This proposal, titled ELLAS: Environment, Leiomyomas, Latinas, and Adipocity Study (ELLAS), seeks to address the significant gap in our knowledge of leiomyomas in the fastest growing group of women in the United States-Latinas. Uterine leiomyomas or fibroids are well-defined, benign smooth muscle tumors of the uterus that represent a significant healthcare burden in women. For the populations on which we have data, largely Caucasian and African-American women, fibroids are present in 30%-50% of reproductive-age women and have an overall cumulative incidence of >70% by the age of 50 years. Fibroids are associated with menorrhagia, anemia, infertility, pelvic pain, and recurrent pregnancy loss. The physiological and psychological sequelae of these symptoms, and the lack of effective medical treatment options, explain why these benign tumors remain the leading cause of hysterectomy in the United States. Recent analyses estimate the cost of fibroids in the U.S. to be as high as $34 billion annually. While we know that fibroids disproportionately affect African-American women, there are very few data on either their prevalence amongst Latinas or whether there are risk factors for fibroids that are unique to Latinas. The Latina population has high rates of obesity and diabetes, both of which have been implicated as risk factors for fibroids. The overall objective of this proposal is to determine the prevalence and growth patterns of leiomyomas amongst Latinas and to examine metabolic dysregulation as a risk factor for leiomyomas in this population. We will recruit 600 premenopausal Latinas between the ages of 25- 45 for evaluation. Pelvic ultrasound will be performed to determine prevalence and survey data, saliva, and blood samples will be collected (Aim 1). Subjects who have fibroids at this initial visit will return for a follow-up visit in 18-24 months to determine fibroid growth ovr that time and to identify factors related to growth (Aim 1). We will also measure adiposity and various biomarkers of metabolism and glucose regulation, and determine their association with fibroid prevalence and growth (Aims 2 and 3). The results of our study will be clinically significant as we currently have limited data for counseling Latinas on the natural history of the disease or its associated risk factors. Our study design is innovative in that pelvic ultrasounds will be performed on all subjects to identify all fibroids present, not just symptomatic fibroids. Furthermore, the follow-up visit will allow us to collect critical growth data on all tumors. Our prospective longitudinal cohort study will be the first to determine whether obesity and/or glucose dysregulation are associated with ultrasound-confirmed fibroid prevalence, and growth in any population and will thus be of benefit to all women. This study presents an ideal opportunity to conduct a novel prospective analysis on an understudied population and generate data needed to counsel Hispanic women about leiomyomas in an evidence-based way.
Uterine fibroids are benign tumors that effect 30%-50% of reproductive-aged women and >70% of all women by the age of 50 years. While fibroids are the leading cause of hysterectomy in the United States and account for more than $34 billion in costs annually, there are very few data on their natural history or on risk factors associated with fibroids in the fastest growing group of women in the U.S.-Latinas. The overall objective of this proposal is to determine the prevalence and growth patterns of fibroids amongst a large cohort of Latinas and to evaluate metabolic dysregulation as a risk factor for fibroids in this population
|Roesch, Ferdinand; OhAinle, Molly; Emerman, Michael (2018) A CRISPR screen for factors regulating SAMHD1 degradation identifies IFITMs as potent inhibitors of lentiviral particle delivery. Retrovirology 15:26|