合起来。该研究通过利用姐妹研究已经到位并顺利运行的基础设施，获得了巨大的运营效率优势（Dale Sandler，PI）。根据第一批10，000名姐妹研究参与者，超过20%的人有一个合格的姐妹，其中80%的人有一个或两个父母生活。 邮寄回来的唾液试剂盒将提供来自病例和父母的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）也将使我们能够确定影响治疗后健康的环境，临床和遗传因素。 我们计划对大约150个候选基因上的1,536个标记进行基因分型，包括一些预计与风险相关的标记和其他预计与预后相关的标记。 此外，存档的DNA将为未来测试最近发表和正在进行的全基因组关联研究中确定的未知候选人提供资源。 基因变异的病例-亲本分析受到保护，不会因遗传遗传的混淆而产生偏倚，并且还允许检测母体介导的遗传效应和亲本起源（印记）效应。 在拟议的研究中，参与的受影响的姐妹篇将完成一个计算机辅助电话采访，就像他们的妹妹将完成的，提供有关个人暴露，生育史和过去的职业暴露的信息。 环境影响将通过受影响和未受影响姐妹篇的配对比较来识别。 将采用新的统计方法评估基因-暴露相互作用。 总之，拟议的研究利用正在进行的姐妹研究，建立一个具有成本效益的，强大的，统计学独立的研究乳腺癌。 与遗传变异和环境因素的综合影响有关的发现可以在姐妹研究中复制。 今年，我们继续开发所需的材料，确保IRB批准这项研究，并通过Susan G.治愈基金会的科门对面谈工作人员进行了培训，并为计算机辅助电话面谈开发了软件。 必须开发与乳腺癌诊断相关的新CATI访谈。 在电子商务支助服务合同的协助下，我们现在已将这项研究投入实地。我们向首批431名姐妹研究参与者发出了邀请信，初步反应令人鼓舞，尽管现在估计反应率还为时过早。

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.