Genetic mutations and their phenotypic manifestation have been recognized as critical factors in tumorigenesis. However, the relationship between these mutations and the pathogenesis of uterine leiomyomas (UL) remains inadequately characterized. There is compelling evidence to suggest a genetic underpinning in UL development, alongside influences from epigenetics, environmental stimuli, growth hormones, and growth factors. A plethora of studies have tried to elucidate the genetic and epigenetic etiologies associated with UL, but the definitive implications of these findings remain unclear. An extensive systematic review was conducted to investigate the genetic etiologies of UL. This systematic review aimed to consolidate current knowledge on genetic and epigenetic causes of UL, offering a comprehensive perspective on the evidence and its relevance in other solid tumors. A secondary focus was to identify the most significant genetic association with the genesis of UL. A total of 60 articles were identified, and 10 chromosomes and 51 genes were found to be implicated in the development of UL. The main trend in fibroid research focuses on genetic abnormalities and aberrations as the etiology of UL development. It has been estimated that 40% of UL can be associated with chromosome-specific aberrations. Chromosomal gain, loss, rearrangement, single nucleotide polymorphism (SNP), and translocation are the most common aberrations associated with UL development. The most recurrent ones include chromosome X and 7q deletions, and rearrangements of 12q15, 6p21 and 10q22. MED12 has been identified as a gene of particular importance in the development of UL.
Tanos et al. (2026) studied this question.