For the first time, a group of scientists at the National Institute of Child Health and Human Development (NICHD) have identified a genetic irregularity associated with the development of both uterine fibroids and keloids. Dr. William Catherino and colleagues at the NICHD Pediatric and Reproductive Endocrinology Branch determined that for both conditions, the extracellular matrix protein, dermatopontin, is present at abnormally low levels. This finding serves not only to illuminate how uterine fibroids and keloids develop, but also to suggest important new avenues for treatment. Statistics suggest that at least 25% of U.S. women experience symptoms of uterine fibroids, or leiomyomas, during their reproductive years. Essentially, fibroids are noncancerous growths or lumps of muscle and fibrous tissue that can develop in the uterine wall tissue. The three main types are submucosal (develop just underneath uterine wall), intramural (develop between muscles of the uterus), and subserosal (develop on the outside of the uterus). Though they often produce no symptoms, some women with uterine fibroids experience reproductive problems, pain during sex, lower back pain, frequent urination, or heavy or painful periods. In turn, keloids manifest as a thick overgrowth of scar tissue that can develop as a wound heals.
There had long been hints that uterine fibroid development had a genetic basis: there is often a family history; African American women are 3.3 times more susceptible; and Asian American women are at lower risk. Catherino’s team therefore undertook a comparison of genes expressed in normal uterine tissue (myometrium) with those expressed in uterine fibroid tissue. Uterine fibroids are known to be responsive to the presence of estrogen. Although the prevailing school of thought suggested that they would discover variations involving estrogen-related genes, instead the differences appeared in the extracellular-matrix proteins, and in particular for dermatopontin, a collagen-binding protein. The extracellular matrix consists of the substances between cells, which provides a structural framework for the cells. Dermatopontin, a protein, is one of these substances. Collagen, an important structural protein is another. The amount of dermatopontin was low or under-expressed in the uterine fibroid tissue regardless of fibroid size or location, patient race or age.
In general, extracellular-matrix proteins such as dermatopontin serve as a lattice to anchor cells, checking their growth and maintaining their position. A deficiency of dermatopontin would permit less regulated uterine tissue growth and the development of fibroids. Once Catherino et al. identified the genetic support for extracellular-matrix protein irregularities, closer scrutiny of tissues revealed visible disorder in the collagen fibril orientation. Notably, this exact same scenario was replicated in keloids, which share the same demographic patterns as uterine fibroids. Further solidifying this link, yet another gene impacting the extracellular-matrix was found at increased levels in both uterine fibroid and keloid tissues.
It is clear that from a treatment perspective, this is an important advance in understanding the biology of fibroids and keloids and this information could lead to new treatments for these conditions. According to the Center for Disease Control and Prevention, uterine fibroids are the single greatest reason women choose to undergo hysterectomies, accounting for approximately 180,000 procedures annually in the U.S. Other conventional treatment approaches include pain medication or myomectomy (removal of fibroids only, rather than the full uterus). As scientists make further progress uncovering the genetic basis for these conditions however, less invasive and more effective treatments may become available in the future.
