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.

项目摘要 我的长期目标是成为健康影响流行病学的独立研究者 酒精，尤其是其在癌症中的作用。我建议这项K01指导研究科学家发展 奖励以实现我先前技能的一系列培训目标，但也以方式扩大我的技能 这对于实现我的长期目标至关重要。我获得该奖项的培训目标是：（1）开发一个 在遗传数据的使用和解释方面的坚实基础，重点是基因环境相互作用； （2）对乳腺癌（BC）的病理生理学和治疗的理解以评估和 表征流行病学研究中的癌症结果； （3）在设计，行为以及 分析随机临床试验。为了实现我的培训目标，我集中了一个全面的 以及具有遗传学，酒精，性激素，卑诗省和临床试验的专业知识的补充指导团队。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，实验室 会议，负责任进行研究，授予写作的培训以及在 专业会议。 我将应用我的培训来进行研究，以探讨是否有一些因素可以修改 酒精与卑诗省之间的关联。有一致的证据表明，每日较高的BC风险 酒精摄入量，即使在每天最多一杯饮料的建议限制之内。但是，重要的差距 关于是否有一些因素是否可以改变酒精与卑诗省之间的关联。这 应用将利用现有数据来研究遵循流行病学队列的女性的BC风险 使用候选基因方法和A测试有关基因环境相互作用的新科学问题 无假设的全基因组方法来识别潜在的修饰符。 此外，拟议的培训奖将支持为期8周 谁报告他们定期每周至少食用一种酒精饮料，目前已开处方 芳香酶抑制剂疗法。该试验将利用经验丰富的临床研究中心和大量 卑诗省的幸存者在该培训奖励的机构接受治疗，以生成试点数据 可以为酒精对卑诗省治疗的影响提供更大的试验。 培训，指导，研究经验和机会，以收集该K01奖中的试点数据 将使我实现成为在流行病学的独立研究的长期职业目标 酒精的健康影响，尤其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

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

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.