RISK FACTORS AND BIOMARKERS FOR IN SITU BREAST CANCER

原位乳腺癌的风险因素和生物标志物

• 批准号: 2429852
• 负责人: LINDA TITUS-ERNSTOFF
• 金额: $ 6.64万
• 依托单位: DARTMOUTH COLLEGE
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-08-01 至 2000-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2429852
• 关键词: alcoholic beverage consumption; biomarker; breast neoplasms; cancer risk; carcinoma; clinical research; female; gene environment interaction; genetic markers; hormone therapy; human genetic material tag; human subject; human tissue; neoplasm /cancer genetics; oral contraceptives; reproduction; single strand conformation polymorphism; tumor suppressor genes

Heightened utilization of mammography has resulted in dramatic increases in the occurrence of breast carcinoma in situ, yet the public health significance of these lesions remains controversial. We propose a multi- center population-based case-control study to evaluate risk factors and biomarkers of breast carcinoma in situ. We will examine the influence of established risk factors for invasive breast carcinoma on BCIS as well as newly identified risk factors, such as alcohol consumption, postmenopausal hormone use, and physical activity. We will evaluate risk factors for BCIS and its major subtypes, lobular carcinoma in situ (LCIS), ductal carcinoma in sine (DCIS), and the aggressive DCIS subtype (comedo-type DCIS). Thus, we will distinguish etiologic factors, including potentially modifiable exposures, that may be related to specific subtypes of biologic significance. In addition, we will be able to compare BCIS risk factors with those identified in our current case- control study of invasive breast cancer. Our unique approach will allow an investigation of risk factors related to tumors of apparently incremental malignant significance. This study will utilize our existing and highly successful consortium of population-based, case-control studies of breast cancer. In the proposed study, we will interview over a 36 month period, 1,570 women with breast carcinoma in situ identified from the WI, MA, and NH state cancer registries. For comparison, about 2,200 population-based controls will be randomly selected from drivers' license lists and from Medicare beneficiary files in each state. This approach will permit the evaluation of two control groups: women with a recent mammographic history, and general population controls. Consenting subjects will participate in a telephone interview. The proposed study, which includes sufficient numbers of BCIS subtypes of disparate malignant potential, provides a unique opportunity to evaluate biomarkers in relation to early disease development. Thus, we propose to evaluate the relationship between BCIS (and its subtypes) to p53 mutations, HER-2/neu amplifications, and NAT2 genotype. These biomarkers are related to invasive breast cancer; our design will allow us to evaluate the extent to which these markers are related to LCIS, DCIS, and the comedo-type DCIS. In addition, we will evaluate the relation between these biomarkers and exposures; this approach may elucidate risk factors involved in early disease development. The findings of this study may have important implications for breast cancer prevention and intervention. In addition, this study will establish the foundation for follow-up studies.

乳房X线照相术的提高使用导致了显着增加 乳腺癌原位癌的发生，但公共卫生 这些病变的意义仍存在争议。我们提出了一个多 中心以人群为基础的病例对照研究，以评估危险因素和 乳腺癌原位癌的生物标志物。我们将考察以下因素的影响 在 BCIS 上也确定了浸润性乳腺癌的危险因素 作为新发现的风险因素，例如饮酒， 绝经后激素的使用和体力活动。我们将评估风险 BCIS 及其主要亚型、小叶原位癌的影响因素 (LCIS)、正弦导管癌 (DCIS) 和侵袭性 DCIS 亚型 （粉刺型 DCIS）。因此，我们将区分病因， 包括潜在可修改的风险暴露，可能与 具有生物学意义的特定亚型。此外，我们将能够 将 BCIS 风险因素与我们当前案例中确定的风险因素进行比较 - 浸润性乳腺癌的对照研究。我们独特的方法将允许 与明显的肿瘤相关的危险因素的调查 递增的恶性意义。本研究将利用我们现有的 以及非常成功的基于人群的病例对照联盟 乳腺癌的研究。在拟议的研究中，我们将采访超过 36 个月期间，1,570 名女性被确诊为乳腺癌原位癌 来自威斯康星州、马萨诸塞州和新罕布什尔州癌症登记处。为了比较，大约 将从驾驶员中随机选择 2,200 个基于人群的对照 许可证列表和每个州的 Medicare 受益人文件。这 该方法将允许对两个对照组进行评估： 最近的乳房X光检查史和一般人口控制。同意 受试者将参加电话采访。拟议的研究， 其中包括足够数量的不同恶性的 BCIS 亚型 潜力，提供了评估生物标志物的独特机会 与早期疾病发展的关系。因此，我们建议评估 BCIS（及其亚型）与 p53 突变、HER-2/neu 之间的关系 扩增和 NAT2 基因型。这些生物标志物与 浸润性乳腺癌；我们的设计将使我们能够评估程度 这些标记与 LCIS、DCIS 和粉刺型相关 导管原位癌。此外，我们将评估这些生物标志物之间的关系 和曝光；这种方法可以阐明早期涉及的风险因素 疾病的发展。这项研究的结果可能具有重要意义 对乳腺癌预防和干预的影响。此外， 本研究将为后续研究奠定基础。