Alcohol and Breast Cancer: Genetic Interactions and Effects on Aromatase Inhibitor Therapy

项目摘要 我的长期目标是成为一名独立的研究人员，在流行病学的健康影响， 酒精，尤其是它在癌症中的作用。我建议K 01指导研究科学家发展 奖励，以实现一系列的培训目标，这些目标建立在我以前的技能基础上，但也扩展了我的技能， 这对实现我的长期目标至关重要我这次获奖的培训目标是：（1）培养一个 在基因数据的使用和解释方面有坚实的基础，重点是基因与环境的相互作用; (2)了解乳腺癌（BC）的病理生理学和治疗方法，以评估和 在流行病学研究中描述癌症结局;（3）在设计、实施和 随机临床试验分析。为了实现我的培训目标，我已经收集了一个全面的 和互补的指导团队，在遗传学，酒精，性激素，BC和临床试验方面的专业知识。我 我还将参加额外的活动，以进一步支持我的职业发展，包括课程，实验室 会议，在负责任的研究行为，赠款写作培训，并提出研究在 专业会议。 我将应用我的培训进行研究，探索是否有因素改变了 酒精与BC的关系有一致的证据表明，与日常饮食有关的BC风险较高。 酒精摄入量，即使在每天最多一杯的建议限度内。然而， 关于是否存在改变酒精和BC之间的关联的因素的知识仍然存在。这 应用程序将利用现有数据研究流行病学队列中随访的妇女的BC风险， 测试新的科学问题的基因环境相互作用，使用候选基因的方法和 无假设的全基因组方法来鉴定潜在的修饰剂。 此外，拟议的培训奖将支持为期8周的试点交叉试验的20个公元前幸存者 他们报告说，他们经常每周至少喝一杯酒精饮料， 芳香化酶抑制剂治疗。本试验将利用经验丰富的临床研究中心和大量的 在参与该培训奖的机构接受治疗的不列颠哥伦比亚幸存者，以生成试点数据， 可能会为更大规模的关于酒精对BC治疗影响的试验提供信息。 培训，指导，研究经验，并有机会收集试点数据在这个K 01奖 这将使我能够实现我的长期职业目标，成为一个独立的流行病学研究， 酒精对健康的影响，特别是它在癌症中的作用。

Project Summary My long-term goal is to become an independent researcher in the epidemiology of health effects of alcohol, and particularly its role in cancer. I am proposing this K01 Mentored Research Scientist Development Award to fulfill a series of training objectives which build upon my prior skills, but also expand my skills in ways which are essential to accomplishing my long-term goal. My training goals for this award are to: (1) develop a solid foundation in the use and interpretation of genetic data, with a focus on gene-environment interactions; (2) develop an understanding of the pathophysiology and treatments for breast cancer (BC) to assess and characterize cancer outcomes in epidemiologic studies; and (3) develop expertise in the design, conduct, and analysis of randomized clinical trials. To achieve my training objectives, I have assembled a comprehensive and complementary mentorship team with expertise in genetics, alcohol, sex hormones, BC and clinical trials. I will also participate in additional activities to further support my career development including coursework, lab meetings, training in the responsible conduct of research, grant writing, and presenting research at professional conferences. I will apply my training to conduct studies that explore whether there are factors that modify the association between alcohol and BC. There is consistent evidence of higher BC risk associated with daily alcohol intake, even within the recommended limit of up to one drink per day. However, important gaps in knowledge remain about whether there are factors that modify the association between alcohol and BC. This application will leverage existing data to study BC risk among women followed in epidemiological cohorts to test novel scientific questions about gene-environment interactions, using a candidate gene approach and a hypothesis-free genome-wide approach to identifying potential modifiers. In addition, the proposed training award will support an 8-week pilot crossover trial of 20 BC survivors who report that they regularly consume at least one alcoholic beverage per week and are currently prescribed aromatase inhibitor therapy. This trial will utilize the experienced clinical research center and large number of BC survivors receiving treatment at the institutions involved in this training award to generate pilot data that may inform a larger trial about the effects of alcohol on BC treatment. The training, mentorship, research experience, and opportunity to collect pilot data in this K01 award will allow me to achieve my long-term career goal of becoming an independent research in the epidemiology of health effects of alcohol and particularly its role in cancer.