Clonal Determination of Uterine Leiomyomas by Analyzing Differential Inactivation of the X-Chromosome-Linked Phosphoglycerokinase Gene

Hashimoto, Kazumasa; Azuma, Chihiro; Kamiura, Shoji; Kimura, Tadashi; Nobunaga, Toshikatsu; Kanai, Takayuki; Sawada, Masumi; Noguchi, Shinzaburo; Saji, Fumitaka

doi:10.1159/000292336

Cited by 90 publications

(40 citation statements)

References 12 publications

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“…We demonstrated that fibroids within the same woman often have different growth rates despite having a similar hormonal milieu. Indeed, each tumor appeared to have its own intrinsic growth rate, consistent with studies showing that fibroids are monoclonal in origin (15,16) with variable molecular characteristics (17)(18)(19)(20)(21). The only other large study of fibroid growth was conducted in Japan, and most of the 70 participants had only a single tumor (11); thus, variation in growth of fibroids from the same woman could not be evaluated.…”

Section: Discussionsupporting

confidence: 57%

Growth of uterine leiomyomata among premenopausal black and white women

Peddada

Laughlin

Miner

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

307

227

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Uterine leiomyomata (fibroids) are the leading cause of hysterectomy in the United States. Black women have a greater fibroid burden than whites, yet no study has systematically evaluated the growth of fibroids in blacks and whites. We prospectively tracked growth for 262 fibroids (size range: 1-13 cm in diameter) from 72 premenopausal participants (38 blacks and 34 whites). Fibroid volume was measured by computerized analysis of up to four MRI scans over 12 months. We used mixed effects models to identify factors that are associated with growth, and results were converted to percent change per 6 months for clinical relevance. The median growth rate was 9% (range: ؊89% to ؉138%). Seven percent of fibroids regressed (>20% shrinkage). Tumors from the same woman grew at different rates (within-woman component of variation was twice the component among women; both were significant, P < 0.001). Black and white women less than 35 years of age had similar fibroid growth rates. However, growth rates declined with age for whites but not for blacks (P ‫؍‬ 0.05). The odds of a tumor growing more than 20% in 6 months also decreased with age for whites but not for blacks (P < 0.01). Growth rates were not influenced by tumor size, location, body mass index, or parity. We conclude that (i) spontaneous regression of fibroids occurs; (ii) fibroids from the same woman grow at different rates, despite a uniform hormonal milieu; (iii) fibroid size does not predict growth rate; and (iv) age-related differences in fibroid growth between blacks and whites may contribute to the higher symptom burden for black women.ethnic ͉ fibroid ͉ MRI ͉ tumor growth ͉ longitudinal data U terine leiomyomata (fibroids) are the leading indication for hysterectomy in the United States (1). Myomectomy and uterine artery embolization are also common treatments, but hysterectomy may be required subsequently (2). Hartmann et al. (3) estimate a $4,600 excess health care cost during the year following each US woman's diagnosis of fibroids. National medical costs associated with fibroids exceed 2 billion dollars annually (4). African Americans have a higher fibroid incidence (5, 6), experience more severe symptoms (7), present with larger tumors (7), and have a threefold higher risk of hysterectomy (8) compared with whites. Symptoms increase with the size of fibroids (7, 9, 10). However, few studies have examined the growth of fibroids over time (11-13), and no study has systematically followed the growth of fibroids in black and white women.The Fibroid Growth Study was designed to measure the growth of fibroids in black and white women with clinically relevant fibroids using MRI technology. We compare growth rates of individual tumors from the same woman; contrast fibroid growth in black and white women; and examine associations with age, parity, body mass index (BMI), and tumor characteristics. ResultsStudy Participants. Characteristics of the 72 participants are shown in Table 1. Our cohort ranged in age from 24 to 54 years, and approximately half were Afri...

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Section: Discussionsupporting

confidence: 57%

Growth of uterine leiomyomata among premenopausal black and white women

Peddada

Laughlin

Miner

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

307

227

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“…They are probably of unicellular origin (12). Although studies have not clarified the exact process, uterine fibroid tumors arise during the reproductive years and tend to enlarge during pregnancy and regress after menopause.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Cardiovascular Risk Factors in Women with Uterine Leimyomata: Is there a Link with Atherosclerosis?

Sivri¹,

Yalta²,

Sayın³

et al. 2012

Balkan Med J

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Objective: Both uterine leimyoma (UL) and cardiovascular disease are public health problems affecting women at different age ranges. Smoking, obesity, and hypertension have been shown to be associated with UL in different random studies. However cardiovascular risk factors have not been evaluated systematically in patients with UL. Accordingly, we aimed to evaluate the cardiovascular risk factors and their relation with the presence of UL.Material and Methods: One hundred and eighty nine patients with the pathological diagnosis of UL and one hundred and eighty nine age matched control subjects without UL were retrospectively included in the study from our data base of the pathology and gynecology departments. Controls were patients with intact uteri who had visited the same physicians for a routine checkup that included a pelvic examination and uterine sonogram and without mention of physical findings consistent with UL. The following clinical and demographic parameters were recorded; age, sex, hypertension, diabetes mellitus, and hypercholesterolemia. Current cigarette smoking was defined as active smoking within the past 12 months. Results:Comparison of cardiovascular risk factors between with and without UL revealed that the presence of hypertension (80 (42.3%) vs 53 (28%) p=0.004) diabetes mellitus (33 (17.4%) vs. 16 (8.4%) p=0.009), smoking (31 (16.4%) vs. 11 (5.8%) p=0.001), were significantly higher in patients with UL than in control subjects. The mean-age and presence of hyperlipidemia were comparable between the two groups. Logistic regression analysis revealed an independent and positive association of UL with the presence of hypertension (odds ratio 2.02 CI: 1.25-3.27 p=0.004), diabetes mellitus (odds ratio 2.43 CI: 1.23-4.79 p=0.010), and smoking status (odds ratio 3.46 CI: 1.65-7.22 p=0.001). Conclusion:We have shown that major cardiovascular risk factors namely, hypertension, diabetes mellitus and smoking are significantly and independently associated with UL. Our findings highlight the possible association of UL with atherosclerosis.

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“…Tumors arising from single cells should contain only one type of inactive (methylated) allele, which will be amplified exclusively following restriction-enzyme digestion of the active (unmethylated) allele, whereas tumors of multicellular origin should contain some cells with one type of inactive allele and other cells with a second type of inactive allele, resulting in the amplification of both alleles following digestion and polymerase chain reaction. This method has been employed for analysis of both the X-linked androgen receptor gene (Mashal et al 1994) and the X-linked phosphoglycerokinase gene (Hashimoto et al 1995). Both studies concluded that the uterine fibroids examined were monoclonal in origin.…”

Section: The Genetic Findingsmentioning

confidence: 99%

Etiology and pathogenesis of uterine leiomyomas: a review.

Flake

Andersen

Dixon

2003

Environ Health Perspect

487

392

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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-β 3, 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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Clonal Determination of Uterine Leiomyomas by Analyzing Differential Inactivation of the X-Chromosome-Linked Phosphoglycerokinase Gene

Cited by 90 publications

References 12 publications

Growth of uterine leiomyomata among premenopausal black and white women

Growth of uterine leiomyomata among premenopausal black and white women

Evaluation of Cardiovascular Risk Factors in Women with Uterine Leimyomata: Is there a Link with Atherosclerosis?

Etiology and pathogenesis of uterine leiomyomas: a review.

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