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起作用。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。这项建议旨在研究护士健康研究I和II中乳腺癌发病途径的各个阶段：1）早期阶段，重点关注青少年饮食与乳腺增生病发病率之间的关系; 2）中期和累积终生暴露，重点关注乳腺增生病的遗传和分子预测因素;和3）通过检查良性乳腺组织中的蛋白质表达和随后的乳腺癌风险的后期阶段。具体来说，我们假设青少年摄入的脂肪总量和特定亚型与乳腺增生性疾病有关;胰岛素样生长因子（IGF）-I途径和孕酮受体的多态性和单倍型，以及IGF-1和IGFBP-3的循环水平，与良性乳腺增生性疾病的发病率有关;良性乳腺疾病组织中分子标记（ER-α、PR、IGF-1 R、Ki 67和细胞角蛋白5/6）的表达与乳腺癌的后续风险相关。 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乳腺增生性疾病。乳腺癌巢式病例对照数据集的额外随访将使我们能够更详细地研究乳腺增生性疾病和随后的乳腺癌之间的关系。使用良性乳腺组织创建组织微阵列将为这项研究和未来的研究奠定基础，以有效地检查分子标记物在乳腺癌发展中的作用。

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.