Metabolite Profiles and Mammographic Density in Premenopausal Women

绝经前女性的代谢物概况和乳房 X 光密度

基本信息

批准号：
10652311
负责人：
Adetunji T Toriola
金额：
$ 35.31万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-01 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10652311
关键词：
Acceleration African American African American population Age Amino Acids Biological Biological Markers Blood Blood specimen Breast Breast Cancer Prevention Breast Cancer Risk Factor Cancer Etiology Case/Control Studies Chemoprevention Coupled Data Development Diagnosis Disease Enrollment Ensure Etiology Fasting Future Health Incidence Lipids Malignant Neoplasms Mammographic Density Mammography Measures Mediating Modeling Molecular Molecular Weight Not Hispanic or Latino Nucleotides Obesity Participant Pathway interactions Performance Population Heterogeneity Premenopause Prevention trial Primary Prevention Questionnaires Race Reproducibility of Results Research Research Design Source Surrogate Markers Techniques Time Tissues Translating Universities Validation Variant Washington Woman aged biological systems biomarker identification breast density density follow-up innovation insight malignant breast neoplasm medical schools metabolome metabolomics novel novel strategies real world application recruit risk prediction routine screening screening secondary analysis study population success tool young woman

项目摘要

ABSTRACT In 2019, approximately 268,600 women in the US will be diagnosed with breast cancer, making it the leading cause of cancer in women. About 25% of these cases occurred in premenopausal women. The annual incidence of breast cancer among women under age 50 has been increasing slowly since the mid-1990s, in contrast to what is observed in women aged over 50 years, where the incidence has remained stable over time. This persistent increase in the incidence among younger women indicates that new approaches to primary prevention in premenopausal women are needed. Mammographic breast density is one of the strongest risk factors for breast cancer, especially in premenopausal women, where an estimated 39% of breast cancer cases is attributable to having dense breasts. A decrease in breast density leads to a reduction in breast cancer incidence. Nevertheless, the molecular basis of mammographic breast density and the mechanisms through which dense breast increases breast cancer risk are poorly understood. A greater understanding of these mechanisms is crucial, and will uncover new biological pathways and actionable biomarkers that can be targeted to prevent breast cancer development. Metabolomics is a promising tool to provide novel insights into disease etiology, biological mechanisms, and pathways. Metabolomics has, however, not been applied to study mammographic breast density. Our pilot analyses show differences in metabolite levels between women with fatty breasts compared to women with dense breasts. Building on these novel findings, we will apply state-of-the art metabolomics platforms to 1) investigate the metabolome of mammographic breast density in premenopausal women; 2) quantify the variation in mammographic breast density explained by the metabolome; 3) determine whether the metabolome of mammographic breast density predicts breast cancer development in premenopausal women. Our overarching hypothesis is that we will leverage metabolomics to uncover the molecular mechanisms, biological pathways, as well as novel actionable biomarkers that are associated with mammographic breast density in premenopausal women. Our study population will consist of premenopausal women recruited during annual screening mammogram at the Joanne Knight Breast Health Center at the Washington University School of Medicine, St. Louis, MO. Mammographic breast density is quantitatively assessed using Volpara. Fasting blood samples are collected on the same day the women have their mammograms. The women also complete a questionnaire with detailed information on breast cancer risk factors and determinants of mammographic density. In conclusion, we will build on our exciting preliminary data to uncover novel, actionable biomarkers associated with mammographic breast density, and also breast cancer development in premenopausal women. These biomarkers could be targeted in breast cancer prevention in future studies.

抽象的 2019年，美国约有268,600名妇女将被诊断出患有乳腺癌，使其成为领先的女性癌症的原因。这些病例中约有25％发生在绝经前妇女中。一年一度自1990年代中期以来，50岁以下女性乳腺癌的发病率一直在缓慢增加与50岁以上的妇女观察到的相比时间。年轻女性发生率的这种持续增加表明需要绝经前妇女的一级预防。乳房乳房乳房密度是乳腺癌的最强危险因素，尤其是绝经前妇女，估计有39％乳腺癌病例归因于乳房致密。乳房密度的降低会导致减少在乳腺癌发病率中。然而，乳房X线乳房密度的分子基础和人们对乳腺癌风险增加乳腺癌风险的机制了解较少。更大了解这些机制至关重要，将发现新的生物学途径和可行可以针对预防乳腺癌发展的生物标志物。代谢组学是一种有前途的工具提供有关疾病病因，生物学机制和途径的新见解。代谢组学有但是，不应用于研究乳房X线乳房密度。我们的飞行员分析显示与乳房密集的女性相比，患有脂肪乳房的女性之间的代谢水平。建立在这些基础上新发现，我们将应用最先进的代谢组学平台1）研究绝经前女性乳房乳房密度； 2）量化乳房X线乳房乳房的变化密度由代谢组解释； 3）确定乳房X线乳房密度的代谢组是否预测绝经前妇女的乳腺癌发展。我们的总体假设是我们将利用代谢组学来揭示分子机制，生物途径以及可操作的新型与绝经前妇女乳房乳房密度相关的生物标志物。我们的研究人口将包括在乔安妮的年度筛选乳房X线照片期间招募的绝经前妇女华盛顿大学医学院的骑士乳房健康中心，密苏里州圣路易斯。乳房X线学使用Volpara定量评估乳房密度。在同一天收集禁食的血液样本女人有乳房X线照片。妇女还填写了一份问卷，并提供有关详细信息乳腺癌的危险因素和乳房X线摄影密度的决定因素。总之，我们将在我们的基础上建立令人兴奋密度，以及绝经前妇女的乳腺癌发展。这些生物标志物可能是针对的在未来的研究中预防乳腺癌。

项目成果

期刊论文数量（12）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Does circulating progesterone mediate the associations of single nucleotide polymorphisms in progesterone receptor (PGR)-related genes with mammographic breast density in premenopausal women?

DOI：
10.1007/s12672-021-00438-1
发表时间：
2021
期刊：
Discover oncology
影响因子：
2.2
作者：
Akinjiyan FA;Han Y;Luo J;Toriola AT
通讯作者：
Toriola AT

Coffee, Tea, and Mammographic Breast Density in Premenopausal Women.

DOI：
10.3390/nu13113852
发表时间：
2021-10-28
期刊：
Nutrients
影响因子：
5.9
作者：
Odama AM;Otti V;Xu S;Adebayo O;Toriola AT
通讯作者：
Toriola AT

Chemoprevention Agents to Reduce Mammographic Breast Density in Premenopausal Women: A Systematic Review of Clinical Trials.

DOI：
10.1093/jncics/pkaa125
发表时间：
2021-03
期刊：
JNCI cancer spectrum
影响因子：
4.4
作者：
Salazar AS;Rakhmankulova M;Simon LE;Toriola AT
通讯作者：
Toriola AT

Reply to Hopper, Nguyen, and Li.

DOI：
10.1093/jncics/pkab052
发表时间：
2021-08
期刊：
JNCI cancer spectrum
影响因子：
4.4
作者：
Salazar AS;Toriola AT
通讯作者：
Toriola AT

Lipidome of mammographic breast density in premenopausal women.

DOI：
10.1186/s13058-023-01725-1
发表时间：
2023-10-09
期刊：
BREAST CANCER RESEARCH
影响因子：
7.4
作者：
Getz, Kayla R.;Jeon, Myung Sik;Luo, Chongliang;Luo, Jingqin;Toriola, Adetunji T.
通讯作者：
Toriola, Adetunji T.