SMOKING & GENETIC INTERACTION IN BREAST CANCER ETIOLOGY

描述：（申请人的描述）候选人，蒂莫西·拉什博士，有 他从职业生涯开始就致力于癌症研究。 他 研究分子生物学，包括肿瘤生物学，作为一个本科生在 马萨诸塞州理工学院。毕业后，他作为一名 需要剂量反应的项目的环境卫生顾问 环境和职业致癌物的评估。 同时他 完成了公共卫生硕士学位和博士学位的课程， 波士顿大学公共卫生学院流行病学科学。 的 这些学位的课程包括许多与癌症直接相关的课程 防治的攻坚 他从事过涉及乳房的研究项目， 癌症病因学、治疗方法和治疗的副作用， 建议的导师（Rebecca Silliman博士）和建议的共同导师 (Dr. Ann Aschengrau）。 拉什博士目前是一个助理教授 波士顿大学公共卫生学院的流行病学。 他花 他75%的精力都花在了与研究项目直接相关的研究上。 提出研究计划。 例如，他是一项研究的项目主任， 他莫昔芬辅助治疗老年人。 Silliman博士是校长 该项目的研究者，将提供乳腺癌的队列 符合第二项拟议研究条件的患者。 拉什博士还与 Aschengrau博士，拟议的共同导师，对活性药物的影响进行分析， 被动吸烟对乳腺癌的影响。 最近的病例对照 进行这些分析的数据集将提供受试者 有资格参加第一次拟议的研究。 波士顿的环境 大学医疗中心是理想的适合完成职业生涯 这个应用的发展目标。 该研究计划提出了两项关于烟草与 吸烟与NAT2或COMT基因多态性。 烟草与 吸烟和乳腺癌风险是复杂的。 已经假设 烟草烟雾暴露可能会导致和预防乳腺癌，这取决于 相对于生殖里程碑的暴露时间。 的相互作用 与烟草烟雾暴露的基因多态性将允许测试 这些假设。 第一项研究将从符合条件的患者中收集口腔拭子， 第二次科德角病例对照研究的参与者（Aschengrau博士是 PI）。 现有的采访信息将与多态性相结合 从拭子中提取的数据，以评估 多态性和烟草吸烟亚组根据生物学为基础的病因 乳腺癌发生模型。 第二项研究将收集口腔拭子 来自辅助他莫昔芬治疗研究的参与者（Silliman博士 PI）。 将进行类似的分析计划，但仅采用个案设计。

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.