Fibroids – uterine leiomyomas (ULMs) – are estrogen-dependent tumors that are more common in African American women. The aetiology for such ethnic disparity is currently unknown. Catechol-O-methyltransferase (COMT) is an essential enzyme in estrogen metabolism.
Women with the high-activity COMT genotype are 2.5 times more likely to develop ULMs than women with other genotypes. The prevalence of this genotype was significantly higher in African American women (47%) compared with white (19%) or Hispanic (30%) women. Myometrial cell lines expressing the Val/Val genotype exhibited significantly enhanced responses to estrogen in proliferation and in estrogen-responsive element reporter assays. COMT-specific inhibitors reversed such a response and induced apoptosis. Myometrial specimens from Val/Val women demonstrated distinct estrogen-regulated gene expression that was consistent with enhanced proliferation and decreased apoptosis.
The results provide a possible explanation for the higher prevalence of ULMs among African American women and offer a potential new target for nonsurgical treatment using COMT inhibitors.
