Benign Breast Disease and Risk of Breast Cancer

描述(由申请人提供)：为了了解乳腺癌发生的多因素性质，我们必须确定哪些因素在每个阶段发挥作用。通过研究良性乳腺疾病，我们可以检查疾病过程的早期阶段。这项建议的目的是在护士健康研究I和II中检查乳腺癌途径的所有阶段：1)早期阶段，重点关注青少年饮食与增生性乳房疾病发病率之间的关系；2)中期和累积终生暴露，通过集中研究增生性乳房疾病的遗传和分子预测因素；以及3)后期阶段，通过检测良性乳腺组织中的蛋白质表达和随后的乳腺癌风险。具体地说，我们假设青少年摄入全部和特定亚型的脂肪与增生性乳腺疾病有关；胰岛素样生长因子(IGF)-I途径和孕激素受体的多态和单倍型以及循环中IGF-1和IGFBP-3的水平与增生性良性乳腺疾病的发病率相关；分子标记物(ER-a、PR、IGF-1R、Ki67和细胞角蛋白5/6)在良性乳腺疾病组织中的表达与随后的乳腺癌风险相关。 这项研究提供了一个独特的机会，前瞻性地检查青少年的饮食和分子标志物与增生性乳腺疾病的关系。对乳腺癌嵌套病例对照数据集的额外跟踪将使我们能够更详细地检查增生性乳腺疾病和后续乳腺癌之间的关系。利用良性乳腺组织创建组织微阵列将为这项研究和未来有效检测分子标记在乳腺癌发展中的作用的研究奠定基础。

DESCRIPTION (provided by applicant): To understand the multi-factorial nature of breast carcinogenesis, we must determine what factors play a role at each stage. By studying benign breast disease we can examine an earlier period in the disease process. This proposal aims to examine a full spectrum of stages on the pathway to breast cancer in Nurses' Health Study I and II: 1) early stages by focusing on the relationship between adolescent diet and incidence of proliferative breast disease; 2) intermediate and cumulative lifetime exposures by concentrating on genetic and molecular predictors of proliferative breast disease; and 3) later stages by examining protein expression in benign breast tissue and subsequent breast cancer risk. Specifically, we hypothesize that adolescent intake of total and specific subtypes of fat are associated with proliferative breast disease; polymorphisms and haplotypes in the insulin-like growth factor (IGF)-I pathway and the progesterone receptor, as well as circulating levels of IGF-1 and IGFBP-3, are related to incidence of proliferative benign breast disease; expression of molecular markers (ER-a, PR, IGF-1 R, Ki67 and cytokeratin 5/6) in benign breast disease tissue is associated with subsequent risk of breast cancer. This study offers a unique opportunity to prospectively examine adolescent diet and molecular markers in relation to proliferative breast disease. Additional follow-up of the breast cancer nested case-control data set will allow us to examine in more detail the relationship between proliferative breast disease and subsequent breast cancer. The creation of tissue microarrays using benign breast tissue will lay the foundation for this and future studies to efficiently examine the role of molecular markers in the development of breast cancer.