内分泌干扰化学物质,血液代谢和表观遗传学对乳腺癌风险的影响:一个多维的门德尔随机化研究
Ningning Song1, Xinquan Xi1, Kuan Yang2
1Department of Breast Surgery, Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Shushan District, Hefei, Anhui 230022, PR China.
Ecotoxicology and environmental safety
|February 4, 2025
概括
环境内分泌干扰化学物质 (EDC),如 parabens 和 phthalates 显示与乳腺癌亚型的特定关联. 咖啡酸硫酸和甲基酸盐可能会调解这些效应,突出显示Luminal A和三阴性乳腺癌 (TNBC) 的潜在生物标志物.
科学领域:
- 环境健康 环境健康
- 遗传学 遗传学 是一个
- 癌症研究 癌症研究
背景情况:
- 将内分泌干扰化学物质 (EDC) 与乳腺癌联系在一起的研究是有限的和不确定的.
- 门德尔随机化 (MR) 提供了一个强大的方法来评估因果关系,通过尽量减少混和反向因果关系.
- 了解EDC对不同乳腺癌亚型的影响对于公共卫生至关重要.
研究的目的:
- 通过MR检测对双,和酸盐对整体乳腺癌及其亚型的因果作用进行研究.
- 探索血液代谢的调解作用和DNA甲基化变化的影响.
- 专注于欧洲人口的遗传相关性.
主要方法:
- 采用孟德尔随机化 (MR) 分析EDC与乳腺癌风险之间的遗传关联.
- 利用调解分析来识别将EDC与特定癌症亚型联系起来的血液代谢物.
- 进行了表观遗传分析,以检查特定CpG位点的EDC相关的DNA甲基化变化.
主要成果:
- 确定了n-丁 (n-BuP) 和Luminal A乳腺癌之间的积极关联.
- 在单甲基甲酸盐和Luminal B乳腺癌之间发现了负面关联.
- 观察到单异布甲酸盐 (MiBP) 和三阴性乳腺癌 (TNBC) 之间的积极关联.
- 咖啡酸硫酸和咖啡因与素的比率介导了n-BuP对Luminal A的影响;甲基糖介导了MiBP对TNBC的影响.
- 与EDC暴露和乳腺癌风险相关的特定DNA甲基化变化 (cg26325335, cg08537847, cg27454300).
结论:
- 特定的EDC,包括n-丁和单异-丁甲酸盐,与不同的乳腺癌亚型有因果关系.
- 血液代谢物和DNA甲基化模式可能会调解EDCs的致癌作用.
- 结果表明早期检测和干预的潜在生物标志物,需要进一步验证.
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