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: 2882420
• 负责人: POLLY A NEWCOMB
• 金额: $ 64.78万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-06-01 至 2002-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2882420
• 关键词: age at pregnancy; alcoholic beverage consumption; biomarker; body physical activity; breast neoplasms; cancer risk; clinical research; gene environment interaction; gene expression; gene mutation; genetic markers; hormone therapy; human genetic material tag; human population study; human subject; interview; molecular oncology; neoplasm /cancer genetics; neoplasm /cancer invasiveness; polymerase chain reaction; postmenopause; single strand conformation polymorphism; statistics /biometry; tobacco abuse; tumor suppressor genes; women's health

Heightened utilization of mammography has resulted in dramatic increases in the occurrence of breast carcinoma in situ (BCIS), 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 situ (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, 1575 women with breast carcinoma in situ identified from the WI, MA, and NH state cancer registries. For comparison, about 2205 population-based controls will be randomly selected from drivers' license lists and 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 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 developments. 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线摄影的使用增加导致了急剧增加 在现场发生乳腺癌（BCIS）时，公众 这些病变的健康意义仍然存在争议。 我们提出了一个 多中心基于人群的病例对照研究，以评估危险因素 和原位乳腺癌的生物标志物。 我们将检查影响 在BCIS上的侵入性乳腺癌的既定风险因素 作为新确定的危险因素，例如饮酒， 绝经后激素的使用和体育锻炼。 我们将评估风险 BCI及其主要亚型的因素，原位肺癌（LCIS）， 导管癌原位（DCIS）和侵略性DCIS亚型（comedo- 键入DCI）。 因此，我们将区分病因学因素，包括 潜在的可修改暴露，可能与特定亚型有关 生物学意义。 此外，我们将能够比较BCIS 我们当前的病例对照研究中确定的风险因素 侵入性乳腺癌。 我们独特的方法将允许调查 与明显递增恶性肿瘤肿瘤有关的风险因素 意义。 这项研究将利用我们现有且非常成功的 乳腺癌基于人群的病例对照研究。 在 拟议的研究，我们将在一个36个月的1575名妇女中采访 从WI，MA和NH状态确定的原位乳腺癌 癌症登记。 为了进行比较，约有2205个基于人群的对照 将从驾驶执照清单和Medicare中随机选择 每个州的受益文件。 这种方法将允许评估 在两个对照组中：有近期乳房X线学史的女性，以及 一般人口控制。 同意主题将参加 电话采访。 拟议的研究包括足够 不同恶性潜力的BCIS亚型数量提供了 评估与早期疾病有关的生物标志物的独特机会 发展。 因此，我们建议评估BCI之间的关系 （及其亚型）至p53突变Nat2基因型。 这些生物标志物是 与侵入性乳腺癌有关；我们的设计将使我们能够评估 这些标记与LCIS，DCI和 Comedo型DCI。 此外，我们将评估 这些生物标志物和暴露；这种方法可能阐明风险因素 参与早期疾病的发展。 这项研究的发现可能 对预防乳腺癌和干预具有重要意义。 此外，这项研究将为后续行动奠定基础 研究。