The Genetics of Uterine Leiomyomata

Abstract

The genetics of many complex diseases, including hypertension, diabetes, and asthma, are receiving intense investigation and beginning to have therapeutic relevance. Family medical history can be a critical source of information for providing optimal patient care. For gynecologists, knowledge of cancer susceptibility genes such as BRCA1 and BRCA2 and the genetic syndrome hereditary nonpolyposis colorectal cancer (Lynch syndrome II) affects how patients are screened for ovarian and endometrial cancers. Similarly, identification of mutations in the fumarate hydratase (FH) gene that lead to a syndrome called hereditary leiomyomatosis and renal cell carcinoma (HLRCC) will impact screening and treatment of women with uterine leiomyomas. Hereditary leiomyomatosis and renal cell carcinoma syndrome is particularly relevant to clinicians and patients because of the resulting increased risk of malignant disease for both the affected woman and her family. The goals of this article are to summarize the evolving genetic information concerning uterine leiomyomas, including hereditary leiomyomatosis and renal cell carcinoma syndrome, and to discuss the clinical importance of these findings. The current role of family medical history and future implications of genes relevant to leiomyoma biology will be reviewed.

Loss of the repressor REST in uterine fibroids promotes aberrant G protein-coupled receptor 10 expression and activates mammalian target of rapamycin pathway

“…Several genetic and environmental risk factors have been suggested to influence the etiology of leiomyomas (1,(3)(4)(5). Although, rare germ-line mutations that give rise to heritable leiomyomas are known, such mutations being rare do not account for the vast majority of uterine fibroids.…”

The Relationship of Age, Parity and Body Mass Index as Risk Factors to the Incidence of Uterine Myoma in Dr. Hasan Sadikin General Hospital

“…In obese patients, the risk of myoma increases to 2.7 times greater than the patients with normal BMI. 7 Besides multiple factors in the growth of myoma have been mentioned, like reproductive hormone and race, 1,3,7,8 there are other factors in the growth of myoma, namely: family history, lifestyle, and environmental condition. 1,3 Uterine myomas are closely associated with estrogen stimulation, especially where there is abundant peripheral conversion of androgen to estrogen in obese patients.…”

“…1,7,8 It possibly occurred since black women are usually women with exposure of oral contraceptives. 1,7 The incidence also increases in women who have the history of uterine myomas in their family.…”

Submucous myomas: diagnosis and therapy

“…In the following years numerous publications have reported cytogenetic, molecular and genetic linkage data supporting and accounting for the evidence for genetic predisposition that had been found before, in epidemiological studies, including familial clustering and racial prevalence [6][7][8]. Probably, the most clinically important syndrome known presently for myomas is the autosomal dominant hereditary disease hereditary leiomyomatosis and renal cell carcinoma (HLRCC) [8].…”