Molecular and clinical attributes of uterine leiomyomas

Abstract

Uterine leiomyomas, also called uterine fibroids or myomas, represent one of the most common benign tumour types in women of a fertile age. Leiomyomas arise due to transformation of the layer of smooth muscle cells of corpus uteri - the myometrium. Despite frequent occurrence of this disease, the molecular mechanisms behind the origin and development of leiomyomas are still relatively unknown. Most predisposed are obese women and women of African origin. In more than half of cases, leiomyomas remain asymptomatic. Genetic factors also have an important impact on the development of these hormone-dependent tumours. However, the clinical and molecular characteristics of familiar and sporadic leiomyomas can widely differ. The main reason is the heterogeneity of this disease and the abundance of factors which can underlie their tumourigenesis. Clinical diagnosis of uterine leiomyomas without surgical interference can be hindered in the case of small, mostly submucosal leiomyomas or if it is necessary to avoid potential malignancy of tumour. Also, medical treatment of uterine leiomyomas cannot be nowadays considered sufficient with many medical agents still being tested only within clinical research. The main goal of this article is to summarise known facts about the aetiology of leiomyomas, risk factors that contribute to their development, known molecular-genetic aberrations connected with the presence of leiomyomas as well as the possibilities of their diagnosis and treatment.

Variants associating with uterine leiomyoma highlight genetic background shared by various cancers and hormone-related traits

“…Uterine leiomyomas, sometimes referred to as fibroids, are benign tumors that arise in the smooth muscle cells of the uterine wall 1 . Leiomyomas represent the most common pelvic tumors in women with prevalence by the age 50, above 80% for African–American women, and nearly 70% for Caucasian women 2 .…”

“…These symptoms include dysmenorrhea, pelvic pain, abnormal bleeding, infertility, and complications during pregnancy 3 . Leiomyomas are estrogen responsive and many of the non-surgical therapeutic options involve some form of hormonal manipulation; however, in many cases, the tumors recur when therapy is discontinued 1 . Leiomyomas are the most common indication for hysterectomy and the second most common cause of surgical intervention for women after cesarean section, with over 600,000 hysterectomies performed per year in the USA 4 .…”

Association between fok1 polymorphism of vitamin D receptor gene with uterine leiomyoma in Turkish populations

“…Uterine leiomyomas are the most common benign muscle tumors ( 1 , 2 , 3 , 4 ), with up to 60% prevalence in women of a fertile age ( 1 ). Leiomyomas can be present in multiples, round, and can vary in size from several millimeters to 20 cm or more ( 2 ).…”

“…It is known that the pathogenesis of uterine leiomyoma is multifactorial, although not exactly elucidated ( 4 ). In patients with uterine leiomyomas, dysmenorrhea, pelvic pain, menorrhagia, infertility, complications during pregnancy ( 1 ), heavy menstrual bleeding and bladder discomfort can be observed ( 5 ). Uterine leiomyomas decrease the quality of life because of these adverse effects.…”

Not so benign

“…Broadly, they can be divided into three main groups, the most common being fibroids with alterations in MED12 (a gene found on the X chromosome), followed by lesions that are deficient in an enzyme called fumarate hydratase, and lesions in which a protein called HMGA2 is overexpressed. Numerous risk factors contribute to fibroid development, including age, obesity, hormones, hypertension and ancestry, with African-American women at the top of the prevalence chart ( Dvorská et al, 2017 ).…”