基因变异通过改变miRNA结合亲和力和m6A修改来降低与POPs相关的结直肠癌风险
Mengfan Guo1, Shuwei Li2, Yifei Cheng2
1Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
Environment international
|August 7, 2024
概括
像PCB153这样的持久有机污染物 (POP) 与结直肠癌有关. 遗传因素,特别是rs67734009变体,通过影响ESR1基因表达和POPs水平来影响这种风险.
科学领域:
- 环境健康 环境健康
- 遗传学 是一个遗传学.
- 癌症研究 癌症研究
背景情况:
- 持久性有机污染物 (POP) 是与各种健康问题相关的环境污染物.
- 暴露于POPs导致结直肠癌 (CRC) 风险的具体机制尚未完全理解.
- 了解POPs,遗传学和表观遗传学之间的相互作用对于评估CRC风险至关重要.
研究的目的:
- 研究与结直肠癌风险有关的POP暴露,遗传变异和表观遗传修饰之间的关联.
- 为了确定与CRC有显著关联的特定POP,并评估它们的预测价值.
- 阐明分子机制,包括遗传和表观遗传因素,是POP暴露和CRC之间的联系的基础.
主要方法:
- 在中国人群中进行了一项病例控制研究.
- 使用气体染色学-并联质谱法 (GC-MS/MS) 测量了24种POPs的血度.
- 用无条件逻辑回归评估遗传变异和CRC风险之间的关联,并进行表达量化特征位点 (eQTL) 分析.
主要成果:
- 与对照组相比,结肠直肠癌患者的大多数测量POP度较高.
- 暴露于PCB153与结直肠癌风险有积极关联,具有很高的预测准确性 (AUC=0.72).
- rs67734009 C等位基因与降低CRC风险和降低血PCB153水平有关,并通过miR-3492结合和m6A修饰影响ESR1表达.
结论:
- 这项研究确定了潜在的遗传和表观遗传机制,将PCB153暴露与结直肠癌风险联系起来.
- 在PCB153暴露的背景下,rs67734009遗传变异在调节CRC风险方面发挥着作用.
- 研究结果为预防结直肠癌提供了针对POP暴露的准确保护策略的见解.
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