Endometriosis-associated ovarian carcinogenesis induced by iron-dependent oxidative stress

铁依赖性氧化应激诱导子宫内膜异位症相关卵巢癌发生

• 批准号: 23390391
• 负责人: KOBAYASHI Hiroshi
• 金额: $ 12.23万
• 依托单位: Nara Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23390391/
• 关键词: 子宮内膜症; 癌化; 卵巣癌; 酸化ストレス; 鉄; 卵巣がん; 細胞周期調節; 子宮内膜症; 癌化; 卵巣癌; 酸化ストレス; 鉄; 卵巣がん; 細胞周期調節

The aim of the present study is to describe genomic instability, genetic polymorphisms and their haplotype, epigenetic alterations associated with endometriosis predisposition, and the key factors that have been linked to endometriosis-related ovarian neoplasms. Retrograde menstruation leads to iron overload, which facilitates the accumulation of somatic mutations through a Fenton reaction-mediated oxidative stress. There seems to be at least three spatiotemporally distinct phases of endometriosis development: The initial phase of genetic background inherited from parents would be followed by the second big wave of epigenetic modifications in the female offspring and the final phase of the iron overload that is subject to dynamic modulation later in life. The dramatic regulation of endometriosis susceptibility genes may come from a mechanism responsible for epigenetic and genetic mutations based on the microenvironmental changes.

本研究的目的是描述基因组不稳定性，遗传多态性及其单倍型，与子宫内膜异位症易感性相关的表观遗传学改变以及与子宫内膜异位相关的卵巢肿瘤有关的关键因素。逆行月经导致铁超负荷，这促进了通过芬顿反应介导的氧化应激的体细胞突变的积累。似乎至少存在三个子宫内膜异位症发育的空间差异阶段：从父母继承的遗传背景的初始阶段之后，在女性后代中的第二大表观遗传修饰和铁超载的最后阶段的最终表观遗传修饰浪潮，这些阶段在以后的生活中会受到动态调节的影响。子宫内膜异位敏感性基因的戏剧性调节可能来自基于微环境变化的表观遗传和遗传突变的机制。