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

酒精和乳腺癌：遗传相互作用和对芳香酶抑制剂治疗的影响

• 批准号: 10680436
• 负责人: Elizabeth Mostofsky
• 金额: $ 14.66万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10680436
• 关键词: Adjuvant Therapy; Affect; Alcohol consumption; Alcoholic Beverages; Alcohols; American; Area; Aromatase Inhibitors; Award; Breast Cancer Risk Factor; Breast Cancer Treatment; Breast Cancer survivor; Breast Cancer therapy; Candidate Disease Gene; Clinical Research; Clinical Trials; Consumption; Cross-Over Trials; Data; Dehydroepiandrosterone Sulfate; Development Plans; Diagnosis; Effectiveness; Epidemiology; Estradiol; Estrogen receptor positive; Estrogens; European ancestry; Female; Foundations; Fruit; Functional disorder; General Population; Genetic; Genetic Risk; Genetic study; Genome; Genomics; Goals; Gonadal Steroid Hormones; Grant; Grapes; Health; Incidence; Institution; Intake; Intervention; Intervention Trial; Israel; Juice; Knowledge; Link; Malignant Neoplasms; Medical center; Mentored Research Scientist Development Award; Mentorship; Metabolic Pathway; Outcome; Participant; Pathway interactions; Persons; Postmenopause; Prevalence; Prevention strategy; Public Health; Randomized; Recommendation; Recurrence; Reporting; Research; Research Personnel; Risk; Role; Series; Solid; Survivors; Testing; Testosterone Sulfate; Training; Twin Multiple Birth; Wine; Woman; Writing; alcohol effect; alcohol free; breast cancer survival; cancer therapy; career; career development; cohort; design; epidemiology study; experience; feeding; gene environment interaction; genetic variant; genome wide association study; genome-wide; high dimensionality; high risk; high risk population; inhibitor therapy; insight; malignant breast neoplasm; meetings; novel; randomized trial; randomized, clinical trials; responsible research conduct; risk minimization; skills; symposium; treatment guidelines; tumor

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.

项目概要 我的长期目标是成为流行病学对健康影响的独立研究者 酒精，特别是它在癌症中的作用。我提议进行 K01 指导研究科学家发展 奖励以实现一系列培训目标，这些目标建立在我之前的技能的基础上，同时也以多种方式扩展我的技能 这对于实现我的长期目标至关重要。我对这个奖项的培训目标是：（1）发展 为遗传数据的使用和解释奠定坚实的基础，重点关注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果； (3) 发展设计、实施和实施方面的专业知识 随机临床试验分析。为了实现我的培训目标，我收集了一个全面的 以及在遗传学、酒精、性激素、BC 和临床试验方面具有专业知识的补充导师团队。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、负责任的研究行为培训、拨款写作以及在 专业会议。 我将运用我的培训来进行研究，探索是否有因素会改变 酒精与 BC 之间的关联。有一致的证据表明，日常饮食与 BC 风险较高相关。 酒精摄入量，即使在每天最多一杯的建议限制内。然而，重要的差距 关于是否存在改变酒精与 BC 之间关联的因素，目前尚不清楚。这 应用程序将利用现有数据来研究流行病学队列中女性的乳腺癌风险 使用候选基因方法和 识别潜在修饰因子的无假设全基因组方法。 此外，拟议的培训奖将支持对 20 名 BC 幸存者进行为期 8 周的试点交叉试验 报告称他们每周至少饮用一种酒精饮料并且目前已接受处方 芳香酶抑制剂治疗。该试验将利用经验丰富的临床研究中心和大量的 不列颠哥伦比亚省幸存者在参与该培训奖的机构接受治疗，以生成试点数据 可能会为更大规模的试验提供关于酒精对 BC 治疗影响的信息。 K01 奖中的培训、指导、研究经验和收集试点数据的机会 将使我能够实现成为流行病学独立研究人员的长期职业目标 酒精对健康的影响，特别是其在癌症中的作用。

项目成果

Politically related stress and low-birth-weight infants among Arab, Asian, Hispanic, non-Hispanic Black, and non-Hispanic White women in Michigan.

• DOI: 10.1177/17455057231178118
• 发表时间: 2023-01
• 期刊: WOMENS HEALTH
• 影响因子: 2.4
• 作者: Dallo, Florence J.;Williams, David R.;Ruterbusch, Julie J.;Mittleman, Murray A.;Sakyi, Kwame S.;Mostofsky, Elizabeth;Rimawi, Asmaa;Qu, Xianggui;Reid, Todd G.;Schwartz, Kendra
• 通讯作者: Schwartz, Kendra

Racial disparities in post-transplant stroke and mortality following stroke in adult cardiac transplant recipients in the United States.

• DOI: 10.1371/journal.pone.0268275
• 发表时间: 2023
• 期刊: PloS one
• 影响因子: 3.7

Racial and Ethnic Disparities in Incidence and Prognosis of Perioperative Stroke Among Pediatric Cardiac Transplant Recipients.

• DOI: 10.1161/jaha.121.025149
• 发表时间: 2022-07-19
• 期刊: JOURNAL OF THE AMERICAN HEART ASSOCIATION
• 影响因子: 5.4
• 作者: Lehman, Laura L.;Mostofsky, Elizabeth;Salia, Soziema;Gupta, Suruchi;Barrera, Francisco J.;Liou, Lathan;Mittleman, Murray A.
• 通讯作者: Mittleman, Murray A.

Associations between migraine attacks and nightly sleep characteristics among adults with episodic migraine: a prospective cohort study.

• DOI: 10.1093/sleep/zsaa001
• 发表时间: 2020-01
• 期刊: Sleep
• 影响因子: 5.6
• 作者: A. Vgontzas;Wenyuan Li;Elizabeth Mostofsky;M. Rueschman;M. Mittleman;S. Bertisch