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子宫肌瘤的种族差异:子宫平滑肌细胞中遗传和环境负担的新见解。

Racial disparity in uterine leiomyoma: new insights of genetic and environmental burden in myometrial cells.

机构信息

Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.

Department of Obstetrics and Gynecology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.

出版信息

Mol Hum Reprod. 2024 Feb 29;30(3). doi: 10.1093/molehr/gaae004.

Abstract

Uterine leiomyoma (LM), also known as uterine fibroids, are common gynecological tumors and can reach a prevalence of 70% among women by the age of 50 years. Notably, the LM burden is much higher in Black women with earlier onset, a greater tumor number, size, and severity compared to White women. Published knowledge shows that there are genetic, environmental, and lifestyle-based risk factors associated with racial disparity for LM. Significant strides have been made on genomic, epigenomic, and transcriptomic data levels in Black and White women to elucidate the underlying pathomolecular reasons of racial disparity in LM development. However, racial disparity of LM remains a major area of concern in gynecological research. This review highlights risk factors of LM and their role in different races. Furthermore, we discuss the genetics and uterine myometrial microenvironment in LM development. Comparative findings revealed that a major racial difference in the disease is linked to myometrial oxidative burden and altered ROS pathways which is relevant to the oxidized guanine in genomic DNA and MED12 mutations that drive the LM genesis. Considering the burden and morbidity of LM, we anticipate that this review on genetic risk and myometrial microenvironment will strengthen understanding and propel the growth of research to address the racial disparity of LM burden.

摘要

子宫肌瘤(LM),又称子宫纤维瘤,是常见的妇科肿瘤,在 50 岁的女性中发病率高达 70%。值得注意的是,与白人女性相比,黑人女性的 LM 负担更高,发病更早,肿瘤数量更多、更大,严重程度也更高。已发表的知识表明,与 LM 的种族差异相关的风险因素包括遗传、环境和生活方式。在黑人和白人女性中,已经在基因组、表观基因组和转录组数据水平上取得了重大进展,以阐明 LM 发展中种族差异的潜在病理分子原因。然而,LM 的种族差异仍然是妇科研究中的一个主要关注点。本综述强调了 LM 的风险因素及其在不同种族中的作用。此外,我们还讨论了 LM 发展中的遗传学和子宫肌层微环境。比较研究结果表明,该疾病的一个主要种族差异与肌层氧化负荷和改变的 ROS 途径有关,这与基因组 DNA 中的氧化鸟嘌呤和驱动 LM 发生的 MED12 突变有关。考虑到 LM 的负担和发病率,我们预计,关于遗传风险和子宫肌层微环境的这篇综述将加强对该疾病的理解,并推动研究的发展,以解决 LM 负担的种族差异问题。

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