DEVELOPING INTERMEDIATE MARKERS OF BREAST CANCER RISK

候选人：彼得·江恩是一位流行病学家， 他最近将自己的职业生涯转向全职研究癌症 预防他目前的工作需要在组织中开发标记， 等离子体和其他流体，以提高电力和生物 乳腺癌和前列腺癌流行病学研究的相关性 风险该奖项将使他能够获得额外的 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员，能够整合新的 实验室技术与常规流行病学。 环境：该奖项的主要赞助商是V.克雷格博士 乔丹，西北大学乳腺癌研究主任 Lurie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 赞助商将指导江恩博士的进展，并提供访问 癌症生物学的实验室设施和机会 训练预防医学部，江恩博士 有他的主要任命，有几个既定的调查员 在慢性病流行病学中。1994年，乳腺癌计划 被授予联邦基金用于其研究和培训 目标. 研究：拟议的研究评估a）来自 乳头抽吸物，和B）来自活组织检查样品的正常乳腺组织 作为中间生物标记物的来源。我们假设 乳腺液中的生长因子（GF）水平反映了 环境影响（激素和非激素）对 上皮细胞的基本生长调节机制， 反映了患乳腺癌的风险。乳腺液 研究（项目1）旨在：i）确定 这些液体中的主要GF（TGF-α、TGF-β、IGF-1、EGF），ii） 评估个体内变异的程度和原因 在GF水平上，iii）确定液体GF、组织GF 和组织学，以及iv）估计相关性 GF水平与已知或疑似乳腺癌风险因素之间的关系 癌第二个项目研究了 与乳腺癌有关的生殖和激素变量， 正常乳腺组织的小叶分化程度。我们 假设某些"高风险"特征将与 小叶发育不成熟。在公认的啮齿类动物中， 模型，终端分化大大降低了 乳腺组织对致癌物的敏感性。江恩博士是 与福克斯蔡斯癌症中心的J. Russo博士合作， 一种简单的技术，用于分类的分化状态， 切除患者的正常石蜡组织中的小叶 活组织检查后来的研究将分化状态与 组织和乳腺液的浓度和实际乳房 癌症发生。江恩博士将负责 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.