Scientists find new genes predisposing to uterine fibroids – genes contributing to higher muscle mass play a key role

Uterine fibroids (leiomyomas) are benign tumours that can cause symptoms reducing the quality of life, such as abnormal menstrual bleeding, pelvic pressure, reduced fertility, and pregnancy complications. Fibroids are common and found in fertile age women; according to estimates, 30-70% of women develop fibroids before the age of 50 years. Despite its high prevalence, there is no curative treatment available, but severe symptoms may lead to surgical removal of the uterus. The recently published FinnGen project-based research conducted under the leadership of the University of Oulu provided valuable information about the genetic factors regulating the risk of fibroids, which can be helpful in developing novel treatment strategies.

Uterine fibroids are common tumours of the uterus that can be present in single or multiple numbers, with sizes ranging from millimetres to over 20 centimetres in diameter. Female sex hormones stimulate the growth of fibroids, and those are almost exclusively found in women of reproductive age. Gynaecologist Outi Uimari from Oulu University Hospital explains that fibroids can cause severe symptoms, such as heavy or prolonged menstrual bleeding, pelvic pressure, reduced fertility, and pregnancy complications. “Since there is no curative medical treatment, fibroids with severe symptoms often lead to hysterectomy”, Uimari points out.

Previous genetic studies of uterine fibroids have mainly focused on non-inherited somatic gene variations. However, the results of the recently published study conducted under the leadership of the University of Oulu indicate that there are more than 70 positions in the human genome that harbour heritable genetic variations modifying fibroid susceptibility. The researchers analyzed genetic and health registry data of a total of 426,558 women from the FinnGen project and from a previous fibroid study conducted in European data.

Many of the identified susceptibility genes, such as myocardin (MYOCD) and cyclin dependent kinase inhibitor 1A (CDKN1A), regulate the division and differentiation of smooth muscle cells. Overall, the genetic factors that modify the biology of muscle tissue seem to be key factors behind fibroids: the researchers found that the genetic tendency to accumulate muscle mass is causal for a higher risk of fibroids. “This is unexpected because, in the light of previous studies, it has appeared that, rather than muscle mass, obesity and elevated blood lipid levels are linked with the risk of myomas”, says Ph.D. Eeva Sliz, the main analyst of the study. “Based on the genetic data, however, it seems that there is no causal relationship between these metabolic risk factors and fibroids, as there is between muscle mass and fibroids”, Sliz continues. The researchers note that genetically obtained natural muscle mass and acquired muscle mass are very different types of properties, and there is no need to quit gym training, for example, in fear of fibroids.

Professor Johannes Kettunen from the University of Oulu emphasizes how valuable information biobank research provides. “The use of genetic and registry data stored in biobanks through the FinnGen project creates unique opportunities for research and further for healthcare”, says Kettunen. “The results obtained here offer a new perspective on the molecular mechanisms causing fibroids, and once the understanding of the disease mechanisms accumulates, the information can be used in the development of new kind of treatments in the future”, Kettunen continues.

Uimari's research group continues to further clarify the main results of this study, and the group has started collecting new research material at Oulu University Hospital in women who undergo hysterectomy for fibroids.

The research conducted as a collaboration between the universities of Oulu and Oxford has been published in the prestigious journal Nature Communications.

Publication: Sliz, E., Tyrmi, J.S., Rahmioglu, N. et al. Evidence of a causal effect of genetic tendency to gain muscle mass on uterine leiomyomata. Nat Commun 14, 542 (2023).

Last updated: 22.2.2023