The associations between the Val158Met in the catechol-O-methyltransferase (COMT) gene and the risk of uterine leiomyoma (ULM)

Feng, Yi; Zhao, Xiaowen; Zhou, Chunfen; Yang, Liqun; Liu, Yingwei; Bian, Ce; Gou, Jinhai; Lin, Xiaojuan; Wang, Zhenling; Zhao, Xia

doi:10.1016/j.gene.2013.07.019

Cited by 16 publications

(10 citation statements)

References 26 publications

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“…On the other hand, various reports suggest a correlation between COMT polymorphisms and cancer risks that could be associated with patient ethnicity. Thus, a specific val158 met COMT polymorphism has been associated with a decreased risk of uterine leiomyoma while a COMT Val/Val genotype is correlated with an increased endometrial cancer risk in some Asian populations [123,124].…”

Section: Effects Of 2-methoxyestradiol On Tumor Cellsmentioning

confidence: 99%

Role of 2-methoxyestradiol, an Endogenous Estrogen Metabolite, in Health and Disease

Parada-Bustamante¹,

Valencia²,

Reuquén³

et al. 2015

MRMC

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Estradiol (E2) is a steroid hormone whose physiological actions are mainly mediated by its interaction with intracellular estrogen receptors (ER) leading to modification on the mRNA and protein synthesis in its target cells. However, estrogens can also activate several intracellular signal transduction cascades by non-genomic mechanisms. Estrogens must be inactivated and removed from blood through its conversion to soluble compounds with an apparent low estrogenic activity and decreased affinity for ER. In this context, 2-methoxyestradiol (2ME2) is generated by a sequential hydroxylation of E2 via the enzyme cytochrome P450 isoform 1A1 to produce 2-hydroxyestradiol (2OHE2) followed by a conjugation reaction catalyzed by the enzyme Catechol-O-Methyltransferase generating 2ME2 from 2OHE2. Recent evidence indicates that physiological concentration of 2ME2 may regulate several biological processes while high concentrations of this metabolite may induce pathophysiological alterations in several tissues. In the last years, 2ME2 has also been described as a promising anticancer drug although its cellular and molecular mechanisms are still being disclosed. Herein, we will review the available literature concerning the role of 2ME2 in health and disease. We will focus on to describing the intracellular mechanisms by which 2ME2 exerts its effects on reproductive and non-reproductive tissues. The promising anticancer effects of 2ME2 and its synthetic derivatives will also be discussed. Finally, a group of 2ME2-target genes that could be used as biomarkers of 2ME2 under physiological or pathophysiological conditions will be reviewed.

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Section: Effects Of 2-methoxyestradiol On Tumor Cellsmentioning

confidence: 99%

Role of 2-methoxyestradiol, an Endogenous Estrogen Metabolite, in Health and Disease

Parada-Bustamante¹,

Valencia²,

Reuquén³

et al. 2015

MRMC

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“…In further studies, this association has been confirmed by Shen et al ,15 16 but has not been found by other authors 9–13. The protective effect of COMT Met/Met and Val/Met genotypes has been proven by meta-analysis 14. Here, we report no statistically significant increase in the COMT Val/Val genotype frequency in women with uterine fibroids (p=0.149, OR 1.77; CI 0.81 to 3.86).…”

Section: Discussionmentioning

confidence: 40%

Catechol-O-methyltransferase Val158Met polymorphism is associated with increased risk of multiple uterine leiomyomas either positive or negative forMED12exon 2 mutations

et al. 2016

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“…The COMT enzyme is essential for estrogenic metabolism and thus, may cause or be involved in the formation of fibroids. Indeed, a recent Meta-analysis confirmed the association between specific COMT polymorphisms and uterine fibroids [50].…”

Section: Differences At the Genetic Level: Catechol-o-methyltransferamentioning

confidence: 90%

Uterine Fibroids Review: Understanding their Origins to Better Understand their Future Treatments

Botía¹,

Camarasa²,

Baixauli³

et al. 2017

J Tumor Res

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Despite the high prevalence and the enormous impact the uterine fibroids has on the healthcare system and the economy, there is no effective medical treatment available to eliminate fibroids. This is due in part to the fact that very little is known about their pathophysiology; in order to look for and potentially find treatments capable of eliminating fibroids; we must gain a deep understanding of the mechanisms behind their initiation, stimulation and growth. In this article, we comprehensively review current knowledge of the pathogenesis of uterine fibroids, with the aim of better understanding their origin, as well as discussing the action of already existing medical treatments in order to highlight ways that potential future therapies may be able to target the disease. A literature search was performed in PubMed to find articles related to the etiopathogenesis of fibroids and their treatments. Myomas comprise areas of disordered smooth muscle fascicles characterized by an excess of a cellular extracellular matrix (ECM) with a deregulated phenotype. Although the initial event is believed to be smooth muscle cell proliferation, it is thought that a complex signalling system is also necessary. Non-hormonal factors may be responsible for initiating the development of uterine fibroids, although hormonal stimulation is an essential factor for their growth. Recent studies have confirmed that the different cell types contained in fibroids are all clonally derived from a parental cell with implied multipotent stem cell properties. Ethnicity also strongly influences the development and clinical severity of fibroids. Many Growth factors and their respective receptors have been implicated in fibroid growth. The available evidence continues to reinforce the importance of progesterone in the development of fibroids. The Ulipristal Acetate mediated volume reduction is due to a series of multifactorial and successive events that lead to a low proliferation rate.

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The associations between the Val158Met in the catechol-O-methyltransferase (COMT) gene and the risk of uterine leiomyoma (ULM)

Cited by 16 publications

References 26 publications

Role of 2-methoxyestradiol, an Endogenous Estrogen Metabolite, in Health and Disease

Role of 2-methoxyestradiol, an Endogenous Estrogen Metabolite, in Health and Disease

Catechol-O-methyltransferase Val158Met polymorphism is associated with increased risk of multiple uterine leiomyomas either positive or negative forMED12exon 2 mutations

Uterine Fibroids Review: Understanding their Origins to Better Understand their Future Treatments

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