TOBACCO SMOKE EXPOSURE AND HORMONAL CHANGES IN WOMEN

女性接触烟草烟雾和荷尔蒙变化

• 批准号: 7608330
• 负责人: Offie P Soldin
• 金额: $ 0.19万
• 依托单位: CHILDREN'S RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-12-01 至 2007-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7608330
• 关键词: Affect; Biological Markers; Blood; Blood specimen; Cancer Etiology; Carcinogens; Child; Cigarette; Complex Mixtures; Computer Retrieval of Information on Scientific Projects Database; Condition; Contracts; Development; Disruption; Environmental Tobacco Smoke; Exposure to; Fertility; Funding; Future; Genes; Genetic; Genetic Polymorphism; Genetic Predisposition to Disease; Goals; Grant; Hormonal; Hormonal Change; Hormones; Individual; Infant; Infertility; Inflammation; Institution; Irritants; Isotopes; Knowledge; Learning; Low Birth Weight Infant; Malignant Neoplasms; Measures; Menopause; Menstrual cycle; Metabolism; Mothers; Mutation; Numbers; Play; Population; Pregnancy; Pregnancy loss; Premenopause; Purpose; Reproductive system; Research; Research Personnel; Resources; Risk; Role; Sampling; Services; Smoke; Smoker; Source; Specificity; Staging; Steroids; System; Technology; Thyroid Hormones; Time; Tobacco smoke; United States National Institutes of Health; Variant; Woman; Women' s Health; cigarette smoking; cost; disorder prevention; gene environment interaction; mutant; non-smoker; steroid hormone; steroid hormone biosynthesis; steroid hormone metabolism; tandem mass spectrometry

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The purpose of this project is to explore the relationship between, and effect of cigarette smoke and genetic predisposition on alterations in hormone levels in premenopausal women. We hope to elucidate the gene-environment interaction in hormonal disruption in order to identify existing adverse exposure, and introduce preventative measures to eliminate risks to mother and future baby. Second-hand smoke is a dynamic, complex mixture of thousands of compounds, including carcinogens and irritants, as well as compounds suspected to cause damage to the reproductive system, increase the likelihood of pregnancy loss and cause low birth weight in infants. A few studies indicate that cigarette smoke may alter hormone levels, which in turn could have an effect on hormone-dependent conditions such as inflammation, cancer, fertility and pregnancy. Changes in hormone function from smoke exposure can significantly impact a woman's ability to have children, their menstrual cycles are shorter, menopause is earlier and they have a higher risk of development of hormone-dependent cancers. How smoke exposure may cause these hormonal changes is not clear. In this study we will try and answer the following two questions: Is there a difference in the levels of steroid hormones between smokers and non-smokers? And is the association between cigarette smoke and hormone levels significantly different in women with normal gene types compared to mutant gene types? Therefore, we will examine if these cigarette smoke-related alterations in hormone concentrations are specific to women who are genetically more prone to these changes. For that purpose, we will examine four genes responsible for steroid hormone metabolism to see if the changes in hormone concentrations due to cigarette smoke are more profound in women who have mutations in these specific genes. Isotope-dilution tandem mass spectrometry (MS/MS) is technology that provides superior specificity for accurate quantification of hormones (or other substances). In this study, we will use MS/MS to accurately measure the concentrations of steroid and thyroid hormones. This is the first study to investigate changes in concentrations of a large number of steroid and thyroid hormones due to exposure to cigarette smoke. To our knowledge, no studies of these hormones and cigarette smoke have been conducted using MS/MS technology. As a result of this study, we expect to learn more about how cigarette smoke and genetics affect hormone systems, and in particular the effects of tobacco smoke on changes in steroid hormone concentrations. If we find evidence that these genes are associated with specific changes in any of the hormones in this population, the findings will help us understand the role these genes play in women's health, infertility and cancer etiology. These hormonal and genetic biomarkers can serve as an early warning for disease prevention. At a later stage, we hope to also examine tobacco smoke effects on steroid and thyroid hormone changes during pregnancy. This study is directly relevant to the goals of FAMRI, to understand the biomedical effects of cigarette smoke. It is cost-effective because it uses GUMC facilities and services without having to contract out, and we will be able to have important results within a short period of time. The study only requires a blood sample, yet it uses the most recent technology to answer very important questions. The steroid hormone analysis is performed on a single sample thus reducing any intra-individual variations and with a small amount of blood we will be able to produce substantial results. Several studies have examined the relationship between cigarette smoke and changes in hormone concentrations. In this study we will determine whether tobacco smoke and polymorphisms in genes involved in steroid hormone biosynthesis and metabolism are associated with hormone changes in women.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 本研究的目的是探讨吸烟和遗传易感性对绝经前妇女激素水平变化的关系和影响。 我们希望阐明激素干扰中的基因-环境相互作用，以确定现有的不良暴露，并引入预防措施，以消除对母亲和未来婴儿的风险。 二手烟是数千种化合物的动态复杂混合物，包括致癌物和刺激物，以及怀疑对生殖系统造成损害的化合物，增加流产的可能性，并导致婴儿出生体重不足。一些研究表明，香烟烟雾可能会改变激素水平，这反过来可能会对炎症，癌症，生育和怀孕等依赖于吸烟的疾病产生影响。吸烟引起的激素功能变化会显著影响女性生育能力，她们的月经周期更短，更年期更早，患依赖性癌症的风险更高。烟雾暴露如何导致这些激素变化尚不清楚。在这项研究中，我们将尝试回答以下两个问题：吸烟者和非吸烟者之间的类固醇激素水平是否存在差异？吸烟和激素水平之间的关系在基因正常的女性和基因突变的女性中是否有显著差异？因此，我们将研究这些与吸烟有关的激素浓度变化是否是遗传上更容易发生这些变化的女性所特有的。为此，我们将检查负责类固醇激素代谢的四个基因，以确定吸烟引起的激素浓度变化是否在这些特定基因突变的女性中更为深刻。同位素稀释串联质谱（MS/MS）是一种为激素（或其他物质）的准确定量提供上级特异性的技术。在本研究中，我们将使用MS/MS来准确地测量类固醇和甲状腺激素的浓度。这是第一个研究由于暴露于香烟烟雾而导致的大量类固醇和甲状腺激素浓度变化的研究。据我们所知，还没有使用MS/MS技术对这些激素和香烟烟雾进行研究。 作为这项研究的结果，我们希望更多地了解香烟烟雾和遗传学如何影响激素系统，特别是烟草烟雾对类固醇激素浓度变化的影响。如果我们发现这些基因与该人群中任何激素的特定变化相关的证据，这些发现将有助于我们了解这些基因在女性健康，不孕症和癌症病因中的作用。这些激素和遗传生物标志物可以作为疾病预防的早期预警。在以后的阶段，我们希望还检查烟草烟雾对怀孕期间类固醇和甲状腺激素变化的影响。这项研究与FAMRI的目标直接相关，即了解香烟烟雾的生物医学效应。它具有成本效益，因为它使用GUMC的设施和服务，而无需外包，我们将能够在短时间内取得重要成果。这项研究只需要一个血液样本，但它使用最新的技术来回答非常重要的问题。类固醇激素分析是在一个单一的样本上进行的，从而减少了任何个体内的变化，并且使用少量的血液，我们将能够产生实质性的结果。一些研究已经检查了吸烟和激素浓度变化之间的关系。在这项研究中，我们将确定烟草烟雾和参与类固醇激素生物合成和代谢的基因多态性是否与女性激素变化有关。