Etiology and pathogenesis of uterine leiomyomas: A review

Comparative Pathobiology Group, Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA.
Environmental Health Perspectives (Impact Factor: 7.03). 07/2003; 111(8):1037-54. DOI: 10.1289/ehp.5787
Source: PubMed

ABSTRACT Uterine leiomyomas, or fibroids, represent a major public health problem. It is believed that these tumors develop in the majority of American women and become symptomatic in one-third of these women. They are the most frequent indication for hysterectomy in the United States. Although the initiator or initiators of fibroids are unknown, several predisposing factors have been identified, including age (late reproductive years), African-American ethnicity, nulliparity, and obesity. Nonrandom cytogenetic abnormalities have been found in about 40% of tumors examined. Estrogen and progesterone are recognized as promoters of tumor growth, and the potential role of environmental estrogens has only recently been explored. Growth factors with mitogenic activity, such as transforming growth factor- (subscript)3(/subscript), basic fibroblast growth factor, epidermal growth factor, and insulin-like growth factor-I, are elevated in fibroids and may be the effectors of estrogen and progesterone promotion. These data offer clues to the etiology and pathogenesis of this common condition, which we have analyzed and summarized in this review.

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Available from: Darlene Dixon, Aug 12, 2015
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    • "Since self-reporting in a clinical setting was used in this study, there may be some experimental bias of the results based on the self-reporting of patients. Additionally, since at least 20% of the controls and cases were in the reproductive age group, ages 31–40, most frequently associated with the diagnosis of UL (Baird et al., 2003; Flake et al., 2003), it was not seen as a limit to this present study, but is presented here as an epidemiological descriptor of UL in Barbados. The associations with waist circumference and obesity indicators in this study clearly need replication in a larger sample size with clinical confirmation by ultrasound. "
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    ABSTRACT: Uterine leiomyoma is a major reproductive health disease among women and in particular Black women. The present study sought to determine whether a single nucleotide polymorphism (SNP) of CYP17 (rs743572) was associated with the risk of developing uterine leiomyoma (UL) in affected women in Barbados; a majority Black population. It also sought to determine if BMI, waist circumference and oestradiol levels were associated with UL in this group. A total of 96 random persons were assessed in a case–control study using a PCR-RFLP assay, and measurements of body mass index, waist circumference, and oestradiol levels were also assessed. Our results showed no genetic association with the risk of UL and this gene. The genetic distribution of CYP 17α- alleles resembled a normal Hardy–Weinberg distribution, and a relatively low risk of 0.25 at a confidence interval at 95%, of UL disease development. However, a significant association was found between oestradiol levels and fibroids, as well as oestradiol levels and BMI, at P < 0.05 among cases. Therefore our study indicates that significant associations between physiochemical factors comprising BMI, waist circumference, and oestrogen levels are disease indicators in this population. In conclusion, our findings suggest that obesity and its associated risk factors are important in a majority Black Caribbean population, although the sample size needs to be increased.
    12/2014; 2:358–365. DOI:10.1016/j.mgene.2014.03.006
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    • "Uterine leiomyoma, the most common gynecologic neoplasm, occurs in .70% of reproductive-age women (Lumsden and Wallace, 1998; Rein, 2000; Flake et al., 2003). Steroid hormones are believed to play critical roles in the pathogenesis of the tumor (Burroughs et al., 2000; Di et al., 2008); however, despite much investigation, including genetic and molecular approaches, the underlying mechanism of uterine leiomyoma remains unclear. "
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    ABSTRACT: STUDY QUESTION Does tumor necrosis factor-α (TNF-α) differentially regulate matrix metalloproteinase-2 (MMP-2) expression in leiomyomas compared with normal myometrium?
    Human Reproduction 11/2014; 30(1). DOI:10.1093/humrep/deu300
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    • "estrogen synthesis and metabolism, interaction with estrogen receptors, and disruption of estrogen function (Flake et al. 2003; Bischoff and Simpson 2004; Kitawaki 2006; Viganò et al. 2007; Bulun 2009). However, few study investigate the joint effects of environmental pollutants and polymorphisms of estrogen-related genes in patients of EDDs. "
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    ABSTRACT: Evidence has shown that polymorphisms of various genes known to be involved in estrogen biosynthesis and function are associated with estrogen-dependent diseases (EDDs). These genes include CYP17A1, estrogen receptor 1 (ESR1), and 2 (ESR2). Phthalates are considered estrogenic endocrine disruptors, and recent research has suggested that they may act as a risk factor for EDDs. However, extremely few studies have assessed the effects of gene-environment interaction on these diseases. We recruited 44 patients with endometriosis or adenomyosis, 36 patients with leiomyoma, and 69 healthy controls from a medical center in Taiwan between 2005 and 2007. Urine samples were collected and analyzed for seven phthalate metabolites using liquid chromatography tandem mass spectrometry. Peripheral lymphocytes were used for DNA extraction to determine the genotype of CYP17A1, ESR1, and ESR2. Compared to controls, patients with leiomyoma had significantly higher levels of total urinary mono-ethylhexyl phthalate (ΣMEHP) (52.1 vs. 29.6 μg/g creatinine, p = 0.040), mono-n-butyl phthalate (MnBP) (75.4 vs. 51.3 μg/g creatinine, p = 0.019), and monoethyl phthalate (MEP) (103.7 vs. 59.3 μg/g creatinine, p = 0.031). In contrast, patients with endometriosis or adenomyosis showed a marginally increased level of urinary MEHP only. Subjects who were homozygous for both the ESR1 C allele (rs2234693) and CYP17A1 C allele (rs743572) showed a significantly increased risk for leiomyoma (OR = 19.8; 95 % CI, 1.70; 231.5; p = 0.017) relative to subjects with other genotypes of ESR1 and CYP17A1. These results were obtained after adjusting for age, cigarette smoking, MEHP level, GSTM1 genotype and other covariates. Our results suggested that both CYP17A1 and ESR1 polymorphisms may modulate the effects of phthalate exposure on the development of leiomyoma.
    Environmental Science and Pollution Research 07/2014; 21(24). DOI:10.1007/s11356-014-3260-6
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