Uterine fibroids are non-cancerous tumours that affect up to 70% of women and have long been a medical enigma. Geneticists in collaboration with clinical experts have delved into the complex world of these fibroids, elucidating their underlying causes and potential treatments. This research not only confirms known risk factors but uncovers 22 new genetic loci associated with uterine fibroids. Surprisingly, the study reveals a link between muscle mass and risk of developing fibroids, challenging previous assumptions. These findings pave the way for targeted therapies and deeper understanding of this widespread but often overlooked health problem.
Uterine fibroids have long remained a perplexing concern for millions of women worldwide. These noncancerous growths within the uterus affect a staggering number of women, with some estimates suggesting that up to 70% may grapple with their presence at some point in their lives. Despite their benign nature, uterine fibroids wield the power to significantly disrupt a woman's life, and for about 5–25% of all women they result in severe pain, anaemia caused by heavy bleeding and fertility problems in some cases.
“For years, the underlying causes and mechanisms of uterine fibroids have eluded scientific understanding, leaving many young women with limited treatment options and often culminating in their uterus being removed by surgery. We conducted a genome-wide association study involving a large cohort of women to obtain deeper insight and identified 22 new loci associated with uterine fibroids, shedding light on the genetic underpinnings of this common condition,” explains Eeva Sliz, Postdoctoral Fellow at the Research Unit of Population Health at the University of Oulu in Finland.
Delving deeply into the genetic factors
Research on uterine fibroids has been ongoing for years. These growths, also known as leiomyomas or myomas, affect a staggering number of women, but despite their widespread occurrence, the precise cause of uterine fibroids remains elusive. Hormones, especially estrogen and progesterone, are thought to contribute to their growth. However, recent advances in genetic research are shedding new light.
“Until recently, the genetics of uterine fibroids has focused on somatic rearrangements: genetic changes happening during the lifetime of an organism. But recent studies suggested that ethnic groups differ in how common this is and that the genes you inherit from your parents probably strongly affect this risk. Our study aimed to delve deeply into the genetic factors contributing to uterine fibroids, using cutting-edge computational biology techniques.”
The research method used is based on a massive data set comprising genetic information from up to 426,558 women in Europe via the FinnGen project and the FibroGENE consortium, enabling comprehensive investigation of the genetic factors contributing to susceptibility to uterine fibroids. The study combined genome-wide association studies and Mendelian randomisation analysis.
“This method can help to determine whether a specific factor, such as a particular lifestyle or drug, causes a particular health outcome, such as a disease. Basically, it helps us determine whether something just seems connected or if one thing actually causes another.”
Potential targets for future therapeutic interventions
The researchers scanned the entire human genome to identify genetic variants associated with uterine fibroids. In addition to the 50 previously known ones, the study identified 22 new genetic loci associated with uterine fibroids. The 72 loci were all linked to various biological processes, including development, growth and cellular senescence, natural biological processes associated with ageing and tissue damage.
“By analysing the massive data set, we hoped to identify some previously unknown genetic markers associated with uterine fibroids. And we did, but the study surprisingly revealed that a genetic predisposition to increased fat-free mass was causally related to a higher risk of uterine fibroids. In particular, the genes regulating smooth muscle cell differentiation and proliferation appear to be involved in developing uterine fibroids.”
The genes operate within the myocardin- and cyclin-dependent kinase inhibitor 1A pathway, suggesting a connection between muscle tissue biology and uterine fibroids.
“The prevailing notion has been that obesity is associated with a higher risk of developing uterine fibroids. Surprisingly, our findings challenge this view, since we found that there is no causal connection between obesity and uterine fibroids – instead, a causal connection was found for fat-free mass.”
Another surprise was that, although previous research focused more on somatic mutations – mutations evolving during life – the new study pointed towards heritable genetic factors contributing to uterine fibroids.
“This opens up new avenues for understanding uterine fibroids and eventually treating the women who have them. Our findings not only expand knowledge of the genetic pathways associated with uterine fibroids but also provide potential targets for future therapeutic interventions. We hope that this research will lead to developing more effective treatments beyond surgical removal of the uterus, ultimately improving the quality of life for the women affected by this extremely common condition,” concludes Eeva Sliz.