Molecular Predictors of Mammographic Density

乳腺X线密度的分子预测因子

基本信息

批准号：
8024569
负责人：
Rulla M Tamimi
金额：
$ 28.18万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-04-04 至 2014-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8024569
关键词：
1,25 (OH) vitamin D 25-hydroxyvitamin D Androgens Applications Grants Belief Binding Biological Assay Biological Markers Biology Blood specimen Breast Breast Cancer Risk Factor Case-Control Studies Collection Data Development Estrogens Estrone Exposure to Film Funding Globulins Gonadal Steroid Hormones Growth Hormonal Hormones Insulin Insulin-Like Growth Factor Binding Protein 3 Insulin-Like Growth Factor I Insulin-Like Growth-Factor Binding Protein 1 Knowledge Laboratories Luteal Phase Mammographic Density Mammography Measurement Measures Mediating Modeling Molecular Molecular Biology Nested Case-Control Study Nurses&apos Health Study Phase Postmenopause Premenopause Prevention strategy Prolactin Public Health Research Design Risk Sampling Screening procedure Sex Hormone-Binding Globulin Time Urine Vitamin D Woman Work breast density cancer risk carcinogenesis follow-up high risk improved malignant breast neoplasm sex urinary

项目摘要

DESCRIPTION (provided by applicant): Women with the highest mammographic density are at a four- to six-fold increased risk of breast cancer as compared with women with the lowest mammographic density. The data examining the underlying mechanisms involved are sparse. The widely hypothesized belief that mammographic density reflects cumulative exposure to estrogens has come under question with data from our own group and others. Most studies to date have focused on postmenopausal women, whose levels of estrogens and breast density are both lower than those of premenopausal women. It is highly plausible that mammographic density may be more reflective of premenopausal hormone levels than postmenopausal levels. In addition, a number of other hormones including insulin-like growth factor-1 and vitamin D, and estrogen metabolites have also been implicated in breast proliferation and carcinogenesis and may be associated with breast density. In my first R01 submission, I propose to explore the underlying mechanism by which mammographic density is related to breast cancer, by focusing on circulating hormone levels and urinary estrogen metabolites in premenopausal women. Specifically, we will: (1) Assess the relationship between circulating levels of estrogens, androgens, prolactin, sex hormone binding globulin, vitamin D and insulin-like growth factor-1, and mammographic density; (2) Examine the association between urinary estrogen metabolites in relation to mammographic density; and (3) Determine if hormonal biomarkers and mammographic density are independent predictors of breast cancer risk. These aims will provide complementary information that will help elucidate the biology of mammographic density. We will collect film mammograms and measure breast density among women in a breast cancer case- control study nested within the Nurses' Health Study II for whom blood samples are available and hormone assays will be conducted as part of another funded project. This case-control study is unique in that sex steroid hormones have been measured in both the early follicular and mid-luteal phases of the menstrual cycle. Recent work from our group highlights important differences observed between phase-specific hormone levels and breast cancer risk. To date, no other study has examined phase-specific sex steroids in relation to mammographic density. We expect to have mammographic density as well as hormone measurements on approximately 636 breast cancer cases (361 with timed samples) and 2 matched controls per case. Measurements of both biomarkers and breast density may help to identify women at particularly high risk of breast cancer. This is an efficient study design to determine the association between hormonal biomarkers and mammographic density and the effects of both on breast cancer risk.

描述（由申请人提供）：与乳腺X线摄影密度最低的女性相比，乳房X线学密度最高的女性乳腺癌风险增加了四至六倍。研究涉及的基本机制的数据很少。广泛假设的信念，即乳房X线摄影密度反映了对雌激素的累积暴露，这对我们自己的小组和其他人的数据受到了质疑。迄今为止，大多数研究都集中在绝经后妇女上，其雌激素和乳房密度的水平都低于绝经前妇女。高度合理的是，乳房X线照相密度可能比绝经后水平更反映绝经前激素水平。此外，许多其他激素，包括胰岛素样生长因子1和维生素D，以及雌激素代谢产物也与乳腺增殖和癌变有关，可能与乳房密度有关。在我的第一次R01提交中，我建议通过专注于循环激素水平和绝经前妇女的尿中雌激素代谢物，探索乳腺X线摄影密度与乳腺癌相关的潜在机制。具体而言，我们将：（1）评估雌激素，雄激素，催乳素，性激素结合球蛋白，维生素D和胰岛素样生长因子-1和乳房X线照相密度之间的循环水平之间的关系；（2）检查与乳房X线摄影密度相关的尿雌激素代谢产物之间的关联；（3）确定激素生物标志物和乳房X线摄影密度是否是乳腺癌风险的独立预测指标。这些目标将提供互补的信息，有助于阐明乳房X线摄影密度的生物学。我们将在嵌套在护士健康研究II中的乳腺癌对照研究中，收集膜乳房X线照片并测量女性的乳房密度，并为其提供血液样本，并将激素分析作为另一个资助项目的一部分进行。这项病例对照研究是独一无二的，因为在月经周期的早期卵泡和中间阶段都测量了性类固醇激素。来自我们小组的最新工作强调了相位特异性激素水平和乳腺癌风险之间观察到的重要差异。迄今为止，尚无其他研究检查相对于乳房X线摄影密度的特异性性类固醇。我们预计将在约636例乳腺癌病例（361例，定时样本）和2个匹配的对照组上具有乳房X线摄影密度和激素测量。生物标志物和乳房密度的测量可能有助于鉴定出乳腺癌风险特别高的女性。这是一种有效的研究设计，旨在确定激素生物标志物与乳房X线摄影密度之间的关联以及两者对乳腺癌风险的影响。