Abstract

GENETIC AND BIOMARKER PERSPECTIVES ON UTERINE FIBROIDS: A REVIEW OF EMERGING MOLECULAR INSIGHTS

*Abid Hussain Rather, Lubna Qasim

Abstract

Up to 70% of women worldwide suffer from uterine fibroids, also known as leiomyomas, which are benign monoclonal tumors originating from the uterine smooth muscle. They can result in infertility, irregular uterine bleeding, and lower quality of life, despite often being asymptomatic. Previously thought to be primarily caused by hormonal imbalances, fibroids are now understood as complex conditions impacted by environmental, genetic, and epigenetic factors. Recent developments in their molecular landscape are summarized in this review, with special attention to driver mutations like MED12, HMGA2 overexpression, FH loss, and chromosomal rearrangements. We discuss the ―two-hit hypothesis,‖ which holds that myometrial stem cells are primed for tumorigenesis after somatic mutations due to early exposure to endocrinedisrupting chemicals. The role of epigenetic changes and ethnic differences in disease heterogeneity is investigated. Biomarkers such as matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), extracellular matrix proteins, circulating microRNAs, MED12-mutant DNA fragments, and vitamin D are discussed in relation to diagnosis, prognosis, and therapeutic targeting. Proteomic profiling and liquid biopsy are examples of novel techniques investigated. The paper concludes by emphasizing integration of molecular diagnostics and personalized medicine into routine fibroid care, enabling precise, less invasive management through combined genomic, epigenomic, and biomarker data.

Keywords: Uterine fibroids, MED12 mutation, HMGA2, matrix metalloproteinases (MMPs), endocrine-disrupting chemicals, personalized medicine.