DEVELOPING INTERMEDIATE MARKERS OF BREAST CANCER RISK

候选人：彼得·甘恩是一位医生兼流行病学家，他有 最近，他将自己的事业转向了全职的癌症研究 预防。他目前的工作是开发组织中的标记， 等离子体和其他液体，以增强功率和生物 乳腺癌和前列腺癌流行病学研究的相关性 风险。拟议的奖励将使他能够获得更多 发展中的细胞和分子生物学方面的培训/专业知识 成为一个独立的调查者，能够整合新的 实验室技术与传统流行病学。 环境：该奖项的主要赞助商是V.Craig博士 乔丹，西北大学乳腺癌研究主任 大学的卢里癌症中心。共同赞助人是菲利普博士 格陵兰，预防医学系主任。这些 赞助商将指导甘恩博士的进展，并提供访问 癌症生物学的实验室设施和机遇 训练。预防医学系，其中江恩博士 有他的主要任命，有几个成熟的调查人员 在慢性病流行病学方面。1994年，乳腺癌项目 因其研究和培训而获得联邦资助 目标。 研究：拟议的研究评估了a)来自 乳头抽吸物，以及b)活检样本中的正常乳腺组织 作为中间生物标记的来源。我们假设 乳汁中的生长因子(GF)水平反映了 环境影响(包括荷尔蒙和非荷尔蒙) 上皮细胞的基本生长调节机制，从而 反映罹患乳腺癌的风险。乳汁 研究(项目1)的目的是：i)确定 这些流体中的主要GFS(转化生长因子-α、转化生长因子-β、胰岛素样生长因子-1、表皮生长因子)，II) 评估个体内部差异的程度和原因 在组织生长因子水平上，确定体液生长因子、组织生长因子之间的关系 和活检患者的组织学，以及iv)估计相关性 乳房已知或可疑危险因素与生长因子水平的关系 癌症。第二个项目考察了两者之间的联系 生殖和荷尔蒙变量与乳腺癌和 正常乳腺组织小叶分化程度。我们 假设某些“高风险”配置文件将与 小叶发育不成熟。在成熟的啮齿动物中 模型，终端分化强烈降低了 乳腺组织对致癌物的敏感性。甘恩博士是 与福克斯·蔡斯癌症中心的J.Russo博士合作开发 一种简单的细胞分化状态分类方法 切除患者正常石蜡组织中的小叶 活组织检查。以后的研究将把分化状态与 组织和乳房积液的浓度和实际乳房 癌症的发生。甘恩博士将承担主要责任 两个项目的设计、监测、分析和报告， 并将直接参与所有实验室工作。

Candidate: Peter Gann is a physician-epidemiologist who has recently redirected his career into full time research on cancer prevention. His current work entails developing markers in tissue, plasma and other fluids to enhance the power and biological relevance of epidemiologic studies on breast and prostate cancer risk. The proposed award will enable him to obtain additional training/expertise in cell and molecular biology while developing into an independent investigator capable of integrating new laboratory techniques with conventional epidemiology. Environment: The primary sponsor for this award is Dr. V. Craig Jordan, Director of Breast Cancer Research at Northwestern University's Lurie Cancer Center. The Co-sponsor is Dr. Philip Greenland, Chair of the Department of Preventive Medicine. These sponsors will guide Dr. Gann's progress and provide access to laboratory facilities and opportunities for cancer biology training. The Department of Preventive Medicine, in which Dr. Gann has his primary appointment, has several established investigators in chronic disease epidemiology. In 1994, the Breast Cancer Program was awarded Federal funding for its research and training objectives. Research: The proposed studies evaluate a) breast fluid from nipple aspirates, and b) normal breast tissue from biopsy samples as sources of intermediate biologic markers. We hypothesize that growth factor (GF) levels in breast fluid reflect the impact of environmental influences (both hormonal and non-hormonal) on the basic growth-regulating mechanisms of the epithelial cells and thus reflect the risk of developing breast cancer. The breast fluid studies (Project 1) aim to: i) identify the relative quantities of major GFs (TGF-alpha, TGF-Beta, IGF-1, EGF) in these fluids, ii) evaluate the extent of and reasons for intra-individual variation in GF level, iii) determine the relations among fluid GF, tissue GF and histology in biopsied patients, and iv) estimate associations between GF level and known or suspected risk factors for breast cancer. The second project examines the association between reproductive and hormonal variables linked to breast cancer and the degree of lobular differentiation in normal breast tissue. We hypothesize that certain "high-risk" profiles will be associated with less mature lobular development. In well-established rodent models, terminal differentiation strongly reduces the susceptibility of mammary tissue to carcinogens. Dr. Gann is working with Dr. J. Russo at the Fox Chase Cancer Center to develop a simple technique for categorizing the differentiation status of lobules in normal, paraffinized tissue from patients with excision biopsies. Later studies will relate differentiation status to tissue and breast fluid of concentrations and to actual breast cancer occurrence. Dr. Gann will assume central responsibility for the design, monitoring, analysis and reporting of both projects, and will be directly involved in all laboratory work.