SMOKING & GENETIC INTERACTION IN BREAST CANCER ETIOLOGY

应聘者描述：应聘者蒂莫西·拉什博士 从他的职业生涯开始，他就致力于癌症研究。他 大学本科学习分子生物学，包括肿瘤生物学。 麻省理工学院。毕业后，他当了一名 在需要剂量反应的项目上担任环境卫生顾问 环境和职业致癌物质的评估。与此同时，他 完成公共卫生硕士学位和攻读博士学位 波士顿大学公共卫生学院的流行病学科学。这个 这些学位的课程包括许多与癌症直接相关的课程。 防控。他从事与乳房有关的研究项目 指导下的肿瘤病因、治疗及副作用 拟议的导师(丽贝卡·西里曼博士)和拟议的共同导师 (Ann Aschengrau博士)。拉什博士目前是麻省理工学院 波士顿大学公共卫生学院的流行病学。他花在 他在研究项目上的75%的努力与 提出了研究计划。例如，他是一项研究的项目总监 老年三苯氧胺辅助治疗。西里曼博士是校长 该项目的调查者，将提供乳腺癌的队列 有资格参加第二项拟议研究的患者。拉什博士还与 Aschengrau博士，建议的联合导师，关于积极的影响的分析 和被动吸烟对乳腺癌发生的影响。最新的病例对照 执行这些分析的数据集将提供受试者 有资格参加第一项拟议的研究。波士顿酒店的环境 大学医学中心是完成职业生涯的理想选择 此应用程序的开发目标。 该研究计划提出了两项关于烟草之间相互作用的研究 吸烟与Nat2或COMT基因多态有关。烟草与烟草之间的联系 吸烟和乳腺癌的风险是复杂的。据推测， 烟草烟雾暴露既可能导致乳腺癌，也可能预防乳腺癌，这取决于 与生殖里程碑相关的暴露时间。互动 暴露在烟草烟雾中的基因多态将允许测试 这些假设。第一项研究将收集符合条件的人的口腔拭子 第二项科德角病例对照研究的参与者(Aschengrau博士 PI)。现有的面试信息将与多态相结合 从拭子中提取的数据，以评估 基于生物的病因学研究中的多态性与吸烟亚群 乳腺癌发生的模型。第二项研究将收集口腔拭子。 来自三苯氧胺辅助疗法研究的参与者(西里曼博士 PI)。将进行类似的分析计划，但设计仅限于案例。

DESCRIPTION: (Applicant's Description) The candidate, Dr. Timothy Lash, has been committed to cancer research since the beginning of his career. He studied molecular biology, including tumor biology, as an undergraduate at the Massachusetts Institute of Technology. Upon graduating, he worked as a consultant in environmental health on projects that required dose-response assessment of environmental and occupational carcinogens. Simultaneously, he completed a Masters of Public Health and the coursework for a Doctorate of Science in Epidemiology at the Boston University School of Public Health. The curricula for these degrees included many courses directly relevant to cancer prevention and control. He has worked on research projects involving breast cancer etiology, therapy, and side-effects of therapy under the direction of the proposed mentor (Dr. Rebecca Silliman) and the proposed co-mentor (Dr. Ann Aschengrau). Dr. Lash is currently an Assistant Professor of Epidemiology at the Boston University School of Public Health. He spends 75 percent of his effort on research projects directly relevant to the proposed research plan. For example, he is the project director on a study of adjuvant tamoxifen therapy in old age. Dr. Silliman is the Principal Investigator of the project, which will provide the cohort of breast cancer patients eligible for the second proposed study. Dr. Lash also works with Dr. Aschengrau, the proposed co-mentor, on analyses of the effect of active and passive smoking on breast cancer occurrence. The most recent case-control data set in which these analyses have been performed will provide the subjects eligible for the first proposed study. The environment at the Boston University Medical Center is ideally suited for accomplishing the career development goals of this application. The research plan proposes two studies of the interaction between tobacco smoke and NAT2 or COMT genetic polymorphisms. The association between tobacco smoke and breast cancer risk is complicated. It has been hypothesized that tobacco smoke exposure may both cause and prevent breast cancer, depending on the timing of exposure relative to reproductive milestones. The interaction with tobacco smoke exposure with the gene polymorphisms will allow tests of these hypotheses. The first study would collect buccal swabs from eligible participants of the second Cape Cod case-control study (Dr. Aschengrau was PI). Existing interview information would be combined with the polymorphism data extracted from the swabs to assess the interaction between the polymorphisms and tobacco smoke subgroups under a biologically based etiologic model of breast carcinogenesis. The second study would collect buccal swabs from participants in the study of adjuvant tamoxifen therapy (Dr. Silliman PI). A similar analytic plan would be conducted, but with a case-only design.