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健康影响流行病学的独立研究员。 酒精，特别是它在癌症中的作用。我建议K01指导研究科学家发展 奖励，以实现一系列的培训目标，这些目标建立在我先前技能的基础上，但也在以下方面扩展了我的技能 这对实现我的长期目标至关重要。我的这个奖项的培训目标是：(1)发展一种 在使用和解释遗传数据方面有扎实的基础，重点是基因与环境的相互作用； (2)加深对乳腺癌(BC)的病理生理和治疗的了解，以评估和 在流行病学研究中确定癌症结果；以及(3)在设计、实施和 随机临床试验分析。为了实现我的训练目标，我组织了一个全面的 以及互补的导师团队，在遗传学、酒精、性激素、BC和临床试验方面具有专业知识。我 我还将参加其他活动，以进一步支持我的职业发展，包括课程作业、实验室 会议，负责任地进行研究的培训，拨款撰写，并在 专业会议。 我将运用我的培训来进行研究，探索是否有因素改变 酒精与卑诗省之间的联系。有一致的证据表明，与日常生活相关的BC风险更高 酒精摄入量，即使在建议的每天最多一杯酒的限制内。然而，在以下方面存在重要差距 关于是否存在改变酒精和BC之间联系的因素，人们仍然知之甚少。这 应用程序将利用现有数据来研究流行病学队列中跟踪调查的女性中的BC风险 测试关于基因-环境相互作用的新科学问题，使用候选基因方法和 识别潜在修饰因子的全基因组无假说方法。 此外，拟议的培训奖励将支持对公元前20名幸存者进行为期8周的试点交叉试验 世卫组织报告说，他们每周至少喝一杯酒精饮料，目前是按处方开的 芳香酶抑制剂治疗。本次试验将利用经验丰富的临床研究中心和大量的 BC幸存者在参与该培训奖项的机构接受治疗，以生成试点数据， 可能会向一项更大的试验报告酒精对BC治疗的影响。 此K01奖项中的培训、指导、研究经验和收集飞行员数据的机会 将使我实现我的长期职业目标，成为一名独立的流行病学研究人员。 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.