饮食代谢物与人类结肠癌的调控风险变体之间的相互作用
Tania N Fabo1,2, Robin M Meyers1,2, Evin Padhi3
1Program in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA.
bioRxiv : the preprint server for biology
|September 18, 2025
概括
饮食代谢物如丁酸盐和脱氧胆酸与遗传变异相互作用,影响结肠直肠癌 (CRC) 风险. 这些相互作用可以改变基因表达,可能导致癌症的发展.
科学领域:
- 遗传学 遗传学 是一个
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 非编码DNA中的遗传变异与结直肠癌 (CRC) 易感性有关.
- 这些调节区域可能与饮食因素相互作用,影响基因表达和癌症风险.
研究的目的:
- 调查CRC相关的饮食代谢物对调控变异的影响.
- 确定影响CRC风险的基因环境相互作用 (GxE).
主要方法:
- 利用大规模并行报告测试 (MPRA) 来测试3703种与CRC相关的变异.
- 评估了丁酸盐和脱氧胆酸对人类结肠细胞变异性活性的影响.
主要成果:
- 确定了1595种变种与饮食中的代谢物相互作用.
- 观察到基因失调,包括MED13L,NKD2和Wnt/β-catenin信号调节器.
- 发现酸和脱氧胆酸对特定位置的相反作用,涉及FOSL1和SP1.
结论:
- 饮食代谢物与CRC遗传风险位相互作用,影响基因表达.
- 这些发现突出了CRC病因学中的潜在基因环境相互作用.
- MPRA与环境因素相结合,为研究常见癌症中的GxE提供了一种方法.
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