TOBACCO SMOKE EXPOSURE AND HORMONAL CHANGES IN WOMEN

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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.