DESCRIPTION (provided by applicant): It is well recognized that African American women have a higher rate, larger size and worse morbidity of uterine leiomyomata (ULM) than white women. Identification of the genetic variants and differences in gene expression in ULM of different races will greatly benefit our understanding of the molecular basis of disease risk. MicroRNAs are a group of small non-coding RNAs that are associated with tumorigenesis in many benign and malignant tumors. In our previous pilot study, we found some microRNAs were significantly differentially expressed in ULM between African American and white women. To determine whether the differentially expressed microRNAs in ULM of different races can be used as markers for risk evaluation in this study, we intend to validate our findings of miRNA expression between racial groups by examining a new large cohort ULM population of African American and white women. Specifically, we would like to know whether the racial differences in miRNA expression are evident in the disease related myometrium or only in ULM. Since several racially related miRNAs are aberrantly expressed in many other solid tumors, we propose that these highly dysregulated microRNAs in ULM of African American women are important contributors to ULM morbidity, due to their downregulation of some major target genes. Their functional roles in relation to leiomyoma growth will be investigated. The study can be accomplished by examining whether the significantly dysregulated microRNAs in ULM of African American women (African American related microRNAs) can regulate major target genes that are significantly dysregulated in ULMs. Accomplishment of the study will allow us to identify the microRNAs and their target genes in ULM as important molecular markers. Future studies will focus on: 1) whether there are potential functional polymorphisms due to the differential expression of the racially related microRNAs (in vitro functional analysis); 2) whether the genetic variants along these racially related microRNAs affect ULM susceptibility (case matched association study by SNP); and 3) whether the racially related microRNAs affect the expression of their target genes in ULM (chip based and case matched comparison of miRNAs and functional gene expression). The long term goal is to find molecular markers for early detections, prediction and prevention. PUBLIC HEALTH RELEVANCE: African American women have a higher rate, larger size and worse morbidity of uterine leiomyomata than white women. Identification of the genetic variants and differences in gene expression in ULM of different races will greatly benefit our understanding of the molecular basis of disease risk. In this study, we intend to identify the molecular differences in uterine leiomyomas between African American and white women.

Narrative African American women have a higher rate, larger size and worse morbidity of uterine leiomyomata than White women. Identification of the genetic variants and differences in gene expression in ULM of different races will greatly benefit our understanding of the molecular basis of disease risk. In this study, we intend to identify the molecular differences in uterine leiomyomas between African American and white women.