一种BaP激活的超级增强剂中的遗传变异通过促进AhR介导的FAM227A表达来增加前列腺癌的风险
Lulu Fan1,2, Hao Wang1,2, Shuai Ben1,2
1Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, China.
Journal of biomedical research
|February 27, 2024
概括
超级增强剂中的遗传变异会影响前列腺癌风险. 子[a]烯暴露通过烯碳化合物受体与这些变体相互作用,促进癌症的发展.
科学领域:
- 遗传学 是一个遗传学.
- 环境健康 环境健康
- 在瘤学瘤学.
背景情况:
- 超级增强剂 (SE) 的遗传变异与疾病风险有关.
- 子[a]烯 (BaP) 暴露与恶性瘤风险有关.
- 在SE变体,BaP和前列腺癌之间的相互作用还不太清楚.
研究的目的:
- 调查SE的遗传变异在前列腺癌风险中的作用.
- 探索将BaP暴露,SE变种和前列腺癌联系在一起的分子机制.
- 要确定是否有基碳化合物受体 (AhR) 调解这些效应.
主要方法:
- 用于遗传关联研究的物流回归分析.
- 生物信息学分析以预测转录因子结合和基因相互作用.
- 功能实验和BaP急性暴露以评估生物功能.
主要成果:
- 22q-SE中的rs5750581T>C变异与前列腺癌风险增加有显著的关联.
- 链接变体rs6001092T>G位于AhR基因中,与FAM227A促进体相互作用.
- 在暴露于BaP时,rs6001092-G基因基因增强了AhR结合,上调FAM227A,并促进恶性前列腺癌表型.
结论:
- AhR作为BaP的环境传感器,调节SE调节的前列腺癌风险.
- 遗传性SE变异可能在环境致癌物暴露下导致前列腺癌风险.
- 这项研究为前列腺癌的病因提供了新的见解,涉及遗传和环境因素.
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